Mary Ann Moon

A woman's risk of premenopausal breast cancer appears to be related to the weight of the placentas from her pregnancies, Sven Cnattingius, M.D., Ph.D., of the Karolinska Institutet, Stockholm, and his associates reported.

The heavier the placental weight, the higher the risk that breast cancer will develop before the woman reaches 50 years of age, the researchers said.

Placental weight can serve as an indirect marker of hormonal exposure during pregnancy, since the placenta is the major source of most pregnancy hormones. “Our findings support the hypothesis that exposure to pregnancy hormones during the limited time-window represented by a pregnancy appears to influence mothers' subsequent risk of breast cancer,” Dr. Cnattingius and his associates said (JAMA 2005;294:2474–80).

The findings appear to show that higher levels of pregnancy hormones substantially raise the risk of breast cancer. Alternatively, it is possible that higher placental weights are associated with lower maternal levels of antiestrogenic hormones such as testosterone and α-fetoprotein, which may play an inhibitory role in the development of breast cancer. Or it may turn out that higher placental weights are related to higher levels of other substances, such as insulinlike growth factor, that may promote carcinogenesis in the breast.

It is also possible that some other, as yet unidentified, factor acts simultaneously to increase placental weight and raise the mother's risk of breast cancer, they said.

They studied prospectively collected data on the singleton births of 314,019 Swedish women who delivered between 1982 and 1989. More than 121,000 of these women also had a second singleton birth during that study period. The women were followed until 2002. A total of 2,216 of these women (0.7%) developed breast cancer during follow-up, and 95% of them were diagnosed before they reached age 50.

The incidence of breast cancer consistently increased with rising placental weight, from 3.99 per 10,000 person-years when placental weight was 499 g or less to 5.30 when placental weight was 700 g or more. In the subset of women who had multiple deliveries, those with higher placental weights in two pregnancies had double the breast cancer risk of women who had lower placental weights in two pregnancies.

In contrast, breast cancer incidence was not related to birth weight or length of gestation, after the data were adjusted for placental weight. This finding indicates that placental weight is “a better indicator of the hormonal milieu than birth weight” or other birth parameters, Dr. Cnattingius and his associates said.

They added that in their study, breast cancer risk was not found to be related to other potentially relevant risk factors such as the infant's gender, pregnancy complications, and maternal demographic traits.

The link between placental weight and breast cancer risk was more pronounced among women who were 30 years of age or older when they had their first child. This finding supports the suggestion that elevated pregnancy hormones may promote the growth of either premalignant cells or preexisting malignant cells in the breast, because women of older childbearing age would be more likely to harbor cells whose malignant transformation has already begun, the investigators said.

They noted that placental weight is “an imprecise measure of the endocrine capacity of placental tissue.” Placental weight includes both vital tissue and degenerative tissue, since the placenta stops growing before the fetus does. “Moreover, the amount of blood in the placenta influences placental weight, and routines to clear the placenta from blood after childbirth may differ between hospitals.”

Despite this limitation, the study “was able to demonstrate a substantially increased risk in maternal breast cancer associated with higher placental weight,” they said.

A woman's risk of premenopausal breast cancer appears to be related to the weight of the placentas from her pregnancies, Sven Cnattingius, M.D., Ph.D., of the Karolinska Institutet, Stockholm, and his associates reported.

The heavier the placental weight, the higher the risk that breast cancer will develop before the woman reaches 50 years of age, the researchers said.

Placental weight can serve as an indirect marker of hormonal exposure during pregnancy, since the placenta is the major source of most pregnancy hormones. “Our findings support the hypothesis that exposure to pregnancy hormones during the limited time-window represented by a pregnancy appears to influence mothers' subsequent risk of breast cancer,” Dr. Cnattingius and his associates said (JAMA 2005;294:2474–80).

The findings appear to show that higher levels of pregnancy hormones substantially raise the risk of breast cancer. Alternatively, it is possible that higher placental weights are associated with lower maternal levels of antiestrogenic hormones such as testosterone and α-fetoprotein, which may play an inhibitory role in the development of breast cancer. Or it may turn out that higher placental weights are related to higher levels of other substances, such as insulinlike growth factor, that may promote carcinogenesis in the breast.

It is also possible that some other, as yet unidentified, factor acts simultaneously to increase placental weight and raise the mother's risk of breast cancer, they said.

They studied prospectively collected data on the singleton births of 314,019 Swedish women who delivered between 1982 and 1989. More than 121,000 of these women also had a second singleton birth during that study period. The women were followed until 2002. A total of 2,216 of these women (0.7%) developed breast cancer during follow-up, and 95% of them were diagnosed before they reached age 50.

The incidence of breast cancer consistently increased with rising placental weight, from 3.99 per 10,000 person-years when placental weight was 499 g or less to 5.30 when placental weight was 700 g or more. In the subset of women who had multiple deliveries, those with higher placental weights in two pregnancies had double the breast cancer risk of women who had lower placental weights in two pregnancies.

In contrast, breast cancer incidence was not related to birth weight or length of gestation, after the data were adjusted for placental weight. This finding indicates that placental weight is “a better indicator of the hormonal milieu than birth weight” or other birth parameters, Dr. Cnattingius and his associates said.

They added that in their study, breast cancer risk was not found to be related to other potentially relevant risk factors such as the infant's gender, pregnancy complications, and maternal demographic traits.

The link between placental weight and breast cancer risk was more pronounced among women who were 30 years of age or older when they had their first child. This finding supports the suggestion that elevated pregnancy hormones may promote the growth of either premalignant cells or preexisting malignant cells in the breast, because women of older childbearing age would be more likely to harbor cells whose malignant transformation has already begun, the investigators said.

They noted that placental weight is “an imprecise measure of the endocrine capacity of placental tissue.” Placental weight includes both vital tissue and degenerative tissue, since the placenta stops growing before the fetus does. “Moreover, the amount of blood in the placenta influences placental weight, and routines to clear the placenta from blood after childbirth may differ between hospitals.”

Despite this limitation, the study “was able to demonstrate a substantially increased risk in maternal breast cancer associated with higher placental weight,” they said.

A woman's risk of premenopausal breast cancer appears to be related to the weight of the placentas from her pregnancies, Sven Cnattingius, M.D., Ph.D., of the Karolinska Institutet, Stockholm, and his associates reported.

The heavier the placental weight, the higher the risk that breast cancer will develop before the woman reaches 50 years of age, the researchers said.

Placental weight can serve as an indirect marker of hormonal exposure during pregnancy, since the placenta is the major source of most pregnancy hormones. “Our findings support the hypothesis that exposure to pregnancy hormones during the limited time-window represented by a pregnancy appears to influence mothers' subsequent risk of breast cancer,” Dr. Cnattingius and his associates said (JAMA 2005;294:2474–80).

The findings appear to show that higher levels of pregnancy hormones substantially raise the risk of breast cancer. Alternatively, it is possible that higher placental weights are associated with lower maternal levels of antiestrogenic hormones such as testosterone and α-fetoprotein, which may play an inhibitory role in the development of breast cancer. Or it may turn out that higher placental weights are related to higher levels of other substances, such as insulinlike growth factor, that may promote carcinogenesis in the breast.

It is also possible that some other, as yet unidentified, factor acts simultaneously to increase placental weight and raise the mother's risk of breast cancer, they said.

They studied prospectively collected data on the singleton births of 314,019 Swedish women who delivered between 1982 and 1989. More than 121,000 of these women also had a second singleton birth during that study period. The women were followed until 2002. A total of 2,216 of these women (0.7%) developed breast cancer during follow-up, and 95% of them were diagnosed before they reached age 50.

The incidence of breast cancer consistently increased with rising placental weight, from 3.99 per 10,000 person-years when placental weight was 499 g or less to 5.30 when placental weight was 700 g or more. In the subset of women who had multiple deliveries, those with higher placental weights in two pregnancies had double the breast cancer risk of women who had lower placental weights in two pregnancies.

In contrast, breast cancer incidence was not related to birth weight or length of gestation, after the data were adjusted for placental weight. This finding indicates that placental weight is “a better indicator of the hormonal milieu than birth weight” or other birth parameters, Dr. Cnattingius and his associates said.

They added that in their study, breast cancer risk was not found to be related to other potentially relevant risk factors such as the infant's gender, pregnancy complications, and maternal demographic traits.

The link between placental weight and breast cancer risk was more pronounced among women who were 30 years of age or older when they had their first child. This finding supports the suggestion that elevated pregnancy hormones may promote the growth of either premalignant cells or preexisting malignant cells in the breast, because women of older childbearing age would be more likely to harbor cells whose malignant transformation has already begun, the investigators said.

They noted that placental weight is “an imprecise measure of the endocrine capacity of placental tissue.” Placental weight includes both vital tissue and degenerative tissue, since the placenta stops growing before the fetus does. “Moreover, the amount of blood in the placenta influences placental weight, and routines to clear the placenta from blood after childbirth may differ between hospitals.”

Despite this limitation, the study “was able to demonstrate a substantially increased risk in maternal breast cancer associated with higher placental weight,” they said.

Women who have placental syndromes are at high risk for premature cardiovascular disease, particularly if there is associated fetal compromise, according to Joel G. Ray, M.D., of the University of Toronto, and his associates.

The level of cardiovascular risk conferred by a placental syndrome—preeclampsia, gestational hypertension, placental abruption, or placental infarction—is comparable with that of such conventional risk factors as hypertension, obesity, diabetes, and dyslipidemia. “We believe that maternal placental syndrome should be considered an additional risk factor for cardiovascular disease in women, especially when the woman's fetus is adversely affected,” Dr. Ray, of the division of obstetrics and gynecology at the university, and his associates said (Lancet 2005;366:1797–803).

They assessed outcomes in a population-based study of Ontario residents who gave birth between 1990 and 2004. The mean maternal age at delivery was 28 years. Of 1,026,265 subjects, 75,380 (7%) were diagnosed as having a placental syndrome.

After a mean of 8.7 years' follow-up, cardiovascular events occurred in more than twice as many women with placental syndromes as in women without placental syndromes, irrespective of the presence of potential confounders such as diabetes. The rate of events was 500/million person-years among those with placental syndromes, compared with 200/million in those without placental syndromes.

The women's mean age was 38 years at the time of the first cardiovascular event. These included coronary, cerebrovascular, or peripheral artery events, or the need for a revascularization procedure.

The risk for cardiovascular events was even higher if the placental syndromes led to fetal growth restriction or intrauterine fetal death. It was higher still in women who had preexisting cardiovascular risk factors when they became pregnant, such as smoking or various features of the metabolic syndrome.

The findings do not imply placental disorders cause cardiovascular events to occur in the near future, the investigators said. “Rather, a more plausible explanation relates to a woman's abnormal metabolic milieu that predates her pregnancy and continues after delivery. This chronic state of dysmetabolism might create an inhospitable environment during the development of the placental spiral arteries, which can adversely affect fetal health, while negatively affecting the large arteries of a woman's heart, brain, and extremities over a broader period of time,” they noted.

Physicians “should try to ensure that women are a healthy weight before they enter their reproductive years.” This should reduce their risk for placental syndromes and fetal compromise as well as for cardiovascular disease, the researchers said.

It remains unknown whether women who have had placental syndromes might lower their risk of premature cardiovascular disease by making lifestyle changes, they added.

Women who have placental syndromes are at high risk for premature cardiovascular disease, particularly if there is associated fetal compromise, according to Joel G. Ray, M.D., of the University of Toronto, and his associates.

The level of cardiovascular risk conferred by a placental syndrome—preeclampsia, gestational hypertension, placental abruption, or placental infarction—is comparable with that of such conventional risk factors as hypertension, obesity, diabetes, and dyslipidemia. “We believe that maternal placental syndrome should be considered an additional risk factor for cardiovascular disease in women, especially when the woman's fetus is adversely affected,” Dr. Ray, of the division of obstetrics and gynecology at the university, and his associates said (Lancet 2005;366:1797–803).

They assessed outcomes in a population-based study of Ontario residents who gave birth between 1990 and 2004. The mean maternal age at delivery was 28 years. Of 1,026,265 subjects, 75,380 (7%) were diagnosed as having a placental syndrome.

After a mean of 8.7 years' follow-up, cardiovascular events occurred in more than twice as many women with placental syndromes as in women without placental syndromes, irrespective of the presence of potential confounders such as diabetes. The rate of events was 500/million person-years among those with placental syndromes, compared with 200/million in those without placental syndromes.

The women's mean age was 38 years at the time of the first cardiovascular event. These included coronary, cerebrovascular, or peripheral artery events, or the need for a revascularization procedure.

The risk for cardiovascular events was even higher if the placental syndromes led to fetal growth restriction or intrauterine fetal death. It was higher still in women who had preexisting cardiovascular risk factors when they became pregnant, such as smoking or various features of the metabolic syndrome.

The findings do not imply placental disorders cause cardiovascular events to occur in the near future, the investigators said. “Rather, a more plausible explanation relates to a woman's abnormal metabolic milieu that predates her pregnancy and continues after delivery. This chronic state of dysmetabolism might create an inhospitable environment during the development of the placental spiral arteries, which can adversely affect fetal health, while negatively affecting the large arteries of a woman's heart, brain, and extremities over a broader period of time,” they noted.

Physicians “should try to ensure that women are a healthy weight before they enter their reproductive years.” This should reduce their risk for placental syndromes and fetal compromise as well as for cardiovascular disease, the researchers said.

It remains unknown whether women who have had placental syndromes might lower their risk of premature cardiovascular disease by making lifestyle changes, they added.

Women who have placental syndromes are at high risk for premature cardiovascular disease, particularly if there is associated fetal compromise, according to Joel G. Ray, M.D., of the University of Toronto, and his associates.

The level of cardiovascular risk conferred by a placental syndrome—preeclampsia, gestational hypertension, placental abruption, or placental infarction—is comparable with that of such conventional risk factors as hypertension, obesity, diabetes, and dyslipidemia. “We believe that maternal placental syndrome should be considered an additional risk factor for cardiovascular disease in women, especially when the woman's fetus is adversely affected,” Dr. Ray, of the division of obstetrics and gynecology at the university, and his associates said (Lancet 2005;366:1797–803).

They assessed outcomes in a population-based study of Ontario residents who gave birth between 1990 and 2004. The mean maternal age at delivery was 28 years. Of 1,026,265 subjects, 75,380 (7%) were diagnosed as having a placental syndrome.

After a mean of 8.7 years' follow-up, cardiovascular events occurred in more than twice as many women with placental syndromes as in women without placental syndromes, irrespective of the presence of potential confounders such as diabetes. The rate of events was 500/million person-years among those with placental syndromes, compared with 200/million in those without placental syndromes.

The women's mean age was 38 years at the time of the first cardiovascular event. These included coronary, cerebrovascular, or peripheral artery events, or the need for a revascularization procedure.

The risk for cardiovascular events was even higher if the placental syndromes led to fetal growth restriction or intrauterine fetal death. It was higher still in women who had preexisting cardiovascular risk factors when they became pregnant, such as smoking or various features of the metabolic syndrome.

The findings do not imply placental disorders cause cardiovascular events to occur in the near future, the investigators said. “Rather, a more plausible explanation relates to a woman's abnormal metabolic milieu that predates her pregnancy and continues after delivery. This chronic state of dysmetabolism might create an inhospitable environment during the development of the placental spiral arteries, which can adversely affect fetal health, while negatively affecting the large arteries of a woman's heart, brain, and extremities over a broader period of time,” they noted.

Physicians “should try to ensure that women are a healthy weight before they enter their reproductive years.” This should reduce their risk for placental syndromes and fetal compromise as well as for cardiovascular disease, the researchers said.

It remains unknown whether women who have had placental syndromes might lower their risk of premature cardiovascular disease by making lifestyle changes, they added.

Updated clinical practice guidelines now call for annual CT scanning of the chest and abdomen in colorectal cancer patients who are at high risk for recurrence and who would be candidates for further resection if metastases were found.

An expert panel of the American Society of Clinical Oncology revisited the issue of stage II or III colon or rectal cancer surveillance because treatment and monitoring of the disease have changed since the previous clinical practice guidelines were issued in 2000. There have been substantial advances in tumor respectability and patient survival, “supporting more aggressive follow-up after diagnosis and treatment,” the panel noted.

The previous guidelines recommended against CT surveillance based on evidence that identification of lung and liver metastases on CT did not influence survival. But the panel's review of studies published since 1999 showed a 25% lower mortality in patients with stage II or III colorectal cancer who have CT monitoring, because it can identify such metastases at an early enough stage to now allow limited but curative surgical resection.

The updated guidelines also now recommend considering annual pelvic CT scanning for surveillance of patients with rectal cancer who have unfavorable prognostic factors, especially those who were not treated with radiotherapy. The data do not justify such surveillance for lower-risk patients, according to the panel.

The guidelines have been published and are posted online at www.jco.org

Updated guidelines for patients, titled “Follow-Up Care for Colorectal Cancer,” are available on the patient Web site, at www.plwc.org

The new guidelines call for serum testing for carcinoembryonic antigen (CEA) every 3 months for at least 3 years after initial diagnosis and treatment. Colonoscopy is recommended postoperatively to document freedom from carcinomas and polyps, as well as at year 3 and at 5-year intervals thereafter.

The guidelines also address American Gastroenterological Association recommendations for more frequent colonoscopy in certain high-risk patients.

The new guidelines recommend regular primary care visits every 3–6 months for the first 3 years, every 6 months during years 4 and 5, and as often as the physician deems necessary thereafter.

Updated clinical practice guidelines now call for annual CT scanning of the chest and abdomen in colorectal cancer patients who are at high risk for recurrence and who would be candidates for further resection if metastases were found.

An expert panel of the American Society of Clinical Oncology revisited the issue of stage II or III colon or rectal cancer surveillance because treatment and monitoring of the disease have changed since the previous clinical practice guidelines were issued in 2000. There have been substantial advances in tumor respectability and patient survival, “supporting more aggressive follow-up after diagnosis and treatment,” the panel noted.

The previous guidelines recommended against CT surveillance based on evidence that identification of lung and liver metastases on CT did not influence survival. But the panel's review of studies published since 1999 showed a 25% lower mortality in patients with stage II or III colorectal cancer who have CT monitoring, because it can identify such metastases at an early enough stage to now allow limited but curative surgical resection.

The updated guidelines also now recommend considering annual pelvic CT scanning for surveillance of patients with rectal cancer who have unfavorable prognostic factors, especially those who were not treated with radiotherapy. The data do not justify such surveillance for lower-risk patients, according to the panel.

The guidelines have been published and are posted online at www.jco.org

Updated guidelines for patients, titled “Follow-Up Care for Colorectal Cancer,” are available on the patient Web site, at www.plwc.org

The new guidelines call for serum testing for carcinoembryonic antigen (CEA) every 3 months for at least 3 years after initial diagnosis and treatment. Colonoscopy is recommended postoperatively to document freedom from carcinomas and polyps, as well as at year 3 and at 5-year intervals thereafter.

The guidelines also address American Gastroenterological Association recommendations for more frequent colonoscopy in certain high-risk patients.

The new guidelines recommend regular primary care visits every 3–6 months for the first 3 years, every 6 months during years 4 and 5, and as often as the physician deems necessary thereafter.

Updated clinical practice guidelines now call for annual CT scanning of the chest and abdomen in colorectal cancer patients who are at high risk for recurrence and who would be candidates for further resection if metastases were found.

An expert panel of the American Society of Clinical Oncology revisited the issue of stage II or III colon or rectal cancer surveillance because treatment and monitoring of the disease have changed since the previous clinical practice guidelines were issued in 2000. There have been substantial advances in tumor respectability and patient survival, “supporting more aggressive follow-up after diagnosis and treatment,” the panel noted.

The previous guidelines recommended against CT surveillance based on evidence that identification of lung and liver metastases on CT did not influence survival. But the panel's review of studies published since 1999 showed a 25% lower mortality in patients with stage II or III colorectal cancer who have CT monitoring, because it can identify such metastases at an early enough stage to now allow limited but curative surgical resection.

The updated guidelines also now recommend considering annual pelvic CT scanning for surveillance of patients with rectal cancer who have unfavorable prognostic factors, especially those who were not treated with radiotherapy. The data do not justify such surveillance for lower-risk patients, according to the panel.

The guidelines have been published and are posted online at www.jco.org

Updated guidelines for patients, titled “Follow-Up Care for Colorectal Cancer,” are available on the patient Web site, at www.plwc.org

The new guidelines call for serum testing for carcinoembryonic antigen (CEA) every 3 months for at least 3 years after initial diagnosis and treatment. Colonoscopy is recommended postoperatively to document freedom from carcinomas and polyps, as well as at year 3 and at 5-year intervals thereafter.

The guidelines also address American Gastroenterological Association recommendations for more frequent colonoscopy in certain high-risk patients.

The new guidelines recommend regular primary care visits every 3–6 months for the first 3 years, every 6 months during years 4 and 5, and as often as the physician deems necessary thereafter.

Tamoxifen substantially cuts the risk of invasive and noninvasive breast cancer, researchers confirmed in an extended follow-up of the National Surgical Adjuvant Breast and Bowel Project that was initially reported in 1998.

This update of the NSABP study involved 13,207 women at high risk of developing breast cancer who had participated in the initial study in 1992–1997 and were followed for an additional 7 years. A total of 6,597 subjects composed the tamoxifen group and 6,610 formed the placebo group.

All the benefits and risks of tamoxifen therapy that had been reported in the initial study were borne out in this extended study, according to Bernard Fisher, M.D., scientific director of the NSABP and distinguished surgical professor at the University of Pittsburgh.

Tamoxifen was linked to a 43% reduction in the cumulative rate of invasive breast cancer. The rate was 24.8 cancers/1,000 women taking tamoxifen, compared with 42.5/1,000 women taking placebo.

Similarly, tamoxifen reduced the cumulative rate of noninvasive breast cancer by 37%. The rate was 10.2 cancers/1,000 women taking tamoxifen, compared with 15.8/1,000 women taking placebo.

The drug cut the risk of breast cancer in all subgroups of subjects categorized by age, history of lobular carcinoma in situ (LCIS), history of atypical hyperplasia, and level of predicted risk of breast cancer.

Among women who took tamoxifen, the incidence of breast cancer remained relatively constant throughout the 7 years of follow-up, remaining stable for at least 2 years after they finished a 5-year course of the drug (J. Natl. Cancer Inst. 2005; 97:1652–62).

As it did in the initial NSBAP study, tamoxifen also reduced the risk of osteoporotic fractures of the hip, spine, and radius in this extended study. Among women aged 50 and older—the group that sustained nearly 90% of such fractures—tamoxifen decreased the fracture rate by 29%.

However, this extended study also confirmed the adverse effects of the drug that had been reported in the 1998 study regarding endometrial cancer, thromboses, and cataracts.

Tamoxifen increased the rate of invasive endometrial cancer in women aged 50 or older. The cumulative rate was 15.6 such cancers/1,000 women, compared with 4.7/1,000 women in the placebo group. However, two related findings were encouraging. A total of 67 of the 70 cases of invasive endometrial cancer were stage I malignancies, and tamoxifen therapy did not alter the risk for cancer at sites other than the breast and endometrium, the investigators noted.

The drug also raised the rate of pulmonary embolism in women aged 50 or older. Tamoxifen also increased the rates of stroke and deep vein thrombosis, but not to a statistically significant degree.

Women who took tamoxifen also were at slightly higher risk of developing cataracts than were those who received placebo.

“Evaluation of the frequency of other adverse eye-related events from tamoxifen failed to demonstrate vision-threatening toxicity,” the investigators said.

Mortality rates were similar among women who took tamoxifen and those who took placebo. This finding was not unexpected, given that it would require much longer follow-up—most likely 15–20 years—to detect a definitive reduction in mortality, Dr. Fisher and associates noted.

New trials on breast cancer prevention currently are underway in postmenopausal women “to evaluate other agents that could be more effective than tamoxifen in decreasing the risk of breast tumors and reducing the frequency of undesirable side effects noted with the drug. … Until one of these trials demonstrates a greater net benefit from an alternative therapy, tamoxifen remains the only proven chemopreventive treatment for breast cancer risk reduction,” they added.

Tamoxifen substantially cuts the risk of invasive and noninvasive breast cancer, researchers confirmed in an extended follow-up of the National Surgical Adjuvant Breast and Bowel Project that was initially reported in 1998.

This update of the NSABP study involved 13,207 women at high risk of developing breast cancer who had participated in the initial study in 1992–1997 and were followed for an additional 7 years. A total of 6,597 subjects composed the tamoxifen group and 6,610 formed the placebo group.

All the benefits and risks of tamoxifen therapy that had been reported in the initial study were borne out in this extended study, according to Bernard Fisher, M.D., scientific director of the NSABP and distinguished surgical professor at the University of Pittsburgh.

Tamoxifen was linked to a 43% reduction in the cumulative rate of invasive breast cancer. The rate was 24.8 cancers/1,000 women taking tamoxifen, compared with 42.5/1,000 women taking placebo.

Similarly, tamoxifen reduced the cumulative rate of noninvasive breast cancer by 37%. The rate was 10.2 cancers/1,000 women taking tamoxifen, compared with 15.8/1,000 women taking placebo.

The drug cut the risk of breast cancer in all subgroups of subjects categorized by age, history of lobular carcinoma in situ (LCIS), history of atypical hyperplasia, and level of predicted risk of breast cancer.

Among women who took tamoxifen, the incidence of breast cancer remained relatively constant throughout the 7 years of follow-up, remaining stable for at least 2 years after they finished a 5-year course of the drug (J. Natl. Cancer Inst. 2005; 97:1652–62).

As it did in the initial NSBAP study, tamoxifen also reduced the risk of osteoporotic fractures of the hip, spine, and radius in this extended study. Among women aged 50 and older—the group that sustained nearly 90% of such fractures—tamoxifen decreased the fracture rate by 29%.

However, this extended study also confirmed the adverse effects of the drug that had been reported in the 1998 study regarding endometrial cancer, thromboses, and cataracts.

Tamoxifen increased the rate of invasive endometrial cancer in women aged 50 or older. The cumulative rate was 15.6 such cancers/1,000 women, compared with 4.7/1,000 women in the placebo group. However, two related findings were encouraging. A total of 67 of the 70 cases of invasive endometrial cancer were stage I malignancies, and tamoxifen therapy did not alter the risk for cancer at sites other than the breast and endometrium, the investigators noted.

The drug also raised the rate of pulmonary embolism in women aged 50 or older. Tamoxifen also increased the rates of stroke and deep vein thrombosis, but not to a statistically significant degree.

Women who took tamoxifen also were at slightly higher risk of developing cataracts than were those who received placebo.

“Evaluation of the frequency of other adverse eye-related events from tamoxifen failed to demonstrate vision-threatening toxicity,” the investigators said.

Mortality rates were similar among women who took tamoxifen and those who took placebo. This finding was not unexpected, given that it would require much longer follow-up—most likely 15–20 years—to detect a definitive reduction in mortality, Dr. Fisher and associates noted.

New trials on breast cancer prevention currently are underway in postmenopausal women “to evaluate other agents that could be more effective than tamoxifen in decreasing the risk of breast tumors and reducing the frequency of undesirable side effects noted with the drug. … Until one of these trials demonstrates a greater net benefit from an alternative therapy, tamoxifen remains the only proven chemopreventive treatment for breast cancer risk reduction,” they added.

Tamoxifen substantially cuts the risk of invasive and noninvasive breast cancer, researchers confirmed in an extended follow-up of the National Surgical Adjuvant Breast and Bowel Project that was initially reported in 1998.

This update of the NSABP study involved 13,207 women at high risk of developing breast cancer who had participated in the initial study in 1992–1997 and were followed for an additional 7 years. A total of 6,597 subjects composed the tamoxifen group and 6,610 formed the placebo group.

All the benefits and risks of tamoxifen therapy that had been reported in the initial study were borne out in this extended study, according to Bernard Fisher, M.D., scientific director of the NSABP and distinguished surgical professor at the University of Pittsburgh.

Tamoxifen was linked to a 43% reduction in the cumulative rate of invasive breast cancer. The rate was 24.8 cancers/1,000 women taking tamoxifen, compared with 42.5/1,000 women taking placebo.

Similarly, tamoxifen reduced the cumulative rate of noninvasive breast cancer by 37%. The rate was 10.2 cancers/1,000 women taking tamoxifen, compared with 15.8/1,000 women taking placebo.

The drug cut the risk of breast cancer in all subgroups of subjects categorized by age, history of lobular carcinoma in situ (LCIS), history of atypical hyperplasia, and level of predicted risk of breast cancer.

Among women who took tamoxifen, the incidence of breast cancer remained relatively constant throughout the 7 years of follow-up, remaining stable for at least 2 years after they finished a 5-year course of the drug (J. Natl. Cancer Inst. 2005; 97:1652–62).

As it did in the initial NSBAP study, tamoxifen also reduced the risk of osteoporotic fractures of the hip, spine, and radius in this extended study. Among women aged 50 and older—the group that sustained nearly 90% of such fractures—tamoxifen decreased the fracture rate by 29%.

However, this extended study also confirmed the adverse effects of the drug that had been reported in the 1998 study regarding endometrial cancer, thromboses, and cataracts.

Tamoxifen increased the rate of invasive endometrial cancer in women aged 50 or older. The cumulative rate was 15.6 such cancers/1,000 women, compared with 4.7/1,000 women in the placebo group. However, two related findings were encouraging. A total of 67 of the 70 cases of invasive endometrial cancer were stage I malignancies, and tamoxifen therapy did not alter the risk for cancer at sites other than the breast and endometrium, the investigators noted.

The drug also raised the rate of pulmonary embolism in women aged 50 or older. Tamoxifen also increased the rates of stroke and deep vein thrombosis, but not to a statistically significant degree.

Women who took tamoxifen also were at slightly higher risk of developing cataracts than were those who received placebo.

“Evaluation of the frequency of other adverse eye-related events from tamoxifen failed to demonstrate vision-threatening toxicity,” the investigators said.

Mortality rates were similar among women who took tamoxifen and those who took placebo. This finding was not unexpected, given that it would require much longer follow-up—most likely 15–20 years—to detect a definitive reduction in mortality, Dr. Fisher and associates noted.

New trials on breast cancer prevention currently are underway in postmenopausal women “to evaluate other agents that could be more effective than tamoxifen in decreasing the risk of breast tumors and reducing the frequency of undesirable side effects noted with the drug. … Until one of these trials demonstrates a greater net benefit from an alternative therapy, tamoxifen remains the only proven chemopreventive treatment for breast cancer risk reduction,” they added.

The early, invasive treatment of acute coronary syndromes that is recommended by the American College of Cardiology, American Heart Association, and European Society of Cardiology was no better than a more conservative approach in a large, randomized clinical trial comparing the two strategies. The trial was undertaken becuase it was unclear if early revascularization lowered mortality in high-risk ACS patients, compared with early, intensive medical therapy followed by revascularization only in selected patients.

In the trial, 604 patients at 42 hospitals in the Netherlands were randomly assigned to undergo early angiography with percutaneous coronary intervention or coronary artery bypass graft surgery when appropriate, and 596 were assigned to medical management and proceeded to revascularization only if medical therapy failed.

Mortality at 1 year was identical in the two groups (2.5%), and freedom from angina was nearly identical. In contrast, the risk of MI was 5% higher in those who had early, invasive treatment, and most of the MIs were procedure related, reported Robbert J. de Winter, M.D., Ph.D., of the Academisch Medisch Centrum, Amsterdam, and his associates (N. Engl. J. Med. 2005;353:1095–104).

The early, invasive treatment of acute coronary syndromes that is recommended by the American College of Cardiology, American Heart Association, and European Society of Cardiology was no better than a more conservative approach in a large, randomized clinical trial comparing the two strategies. The trial was undertaken becuase it was unclear if early revascularization lowered mortality in high-risk ACS patients, compared with early, intensive medical therapy followed by revascularization only in selected patients.

In the trial, 604 patients at 42 hospitals in the Netherlands were randomly assigned to undergo early angiography with percutaneous coronary intervention or coronary artery bypass graft surgery when appropriate, and 596 were assigned to medical management and proceeded to revascularization only if medical therapy failed.

Mortality at 1 year was identical in the two groups (2.5%), and freedom from angina was nearly identical. In contrast, the risk of MI was 5% higher in those who had early, invasive treatment, and most of the MIs were procedure related, reported Robbert J. de Winter, M.D., Ph.D., of the Academisch Medisch Centrum, Amsterdam, and his associates (N. Engl. J. Med. 2005;353:1095–104).

The early, invasive treatment of acute coronary syndromes that is recommended by the American College of Cardiology, American Heart Association, and European Society of Cardiology was no better than a more conservative approach in a large, randomized clinical trial comparing the two strategies. The trial was undertaken becuase it was unclear if early revascularization lowered mortality in high-risk ACS patients, compared with early, intensive medical therapy followed by revascularization only in selected patients.

In the trial, 604 patients at 42 hospitals in the Netherlands were randomly assigned to undergo early angiography with percutaneous coronary intervention or coronary artery bypass graft surgery when appropriate, and 596 were assigned to medical management and proceeded to revascularization only if medical therapy failed.

Mortality at 1 year was identical in the two groups (2.5%), and freedom from angina was nearly identical. In contrast, the risk of MI was 5% higher in those who had early, invasive treatment, and most of the MIs were procedure related, reported Robbert J. de Winter, M.D., Ph.D., of the Academisch Medisch Centrum, Amsterdam, and his associates (N. Engl. J. Med. 2005;353:1095–104).

Low-Dose Coated Aspirin Inadequate

Many patients taking daily low-dose enteric-coated aspirin to prevent cardiovascular events show incomplete platelet inhibition, reported Andrew O. Maree, M.D., of the Royal College of Surgeons, Dublin, and his associates.

In a study involving healthy volunteers, Dr. Maree and his associates found that enteric-coated aspirin was less effective than plain aspirin at achieving platelet inhibition. They then assessed platelet response in 131 patients with stable cardiovascular disease (median age 63 years) who were taking 75 mg of coated aspirin daily.

Fifty-eight of these subjects (44%) showed an inadequate response to aspirin therapy, a finding “of increasing importance because many patients who take aspirin … for secondary prevention of CV events now receive low-dose enteric-coated preparations,” the investigators said (J. Am. Coll. Cardiol. 2005;47:1258–63).

Patient weight, body mass index, and age were significant predictors of this so-called aspirin resistance, with heavier and younger patients less likely to respond to aspirin therapy. It's likely that coated aspirin is less bioavailable than plain aspirin, which makes low doses of it insufficient to inhibit platelets in larger patients. It's also possible that younger patients are less responsive to aspirin because they have not yet developed age-related increases in drug sensitivity.

ED Signals Early Atherosclerosis

Erectile dysfunction predicted both the presence and the severity of subclinical coronary atherosclerosis in a study of 143 men, independently of traditional CAD risk factors, according to Emilio Chiurlia, Ph.D., and his associates at the University of Modena (Italy) Institute of Cardiology.

The researchers used CT-based estimates of coronary artery calcification to noninvasively assess 70 men with ED but no known CAD, as well as 73 control subjects matched for age, race, and coronary risk score. Asymptomatic atherosclerosis was more prevalent and more severe in the ED group. Endothelial function was significantly impaired in the ED patients, and their levels of subclinical systemic inflammation were significantly higher than those of controls (J. Am. Coll. Cardiol. 2005;46:1503–6).

“These data suggest that ED may be the earliest manifestation of a generalized vascular disease and that these patients may be at an increased risk of later developing CAD,” the investigators said.

Black Ethnicity a Risk Factor for PAD

African Americans have a significantly higher probability of developing peripheral artery disease than other ethnic groups—so much so that black ethnicity “can now be considered a consistent and independent risk factor for PAD at a magnitude similar to that of other established risk factors,” reported Michael H. Criqui, M.D., and his associates at the University of California, San Diego.

The researchers assessed the prevalence of PAD in a study of 2,343 current and retired UCSD employees and their spouses. They found 104 cases of PAD, for an overall prevalence of 4.4%. Blacks had the highest prevalence of PAD (7.8%), followed by whites (4.9%), Hispanics (1.8%), and Asians (1.4%) (Circulation 2005;112:2703–7).

The reason for this excess in PAD remains unknown. Although black subjects in general had lower occupational status and higher rates of diabetes and hypertension, those factors only partly accounted for their excess risk. It is possible that blacks have a greater genetic susceptibility to PAD, or that some unmeasured psychosocial variables may play a role, the investigators said.

Dyspnea Tied to High Mortality Risk

Patients who present for noninvasive cardiac testing with the sole symptom of dyspnea are at increased risk for cardiac death and death from any cause, even if they have no evidence of coronary artery disease or left ventricular systolic dysfunction.

This finding, from a study of nearly 18,000 subjects followed for a mean of 2 years, suggests that it may be appropriate to evaluate dyspnea in all patients referred for cardiac testing, said Aiden Abidov, M.D., Ph.D., of Cedars-Sinai Medical Center, Los Angeles, and his associates.

The researchers collected data on dyspnea from all patients undergoing myocardial-perfusion SPECT at rest and during exercise testing. They assessed data on 17,991 such patients and found that those with dyspnea but no other symptoms had a fourfold higher risk of cardiac death and more than twice the risk of noncardiac death during follow-up than patients with typical angina (N. Engl. J. Med. 2005;353:1889–98).

In an editorial, Thomas H. Marwick, M.B., Ph.D., of the University of Queensland, Brisbane, Australia, noted that these results “should remind us that cardiac symptoms other than chest pain are of value in evaluating patients with suspected CAD” (N. Engl. J. Med. 2005;353:1963–4).

Low-Dose Coated Aspirin Inadequate

Many patients taking daily low-dose enteric-coated aspirin to prevent cardiovascular events show incomplete platelet inhibition, reported Andrew O. Maree, M.D., of the Royal College of Surgeons, Dublin, and his associates.

In a study involving healthy volunteers, Dr. Maree and his associates found that enteric-coated aspirin was less effective than plain aspirin at achieving platelet inhibition. They then assessed platelet response in 131 patients with stable cardiovascular disease (median age 63 years) who were taking 75 mg of coated aspirin daily.

Fifty-eight of these subjects (44%) showed an inadequate response to aspirin therapy, a finding “of increasing importance because many patients who take aspirin … for secondary prevention of CV events now receive low-dose enteric-coated preparations,” the investigators said (J. Am. Coll. Cardiol. 2005;47:1258–63).

Patient weight, body mass index, and age were significant predictors of this so-called aspirin resistance, with heavier and younger patients less likely to respond to aspirin therapy. It's likely that coated aspirin is less bioavailable than plain aspirin, which makes low doses of it insufficient to inhibit platelets in larger patients. It's also possible that younger patients are less responsive to aspirin because they have not yet developed age-related increases in drug sensitivity.

ED Signals Early Atherosclerosis

Erectile dysfunction predicted both the presence and the severity of subclinical coronary atherosclerosis in a study of 143 men, independently of traditional CAD risk factors, according to Emilio Chiurlia, Ph.D., and his associates at the University of Modena (Italy) Institute of Cardiology.

The researchers used CT-based estimates of coronary artery calcification to noninvasively assess 70 men with ED but no known CAD, as well as 73 control subjects matched for age, race, and coronary risk score. Asymptomatic atherosclerosis was more prevalent and more severe in the ED group. Endothelial function was significantly impaired in the ED patients, and their levels of subclinical systemic inflammation were significantly higher than those of controls (J. Am. Coll. Cardiol. 2005;46:1503–6).

“These data suggest that ED may be the earliest manifestation of a generalized vascular disease and that these patients may be at an increased risk of later developing CAD,” the investigators said.

Black Ethnicity a Risk Factor for PAD

African Americans have a significantly higher probability of developing peripheral artery disease than other ethnic groups—so much so that black ethnicity “can now be considered a consistent and independent risk factor for PAD at a magnitude similar to that of other established risk factors,” reported Michael H. Criqui, M.D., and his associates at the University of California, San Diego.

The researchers assessed the prevalence of PAD in a study of 2,343 current and retired UCSD employees and their spouses. They found 104 cases of PAD, for an overall prevalence of 4.4%. Blacks had the highest prevalence of PAD (7.8%), followed by whites (4.9%), Hispanics (1.8%), and Asians (1.4%) (Circulation 2005;112:2703–7).

The reason for this excess in PAD remains unknown. Although black subjects in general had lower occupational status and higher rates of diabetes and hypertension, those factors only partly accounted for their excess risk. It is possible that blacks have a greater genetic susceptibility to PAD, or that some unmeasured psychosocial variables may play a role, the investigators said.

Dyspnea Tied to High Mortality Risk

Patients who present for noninvasive cardiac testing with the sole symptom of dyspnea are at increased risk for cardiac death and death from any cause, even if they have no evidence of coronary artery disease or left ventricular systolic dysfunction.

This finding, from a study of nearly 18,000 subjects followed for a mean of 2 years, suggests that it may be appropriate to evaluate dyspnea in all patients referred for cardiac testing, said Aiden Abidov, M.D., Ph.D., of Cedars-Sinai Medical Center, Los Angeles, and his associates.

The researchers collected data on dyspnea from all patients undergoing myocardial-perfusion SPECT at rest and during exercise testing. They assessed data on 17,991 such patients and found that those with dyspnea but no other symptoms had a fourfold higher risk of cardiac death and more than twice the risk of noncardiac death during follow-up than patients with typical angina (N. Engl. J. Med. 2005;353:1889–98).

In an editorial, Thomas H. Marwick, M.B., Ph.D., of the University of Queensland, Brisbane, Australia, noted that these results “should remind us that cardiac symptoms other than chest pain are of value in evaluating patients with suspected CAD” (N. Engl. J. Med. 2005;353:1963–4).

Low-Dose Coated Aspirin Inadequate

Many patients taking daily low-dose enteric-coated aspirin to prevent cardiovascular events show incomplete platelet inhibition, reported Andrew O. Maree, M.D., of the Royal College of Surgeons, Dublin, and his associates.

In a study involving healthy volunteers, Dr. Maree and his associates found that enteric-coated aspirin was less effective than plain aspirin at achieving platelet inhibition. They then assessed platelet response in 131 patients with stable cardiovascular disease (median age 63 years) who were taking 75 mg of coated aspirin daily.

Fifty-eight of these subjects (44%) showed an inadequate response to aspirin therapy, a finding “of increasing importance because many patients who take aspirin … for secondary prevention of CV events now receive low-dose enteric-coated preparations,” the investigators said (J. Am. Coll. Cardiol. 2005;47:1258–63).

Patient weight, body mass index, and age were significant predictors of this so-called aspirin resistance, with heavier and younger patients less likely to respond to aspirin therapy. It's likely that coated aspirin is less bioavailable than plain aspirin, which makes low doses of it insufficient to inhibit platelets in larger patients. It's also possible that younger patients are less responsive to aspirin because they have not yet developed age-related increases in drug sensitivity.

ED Signals Early Atherosclerosis

Erectile dysfunction predicted both the presence and the severity of subclinical coronary atherosclerosis in a study of 143 men, independently of traditional CAD risk factors, according to Emilio Chiurlia, Ph.D., and his associates at the University of Modena (Italy) Institute of Cardiology.

The researchers used CT-based estimates of coronary artery calcification to noninvasively assess 70 men with ED but no known CAD, as well as 73 control subjects matched for age, race, and coronary risk score. Asymptomatic atherosclerosis was more prevalent and more severe in the ED group. Endothelial function was significantly impaired in the ED patients, and their levels of subclinical systemic inflammation were significantly higher than those of controls (J. Am. Coll. Cardiol. 2005;46:1503–6).

“These data suggest that ED may be the earliest manifestation of a generalized vascular disease and that these patients may be at an increased risk of later developing CAD,” the investigators said.

Black Ethnicity a Risk Factor for PAD

African Americans have a significantly higher probability of developing peripheral artery disease than other ethnic groups—so much so that black ethnicity “can now be considered a consistent and independent risk factor for PAD at a magnitude similar to that of other established risk factors,” reported Michael H. Criqui, M.D., and his associates at the University of California, San Diego.

The researchers assessed the prevalence of PAD in a study of 2,343 current and retired UCSD employees and their spouses. They found 104 cases of PAD, for an overall prevalence of 4.4%. Blacks had the highest prevalence of PAD (7.8%), followed by whites (4.9%), Hispanics (1.8%), and Asians (1.4%) (Circulation 2005;112:2703–7).

The reason for this excess in PAD remains unknown. Although black subjects in general had lower occupational status and higher rates of diabetes and hypertension, those factors only partly accounted for their excess risk. It is possible that blacks have a greater genetic susceptibility to PAD, or that some unmeasured psychosocial variables may play a role, the investigators said.

Dyspnea Tied to High Mortality Risk

Patients who present for noninvasive cardiac testing with the sole symptom of dyspnea are at increased risk for cardiac death and death from any cause, even if they have no evidence of coronary artery disease or left ventricular systolic dysfunction.

This finding, from a study of nearly 18,000 subjects followed for a mean of 2 years, suggests that it may be appropriate to evaluate dyspnea in all patients referred for cardiac testing, said Aiden Abidov, M.D., Ph.D., of Cedars-Sinai Medical Center, Los Angeles, and his associates.

The researchers collected data on dyspnea from all patients undergoing myocardial-perfusion SPECT at rest and during exercise testing. They assessed data on 17,991 such patients and found that those with dyspnea but no other symptoms had a fourfold higher risk of cardiac death and more than twice the risk of noncardiac death during follow-up than patients with typical angina (N. Engl. J. Med. 2005;353:1889–98).

In an editorial, Thomas H. Marwick, M.B., Ph.D., of the University of Queensland, Brisbane, Australia, noted that these results “should remind us that cardiac symptoms other than chest pain are of value in evaluating patients with suspected CAD” (N. Engl. J. Med. 2005;353:1963–4).

Thrombolytic Tx in Kidney Patients

Thrombolytic therapy is delayed in patients with kidney disease who develop MI, which is “particularly unfortunate” in this patient population because of their large burden of cardiovascular disease and high CVD mortality, according to Britt B. Newsome, M.D., of the Birmingham (Ala.) Veterans Affairs Medical Center, and associates.

The researchers analyzed data from 109,169 MI patients who were treated at more than 6,000 U.S. acute-care hospitals, and found that “door-to-needle time” increased as severity of kidney disease worsened.

They also found that patients with kidney disease were no more likely than those with normal kidney function to develop bleeding complications from thrombolytic therapy (Am. J. Kidney Dis. 2005;46:595–602).

The treatment delay may be due to clinicians' perception that kidney patients are more frail, less likely to benefit from treatment, or more likely to develop adverse effects, particularly bleeding complications, than other patients. But the study results suggest that such concerns are not warranted.

This study also disproved another possible explanation for the treatment delay, namely that patients with kidney disease have more comorbidities than other patients, which complicates their medical care and increases the time needed to make treatment decisions. Also, the subjects with kidney disease did have more comorbidities, but comorbidities did not correlate with treatment delays, the investigators noted.

Statins: Benefits Outweigh Hazards

Statin therapy doesn't raise the risk of cancer or any specific cause of death, and it carries an extremely low risk of rhabdomyolysis, according to investigators in the Cholesterol Treatment Trialists' collaborative study.

The CTT collaborators will report on periodic metaanalyses of morbidity and mortality data from all the large randomized trials of lipid therapies. In the first such report, which involved 14 statin trials, the CTT found a direct linear relationship between reductions in LDL cholesterol level and reductions in coronary and other vascular events (Lancet 2005;366:1267–77).

Although previous research had suggested that statin use might raise the risk of nonvascular causes of death, particularly cancer, this concern was not borne out in the metaanalysis.

The safety of statins was further confirmed by the finding of an excess risk of rhabdomyolysis of only 0.01% after 5 years of treatment.

“The potential hazards of lowering LDL cholesterol with these statin regimens seemed to be extremely small in relation to the clear benefits in many circumstances,” the CTT researchers said.

Endocarditis Rate Remains Stable

The incidence of infective endocarditis hasn't changed over the past 30 years in many areas of the United States, and Streptococci—not Staphylococcus aureus—continue to be the most common cause of infection, reported Imad M. Tleyjeh, M.D., of the Mayo Clinic, Rochester, Minn., and associates.

In a community surveillance study, all 107 cases of infective endocarditis treated in one Minnesota county between 1970 and 2000 were reviewed. The incidence remained stable throughout the study, with annual rates ranging from 5.0 to 7.0 cases per 100,000 person-years (JAMA 2005;293:3022–8).

Other researchers have reported an increasing frequency of S. aureus endocarditis or a drop in streptococcal endocarditis, “leading to a general consensus that S. aureus has surpassed viridans group streptococci as the leading cause” of the infection.

“In contrast, we found that viridans group streptococci continue to be the most common cause of infective endocarditis in the study population and that its incidence rate is approximately twice that of S. aureus,” they noted.

Drug Treatment Mismatched in HF

Among patients hospitalized with heart failure, those who are at the highest risk of death are the least likely to be given drugs of proven benefit, according to Douglas S. Lee, M.D., Ph.D., of the University of Toronto, and his associates.

They assessed drug treatment in relation to predicted 1-year mortality risk, using data from a study of 1,418 heart-failure patients treated at 103 acute-care hospitals across Ontario.

The number of prescriptions written at hospital discharge for ACE inhibitors, angiotensin II-receptor blockers, and ?-adrenoreceptor antagonists decreased as mortality risk increased, the investigators said (JAMA 2005;294:1240–7).

The mismatch between mortality risk and drug prescriptions persisted even in patients who had no perceived contraindications to the drugs and no life-limiting comorbidities that could confound a risk-benefit assessment. It seems likely that clinicians undertreated these patients because either they didn't appreciate the benefits of therapy or they mistakenly believed that high-risk patients are more susceptible to the medications' adverse effects, Dr. Lee and his associates said.

Thrombolytic Tx in Kidney Patients

Thrombolytic therapy is delayed in patients with kidney disease who develop MI, which is “particularly unfortunate” in this patient population because of their large burden of cardiovascular disease and high CVD mortality, according to Britt B. Newsome, M.D., of the Birmingham (Ala.) Veterans Affairs Medical Center, and associates.

The researchers analyzed data from 109,169 MI patients who were treated at more than 6,000 U.S. acute-care hospitals, and found that “door-to-needle time” increased as severity of kidney disease worsened.

They also found that patients with kidney disease were no more likely than those with normal kidney function to develop bleeding complications from thrombolytic therapy (Am. J. Kidney Dis. 2005;46:595–602).

The treatment delay may be due to clinicians' perception that kidney patients are more frail, less likely to benefit from treatment, or more likely to develop adverse effects, particularly bleeding complications, than other patients. But the study results suggest that such concerns are not warranted.

This study also disproved another possible explanation for the treatment delay, namely that patients with kidney disease have more comorbidities than other patients, which complicates their medical care and increases the time needed to make treatment decisions. Also, the subjects with kidney disease did have more comorbidities, but comorbidities did not correlate with treatment delays, the investigators noted.

Statins: Benefits Outweigh Hazards

Statin therapy doesn't raise the risk of cancer or any specific cause of death, and it carries an extremely low risk of rhabdomyolysis, according to investigators in the Cholesterol Treatment Trialists' collaborative study.

The CTT collaborators will report on periodic metaanalyses of morbidity and mortality data from all the large randomized trials of lipid therapies. In the first such report, which involved 14 statin trials, the CTT found a direct linear relationship between reductions in LDL cholesterol level and reductions in coronary and other vascular events (Lancet 2005;366:1267–77).

Although previous research had suggested that statin use might raise the risk of nonvascular causes of death, particularly cancer, this concern was not borne out in the metaanalysis.

The safety of statins was further confirmed by the finding of an excess risk of rhabdomyolysis of only 0.01% after 5 years of treatment.

“The potential hazards of lowering LDL cholesterol with these statin regimens seemed to be extremely small in relation to the clear benefits in many circumstances,” the CTT researchers said.

Endocarditis Rate Remains Stable

The incidence of infective endocarditis hasn't changed over the past 30 years in many areas of the United States, and Streptococci—not Staphylococcus aureus—continue to be the most common cause of infection, reported Imad M. Tleyjeh, M.D., of the Mayo Clinic, Rochester, Minn., and associates.

In a community surveillance study, all 107 cases of infective endocarditis treated in one Minnesota county between 1970 and 2000 were reviewed. The incidence remained stable throughout the study, with annual rates ranging from 5.0 to 7.0 cases per 100,000 person-years (JAMA 2005;293:3022–8).

Other researchers have reported an increasing frequency of S. aureus endocarditis or a drop in streptococcal endocarditis, “leading to a general consensus that S. aureus has surpassed viridans group streptococci as the leading cause” of the infection.

“In contrast, we found that viridans group streptococci continue to be the most common cause of infective endocarditis in the study population and that its incidence rate is approximately twice that of S. aureus,” they noted.

Drug Treatment Mismatched in HF

Among patients hospitalized with heart failure, those who are at the highest risk of death are the least likely to be given drugs of proven benefit, according to Douglas S. Lee, M.D., Ph.D., of the University of Toronto, and his associates.

They assessed drug treatment in relation to predicted 1-year mortality risk, using data from a study of 1,418 heart-failure patients treated at 103 acute-care hospitals across Ontario.

The number of prescriptions written at hospital discharge for ACE inhibitors, angiotensin II-receptor blockers, and ?-adrenoreceptor antagonists decreased as mortality risk increased, the investigators said (JAMA 2005;294:1240–7).

The mismatch between mortality risk and drug prescriptions persisted even in patients who had no perceived contraindications to the drugs and no life-limiting comorbidities that could confound a risk-benefit assessment. It seems likely that clinicians undertreated these patients because either they didn't appreciate the benefits of therapy or they mistakenly believed that high-risk patients are more susceptible to the medications' adverse effects, Dr. Lee and his associates said.

Thrombolytic Tx in Kidney Patients

Thrombolytic therapy is delayed in patients with kidney disease who develop MI, which is “particularly unfortunate” in this patient population because of their large burden of cardiovascular disease and high CVD mortality, according to Britt B. Newsome, M.D., of the Birmingham (Ala.) Veterans Affairs Medical Center, and associates.

The researchers analyzed data from 109,169 MI patients who were treated at more than 6,000 U.S. acute-care hospitals, and found that “door-to-needle time” increased as severity of kidney disease worsened.

They also found that patients with kidney disease were no more likely than those with normal kidney function to develop bleeding complications from thrombolytic therapy (Am. J. Kidney Dis. 2005;46:595–602).

The treatment delay may be due to clinicians' perception that kidney patients are more frail, less likely to benefit from treatment, or more likely to develop adverse effects, particularly bleeding complications, than other patients. But the study results suggest that such concerns are not warranted.

This study also disproved another possible explanation for the treatment delay, namely that patients with kidney disease have more comorbidities than other patients, which complicates their medical care and increases the time needed to make treatment decisions. Also, the subjects with kidney disease did have more comorbidities, but comorbidities did not correlate with treatment delays, the investigators noted.

Statins: Benefits Outweigh Hazards

Statin therapy doesn't raise the risk of cancer or any specific cause of death, and it carries an extremely low risk of rhabdomyolysis, according to investigators in the Cholesterol Treatment Trialists' collaborative study.

The CTT collaborators will report on periodic metaanalyses of morbidity and mortality data from all the large randomized trials of lipid therapies. In the first such report, which involved 14 statin trials, the CTT found a direct linear relationship between reductions in LDL cholesterol level and reductions in coronary and other vascular events (Lancet 2005;366:1267–77).

Although previous research had suggested that statin use might raise the risk of nonvascular causes of death, particularly cancer, this concern was not borne out in the metaanalysis.

The safety of statins was further confirmed by the finding of an excess risk of rhabdomyolysis of only 0.01% after 5 years of treatment.

“The potential hazards of lowering LDL cholesterol with these statin regimens seemed to be extremely small in relation to the clear benefits in many circumstances,” the CTT researchers said.

Endocarditis Rate Remains Stable

The incidence of infective endocarditis hasn't changed over the past 30 years in many areas of the United States, and Streptococci—not Staphylococcus aureus—continue to be the most common cause of infection, reported Imad M. Tleyjeh, M.D., of the Mayo Clinic, Rochester, Minn., and associates.

In a community surveillance study, all 107 cases of infective endocarditis treated in one Minnesota county between 1970 and 2000 were reviewed. The incidence remained stable throughout the study, with annual rates ranging from 5.0 to 7.0 cases per 100,000 person-years (JAMA 2005;293:3022–8).

Other researchers have reported an increasing frequency of S. aureus endocarditis or a drop in streptococcal endocarditis, “leading to a general consensus that S. aureus has surpassed viridans group streptococci as the leading cause” of the infection.

“In contrast, we found that viridans group streptococci continue to be the most common cause of infective endocarditis in the study population and that its incidence rate is approximately twice that of S. aureus,” they noted.

Drug Treatment Mismatched in HF

Among patients hospitalized with heart failure, those who are at the highest risk of death are the least likely to be given drugs of proven benefit, according to Douglas S. Lee, M.D., Ph.D., of the University of Toronto, and his associates.

They assessed drug treatment in relation to predicted 1-year mortality risk, using data from a study of 1,418 heart-failure patients treated at 103 acute-care hospitals across Ontario.

The number of prescriptions written at hospital discharge for ACE inhibitors, angiotensin II-receptor blockers, and ?-adrenoreceptor antagonists decreased as mortality risk increased, the investigators said (JAMA 2005;294:1240–7).

The mismatch between mortality risk and drug prescriptions persisted even in patients who had no perceived contraindications to the drugs and no life-limiting comorbidities that could confound a risk-benefit assessment. It seems likely that clinicians undertreated these patients because either they didn't appreciate the benefits of therapy or they mistakenly believed that high-risk patients are more susceptible to the medications' adverse effects, Dr. Lee and his associates said.

Both percutaneous coronary interventions and coronary artery bypass grafting are seriously underused in patients with MI complicated by cardiogenic shock, according to a nationwide survey.

The American College of Cardiology and the American Heart Association revised their guidelines in 1999, elevating early mechanical intervention for cardiogenic shock to a class I recommendation for patients younger than 75 with an ST-elevation left bundle-branch block acute MI. However, a national database that has tracked practice patterns and MI outcomes since 1990 showed that physicians have been slow to comply with this change and had only marginally increased the use of PCI and CABG in this patient group by early 2004, the most recent year for which data were available, said Anvar Babaev, M.D., of New York University, New York, and colleagues (JAMA 2005;294:448–54).

The database included nearly 300,000 MI patients treated at 775 hospitals with revascularization capability. Of these, more than 25,000 (8.6%) had cardiogenic shock. Mortality clearly decreased with increasing use of revascularization, illustrating the benefit of early mechanical intervention. But physicians may still be reluctant to try these interventions in high-risk patients, the investigators said.

Both percutaneous coronary interventions and coronary artery bypass grafting are seriously underused in patients with MI complicated by cardiogenic shock, according to a nationwide survey.

The American College of Cardiology and the American Heart Association revised their guidelines in 1999, elevating early mechanical intervention for cardiogenic shock to a class I recommendation for patients younger than 75 with an ST-elevation left bundle-branch block acute MI. However, a national database that has tracked practice patterns and MI outcomes since 1990 showed that physicians have been slow to comply with this change and had only marginally increased the use of PCI and CABG in this patient group by early 2004, the most recent year for which data were available, said Anvar Babaev, M.D., of New York University, New York, and colleagues (JAMA 2005;294:448–54).

The database included nearly 300,000 MI patients treated at 775 hospitals with revascularization capability. Of these, more than 25,000 (8.6%) had cardiogenic shock. Mortality clearly decreased with increasing use of revascularization, illustrating the benefit of early mechanical intervention. But physicians may still be reluctant to try these interventions in high-risk patients, the investigators said.

Both percutaneous coronary interventions and coronary artery bypass grafting are seriously underused in patients with MI complicated by cardiogenic shock, according to a nationwide survey.

The American College of Cardiology and the American Heart Association revised their guidelines in 1999, elevating early mechanical intervention for cardiogenic shock to a class I recommendation for patients younger than 75 with an ST-elevation left bundle-branch block acute MI. However, a national database that has tracked practice patterns and MI outcomes since 1990 showed that physicians have been slow to comply with this change and had only marginally increased the use of PCI and CABG in this patient group by early 2004, the most recent year for which data were available, said Anvar Babaev, M.D., of New York University, New York, and colleagues (JAMA 2005;294:448–54).

The database included nearly 300,000 MI patients treated at 775 hospitals with revascularization capability. Of these, more than 25,000 (8.6%) had cardiogenic shock. Mortality clearly decreased with increasing use of revascularization, illustrating the benefit of early mechanical intervention. But physicians may still be reluctant to try these interventions in high-risk patients, the investigators said.

People who first develop bipolar affective disorder at age 60 years or older are less ill overall than are those with the more typical pattern of early-onset bipolar disorder, said Martha Sajatovic, M.D., of the University Hospitals of Cleveland, and her associates.

The researchers used a large Veterans Affairs (VA) database to compare differences between early-onset and late-onset bipolar disorder in clinical presentation, use of health care services, and use of psychotropic medications over a 2-year period.

They identified 16,330 patients aged 60 years or older with bipolar disorder who were treated in 2001. These patients represented nearly one-fourth of all patients with bipolar disorder in the VA system at that time. Those who had their first diagnosis before 2001 were considered early-onset patients. Although late onset has not been clearly defined, those whose first bipolar disorder diagnosis was made in 2001 and who were not diagnosed with psychosis or depression before that time were considered to have new-onset illness (NOI).

The great majority of these older patients with bipolar disorder (82.5%) had early-onset disease, whereas only 6.1% had NOI. The remaining patients either were new to the VA or had a questionable diagnosis and were excluded from the study.

Given that this was a sample of older veterans, it was a predominantly male and white population. The percentages of female and African American subjects were quite low, at 4.5% and 5.0%, respectively, the investigators noted (Am. J. Geriatr. Psych. 2005;13:282–9).

Patients with early-onset bipolar disorder were hospitalized for mania much more often than those with NOI. They had a similar number of hospitalizations for depression, and a similar rate of homelessness and substance abuse. Those with early-onset bipolar disorder were more likely to be divorced or separated.

There was a substantial difference between the two groups in length of hospital stay. Total length of stay averaged 59.7 days for patients with early-onset bipolar disorder, compared with 43.5 days for those with NOI. The median duration of inpatient stay was 22 days for the early-onset bipolar disorder group, compared with 16 days for the NOI group.

Patients with early-onset bipolar disorder also utilized other health care services to a much greater degree than did those with NOI. In particular, they showed “substantial utilization of inpatient nonpsychiatric care,” the researchers noted.

Those with early-onset bipolar disorder also were much more likely to be treated with lithium or any mood stabilizer than were patients with NOI. Those with early-onset bipolar disorder also were much more likely to receive an atypical antipsychotic compound.

Thus, older individuals with early-onset bipolar disorder appear to be generally more severely ill than their late-onset counterparts, Dr. Sajatovic and her associates said.

These findings suggest that “these are indeed two separate subgroups of older adults with bipolar disorder,” they said.

In this study, patients with NOI were nearly twice as likely to receive a diagnosis of “type II/not otherwise specified bipolar illness.” This increased prevalence might be explained by aging-related vascular and CNS pathology in such patients, the investigators said.

They also noted that in this study, fewer than two-thirds of the patients with early-onset bipolar disorder—and just 30% of those with NOI—were receiving mood stabilizers, which “is at odds with current treatment guidelines for bipolar disorder in adults.”

It may be that treatments “known to be efficacious and well tolerated in younger bipolar populations” do not work as well in geriatric bipolar patients. Moreover, in older patients, “first-line treatments have not been definitively established,” Dr. Sajatovic and her associates said.

People who first develop bipolar affective disorder at age 60 years or older are less ill overall than are those with the more typical pattern of early-onset bipolar disorder, said Martha Sajatovic, M.D., of the University Hospitals of Cleveland, and her associates.

The researchers used a large Veterans Affairs (VA) database to compare differences between early-onset and late-onset bipolar disorder in clinical presentation, use of health care services, and use of psychotropic medications over a 2-year period.

They identified 16,330 patients aged 60 years or older with bipolar disorder who were treated in 2001. These patients represented nearly one-fourth of all patients with bipolar disorder in the VA system at that time. Those who had their first diagnosis before 2001 were considered early-onset patients. Although late onset has not been clearly defined, those whose first bipolar disorder diagnosis was made in 2001 and who were not diagnosed with psychosis or depression before that time were considered to have new-onset illness (NOI).

The great majority of these older patients with bipolar disorder (82.5%) had early-onset disease, whereas only 6.1% had NOI. The remaining patients either were new to the VA or had a questionable diagnosis and were excluded from the study.

Given that this was a sample of older veterans, it was a predominantly male and white population. The percentages of female and African American subjects were quite low, at 4.5% and 5.0%, respectively, the investigators noted (Am. J. Geriatr. Psych. 2005;13:282–9).

Patients with early-onset bipolar disorder were hospitalized for mania much more often than those with NOI. They had a similar number of hospitalizations for depression, and a similar rate of homelessness and substance abuse. Those with early-onset bipolar disorder were more likely to be divorced or separated.

There was a substantial difference between the two groups in length of hospital stay. Total length of stay averaged 59.7 days for patients with early-onset bipolar disorder, compared with 43.5 days for those with NOI. The median duration of inpatient stay was 22 days for the early-onset bipolar disorder group, compared with 16 days for the NOI group.

Patients with early-onset bipolar disorder also utilized other health care services to a much greater degree than did those with NOI. In particular, they showed “substantial utilization of inpatient nonpsychiatric care,” the researchers noted.

Those with early-onset bipolar disorder also were much more likely to be treated with lithium or any mood stabilizer than were patients with NOI. Those with early-onset bipolar disorder also were much more likely to receive an atypical antipsychotic compound.

Thus, older individuals with early-onset bipolar disorder appear to be generally more severely ill than their late-onset counterparts, Dr. Sajatovic and her associates said.

These findings suggest that “these are indeed two separate subgroups of older adults with bipolar disorder,” they said.

In this study, patients with NOI were nearly twice as likely to receive a diagnosis of “type II/not otherwise specified bipolar illness.” This increased prevalence might be explained by aging-related vascular and CNS pathology in such patients, the investigators said.

They also noted that in this study, fewer than two-thirds of the patients with early-onset bipolar disorder—and just 30% of those with NOI—were receiving mood stabilizers, which “is at odds with current treatment guidelines for bipolar disorder in adults.”

It may be that treatments “known to be efficacious and well tolerated in younger bipolar populations” do not work as well in geriatric bipolar patients. Moreover, in older patients, “first-line treatments have not been definitively established,” Dr. Sajatovic and her associates said.

People who first develop bipolar affective disorder at age 60 years or older are less ill overall than are those with the more typical pattern of early-onset bipolar disorder, said Martha Sajatovic, M.D., of the University Hospitals of Cleveland, and her associates.

The researchers used a large Veterans Affairs (VA) database to compare differences between early-onset and late-onset bipolar disorder in clinical presentation, use of health care services, and use of psychotropic medications over a 2-year period.

They identified 16,330 patients aged 60 years or older with bipolar disorder who were treated in 2001. These patients represented nearly one-fourth of all patients with bipolar disorder in the VA system at that time. Those who had their first diagnosis before 2001 were considered early-onset patients. Although late onset has not been clearly defined, those whose first bipolar disorder diagnosis was made in 2001 and who were not diagnosed with psychosis or depression before that time were considered to have new-onset illness (NOI).

The great majority of these older patients with bipolar disorder (82.5%) had early-onset disease, whereas only 6.1% had NOI. The remaining patients either were new to the VA or had a questionable diagnosis and were excluded from the study.

Given that this was a sample of older veterans, it was a predominantly male and white population. The percentages of female and African American subjects were quite low, at 4.5% and 5.0%, respectively, the investigators noted (Am. J. Geriatr. Psych. 2005;13:282–9).

Patients with early-onset bipolar disorder were hospitalized for mania much more often than those with NOI. They had a similar number of hospitalizations for depression, and a similar rate of homelessness and substance abuse. Those with early-onset bipolar disorder were more likely to be divorced or separated.

There was a substantial difference between the two groups in length of hospital stay. Total length of stay averaged 59.7 days for patients with early-onset bipolar disorder, compared with 43.5 days for those with NOI. The median duration of inpatient stay was 22 days for the early-onset bipolar disorder group, compared with 16 days for the NOI group.

Patients with early-onset bipolar disorder also utilized other health care services to a much greater degree than did those with NOI. In particular, they showed “substantial utilization of inpatient nonpsychiatric care,” the researchers noted.

Those with early-onset bipolar disorder also were much more likely to be treated with lithium or any mood stabilizer than were patients with NOI. Those with early-onset bipolar disorder also were much more likely to receive an atypical antipsychotic compound.

Thus, older individuals with early-onset bipolar disorder appear to be generally more severely ill than their late-onset counterparts, Dr. Sajatovic and her associates said.

These findings suggest that “these are indeed two separate subgroups of older adults with bipolar disorder,” they said.

In this study, patients with NOI were nearly twice as likely to receive a diagnosis of “type II/not otherwise specified bipolar illness.” This increased prevalence might be explained by aging-related vascular and CNS pathology in such patients, the investigators said.

They also noted that in this study, fewer than two-thirds of the patients with early-onset bipolar disorder—and just 30% of those with NOI—were receiving mood stabilizers, which “is at odds with current treatment guidelines for bipolar disorder in adults.”

It may be that treatments “known to be efficacious and well tolerated in younger bipolar populations” do not work as well in geriatric bipolar patients. Moreover, in older patients, “first-line treatments have not been definitively established,” Dr. Sajatovic and her associates said.

Lipid Measures in Dialysis Patients

Lipid management can be accomplished in hemodialysis patients without requiring them to fast overnight—a significant difficulty for those who have diabetes and those with an afternoon or evening dialysis schedule, reported Simon Desmeules, M.D., and his associates at the University of Quebec Hospital Center.

Aggressive lipid management is required in dialysis patients because their cardiovascular mortality is 20 times higher than that of the general population, the investigators noted (Am. J. Kidney Dis. 2005;45:1067–72).

Levels of LDL, intermediate-density lipoprotein (IDL), and very-low-density lipoprotein (VLDL) must be measured in the fasting state to be accurate, but nonfasting levels of HDL and total cholesterol generally are accurate. So rather than directly measuring LDL, IDL, and VLDL, the researchers proposed sidestepping the fasting requirement and calculating an overall “non-HDL” level by simply subtracting the nonfasting HDL level from the nonfasting total cholesterol level.

They tested this hypothesis in a study of 48 patients on long-term hemodialysis, 20 of whom (42%) had diabetes. This nonfasting, calculated “non-HDL” cholesterol level was found to be accurate, compared with direct measurement of fasting lipid levels, and now can be considered adequate for assessing dyslipidemia in dialysis patients.

PCI Takes Longer During Off-Hours

For MI patients, the interval between hospital arrival and percutaneous coronary intervention (PCI) reperfusion is substantially longer if they are stricken at night or on weekends than it is on weekdays, even at high-volume PCI centers. This is largely because most catheterization labs must summon staff from off-site during off-hours.

In contrast, the interval between hospital arrival and administration of fibrinolysis is no longer during off-hours than on weekdays, presumably because fibrinolytic therapy doesn't require the catheterization lab staff, according to David J. Magid, M.D., of the University of Colorado, Denver, and his associates (JAMA 2005;294:803–12).

They analyzed a national database including 68,439 patients given fibrinolysis and 33,647 given PCI at more than 1,000 U.S. hospitals; approximately two-thirds were treated during off-hours. Door-to-balloon times were 21 minutes longer on average during nights and weekends, and patients were markedly less likely to undergo PCI within the recommended 90 minutes if they presented during off-hours.

Cell Count Predicts CV Events, Death

A one-time measurement of the number of circulating endothelial progenitor cells can predict cardiovascular events and mortality, independent of traditional cardiovascular risk factors, reported Nikos Werner, M.D., and associates at the University of Saarland, Homburg-Saar, Germany.

Although researchers suspected that such progenitor cells in the peripheral blood might indicate endothelial regenerative capacity, they didn't know whether cell counts alone would be useful markers. Dr. Werner and associates obtained counts of CD34+KDR+ progenitor cells from arterial blood samples taken just before cardiac catheterization in 519 patients undergoing angiography, and then followed the patients for 1 year (N. Engl. J. Med. 2005;353:999–1007).

Subjects with low circulating numbers of these cells had significantly higher rates of first major CV events and mortality from CV causes, compared with those with high counts. The findings suggest that such counts constitute a new marker for risk stratification and also support “the underlying biologic concept that endothelial-cell regeneration through circulating progenitor cells is necessary for vascular healing,” the investigators said.

Gender Predicts CABG Mortality

Women undergoing coronary artery bypass graft remain at higher risk for operative mortality than men, even after all known risk factors and a few theoretical ones are taken into account, reported Ron Blankstein, M.D., of the University of Chicago Hospitals, and his associates.

Their study was designed to gauge the influence of hundreds of potential confounding factors and to assess whether “all other factors being equal, there is a significant difference in operative mortality between men and women undergoing CABG.” The analysis included data on 15,440 consecutive CABG patients at 31 hospitals in 1999–2000.

Before the data were adjusted for standard clinical risk factors, women were 90% more likely than men to die perioperatively. After adjusting for these risk factors—for example, women's much higher rates of valvular disease, chronic obstructive pulmonary disease, and diabetes—that discrepancy was reduced to 49%, the researchers said (Circulation 2005;112:323–7).

Lipid Measures in Dialysis Patients

Lipid management can be accomplished in hemodialysis patients without requiring them to fast overnight—a significant difficulty for those who have diabetes and those with an afternoon or evening dialysis schedule, reported Simon Desmeules, M.D., and his associates at the University of Quebec Hospital Center.

Aggressive lipid management is required in dialysis patients because their cardiovascular mortality is 20 times higher than that of the general population, the investigators noted (Am. J. Kidney Dis. 2005;45:1067–72).

Levels of LDL, intermediate-density lipoprotein (IDL), and very-low-density lipoprotein (VLDL) must be measured in the fasting state to be accurate, but nonfasting levels of HDL and total cholesterol generally are accurate. So rather than directly measuring LDL, IDL, and VLDL, the researchers proposed sidestepping the fasting requirement and calculating an overall “non-HDL” level by simply subtracting the nonfasting HDL level from the nonfasting total cholesterol level.

They tested this hypothesis in a study of 48 patients on long-term hemodialysis, 20 of whom (42%) had diabetes. This nonfasting, calculated “non-HDL” cholesterol level was found to be accurate, compared with direct measurement of fasting lipid levels, and now can be considered adequate for assessing dyslipidemia in dialysis patients.

PCI Takes Longer During Off-Hours

For MI patients, the interval between hospital arrival and percutaneous coronary intervention (PCI) reperfusion is substantially longer if they are stricken at night or on weekends than it is on weekdays, even at high-volume PCI centers. This is largely because most catheterization labs must summon staff from off-site during off-hours.

In contrast, the interval between hospital arrival and administration of fibrinolysis is no longer during off-hours than on weekdays, presumably because fibrinolytic therapy doesn't require the catheterization lab staff, according to David J. Magid, M.D., of the University of Colorado, Denver, and his associates (JAMA 2005;294:803–12).

They analyzed a national database including 68,439 patients given fibrinolysis and 33,647 given PCI at more than 1,000 U.S. hospitals; approximately two-thirds were treated during off-hours. Door-to-balloon times were 21 minutes longer on average during nights and weekends, and patients were markedly less likely to undergo PCI within the recommended 90 minutes if they presented during off-hours.

Cell Count Predicts CV Events, Death

A one-time measurement of the number of circulating endothelial progenitor cells can predict cardiovascular events and mortality, independent of traditional cardiovascular risk factors, reported Nikos Werner, M.D., and associates at the University of Saarland, Homburg-Saar, Germany.

Although researchers suspected that such progenitor cells in the peripheral blood might indicate endothelial regenerative capacity, they didn't know whether cell counts alone would be useful markers. Dr. Werner and associates obtained counts of CD34+KDR+ progenitor cells from arterial blood samples taken just before cardiac catheterization in 519 patients undergoing angiography, and then followed the patients for 1 year (N. Engl. J. Med. 2005;353:999–1007).

Subjects with low circulating numbers of these cells had significantly higher rates of first major CV events and mortality from CV causes, compared with those with high counts. The findings suggest that such counts constitute a new marker for risk stratification and also support “the underlying biologic concept that endothelial-cell regeneration through circulating progenitor cells is necessary for vascular healing,” the investigators said.

Gender Predicts CABG Mortality

Women undergoing coronary artery bypass graft remain at higher risk for operative mortality than men, even after all known risk factors and a few theoretical ones are taken into account, reported Ron Blankstein, M.D., of the University of Chicago Hospitals, and his associates.

Their study was designed to gauge the influence of hundreds of potential confounding factors and to assess whether “all other factors being equal, there is a significant difference in operative mortality between men and women undergoing CABG.” The analysis included data on 15,440 consecutive CABG patients at 31 hospitals in 1999–2000.

Before the data were adjusted for standard clinical risk factors, women were 90% more likely than men to die perioperatively. After adjusting for these risk factors—for example, women's much higher rates of valvular disease, chronic obstructive pulmonary disease, and diabetes—that discrepancy was reduced to 49%, the researchers said (Circulation 2005;112:323–7).

Lipid Measures in Dialysis Patients

Lipid management can be accomplished in hemodialysis patients without requiring them to fast overnight—a significant difficulty for those who have diabetes and those with an afternoon or evening dialysis schedule, reported Simon Desmeules, M.D., and his associates at the University of Quebec Hospital Center.

Aggressive lipid management is required in dialysis patients because their cardiovascular mortality is 20 times higher than that of the general population, the investigators noted (Am. J. Kidney Dis. 2005;45:1067–72).

Levels of LDL, intermediate-density lipoprotein (IDL), and very-low-density lipoprotein (VLDL) must be measured in the fasting state to be accurate, but nonfasting levels of HDL and total cholesterol generally are accurate. So rather than directly measuring LDL, IDL, and VLDL, the researchers proposed sidestepping the fasting requirement and calculating an overall “non-HDL” level by simply subtracting the nonfasting HDL level from the nonfasting total cholesterol level.

They tested this hypothesis in a study of 48 patients on long-term hemodialysis, 20 of whom (42%) had diabetes. This nonfasting, calculated “non-HDL” cholesterol level was found to be accurate, compared with direct measurement of fasting lipid levels, and now can be considered adequate for assessing dyslipidemia in dialysis patients.

PCI Takes Longer During Off-Hours

For MI patients, the interval between hospital arrival and percutaneous coronary intervention (PCI) reperfusion is substantially longer if they are stricken at night or on weekends than it is on weekdays, even at high-volume PCI centers. This is largely because most catheterization labs must summon staff from off-site during off-hours.

In contrast, the interval between hospital arrival and administration of fibrinolysis is no longer during off-hours than on weekdays, presumably because fibrinolytic therapy doesn't require the catheterization lab staff, according to David J. Magid, M.D., of the University of Colorado, Denver, and his associates (JAMA 2005;294:803–12).

They analyzed a national database including 68,439 patients given fibrinolysis and 33,647 given PCI at more than 1,000 U.S. hospitals; approximately two-thirds were treated during off-hours. Door-to-balloon times were 21 minutes longer on average during nights and weekends, and patients were markedly less likely to undergo PCI within the recommended 90 minutes if they presented during off-hours.

Cell Count Predicts CV Events, Death

A one-time measurement of the number of circulating endothelial progenitor cells can predict cardiovascular events and mortality, independent of traditional cardiovascular risk factors, reported Nikos Werner, M.D., and associates at the University of Saarland, Homburg-Saar, Germany.

Although researchers suspected that such progenitor cells in the peripheral blood might indicate endothelial regenerative capacity, they didn't know whether cell counts alone would be useful markers. Dr. Werner and associates obtained counts of CD34+KDR+ progenitor cells from arterial blood samples taken just before cardiac catheterization in 519 patients undergoing angiography, and then followed the patients for 1 year (N. Engl. J. Med. 2005;353:999–1007).

Subjects with low circulating numbers of these cells had significantly higher rates of first major CV events and mortality from CV causes, compared with those with high counts. The findings suggest that such counts constitute a new marker for risk stratification and also support “the underlying biologic concept that endothelial-cell regeneration through circulating progenitor cells is necessary for vascular healing,” the investigators said.

Gender Predicts CABG Mortality

Women undergoing coronary artery bypass graft remain at higher risk for operative mortality than men, even after all known risk factors and a few theoretical ones are taken into account, reported Ron Blankstein, M.D., of the University of Chicago Hospitals, and his associates.

Their study was designed to gauge the influence of hundreds of potential confounding factors and to assess whether “all other factors being equal, there is a significant difference in operative mortality between men and women undergoing CABG.” The analysis included data on 15,440 consecutive CABG patients at 31 hospitals in 1999–2000.

Before the data were adjusted for standard clinical risk factors, women were 90% more likely than men to die perioperatively. After adjusting for these risk factors—for example, women's much higher rates of valvular disease, chronic obstructive pulmonary disease, and diabetes—that discrepancy was reduced to 49%, the researchers said (Circulation 2005;112:323–7).