User login
One in five of your patients could suffer a heart attack in the near future—unless you take steps to ensure their heart health.
Psychiatric patients have more modifiable risk factors for coronary artery disease (CAD) compared with the general population.When depression treatment goes nowhere,” Current Psychiatry, August 2005.)
To help keep you abreast of constantly changing guidelines and strategies for recognizing and minimizing CAD risk, this article discusses:
- preventive and diagnostic guidelines for managing hypertension, diabetes, and dyslipidemia
- practical advice on convincing at-risk patients to adopt a healthier lifestyle and have a primary care doctor monitor their health.
Case: cigarettes and supersizing
Mr. H, age 54, is receiving cognitive-behavioral therapy for mild depression. He has been smoking one pack of cigarettes per day for 20 years and has never seriously considered quitting.
The patient, a school teacher, says his “busy schedule” keeps him from exercising and eating properly; he eats fast-food hamburgers and fries approximately five times per week. His father had a heart attack at age 52 and died in his sleep 10 years later.
Mr. H says he feels fine and has never seen a physician other than his psychiatrist. He is reluctant to see a primary care physician for a check-up and, because he is asymptomatic, has no incentive to do so. The psychiatrist thus decides to do a routine examination.
Blood pressure is 148/86; other vital signs are normal. Mr. H’s waist size is 42 inches, he weighs 242 lbs, and his body mass index (BMI) is 34 kg/m2, indicating clinical obesity. Cardiovascular, pulmonary, and abdominal exams are unremarkable.
Discussion. Mr. H is at high risk of a myocardial ischemic event in the near future. He has six risk factors for CAD (Table 1)—four of which are modifiable:
- family history
- age
- current cigarette use
- provisional hypertension diagnosis
- obesity
- physical inactivity.
Table 1
Risk factors for coronary artery disease
Core risk factors |
Age ≥45 for men* |
Age ≥55 for women or premature menopause without estrogen-replacement therapy* |
Family history: premature coronary artery disease with myocardial infarction or sudden death before:
|
Current cigarette smoking |
Hypertension or antihypertensive treatment* |
Elevated LDL cholesterol (>130 mg/dL in patients with low cardiac risk) |
HDL cholesterol |
Triglycerides >150 mg/dL |
Total cholesterol >200 mg/dL* |
Obesity (BMI >30 kg/m2)† |
Sedentary lifestyle |
Other risk factors |
Elevated C-reactive protein |
Elevated homocysteine |
Chronic renal failure |
Depression |
Negative (cardio-protective) risk factors |
HDL >60 mg/dL |
Moderate alcohol use—no more than 1 to 2 drinks per day (1 drink = 12 oz beer or 5 oz of wine) |
If >1 risk factor, refer to primary care doctor or quantify 10-year risk by using the Framingham/ATP III point system scale (www.nhlbi.nih.gov). |
* Framingham/ATP III point system scale variables |
† Use BMI calculator (http://www.nhlbisupport.com/bmi/bmicalc.htm) to determine body mass index. |
HDL: High-density lipoprotein |
LDL: Low-density lipoprotein |
Source: References 9,10 |
Tools for assessing risk
The lifetime risk at age 40 for developing CAD is 49% and 32% in men and women, respectively.6
The National Cholesterol Education Program Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel) has focused on decreasing heart disease incidence by educating patients and providers. Preventive strategies and standards of care have changed several times over the past decade; the Adult Treatment Panel (ATP III) was last revised in July 2004.7
The American College of Cardiology and American Heart Association both endorse the modified Framingham/ATP III scale to measure CAD risk (see Related resources). Although this somewhat tedious point system has limitations, it can precisely calculate coronary risk across 10 years.8 Variables not included in the scoring system—such as C-reactive protein, homocysteine, and postmenopausal state—may be clinically significant and should be gauged separately.
An easier-to-use alternative, the ATP III “core risk factors” scale, estimates hypertension, hypercholesterolemia, family history, current cigarette smoking, and age as low, intermediate, or high (“risk equivalent”) risks (Table 1).8 Psychiatrists can quickly obtain this information from a brief history, blood pressure assessment, and relatively inexpensive lab studies.
Generally, the more risk factors present, the higher the risk of having a major coronary event. Presence of ≥ 2 risk factors signals intermediate or high risk and necessitates referral to a primary care doctor for monitoring.
Patients with a cardiac “risk equivalent” face a >20% risk of having a cardiac ischemic event within 10 years8 (Table 2). Examples of risk equivalents include diabetes or significant vascular disease in any artery.
“Non-core” variables. Also consider certain “non-core” variables—such as pre-existing psychiatric illness—when estimating clinical risk for heart disease. Depression, anxiety, and stress are correlated with an increase in pro-inflammatory markers such as C-reactive protein and predispose patients to CAD.11,12 Depression has repeatedly been shown to increase morbidity and mortality two- to four-fold after myocardial infarction (MI).9,13,14 Interestingly, however, depression treatment after an acute coronary event does not clearly decrease mortality.15 Although prospective, randomized studies are lacking, mood and anxiety disorder treatment is presumed to help prevent CAD development.16
Table 2
Risk equivalents for CAD*
Established coronary artery disease |
Symptomatic carotid artery disease |
Peripheral vascular disease |
Abdominal aortic aneurism |
Diabetes mellitus |
*Risk equivalent: Patient is assumed to have coronary artery disease (CAD). |
Recognizing cad risk
At what point do hypertension and dyslipidemia become risk factors for CAD? When and how often should patients be screened for diabetes mellitus?
Hypertension is one of the most common and deadly CAD risk factors, affecting 50 million Americans.10 Although hypertension awareness and treatment have improved, only 35% of adults have “controlled” blood pressure (
According to the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7), normalizing blood pressure can reduce stroke incidence by 35% and MI by 25%, respectively. JNC 7, however, also found that 90% of persons who are normotensive at age 55 eventually develop hypertension.10
Based on these findings, JNC 7 in 2003 drastically changed the standard of care for diagnosing hypertension. JNC 7 defines normal blood pressure as
- systolic blood pressure 120 to 139 mm Hg
- diastolic blood pressure 80 to 89 mm Hg (Table 3).
Patients with diabetes mellitus or chronic kidney disease are considered hypertensive with blood pressure >130 mm Hg systolic and/or >80 mm Hg diastolic.
As with Mr. H, a blood pressure check is imperative for patients who have rarely or never seen a primary care physician in recent years. The U.S. Preventive Services Task Force strongly recommends measuring blood pressure during a routine medical evaluation at least every 2 years. A second abnormal reading at a separate visit at any time should prompt a hypertension diagnosis. Once diagnosed with hypertension, patients should be treated and checked monthly until stable, then monitored every 3 to 6 months indefinitely.10
If you cannot measure blood pressure in the office, urge patients to use an over-the-counter blood pressure measuring device and refer them to a primary care physician. Check the patient’s self-test reading for accuracy against a clinician’s measurement.
Diabetes is now considered a risk equivalent for CAD development.8 Patients diagnosed with diabetes are extremely likely to have established vascular disease,8 which predisposes them to MI, stroke, kidney disease, blindness, and lower-extremity amputations.17 Those with type 1 diabetes usually present with acute symptoms—including polyuria, polydipsia, weight loss, malaise, dry mouth, and blurred vision—and are readily diagnosed with elevated plasma glucose.
Screening for diabetes is critical because one-third of patients with the disease are undiagnosed. Also, more than 90% of patients with diabetes are non-insulin-dependent (type 2) and are asymptomatic early in the disease course.
No data definitively show benefits from screening asymptomatic adults. Recently revised diagnostic criteria for diabetes, however, call for re-testing asymptomatic patients who were found to have normal fasting plasma glucose (FPG) levels and were considered “free” of diabetes. The American Diabetes Association recommends measuring FPG after no caloric intake for ≥ 8 hours for asymptomatic patients.
FPG measurement is cost-effective and generally more convenient than other diabetes tests.17 Expert consensus strongly suggests checking FPG every 3 years beginning at age 45:17
- FPG
- FPG 100 to 125 mg/dL suggests prediabetes or impaired fasting glucose
- FPG ≥ 126 mg/dL demands a provisional diabetes diagnosis and a follow-up test on another day to confirm the diagnosis.
- comorbid cardiac risk factors
- history of polycystic ovary disease
- a first-degree relative with diabetes
- habitual inactivity
- or FPG 100 to 125 mg/dL.
Do not base diabetes diagnosis on glycosylated hemoglobin measurements, as this test can produce false-negative results in patients with new-onset diabetes.
Dyslipidemia. Every 10% reduction in serum cholesterol reduces cardiovascular mortality by 10% to 15%.19 Data from the large, prospective Framingham heart study show a 25% increase in MIs with each 5-mg/dL decrease in high-density lipoprotein cholesterol (HDL) below the age-based median for men and women.20 Serum triglycerides >150 mg/dL clearly predict future CAD and increase the likelihood of abnormally low HDL.
Every 30-mg/dL increase in low-density lipoprotein cholesterol (LDL) raises the relative risk for CAD by 30%.7 ATP III classifies LDL as the “primary target of cholesterol-lowering therapy.”8Table 4 lists LDL target levels based on other CAD risk factors.
Check fasting lipid profile or serum cholesterol, LDL, HDL, and triglycerides beginning at age 20 and about every 5 years thereafter.8 Total cholesterol
Table 3
JNC 7: What blood pressure readings mean
Category | Systolic BP (mm Hg) | Diastolic BP (mm Hg) |
---|---|---|
Normal | and | |
Prehypertension | 120-139 | or 80-89 |
Stage 1 hypertension* | 140-159 | or 90-99 |
Stage 2 hypertension | 160 | or ≥100 |
JNC 7: Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure | ||
*Patients with diabetes mellitus or chronic kidney disease have stage 1 hypertension at >130/80 mm Hg. | ||
Source: Reference 10 |
Acceptable LDL cholesterol levels for adults based on CAD risk
Risk category | Existing CAD risk factors | LDL goal |
---|---|---|
High risk (10-year risk > 20%) | History of diabetes, CAD, symptomatic carotid artery disease, peripheral vascular disease, or abdominal aortic aneurysm | |
Moderate high risk* (10-year risk 10 to 20%) | >2 risk factors | |
Moderate risk* (10-year risk | >2 risk factors | |
Low risk | 0 to 1 risk factor | ≤160 mg/dL |
CAD: Coronary artery disease | ||
*Same goals apply to managing moderate high and moderate risk. Find 10-year risk calculations at nhlbi.nih.gov/guidelines/cholesterol. | ||
Source: Reference 7 |
Addressing smoking, obesity
Smoking. Before trying nicotine patches or bupropion, Mr. H should realistically contemplate his risks with continued smoking; if he doesn’t want to stop, periodically encourage him to reconsider.10 Most people know the dangers of smoking but few understand that complete cessation for 1 to 2 years often nearly reverses cardiovascular disease.21
Obesity and lack of exercise go hand in hand. Reducing Mr. H’s waist size to 2 is a reasonable short-term goal. To that end, encourage him to:
- decrease his number of weekly fast-food meals from five to three, with an eventual goal of one per week. As an alternative, microwaveable, low-calorie meals—each with at least two servings of fruits or vegetables—can be prepared at home or work.
- walk 30 minutes three times weekly and progress to 1 hour five times weekly over 6 months. As with any exercise program, remind Mr. H to “start low and go slow.”
The patient’s role in treatment. Patients often feel overwhelmed after getting large amounts of information on CAD risk and may feel hopeless and unenthusiastic about improving their physical health. Work with the primary care doctor to emphasize a patient care plan that clearly defines easily attainable, step-by-step goals. Make sure the patient agrees to these goals.
Case continued: no more supersizing
Mr. H now understands the importance of minimizing his CAD risk and realizes that CAD and many associated risk factors are asymptomatic in the early stages of development.
With help from his doctors, Mr. H quit smoking. He also became more mindful of his caloric intake and the types of foods he was eating. He advanced from briskly walking 30 minutes three times per week to slow jogging 40 minutes five times weekly. He still eats at fast-food restaurants but usually orders broiled chicken, salads, or the occasional burger.
- National Cholesterol Education Program. CAD risk assessment tool and ATP III guidelines. www.nhlbi.nih.gov/guidelines/cholesterol/.
- U.S. Preventive Services Task Force preventive guidelines. www.ahrq.gov/clinic/uspstfix.htm.
- National Heart, Lung, and Blood Institute. Calculate your body mass index. http://nhlbisupport.com/bmi/.
- American Heart Association. www.americanheart.org.
1. Holt RI, Peveler RC, Byrne CD. Schizophrenia, the metabolic syndrome and diabetes. Diabetes Med 2004;21:515-23.
2. Carney RM, Freedland KE, Miller GE, Jaffe AS. Depression as a risk factor for cardiac mortality and morbidity: a review of potential mechanisms. J Psychosom Res 2002;53:897-902.
3. Weiser M, Reichenberg A, Grotto I, et al. Higher rates of cigarette smoking in male adolescents before the onset of schizophrenia: a historical-prospective cohort study. Am J Psychiatry 2004;161:1219-23.
4. Druss B, Rosenheck R. Mental disorders and access to medical care in the United States. Am J Psychiatry 1998;155:1775-7.
5. Druss B, Rosenheck R, Desai MM, Perlin JB. Quality of preventive medical care for patients with mental disorders. Med Care 2002;40:129-36.
6. Lloyd-Jones DM, Larson MG, Beiser A, Levy D. Lifetime risk of developing coronary heart disease. Lancet 1999;353(9147):89-92.
7. Grundy SM, Cleeman JI, Merz CN, et al. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation 2004;110:227-9.
8. Expert Panel on Detection. Evaluation and Treatment of High Blood Cholesterol in Adults. Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA 2001;285:2486-97.
9. Frasure-Smith N, Lesperance F, Talajic M, et al. Depression and 18-month prognosis after myocardial infarction. Circulation 1995;91:999-1005.
10. Chobanian AV, Bakris GL, Black HR, et al. Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure: the JNC 7 report. JAMA 2003;289:2560-72.
11. Ford DE, Erlinger TP. Depression and C-reactive protein in U.S. adults: data from the Third National Health and Nutrition Examination Survey. Arch Intern Med 2004;164:1010-14.
12. Panagiotakos DB, Pitsavos C, Chrysohoou C, et al. Inflammation, coagulation and depressive symptomatology in cardiovascular disease-free people: the ATTICA study. Eur Heart J 2004;25:492-9.
13. Frasure-Smith N, Lesperance F, Talajic M. Depression following myocardial infarction. Impact on 6-month survival. JAMA 1993;270:1819-25.
14. Ladwig KH, Kieser M, Konig J, et al. Affective disorders and survival after acute myocardial infarction: results from the post-infarction late potential study. Eur Heart J 1991;12:959-64.
15. Berkman LF, Blumenthal J, Burg M, et al. Effects of treating depression and low perceived social support on clinical events after myocardial infarction: the Enhancing Recovery in Coronary Artery Heart Disease Patients (ENRICHD) randomized trial. JAMA 2003;289:3106-16.
16. Rosengren A, Hawken S, Ounpuu S, et al. Association of psychological risk factors with risk of acute myocardial infarction in 11,119 cases and 13,648 controls from 52 countries (the INTERHEART study). Lancet 2004;364:953-62.
17. American Diabetes Association. Screening for type 2 diabetes. Diabetes Care 2004;27(suppl 1):11-14.
18. American Diabetes Association; American Psychiatric Association. American Association of Clinical Endocrinologists; North American Association for the Study of Obesity. Consensus development conference on antipsychotic drugs and obesity and diabetes. Diabetes Care 2004;27:596-601.
19. Gould AL, Rossouw JE, Santanello NC, et al. Cholesterol reduction yields clinical benefit; impact of statin trials. Circulation 1998;97:946-52.
20. Gordon T, Castelli WP, Hjortland MC, et al. High density lipoprotein as a protective factor against coronary artery disease. The Framingham Study. Am J Med 1977;62:707-14.
21. Rigotti N, Pasternak L. Changing the natural history of coronary artery disease. Cardiology Clinics 1996;14:51-68.
One in five of your patients could suffer a heart attack in the near future—unless you take steps to ensure their heart health.
Psychiatric patients have more modifiable risk factors for coronary artery disease (CAD) compared with the general population.When depression treatment goes nowhere,” Current Psychiatry, August 2005.)
To help keep you abreast of constantly changing guidelines and strategies for recognizing and minimizing CAD risk, this article discusses:
- preventive and diagnostic guidelines for managing hypertension, diabetes, and dyslipidemia
- practical advice on convincing at-risk patients to adopt a healthier lifestyle and have a primary care doctor monitor their health.
Case: cigarettes and supersizing
Mr. H, age 54, is receiving cognitive-behavioral therapy for mild depression. He has been smoking one pack of cigarettes per day for 20 years and has never seriously considered quitting.
The patient, a school teacher, says his “busy schedule” keeps him from exercising and eating properly; he eats fast-food hamburgers and fries approximately five times per week. His father had a heart attack at age 52 and died in his sleep 10 years later.
Mr. H says he feels fine and has never seen a physician other than his psychiatrist. He is reluctant to see a primary care physician for a check-up and, because he is asymptomatic, has no incentive to do so. The psychiatrist thus decides to do a routine examination.
Blood pressure is 148/86; other vital signs are normal. Mr. H’s waist size is 42 inches, he weighs 242 lbs, and his body mass index (BMI) is 34 kg/m2, indicating clinical obesity. Cardiovascular, pulmonary, and abdominal exams are unremarkable.
Discussion. Mr. H is at high risk of a myocardial ischemic event in the near future. He has six risk factors for CAD (Table 1)—four of which are modifiable:
- family history
- age
- current cigarette use
- provisional hypertension diagnosis
- obesity
- physical inactivity.
Table 1
Risk factors for coronary artery disease
Core risk factors |
Age ≥45 for men* |
Age ≥55 for women or premature menopause without estrogen-replacement therapy* |
Family history: premature coronary artery disease with myocardial infarction or sudden death before:
|
Current cigarette smoking |
Hypertension or antihypertensive treatment* |
Elevated LDL cholesterol (>130 mg/dL in patients with low cardiac risk) |
HDL cholesterol |
Triglycerides >150 mg/dL |
Total cholesterol >200 mg/dL* |
Obesity (BMI >30 kg/m2)† |
Sedentary lifestyle |
Other risk factors |
Elevated C-reactive protein |
Elevated homocysteine |
Chronic renal failure |
Depression |
Negative (cardio-protective) risk factors |
HDL >60 mg/dL |
Moderate alcohol use—no more than 1 to 2 drinks per day (1 drink = 12 oz beer or 5 oz of wine) |
If >1 risk factor, refer to primary care doctor or quantify 10-year risk by using the Framingham/ATP III point system scale (www.nhlbi.nih.gov). |
* Framingham/ATP III point system scale variables |
† Use BMI calculator (http://www.nhlbisupport.com/bmi/bmicalc.htm) to determine body mass index. |
HDL: High-density lipoprotein |
LDL: Low-density lipoprotein |
Source: References 9,10 |
Tools for assessing risk
The lifetime risk at age 40 for developing CAD is 49% and 32% in men and women, respectively.6
The National Cholesterol Education Program Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel) has focused on decreasing heart disease incidence by educating patients and providers. Preventive strategies and standards of care have changed several times over the past decade; the Adult Treatment Panel (ATP III) was last revised in July 2004.7
The American College of Cardiology and American Heart Association both endorse the modified Framingham/ATP III scale to measure CAD risk (see Related resources). Although this somewhat tedious point system has limitations, it can precisely calculate coronary risk across 10 years.8 Variables not included in the scoring system—such as C-reactive protein, homocysteine, and postmenopausal state—may be clinically significant and should be gauged separately.
An easier-to-use alternative, the ATP III “core risk factors” scale, estimates hypertension, hypercholesterolemia, family history, current cigarette smoking, and age as low, intermediate, or high (“risk equivalent”) risks (Table 1).8 Psychiatrists can quickly obtain this information from a brief history, blood pressure assessment, and relatively inexpensive lab studies.
Generally, the more risk factors present, the higher the risk of having a major coronary event. Presence of ≥ 2 risk factors signals intermediate or high risk and necessitates referral to a primary care doctor for monitoring.
Patients with a cardiac “risk equivalent” face a >20% risk of having a cardiac ischemic event within 10 years8 (Table 2). Examples of risk equivalents include diabetes or significant vascular disease in any artery.
“Non-core” variables. Also consider certain “non-core” variables—such as pre-existing psychiatric illness—when estimating clinical risk for heart disease. Depression, anxiety, and stress are correlated with an increase in pro-inflammatory markers such as C-reactive protein and predispose patients to CAD.11,12 Depression has repeatedly been shown to increase morbidity and mortality two- to four-fold after myocardial infarction (MI).9,13,14 Interestingly, however, depression treatment after an acute coronary event does not clearly decrease mortality.15 Although prospective, randomized studies are lacking, mood and anxiety disorder treatment is presumed to help prevent CAD development.16
Table 2
Risk equivalents for CAD*
Established coronary artery disease |
Symptomatic carotid artery disease |
Peripheral vascular disease |
Abdominal aortic aneurism |
Diabetes mellitus |
*Risk equivalent: Patient is assumed to have coronary artery disease (CAD). |
Recognizing cad risk
At what point do hypertension and dyslipidemia become risk factors for CAD? When and how often should patients be screened for diabetes mellitus?
Hypertension is one of the most common and deadly CAD risk factors, affecting 50 million Americans.10 Although hypertension awareness and treatment have improved, only 35% of adults have “controlled” blood pressure (
According to the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7), normalizing blood pressure can reduce stroke incidence by 35% and MI by 25%, respectively. JNC 7, however, also found that 90% of persons who are normotensive at age 55 eventually develop hypertension.10
Based on these findings, JNC 7 in 2003 drastically changed the standard of care for diagnosing hypertension. JNC 7 defines normal blood pressure as
- systolic blood pressure 120 to 139 mm Hg
- diastolic blood pressure 80 to 89 mm Hg (Table 3).
Patients with diabetes mellitus or chronic kidney disease are considered hypertensive with blood pressure >130 mm Hg systolic and/or >80 mm Hg diastolic.
As with Mr. H, a blood pressure check is imperative for patients who have rarely or never seen a primary care physician in recent years. The U.S. Preventive Services Task Force strongly recommends measuring blood pressure during a routine medical evaluation at least every 2 years. A second abnormal reading at a separate visit at any time should prompt a hypertension diagnosis. Once diagnosed with hypertension, patients should be treated and checked monthly until stable, then monitored every 3 to 6 months indefinitely.10
If you cannot measure blood pressure in the office, urge patients to use an over-the-counter blood pressure measuring device and refer them to a primary care physician. Check the patient’s self-test reading for accuracy against a clinician’s measurement.
Diabetes is now considered a risk equivalent for CAD development.8 Patients diagnosed with diabetes are extremely likely to have established vascular disease,8 which predisposes them to MI, stroke, kidney disease, blindness, and lower-extremity amputations.17 Those with type 1 diabetes usually present with acute symptoms—including polyuria, polydipsia, weight loss, malaise, dry mouth, and blurred vision—and are readily diagnosed with elevated plasma glucose.
Screening for diabetes is critical because one-third of patients with the disease are undiagnosed. Also, more than 90% of patients with diabetes are non-insulin-dependent (type 2) and are asymptomatic early in the disease course.
No data definitively show benefits from screening asymptomatic adults. Recently revised diagnostic criteria for diabetes, however, call for re-testing asymptomatic patients who were found to have normal fasting plasma glucose (FPG) levels and were considered “free” of diabetes. The American Diabetes Association recommends measuring FPG after no caloric intake for ≥ 8 hours for asymptomatic patients.
FPG measurement is cost-effective and generally more convenient than other diabetes tests.17 Expert consensus strongly suggests checking FPG every 3 years beginning at age 45:17
- FPG
- FPG 100 to 125 mg/dL suggests prediabetes or impaired fasting glucose
- FPG ≥ 126 mg/dL demands a provisional diabetes diagnosis and a follow-up test on another day to confirm the diagnosis.
- comorbid cardiac risk factors
- history of polycystic ovary disease
- a first-degree relative with diabetes
- habitual inactivity
- or FPG 100 to 125 mg/dL.
Do not base diabetes diagnosis on glycosylated hemoglobin measurements, as this test can produce false-negative results in patients with new-onset diabetes.
Dyslipidemia. Every 10% reduction in serum cholesterol reduces cardiovascular mortality by 10% to 15%.19 Data from the large, prospective Framingham heart study show a 25% increase in MIs with each 5-mg/dL decrease in high-density lipoprotein cholesterol (HDL) below the age-based median for men and women.20 Serum triglycerides >150 mg/dL clearly predict future CAD and increase the likelihood of abnormally low HDL.
Every 30-mg/dL increase in low-density lipoprotein cholesterol (LDL) raises the relative risk for CAD by 30%.7 ATP III classifies LDL as the “primary target of cholesterol-lowering therapy.”8Table 4 lists LDL target levels based on other CAD risk factors.
Check fasting lipid profile or serum cholesterol, LDL, HDL, and triglycerides beginning at age 20 and about every 5 years thereafter.8 Total cholesterol
Table 3
JNC 7: What blood pressure readings mean
Category | Systolic BP (mm Hg) | Diastolic BP (mm Hg) |
---|---|---|
Normal | and | |
Prehypertension | 120-139 | or 80-89 |
Stage 1 hypertension* | 140-159 | or 90-99 |
Stage 2 hypertension | 160 | or ≥100 |
JNC 7: Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure | ||
*Patients with diabetes mellitus or chronic kidney disease have stage 1 hypertension at >130/80 mm Hg. | ||
Source: Reference 10 |
Acceptable LDL cholesterol levels for adults based on CAD risk
Risk category | Existing CAD risk factors | LDL goal |
---|---|---|
High risk (10-year risk > 20%) | History of diabetes, CAD, symptomatic carotid artery disease, peripheral vascular disease, or abdominal aortic aneurysm | |
Moderate high risk* (10-year risk 10 to 20%) | >2 risk factors | |
Moderate risk* (10-year risk | >2 risk factors | |
Low risk | 0 to 1 risk factor | ≤160 mg/dL |
CAD: Coronary artery disease | ||
*Same goals apply to managing moderate high and moderate risk. Find 10-year risk calculations at nhlbi.nih.gov/guidelines/cholesterol. | ||
Source: Reference 7 |
Addressing smoking, obesity
Smoking. Before trying nicotine patches or bupropion, Mr. H should realistically contemplate his risks with continued smoking; if he doesn’t want to stop, periodically encourage him to reconsider.10 Most people know the dangers of smoking but few understand that complete cessation for 1 to 2 years often nearly reverses cardiovascular disease.21
Obesity and lack of exercise go hand in hand. Reducing Mr. H’s waist size to 2 is a reasonable short-term goal. To that end, encourage him to:
- decrease his number of weekly fast-food meals from five to three, with an eventual goal of one per week. As an alternative, microwaveable, low-calorie meals—each with at least two servings of fruits or vegetables—can be prepared at home or work.
- walk 30 minutes three times weekly and progress to 1 hour five times weekly over 6 months. As with any exercise program, remind Mr. H to “start low and go slow.”
The patient’s role in treatment. Patients often feel overwhelmed after getting large amounts of information on CAD risk and may feel hopeless and unenthusiastic about improving their physical health. Work with the primary care doctor to emphasize a patient care plan that clearly defines easily attainable, step-by-step goals. Make sure the patient agrees to these goals.
Case continued: no more supersizing
Mr. H now understands the importance of minimizing his CAD risk and realizes that CAD and many associated risk factors are asymptomatic in the early stages of development.
With help from his doctors, Mr. H quit smoking. He also became more mindful of his caloric intake and the types of foods he was eating. He advanced from briskly walking 30 minutes three times per week to slow jogging 40 minutes five times weekly. He still eats at fast-food restaurants but usually orders broiled chicken, salads, or the occasional burger.
- National Cholesterol Education Program. CAD risk assessment tool and ATP III guidelines. www.nhlbi.nih.gov/guidelines/cholesterol/.
- U.S. Preventive Services Task Force preventive guidelines. www.ahrq.gov/clinic/uspstfix.htm.
- National Heart, Lung, and Blood Institute. Calculate your body mass index. http://nhlbisupport.com/bmi/.
- American Heart Association. www.americanheart.org.
One in five of your patients could suffer a heart attack in the near future—unless you take steps to ensure their heart health.
Psychiatric patients have more modifiable risk factors for coronary artery disease (CAD) compared with the general population.When depression treatment goes nowhere,” Current Psychiatry, August 2005.)
To help keep you abreast of constantly changing guidelines and strategies for recognizing and minimizing CAD risk, this article discusses:
- preventive and diagnostic guidelines for managing hypertension, diabetes, and dyslipidemia
- practical advice on convincing at-risk patients to adopt a healthier lifestyle and have a primary care doctor monitor their health.
Case: cigarettes and supersizing
Mr. H, age 54, is receiving cognitive-behavioral therapy for mild depression. He has been smoking one pack of cigarettes per day for 20 years and has never seriously considered quitting.
The patient, a school teacher, says his “busy schedule” keeps him from exercising and eating properly; he eats fast-food hamburgers and fries approximately five times per week. His father had a heart attack at age 52 and died in his sleep 10 years later.
Mr. H says he feels fine and has never seen a physician other than his psychiatrist. He is reluctant to see a primary care physician for a check-up and, because he is asymptomatic, has no incentive to do so. The psychiatrist thus decides to do a routine examination.
Blood pressure is 148/86; other vital signs are normal. Mr. H’s waist size is 42 inches, he weighs 242 lbs, and his body mass index (BMI) is 34 kg/m2, indicating clinical obesity. Cardiovascular, pulmonary, and abdominal exams are unremarkable.
Discussion. Mr. H is at high risk of a myocardial ischemic event in the near future. He has six risk factors for CAD (Table 1)—four of which are modifiable:
- family history
- age
- current cigarette use
- provisional hypertension diagnosis
- obesity
- physical inactivity.
Table 1
Risk factors for coronary artery disease
Core risk factors |
Age ≥45 for men* |
Age ≥55 for women or premature menopause without estrogen-replacement therapy* |
Family history: premature coronary artery disease with myocardial infarction or sudden death before:
|
Current cigarette smoking |
Hypertension or antihypertensive treatment* |
Elevated LDL cholesterol (>130 mg/dL in patients with low cardiac risk) |
HDL cholesterol |
Triglycerides >150 mg/dL |
Total cholesterol >200 mg/dL* |
Obesity (BMI >30 kg/m2)† |
Sedentary lifestyle |
Other risk factors |
Elevated C-reactive protein |
Elevated homocysteine |
Chronic renal failure |
Depression |
Negative (cardio-protective) risk factors |
HDL >60 mg/dL |
Moderate alcohol use—no more than 1 to 2 drinks per day (1 drink = 12 oz beer or 5 oz of wine) |
If >1 risk factor, refer to primary care doctor or quantify 10-year risk by using the Framingham/ATP III point system scale (www.nhlbi.nih.gov). |
* Framingham/ATP III point system scale variables |
† Use BMI calculator (http://www.nhlbisupport.com/bmi/bmicalc.htm) to determine body mass index. |
HDL: High-density lipoprotein |
LDL: Low-density lipoprotein |
Source: References 9,10 |
Tools for assessing risk
The lifetime risk at age 40 for developing CAD is 49% and 32% in men and women, respectively.6
The National Cholesterol Education Program Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel) has focused on decreasing heart disease incidence by educating patients and providers. Preventive strategies and standards of care have changed several times over the past decade; the Adult Treatment Panel (ATP III) was last revised in July 2004.7
The American College of Cardiology and American Heart Association both endorse the modified Framingham/ATP III scale to measure CAD risk (see Related resources). Although this somewhat tedious point system has limitations, it can precisely calculate coronary risk across 10 years.8 Variables not included in the scoring system—such as C-reactive protein, homocysteine, and postmenopausal state—may be clinically significant and should be gauged separately.
An easier-to-use alternative, the ATP III “core risk factors” scale, estimates hypertension, hypercholesterolemia, family history, current cigarette smoking, and age as low, intermediate, or high (“risk equivalent”) risks (Table 1).8 Psychiatrists can quickly obtain this information from a brief history, blood pressure assessment, and relatively inexpensive lab studies.
Generally, the more risk factors present, the higher the risk of having a major coronary event. Presence of ≥ 2 risk factors signals intermediate or high risk and necessitates referral to a primary care doctor for monitoring.
Patients with a cardiac “risk equivalent” face a >20% risk of having a cardiac ischemic event within 10 years8 (Table 2). Examples of risk equivalents include diabetes or significant vascular disease in any artery.
“Non-core” variables. Also consider certain “non-core” variables—such as pre-existing psychiatric illness—when estimating clinical risk for heart disease. Depression, anxiety, and stress are correlated with an increase in pro-inflammatory markers such as C-reactive protein and predispose patients to CAD.11,12 Depression has repeatedly been shown to increase morbidity and mortality two- to four-fold after myocardial infarction (MI).9,13,14 Interestingly, however, depression treatment after an acute coronary event does not clearly decrease mortality.15 Although prospective, randomized studies are lacking, mood and anxiety disorder treatment is presumed to help prevent CAD development.16
Table 2
Risk equivalents for CAD*
Established coronary artery disease |
Symptomatic carotid artery disease |
Peripheral vascular disease |
Abdominal aortic aneurism |
Diabetes mellitus |
*Risk equivalent: Patient is assumed to have coronary artery disease (CAD). |
Recognizing cad risk
At what point do hypertension and dyslipidemia become risk factors for CAD? When and how often should patients be screened for diabetes mellitus?
Hypertension is one of the most common and deadly CAD risk factors, affecting 50 million Americans.10 Although hypertension awareness and treatment have improved, only 35% of adults have “controlled” blood pressure (
According to the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7), normalizing blood pressure can reduce stroke incidence by 35% and MI by 25%, respectively. JNC 7, however, also found that 90% of persons who are normotensive at age 55 eventually develop hypertension.10
Based on these findings, JNC 7 in 2003 drastically changed the standard of care for diagnosing hypertension. JNC 7 defines normal blood pressure as
- systolic blood pressure 120 to 139 mm Hg
- diastolic blood pressure 80 to 89 mm Hg (Table 3).
Patients with diabetes mellitus or chronic kidney disease are considered hypertensive with blood pressure >130 mm Hg systolic and/or >80 mm Hg diastolic.
As with Mr. H, a blood pressure check is imperative for patients who have rarely or never seen a primary care physician in recent years. The U.S. Preventive Services Task Force strongly recommends measuring blood pressure during a routine medical evaluation at least every 2 years. A second abnormal reading at a separate visit at any time should prompt a hypertension diagnosis. Once diagnosed with hypertension, patients should be treated and checked monthly until stable, then monitored every 3 to 6 months indefinitely.10
If you cannot measure blood pressure in the office, urge patients to use an over-the-counter blood pressure measuring device and refer them to a primary care physician. Check the patient’s self-test reading for accuracy against a clinician’s measurement.
Diabetes is now considered a risk equivalent for CAD development.8 Patients diagnosed with diabetes are extremely likely to have established vascular disease,8 which predisposes them to MI, stroke, kidney disease, blindness, and lower-extremity amputations.17 Those with type 1 diabetes usually present with acute symptoms—including polyuria, polydipsia, weight loss, malaise, dry mouth, and blurred vision—and are readily diagnosed with elevated plasma glucose.
Screening for diabetes is critical because one-third of patients with the disease are undiagnosed. Also, more than 90% of patients with diabetes are non-insulin-dependent (type 2) and are asymptomatic early in the disease course.
No data definitively show benefits from screening asymptomatic adults. Recently revised diagnostic criteria for diabetes, however, call for re-testing asymptomatic patients who were found to have normal fasting plasma glucose (FPG) levels and were considered “free” of diabetes. The American Diabetes Association recommends measuring FPG after no caloric intake for ≥ 8 hours for asymptomatic patients.
FPG measurement is cost-effective and generally more convenient than other diabetes tests.17 Expert consensus strongly suggests checking FPG every 3 years beginning at age 45:17
- FPG
- FPG 100 to 125 mg/dL suggests prediabetes or impaired fasting glucose
- FPG ≥ 126 mg/dL demands a provisional diabetes diagnosis and a follow-up test on another day to confirm the diagnosis.
- comorbid cardiac risk factors
- history of polycystic ovary disease
- a first-degree relative with diabetes
- habitual inactivity
- or FPG 100 to 125 mg/dL.
Do not base diabetes diagnosis on glycosylated hemoglobin measurements, as this test can produce false-negative results in patients with new-onset diabetes.
Dyslipidemia. Every 10% reduction in serum cholesterol reduces cardiovascular mortality by 10% to 15%.19 Data from the large, prospective Framingham heart study show a 25% increase in MIs with each 5-mg/dL decrease in high-density lipoprotein cholesterol (HDL) below the age-based median for men and women.20 Serum triglycerides >150 mg/dL clearly predict future CAD and increase the likelihood of abnormally low HDL.
Every 30-mg/dL increase in low-density lipoprotein cholesterol (LDL) raises the relative risk for CAD by 30%.7 ATP III classifies LDL as the “primary target of cholesterol-lowering therapy.”8Table 4 lists LDL target levels based on other CAD risk factors.
Check fasting lipid profile or serum cholesterol, LDL, HDL, and triglycerides beginning at age 20 and about every 5 years thereafter.8 Total cholesterol
Table 3
JNC 7: What blood pressure readings mean
Category | Systolic BP (mm Hg) | Diastolic BP (mm Hg) |
---|---|---|
Normal | and | |
Prehypertension | 120-139 | or 80-89 |
Stage 1 hypertension* | 140-159 | or 90-99 |
Stage 2 hypertension | 160 | or ≥100 |
JNC 7: Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure | ||
*Patients with diabetes mellitus or chronic kidney disease have stage 1 hypertension at >130/80 mm Hg. | ||
Source: Reference 10 |
Acceptable LDL cholesterol levels for adults based on CAD risk
Risk category | Existing CAD risk factors | LDL goal |
---|---|---|
High risk (10-year risk > 20%) | History of diabetes, CAD, symptomatic carotid artery disease, peripheral vascular disease, or abdominal aortic aneurysm | |
Moderate high risk* (10-year risk 10 to 20%) | >2 risk factors | |
Moderate risk* (10-year risk | >2 risk factors | |
Low risk | 0 to 1 risk factor | ≤160 mg/dL |
CAD: Coronary artery disease | ||
*Same goals apply to managing moderate high and moderate risk. Find 10-year risk calculations at nhlbi.nih.gov/guidelines/cholesterol. | ||
Source: Reference 7 |
Addressing smoking, obesity
Smoking. Before trying nicotine patches or bupropion, Mr. H should realistically contemplate his risks with continued smoking; if he doesn’t want to stop, periodically encourage him to reconsider.10 Most people know the dangers of smoking but few understand that complete cessation for 1 to 2 years often nearly reverses cardiovascular disease.21
Obesity and lack of exercise go hand in hand. Reducing Mr. H’s waist size to 2 is a reasonable short-term goal. To that end, encourage him to:
- decrease his number of weekly fast-food meals from five to three, with an eventual goal of one per week. As an alternative, microwaveable, low-calorie meals—each with at least two servings of fruits or vegetables—can be prepared at home or work.
- walk 30 minutes three times weekly and progress to 1 hour five times weekly over 6 months. As with any exercise program, remind Mr. H to “start low and go slow.”
The patient’s role in treatment. Patients often feel overwhelmed after getting large amounts of information on CAD risk and may feel hopeless and unenthusiastic about improving their physical health. Work with the primary care doctor to emphasize a patient care plan that clearly defines easily attainable, step-by-step goals. Make sure the patient agrees to these goals.
Case continued: no more supersizing
Mr. H now understands the importance of minimizing his CAD risk and realizes that CAD and many associated risk factors are asymptomatic in the early stages of development.
With help from his doctors, Mr. H quit smoking. He also became more mindful of his caloric intake and the types of foods he was eating. He advanced from briskly walking 30 minutes three times per week to slow jogging 40 minutes five times weekly. He still eats at fast-food restaurants but usually orders broiled chicken, salads, or the occasional burger.
- National Cholesterol Education Program. CAD risk assessment tool and ATP III guidelines. www.nhlbi.nih.gov/guidelines/cholesterol/.
- U.S. Preventive Services Task Force preventive guidelines. www.ahrq.gov/clinic/uspstfix.htm.
- National Heart, Lung, and Blood Institute. Calculate your body mass index. http://nhlbisupport.com/bmi/.
- American Heart Association. www.americanheart.org.
1. Holt RI, Peveler RC, Byrne CD. Schizophrenia, the metabolic syndrome and diabetes. Diabetes Med 2004;21:515-23.
2. Carney RM, Freedland KE, Miller GE, Jaffe AS. Depression as a risk factor for cardiac mortality and morbidity: a review of potential mechanisms. J Psychosom Res 2002;53:897-902.
3. Weiser M, Reichenberg A, Grotto I, et al. Higher rates of cigarette smoking in male adolescents before the onset of schizophrenia: a historical-prospective cohort study. Am J Psychiatry 2004;161:1219-23.
4. Druss B, Rosenheck R. Mental disorders and access to medical care in the United States. Am J Psychiatry 1998;155:1775-7.
5. Druss B, Rosenheck R, Desai MM, Perlin JB. Quality of preventive medical care for patients with mental disorders. Med Care 2002;40:129-36.
6. Lloyd-Jones DM, Larson MG, Beiser A, Levy D. Lifetime risk of developing coronary heart disease. Lancet 1999;353(9147):89-92.
7. Grundy SM, Cleeman JI, Merz CN, et al. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation 2004;110:227-9.
8. Expert Panel on Detection. Evaluation and Treatment of High Blood Cholesterol in Adults. Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA 2001;285:2486-97.
9. Frasure-Smith N, Lesperance F, Talajic M, et al. Depression and 18-month prognosis after myocardial infarction. Circulation 1995;91:999-1005.
10. Chobanian AV, Bakris GL, Black HR, et al. Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure: the JNC 7 report. JAMA 2003;289:2560-72.
11. Ford DE, Erlinger TP. Depression and C-reactive protein in U.S. adults: data from the Third National Health and Nutrition Examination Survey. Arch Intern Med 2004;164:1010-14.
12. Panagiotakos DB, Pitsavos C, Chrysohoou C, et al. Inflammation, coagulation and depressive symptomatology in cardiovascular disease-free people: the ATTICA study. Eur Heart J 2004;25:492-9.
13. Frasure-Smith N, Lesperance F, Talajic M. Depression following myocardial infarction. Impact on 6-month survival. JAMA 1993;270:1819-25.
14. Ladwig KH, Kieser M, Konig J, et al. Affective disorders and survival after acute myocardial infarction: results from the post-infarction late potential study. Eur Heart J 1991;12:959-64.
15. Berkman LF, Blumenthal J, Burg M, et al. Effects of treating depression and low perceived social support on clinical events after myocardial infarction: the Enhancing Recovery in Coronary Artery Heart Disease Patients (ENRICHD) randomized trial. JAMA 2003;289:3106-16.
16. Rosengren A, Hawken S, Ounpuu S, et al. Association of psychological risk factors with risk of acute myocardial infarction in 11,119 cases and 13,648 controls from 52 countries (the INTERHEART study). Lancet 2004;364:953-62.
17. American Diabetes Association. Screening for type 2 diabetes. Diabetes Care 2004;27(suppl 1):11-14.
18. American Diabetes Association; American Psychiatric Association. American Association of Clinical Endocrinologists; North American Association for the Study of Obesity. Consensus development conference on antipsychotic drugs and obesity and diabetes. Diabetes Care 2004;27:596-601.
19. Gould AL, Rossouw JE, Santanello NC, et al. Cholesterol reduction yields clinical benefit; impact of statin trials. Circulation 1998;97:946-52.
20. Gordon T, Castelli WP, Hjortland MC, et al. High density lipoprotein as a protective factor against coronary artery disease. The Framingham Study. Am J Med 1977;62:707-14.
21. Rigotti N, Pasternak L. Changing the natural history of coronary artery disease. Cardiology Clinics 1996;14:51-68.
1. Holt RI, Peveler RC, Byrne CD. Schizophrenia, the metabolic syndrome and diabetes. Diabetes Med 2004;21:515-23.
2. Carney RM, Freedland KE, Miller GE, Jaffe AS. Depression as a risk factor for cardiac mortality and morbidity: a review of potential mechanisms. J Psychosom Res 2002;53:897-902.
3. Weiser M, Reichenberg A, Grotto I, et al. Higher rates of cigarette smoking in male adolescents before the onset of schizophrenia: a historical-prospective cohort study. Am J Psychiatry 2004;161:1219-23.
4. Druss B, Rosenheck R. Mental disorders and access to medical care in the United States. Am J Psychiatry 1998;155:1775-7.
5. Druss B, Rosenheck R, Desai MM, Perlin JB. Quality of preventive medical care for patients with mental disorders. Med Care 2002;40:129-36.
6. Lloyd-Jones DM, Larson MG, Beiser A, Levy D. Lifetime risk of developing coronary heart disease. Lancet 1999;353(9147):89-92.
7. Grundy SM, Cleeman JI, Merz CN, et al. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation 2004;110:227-9.
8. Expert Panel on Detection. Evaluation and Treatment of High Blood Cholesterol in Adults. Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA 2001;285:2486-97.
9. Frasure-Smith N, Lesperance F, Talajic M, et al. Depression and 18-month prognosis after myocardial infarction. Circulation 1995;91:999-1005.
10. Chobanian AV, Bakris GL, Black HR, et al. Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure: the JNC 7 report. JAMA 2003;289:2560-72.
11. Ford DE, Erlinger TP. Depression and C-reactive protein in U.S. adults: data from the Third National Health and Nutrition Examination Survey. Arch Intern Med 2004;164:1010-14.
12. Panagiotakos DB, Pitsavos C, Chrysohoou C, et al. Inflammation, coagulation and depressive symptomatology in cardiovascular disease-free people: the ATTICA study. Eur Heart J 2004;25:492-9.
13. Frasure-Smith N, Lesperance F, Talajic M. Depression following myocardial infarction. Impact on 6-month survival. JAMA 1993;270:1819-25.
14. Ladwig KH, Kieser M, Konig J, et al. Affective disorders and survival after acute myocardial infarction: results from the post-infarction late potential study. Eur Heart J 1991;12:959-64.
15. Berkman LF, Blumenthal J, Burg M, et al. Effects of treating depression and low perceived social support on clinical events after myocardial infarction: the Enhancing Recovery in Coronary Artery Heart Disease Patients (ENRICHD) randomized trial. JAMA 2003;289:3106-16.
16. Rosengren A, Hawken S, Ounpuu S, et al. Association of psychological risk factors with risk of acute myocardial infarction in 11,119 cases and 13,648 controls from 52 countries (the INTERHEART study). Lancet 2004;364:953-62.
17. American Diabetes Association. Screening for type 2 diabetes. Diabetes Care 2004;27(suppl 1):11-14.
18. American Diabetes Association; American Psychiatric Association. American Association of Clinical Endocrinologists; North American Association for the Study of Obesity. Consensus development conference on antipsychotic drugs and obesity and diabetes. Diabetes Care 2004;27:596-601.
19. Gould AL, Rossouw JE, Santanello NC, et al. Cholesterol reduction yields clinical benefit; impact of statin trials. Circulation 1998;97:946-52.
20. Gordon T, Castelli WP, Hjortland MC, et al. High density lipoprotein as a protective factor against coronary artery disease. The Framingham Study. Am J Med 1977;62:707-14.
21. Rigotti N, Pasternak L. Changing the natural history of coronary artery disease. Cardiology Clinics 1996;14:51-68.