Detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III)

Resistance to insulin-stimulated glucose uptake is present in the majority of patients with impaired glucose tolerance (IGT) or non-insulin-dependent diabetes mellitus (NIDDM) and in ∼25% of nonobese individuals with normal oral glucose tolerance. In these conditions, deterioration of glucose tolerance can only be prevented if the β-cell is able to increase its insulin secretory response and maintain a state of chronic hyperinsulinemia. When this goal cannot be achieved, gross decompensation of glucose homeostasis occurs. The relationship between insulin resistance, plasma insulin level, and glucose intolerance is mediated to a significant degree by changes in ambient plasma free-fatty acid (FFA) concentration. Patients with NIDDM are also resistant to insulin suppression of plasma FFA concentration, but plasma FFA concentrations can be reduced by relatively small increments in insulin concentration.Consequently, elevations of circulating plasma FFA concentration can be prevented if large amounts of insulin can be secreted. If hyperinsulinemia cannot be maintained, plasma FFA concentration will not be suppressed normally, and the resulting increase in plasma FFA concentration will lead to increased hepatic glucose production. Because these events take place in individuals who are quite resistant to insulinstimulated glucose uptake, it is apparent that even small increases in hepatic glucose production are likely to lead to significant fasting hyperglycemia under these conditions. Although hyperinsulinemia may prevent frank decompensation of glucose homeostasis in insulin-resistant individuals, this compensatory response of the endocrine pancreas is not without its price. Patients with hypertension, treated or untreated, are insulin resistant, hyperglycemic, and hyperinsulinemic. In addition, a direct relationship between plasma insulin concentration and blood pressure has been noted. Hypertension can also be produced in normal rats when they are fed a fructose-enriched diet, an intervention that also leads to the development of insulin resistance and hyperinsulinemia. The development of hypertension in normal rats by an experimental manipulation known to induce insulin resistance and hyperinsulinemia provides further support for the view that the relationship between the three variables may be a causal one. However, even if insulin resistance and hyperinsulinemia are not involved in the etiology of hypertension, it is likely that the increased risk of coronary artery disease (CAD) in patients with hypertension and the fact that this risk if not reduced with antihypertensive treatment are due to the clustering of risk factors for CAD, in addition to high blood pressure, associated with insulin resistance. These include hyperinsulinemia, IGT, increased plasma triglyceride concentration, and decreased high-density lipoprotein cholesterol concentration, all of which are associated with increased risk for CAD. It is likely that the same risk factors play a significant role in the genesis of CAD in the population as a whole. Based on these considerations the possibility is raised that resistance to insulin-stimulated glucose uptake and hyperinsulinemia are involved in the etiology and clinical course of three major related diseases— NIDDM, hypertension, and CAD.

Role of Insulin Resistance in Human Disease

Background—The objective of this study was to examine the association of Joint National Committee (JNC-V) blood pressure and National Cholesterol Education Program (NCEP) cholesterol categories with coronary heart disease (CHD) risk, to incorporate them into coronary prediction algorithms, and to compare the discrimination properties of this approach with other noncategorical prediction functions. Methods and Results—This work was designed as a prospective, single-center study in the setting of a community-based cohort. The patients were 2489 men and 2856 women 30 to 74 years old at baseline with 12 years of follow-up. During the 12 years of follow-up, a total of 383 men and 227 women developed CHD, which was significantly associated with categories of blood pressure, total cholesterol, LDL cholesterol, and HDL cholesterol (all P,.001). Sex-specific prediction equations were formulated to predict CHD risk according to age, diabetes, smoking, JNC-V blood pressure categories, and NCEP total cholesterol and LDL cholesterol categories. The accuracy of this categorical approach was found to be comparable to CHD prediction when the continuous variables themselves were used. After adjustment for other factors, ’28% of CHD events in men and 29% in women were attributable to blood pressure levels that exceeded high normal ($130/85). The corresponding multivariable-adjusted attributable risk percent associated with elevated total cholesterol ($200 mg/dL) was 27% in men and 34% in women. Conclusions—Recommended guidelines of blood pressure, total cholesterol, and LDL cholesterol effectively predict CHD risk in a middle-aged white population sample. A simple coronary disease prediction algorithm was developed using categorical variables, which allows physicians to predict multivariate CHD risk in patients without overt CHD. (Circulation. 1998;97:1837-1847.)

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Prediction of Coronary Heart Disease Using Risk Factor Categories

1. About These Statistics…e70

2. Cardiovascular Diseases…e72

3. Coronary Heart Disease, Acute Coronary Syndrome, and Angina Pectoris…e89

4. Stroke…e99

5. High Blood Pressure…e111

6. Congenital Cardiovascular Defects…e116

7. Heart Failure…e119

8. Other Cardiovascular Diseases…e122 

9. Risk Factor: Smoking/Tobacco Use…e128

10. Risk Factor: High Blood Cholesterol and Other Lipids…e132

11. Risk Factor: Physical Inactivity…e136

12. Risk Factor: Overweight and Obesity…e139

13. Risk Factor: Diabetes Mellitus…e143

14. End-Stage Renal Disease and Chronic Kidney Disease…e149

15. Metabolic Syndrome…e151

16. Nutrition…e153

17. Quality of Care…e155

18. Medical Procedures…e159

19. Economic Cost of Cardiovascular Diseases…e162

20. At-a-Glance Summary Tables…e164 

21. Glossary and Abbreviation Guide…e168
    Writing Group Disclosures…e171



Appendix I: List of Statistical Fact Sheets:

http://www.americanheart.org/presenter.jhtml?identifier=2007

We thank Drs Robert Adams, Philip Gorelick, Matt Wilson, and Philip Wolf (members of the Statistics Committee or Stroke Statistics Subcommittee); Brian Eigel; Gregg Fonarow; Kathy Jenkins; Gail Pearson; and Michael Wolz for their valuable comments and contributions. We would like to acknowledge Tim Anderson and Tom Schneider for their editorial contributions and Karen Modesitt for her administrative assistance.

# 1. About These Statistics {#article-title-2}

The American Heart Association (AHA) works with the Centers for Disease Control and Prevention’s National Center for Health Statistics (CDC/NCHS); the National Heart, Lung, and Blood Institute (NHLBI); the National Institute of Neurological Disorders and Stroke (NINDS); and other government agencies to derive the annual statistics in this Update. This chapter describes the most important sources and the types of data we use from them. For more details and an alphabetical list of abbreviations, see Chapter 21 of this document, the Glossary and Abbreviation Guide.

The surveys used are:

Heart Disease and Stroke Statistics—2007 Update A Report From the American Heart Association Statistics Committee and Stroke Statistics Subcommittee

Impotence and its medical and psychosocial correlates: results of the Massachusetts Male Aging Study.

High density lipoprotein as a protective factor against coronary heart disease: The Framingham study

The incidence of congestive heart failure was determined in relation to prior diabetic status in 5,209 men and women aged 30 to 62 years followed up for 18 years in the Framingham study Men aged 45 to 74 years had more than twice the frequency of congestive failure as their nondiabetic cohorts, and diabetic women had a fivefold increased risk This excessive risk appears to be caused by factors other than accelerated atherogenesis and coronary heart disease Even when patients with prior coronary or rheumatic heart disease were excluded, the diabetic subjects had a four- to fivefold increased risk of congestive heart failure In women (but not men) with prior coronary disease, diabetes also imposed a threefold increased risk of congestive failure Furthermore, the increased risk of heart failure in the diabetic patients persisted after taking into account age, blood pressure, weight and cholesterol values as well as coronary heart disease Women with diabetes appeared to be especially vulnerable and, irrespective of coronary disease status, had twice the frequency of congestive heart failure as men The excessive risk of heart failure among diabetic subjects was confined to those treated with insulin The data suggest that diabetes is another discrete cause of congestive heart failure and that some form of cardiomyopathy is associated with diabetes, as a result of either small vessel disease or metabolic disorders

Role of diabetes in congestive heart failure: the Framingham study.

The relation between coronary heart disease (CHD) prevalence and fasting lipid levels was assessed by a case-control study in five populations with a total of 6859 men and women of black, Japanese and white ancestry drawn from subjects aged 40 years and older from populations in Albany, Framingham, Evans County, Honolulu and San Francisco. In each major study group mean levels of high density lipoprotein (HDL) cholesterol were lower in persons with CHD than in those without the disease. The average difference was small -- typically 3-4 mg/dl -- but statistically significant. It was found in most age-race-sex specific groups. The inverse HDL cholesterol-CHD association was not appreciably diminished when adjusted for levels of low density lipoprotein (LDL) cholesterol and triglyceride. LDL, totoal cholesterol and triglycerides were directly related to CHD prevalence; surprisingly, these findings were less uniformly present in the various study groups than the inverse HDL cholesterol-CHD association.

HDL cholesterol and other lipids in coronary heart disease. The cooperative lipoprotein phenotyping study.

The relation of menopause to cardiovascular disease incidence was examined in women less than 55 years old from the cohort of 2873 women in the initial Framingham examination. Although the number of person-years of experience during the 20 years of observation was nearly the same for premenopausal and postmenopausal status, there were only 20 cardiovascular events among the premenopausal women in this age group whereas 70 events occurred among the postmenopausal women of the same age. In each specific age group studied incidence rates were lower in premenopausal than postmenopausal women. This was also true for coronary heart disease. Contrast for "hard" diagnoses of cardiovascular disease (excluding diagnoses of angina pectoris and intermittent claudication) was in the same direction. Although cholesterol and hemoglobin did rise somewhat more steeply in women undergoing the menopause, this greater incidence of cardiovascular disease in postmenopausal women could not be explained by the influence of the menopause on the usual cardiovascular risk factors.

Menopause and Risk of Cardiovascular Disease: The Framingham Study

A rise in coronary heart disease incidence after menopause and a dramatic increase in the severity of the presenting diseases are noted in a cohort of 2873 Framingham women who were followed up for 24 years. No premenopausal woman developed a myocardial infarction or died of coronary heart disease. Such events were common in postmenopausal women. Even in women under 55, 40% of the postmenopausal coronary heart disease presented in these more serious forms, whether menopause was natural or surgical. The contrast was especially marked in the age group 40 to 44 years. In the age groups 45 to 49 and 50 to 54 years, incidence rates in menopausal and postmenopausal intervals were more than double those in premenopausal intervals, whether menopause was natural or surgical. In surgical menopause there was excess incidence whether the ovaries were removed or not. Postmenopausal women on hormones had a doubled risk of coronary heart disease.

Marthana C. Hjortland

Papers

High density lipoprotein as a protective factor against coronary heart disease: The Framingham study

Role of diabetes in congestive heart failure: the Framingham study.

HDL cholesterol and other lipids in coronary heart disease. The cooperative lipoprotein phenotyping study.

Menopause and Risk of Cardiovascular Disease: The Framingham Study

Menopause and Coronary Heart Disease: The Framingham Study