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

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It is important that the medical profession play a significant role in critically evaluating the use of diagnostic procedures and therapies as they are introduced in the detection, management,

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ACC/AHA 2006 Guidelines for the Management of Patients With Valvular Heart Disease

The impact of nonrheumatic atrial fibrillation, hypertension, coronary heart disease, and cardiac failure on stroke incidence was examined in 5,070 participants in the Framingham Study after 34 years of follow-up. Compared with subjects free of these conditions, the age-adjusted incidence of stroke was more than doubled in the presence of coronary heart disease (p less than 0.001) and more than trebled in the presence of hypertension (p less than 0.001). There was a more than fourfold excess of stroke in subjects with cardiac failure (p less than 0.001) and a near fivefold excess when atrial fibrillation was present (p less than 0.001). In persons with coronary heart disease or cardiac failure, atrial fibrillation doubled the stroke risk in men and trebled the risk in women. With increasing age the effects of hypertension, coronary heart disease, and cardiac failure on the risk of stroke became progressively weaker (p less than 0.05). Advancing age, however, did not reduce the significant impact of atrial...

https://www.ahajournals.org/doi/pdf/10.1161/01.STR.22.8.983

Atrial fibrillation as an independent risk factor for stroke: the Framingham Study.

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

Abstract Risk of coronary heart disease over 14 years was examined prospectively in 2,282 men and 2,845 women according to their antecedent cholesterol and lipoprotein status. An increased risk pro...

Serum Cholesterol, Lipoproteins, and the Risk of Coronary Heart Disease: The Framingham Study

In a sixteen year follow-up study in Framingham, it was found that diabetics in general show an increased morbidity and mortality from all cardiovascular causes. Insulin-treated diabetic women showed the greatest relative mortality from coronary heart disease. Diabetics were found to have higher lipid values, more hypertension and more obesity, even prior to diagnosis. When all the associated risk factors, individually or together, were taken into consideration their presence could not entirely explain the increase in cardiovascular morbidity and mortality experienced by the diabetic. An as yet unknown factor appears to be present in diabetics that could be responsible for much of the higher incidence of cardiovascular complications in diabetics.

Morbidity and Mortality in Diabetics In the Framingham Population: Sixteen Year Follow-up 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.

Prospective data at Framingham and elsewhere have shown conclusively that risk of coronary heart disease in persons younger than age 50 is strikingly related to the serum total cholesterol level. Within so-called normal limits risk has been found to mount over a 5-fold range. The impact has been found to be augmented by other risk factors. The contribution of the serum total cholesterol to risk has also been found to be determined by its partition in the various lipoprotein fractions. A relatively large amount of cholesterol in the low-density lipoprotein fraction is atherogenic whereas that in the high-density fraction appears protective. The independent contribution of very-low-density lipoprotein and its triglyceride or cholesterol content has on the other hand not been established. The previous position that virtually all of the lipid information pertaining to coranary heart disease resided in the serum total cholesterol must be accordingly modified. (authors)

Tavia Gordon

Papers

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

Serum Cholesterol, Lipoproteins, and the Risk of Coronary Heart Disease: The Framingham Study

Morbidity and Mortality in Diabetics In the Framingham Population: Sixteen Year Follow-up Study

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

Cholesterol in the prediction of atherosclerotic disease. New perspectives based on the Framingham study.