Lipids- The serum cholesterol concentration in the blood is comprised of several major fractions, which are categorized according to their relative density.

The serum total cholesterol concentration is a clear risk factor for coronary heart disease. In the Multiple Risk Factor Intervention Trial (MRFIT) of more than 350000 middle aged American men, the risk of CHD progressively increases with high values for serum total cholesterol.

Serum total cholesterol has been used to screen adults at risk for CHD, but more recent data emphasize the advantages in knowing the concentrations of lipid fractions, such as low density lipoprotein (LDL) and HDL. Approximately two-thirds of the blood cholesterol is found in the LDL fraction and higher LDL cholesterol concentrations have been associated with an increased incidence of coronary artery disease in a large number of studies. The following criteria are used for serum LDL-cholesterol concentrations.

• High risk - Above 160- mg/dl.
• Borderline high-risk 130 to 159 mg/dl
• Desirable below 130 mg/dl

The total cholesterol (or LDL cholesterol) to HDL cholesterol ratio represents a simple, efficient way to help estimate coronary disease risk. Data from the Lipid Research Clinics and the Framingham Heart Study demonstra ted the following advantages of the ratio.

• Among men, a ratio of 6.4 or more identified a group at 2 to 14 percent greater risk than predicted from serum total or LDL- Cholesterol.
• Among women, a ratio of 5.6 or more identified a group at 25 to 45 percent greater risk than predicted from serum total or LDL-Cholesterol.

In contrast, serum total or LDL-Cholesterol did not add independent predictive value to the ratio.

The roles of hypertriglyceridemia and elevated levels of Lp(a) as determinants of cardiovascular risk are less clear .

A number of clinical trials have demonstrated that sustained reductions in total and LDL-cholesterol levels among adults lead to a lower incidence of CHD. Two important issues have been clarified by recent trials in which lipid lowering was achieved with a HMG CoA Reductase inhibitors (STATINS).

• Cholesterol lowering reduces coronary events and mortality when given for primary prevention in men.
• Cholesterol lowering reduces coronary events and mortality in almost all patients with a myocardial infarction (ie. Secondary prevention).

Hypertension : Hypertension is a well-established risk factor for CHD and congestive heart failure. Systolic blood pressure is at least as powerful a coronary risk factor as the diastolic blood pressure and isolated systolic hypertension is now established as a major hazard for coronary heart disease and stroke. Although controlled trials have demonstrated clear benefits in terms of stroke and heart failure reduction, they have not been as consistent in a benefit in coronary events, particularly in patients with mild hypertension.

The excess coronary risk associated with hypertension is primarily evident in subgroups with other risk factors or underlying target organ damage and individuals in these subgroups benefit the most from antihypertensive therapy. The recommendations of the Sixth Joint National Committee provide guidelines for therapy according to stratifications based upon blood pressure level and presence or absence of underlying conditions. (See Chapter on Hypertension - Page No. DFH-IM-19).

Pulse pressure : The principle components of blood pressure consist of both a steady component (mean arterial pressure) and a pulsatile component (pulse pressure), which is the difference between the systolic and diastolic blood pressures. There is increasing evidence that, in middle-aged and older subjects, the pulse pressure is an independent predictor of risk for CHD, compared to the mean arterial pressure. In a 20-year follow-up of individuals between 50 and 79 years of age in the Framingham Heart Study, higher pulse pressure at any level of systolic blood pressure was an important component of CHD risk.

Glucose intolerance and diabetes mellitus - Insulin resistance, hyperinsulinemia and glucose intolerance appear to promote atherosclerosis. In the Framingham Heart Study, diabetes, impaired glucose tolerance, and high-normal levels of glycosylated hemoglobin were powerful contributors to atherosclerotic cardiovascular events, particularly in women. In South Asians, with or without impaired glucose intolerance, a moderately elevated fasting glucose level (> or = 4.9 mmol/L or 88 mg/dL) was a continuous risk factor for myocardial infarction; in those without glucose intolerance, a 1.2 mmol/l (21 mg/dl) increase in postprandial glucose independently increased the odds of myocardial infarction. Diabetics have a greater burden of other atherogenic risk factors than nondiabetics, including hypertension, hypertriglyceridemia, increased total-to-HDL cholesterol ration, and elevated plasma fibrinogen. The CHD risk in diabetics varies widely with the intensity of these cardiovascular risk factors. (See forthcoming chapter on Lipids). Thus, the guidelines published by the National Cholesterol Education Programme and the sixth Joint National Committee have provided a framework to treat coronary risk factors aggressively in diabetics. In addition, there is increasing evidence of the value to aggressive blood pressure control in diabetics. On the other hand, strict glycemic control does not appear to reduce macrovascular disease despite its clear benefit in microvascular disease.