Monumental advances in the field of lipid metabolism and its relationship to atherosclerotic
cardiovascular disease have been achieved during the last half century. Epidemiologic studies have defined
lipid disorders as highly significant independent risk factors for
coronary heart disease, along with
diabetes mellitus,
hypertension and smoking. Primary and
secondary prevention studies including the Coronary Primary Prevention Trial, Helsinki Heart Study, and the Coronary
Drug Project have shown that lowering the atherogenic
low density lipoproteins (
LDL) and
very low density lipoproteins (VLDL) whilst raising the
high density lipoproteins (HDL) significantly decreases the risk for
coronary disease. Striking evidence that aggressive
therapy (to sharply lower
LDL and raise HDL with newer drugs) prevents progression and induces regression of coronary narrowing has been obtained in numerous recent studies using quantitative coronary arteriography. An interesting and unexpected lesson learned from these arteriographic studies was that a highly significant reduction within months in several studies in coronary events was out of proportion to improvements in
luminal narrowing. Recently, three major clinical trials to assess the effects of
cholesterol reduction by the newly discovered
HMG CoA reductase inhibitors (
statins) have been published.
Pravastatin significantly reduced coronary events in hypercholesterolemic patients [mean
LDL-Chol. = 5.0 mM/L (192 mg/dl)] without a history of
myocardial infarction. In a
secondary prevention study,
simvastatin also reduced coronary complications in hypercholesterolemic patients [mean
LDL-Chol. = 4.9 mM/L (190 mg/dl)] with pre-existing
coronary disease. Very recently,
pravastatin treatment significantly reduced coronary events and
stroke in patients with a history of
myocardial infarction and average
cholesterol levels [mean
LDL-Chol. = 3.6 mM/L (139 mg/dl)], representing the majority of patients with
coronary disease. In all these studies, reduction in cardiovascular events was approximately one-third. In subgroup analyses, men, women, elderly, smokers and hypertensives benefited from
cholesterol lowering. There was no significant increase in non-cardiovascular causes of death. In the United States of America, the National
Cholesterol Education Program (NCEP) Adult Treatment Panel, representing major health organizations, developed national guidelines on the detection, evaluation and treatment of high blood
cholesterol in adults. In a given patient, the Panel recognizes the importance of weighing all
cardiovascular disease risk factors including age (men > 45 years, postmenopausal women), family history of premature
coronary disease, smoking,
hypertension, diabetes and
HDL-Cholesterol (< 35 mg/dl) in determining how aggressive
therapy should be. The patient with manifest
coronary heart disease (CHD) is given a special position as such patients are at highest risk for recurrent events. Major goals of
therapy are to lower the
LDL-Cholesterol to 2.6 mM/L (< 100 mg/dl) in the CHD patient. In non-CHD patients with two or more risk factors, the
LDL-Cholesterol goal is 3.4 mM/L (130 mg/dl). In those with fewer risk factors, the goal is 4.2 mM/L (160 mg/dl). These guidelines should be modified as appropriate for Singapore. Patients with elevated
triglycerides usually have low
HDL-Cholesterol levels and often represent a heterogeneous group who may have other concurrent abnormalities including the presence of small dense
LDL,
insulin resistance,
hypertension,
obesity, overt diabetes and combined
hyperlipidemia. Such patients merit individualized treatment. The prevalence of this syndrome may be more common in Singapore and requires further investigation. Current therapeutic guidelines emphasize the need for
weight loss and
dietary restriction of total and especially saturated fat (< 7% to 10% total calories),
cholesterol (< 200 to 300 mg/day), and exercise. (ABSTRACT TRUNCATED)