Psychosocial and other features of coronary heart disease: insights from the Framingham Study

Contributors to CHD include atherogenic personal attributes, living habits which promote these, signs of preclinical disease, and host susceptibility to these influences. Atherogenic traits include the blood lipids, blood pressure, and glucose tolerance. High LDL cholesterol is positively and high HDL cholesterol inversely related to CHD incidence. Hypertension, whether systolic or diastolic, labile or fixed, casual or basal, at any age in either sex contributes powerfully to coronary heart disease. The impact of diabetes on CHD is greater for women than for men and varies according to the level of the foregoing risk factors. The faulty life-style is typified by a diet excessive in calories, fat, and salt, a sedentary habit, unrestrained weight gain, and cigarettes. Alcohol used in moderation may be beneficial. Oral contraceptives worsen atherogenic traits and, when used for long periods beyond age 35 in conjunction with cigarettes, predispose to thromboembolism. Type A persons with an overdeveloped sense of time urgency, drive, and competitiveness develop an excess of angina pectoris. Men married to more highly educated women are at increased risk, as are men married to women in white-collar jobs. Preclinical signs of a compromised coronary circulation include silent MI, ECG-LVH, blocked intraventricular conduction, and repolarization abnormalities. Exercise ECG may elicit still earlier evidence. Measures of innate susceptibility include a family history of premature cardiovascular disease, diabetes, hypertension, and gout. Optimal prediction of CHD requires a quantitative combination of risk factors in multiple logistic risk formulations that identify high-risk persons with multiple marginal abnormalities. Preventive management should also be multifactorial.(ABSTRACT TRUNCATED AT 250 WORDS)     

CHD: a major burden in type 2 diabetes

Patients with type 2 diabetes have a two- to four-fold greater risk of cardiovascular mortality than non-diabetic individuals. In order to prevent coronary events in the diabetic population, it is important to treat modifiable cardiovascular risk factors. Data from the Multiple Risk Factor Intervention Trial (MRFIT) show that serum cholesterol level, systolic blood pressure level and cigarette smoking were significant predictors of cardiovascular disease mortality in men with and without diabetes. At every risk factor level, the absolute risk of age-adjusted coronary death rate was three times greater for diabetic men than non-diabetic men (p<0.0001). Patients with diabetes have an abnormal (dyslipidaemic) lipoprotein profile with high levels of very low density lipoprotein cholesterol and triglycerides, and a low level of high density lipoprotein cholesterol. Although levels of total cholesterol or low density lipoprotein (LDL) cholesterol do not differ significantly between patients with and without diabetes, those with diabetes have higher levels of atherogenic small dense LDL particles. MRFIT data show that at any serum cholesterol level, diabetes confers two-three times the risk for a coronary event. These findings constitute the rationale for considering hypolipaemic therapy, e.g. with HMG-CoA reductase inhibitors (statins), in diabetic patients with dyslipidaemia, particularly in those with evidence of coronary heart disease. Evidence shows that statins significantly lower cholesterol, exhibit beneficial effects on many components of atherosclerosis, and can significantly reduce the incidence of stroke.     

Hypercholesterolemia. The evidence supports use of statins

Using statins to treat older men and women with coronary artery disease (CAD) and hypercholesterolemia reduces the risk of all-cause mortality, cardiovascular mortality, coronary events, coronary revascularization, stroke, Intermittent claudication, and congestive heart failure. The target serum low-density lipoprotein (LDL) cholesterol level is < 100 mg in older patients with CAD, prior stroke, peripheral arterial disease, extracranial carotid arterial disease, abdominal aortic aneurysm, diabetes meilitus, and the metabolic syndrome. Statins are also effective in reducing cardiovascular events in older persons with hypercholesterolemia without cardiovascular disease. Consider using statins in older persons without cardiovascular disease but with a serum LDL cholesterol > or = 130 mg/dL, or a serum high-density lipoprotein cholesterol < 50 mg/dL. Data from the Heart Protection Study favor treating patients at high risk for vascular events with statins regardless of age or initial serum lipids.     

Coronary risk prediction in adults (the Framingham Heart Study)

The Framingham Heart Study, an ongoing prospective study of adult men and women, has shown that certain risk factors can be used to predict the development of coronary artery disease. These factors include age, gender, total cholesterol level, high density lipoprotein cholesterol level, systolic blood pressure, cigarette smoking, glucose intolerance and cardiac enlargement (left ventricular hypertrophy on electrocardiogram or enlarged heart on chest x-ray). Calculators and computers can be easily programmed using a multivariate logistic function that allows calculation of the conditional probability of cardiovascular events. These determinations, based on experience with 5,209 men and women participating in the Framingham study, estimate coronary artery disease risk over variable periods of follow-up. Modeled incidence rates range from less than 1% to greater than 80% over an arbitrarily selected 6-year interval; however, they are typically less than 10%, and rarely exceed 45% in men and 25% in women.     

Influence of high-density lipoprotein cholesterol and rheological factors on the sex difference in cardiovascular disease

BACKGROUND: It is well established that the incidence of cardiovascular disease among men is higher than that among women. OBJECTIVE: To determine whether differences between men and women in terms of a range of conventional and rheological risk factors could explain this sex difference. DESIGN: This was a population-based cohort study (the Edinburgh Artery Study). METHODS: Men and women aged 55-74 years (n = 1592) were selected at random from the general population of Edinburgh and followed up for 5 years. Baseline cardiovascular risk factors were measured and related to incidence of disease among men and women. RESULTS: Men had higher levels of cigarette smoking, haematocrit and blood viscosity and lower levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol and plasma fibrinogen than did women. The incidences of cardiovascular events among men and women were 48.3 and 26.1 per 1000 person-years, respectively. Adjustment for level of HDL cholesterol reduced the male:female ratio for sex-specific incidence rates of cardiovascular events from 1.80 [95% confidence interval (CI) 1.43-2.27] to 1.34 (95% CI 1.04-1.73). This reduction was partially reversed after further adjustment for the other cardiovascular risk factors. The impact of blood viscosity, plasma viscosity and plasma level of fibrinogen on the risk of cardiovascular disease was higher for men than it was for women (multivariate relative risk for blood viscosity were 1.24, 95% CI 1.08-1.43, for men and 0.81, 95% CI 0.61-1.06, for women). CONCLUSIONS: Levels of HDL cholesterol levels in women being higher than those in men may explain some, but not all, of the sex difference in incidence of cardiovascular disease. Greater susceptibility of men to rheological factors might also be important.     

Dyslipoproteinemia in women. Special considerations

Heart disease is the number one cause of death in women, as it is in men; risk factors include high cholesterol, high triglycerides, low HDL-C, diabetes, hypertension, and cigarette smoking. Most of these factors are alterable. The lipoprotein profile of a woman undergoes many changes during her lifetime because of the effects of endogenous hormones at pregnancy, the administration of oral contraceptives, and estrogen replacement at the menopause. Endogenous estrogen reduces the risk of heart disease in women as does unopposed estrogen replacement in the menopause. Oral contraceptives, on the other hand, can increase risk depending on the dose prescribed. Careful attention to a woman's native lipid profile, as well as to the impact of administered hormones on her lipids, is important. It is the responsibility of the physician to help patients achieve and maintain the least atherogenic lipid profile possible as well as to identify and reduce other cardiovascular risk factors.     

Diabetes, blood lipids, and the role of obesity in coronary heart disease risk for women. The Framingham study.

Diabetes and a low high-density lipoprotein cholesterol level are associated with each other and with a higher coronary heart disease risk in women. Moreover, both are strongly associated with obesity. These findings are reported from the Framington Study, in which persons aged 49 to 82 were characterized, after overnight fast, for blood lipids by the method of Fredrickson and Levy and then followed for the subsequent development of coronary heart disease. Low-density lipoprotein cholesterol was also associated with coronary heart disease risk in women, but fasting triglycerides were not associated with risk after allowing for the association with high-density lipoprotein cholesterol and diabetes. A low high-density lipoprotein cholesterol in the presence of diabetes appeared to raise the coronary heart disease risk in women relative to that of men.     

Role of non-high-density lipoprotein cholesterol in prevention of cardiovascular disease: updated evidence from clinical trials

PURPOSE OF REVIEW: Although current clinical practice and treatment guidelines focus on low-density lipoprotein cholesterol as the basis for diagnosing and treating atherogenic dyslipidemias, many persons who develop cardiovascular disease do not have substantially elevated low-density lipoprotein cholesterol levels but may have low levels of high-density lipoprotein cholesterol and elevated triglycerides. Assessment of non-high-density lipoprotein cholesterol level provides a measure of cholesterol contained in all atherogenic particles, including low-density lipoprotein, lipoprotein(a), and triglyceride-rich particles such as very low density lipoprotein, very low density lipoprotein remnants, and intermediate-density lipoprotein. In the third Adult Treatment Panel guidelines of the US National Cholesterol Education Program, non-high-density lipoprotein cholesterol was introduced as a secondary target of therapy in persons with high triglyceride levels. RECENT FINDINGS: A growing number of epidemiological studies and clinical trials have examined the relation between non-high-density lipoprotein cholesterol level and cardiovascular disease events. Non-high-density lipoprotein cholesterol has been shown to be a better predictor for cardiovascular events than low-density lipoprotein cholesterol, and trials of statin therapy have demonstrated reductions in non-high-density lipoprotein cholesterol as well as low-density lipoprotein cholesterol. SUMMARY: Clinical trial evidence indicates the importance of incorporating all atherogenic lipoprotein particles in risk stratification. Non-high-density lipoprotein cholesterol is the most readily available surrogate marker for assessment of these particles and may also be a potential target of lipid-altering therapy. Statin therapy, which has already been demonstrated to decrease cardiovascular morbidity and mortality, provides significant reductions in non-high-density lipoprotein cholesterol.     

Lipids in type 2 diabetes

Type 2 diabetes increases the risk of cardiovascular disease two- to fourfold compared to the risk in nondiabetic subjects. Although type 2 diabetes is associated with a clustering of risk factors, the cause for an excess risk of cardiovascular disease remains unknown. Lipid and lipoprotein abnormalities in type 2 diabetes include particularly elevated levels of total and very low-density lipoprotein triglycerides and reduced levels of high-density lipoprotein (HDL) cholesterol. Total and low-density lipoprotein (LDL) cholesterol levels are usually normal if glycemic control is adequate but LDL particles are small and dense. According to prospective population-based studies, total cholesterol is a similar risk factor for coronary heart disease (CHD) in patients with type 2 diabetes as it is in nondiabetic subjects. High total triglycerides and low HDL cholesterol may be even stronger risk factors for CHD in patients with type 2 diabetes than in nondiabetic subjects. Recent drug treatment trials have indicated that the lowering of total and LDL cholesterol by statins, and the lowering of total triglycerides and the raising of HDL cholesterol by fibrates, are at least as beneficial in diabetic patients as in nondiabetic subjects in the prevention of cardiovascular disease.     

Risk factors for symptomatic peripheral arterial disease in older persons in an academic hospital-based geriatrics practice

OBJECTIVE: To investigate risk factors for symptomatic peripheral arterial disease (PAD) in older persons. DESIGN: A retrospective analysis of charts from all older persons seen from January 1, 1998, through June 15, 1999, at an academic, hospital-based geriatrics practice. SETTING: An academic, hospital-based geriatrics practice staffed by fellows in a geriatrics training program and full-time faculty geriatricians. PATIENTS: A total of 467 men, mean age 80 +/- 8 years, and 1444 women, mean age 81 +/- 8 years, were included in the study. MEASUREMENTS AND MAIN RESULTS: Symptomatic PAD was present in 93 of 467 men (20%) and in 191 of 1444 women (13%) (P = .001). Significant risk factors for symptomatic PAD by univariate analysis were: age (P = .021 in women); cigarette smoking, hypertension, diabetes mellitus, serum total cholesterol, serum high-density lipoprotein (HDL) cholesterol (inverse association), and serum low-density lipoprotein (LDL) cholesterol (P < .001 in men and women); obesity (P = .013 in men and .002 in women); and serum triglycerides (P = .027 in women). Significant independent risk factors for symptomatic PAD by stepwise logistic regression analysis were: age (odds ratio = 1.052 in men and 1.025 in women); cigarette smoking (odds ratio = 2.552 in men and 4.634 in women); hypertension (odds ratio = 2.196 in men and 2.777 in women); diabetes mellitus (odds ratio = 6.054 in men and 3.594 in women); serum HDL cholesterol (odds ratio = .948 in men and .965 in women); and serum LDL cholesterol (odds ratio = 1.019 in men and women). CONCLUSIONS: Significant independent risk factors for symptomatic PAD in older men and women were age, cigarette smoking, hypertension, diabetes mellitus, serum HDL cholesterol (inverse association), and serum LDL cholesterol.     

Lipid and lipoprotein abnormalities in diabetic patients with peripheral vascular disease

Coronary heart disease in insulin-dependent (IDDM) and in non-insulin-dependent diabetes (NIDDM) is associated with lipid and lipoprotein changes favouring atherosclerosis. Whether lipid and lipoprotein abnormalities are associated also with peripheral vascular disease in both types of diabetes is largely unknown. Therefore, we studied lipid and lipoprotein levels and their association with claudication in a representative sample of diabetic and non-diabetic subjects in East Finland. Altogether 87 subjects had IDDM (43 men, 44 women), 264 subjects NIDDM (126 men, 138 women) and 120 subjects were non-diabetic controls (63 men, 57 women). Patients with IDDM had an increased level of HDL and HDL2-cholesterol and patients with NIDDM a decreased level of HDL and HDL2-cholesterol and an increased level of total, LDL and VLDL triglycerides than did non-diabetic subjects. Analyses in both types of diabetes by claudication status revealed that total and LDL-cholesterol and total and VLDL triglycerides tended to be higher and HDL and HDL2-cholesterol lower in those having claudication as compared to those without a claudication symptom. Similarly, total cholesterol/HDL-cholesterol ratio and LDL-cholesterol/HDL-cholesterol ratio were also more atherogenic in patients with claudication than in those without claudication. In conclusion, our results indicate that in both types of diabetes peripheral vascular disease is associated with lipid and lipoprotein abnormalities favouring atherosclerosis.     

The significance of high levels of lipoprotein (a) compared with established risk factors in premature coronary artery disease: differences between men and women.

It was shown in a series of studies that increased lipoprotein (a) concentration is a strong and independent risk factor for coronary artery disease. The goal of this study was to determine the significance of elevated lipoprotein (a) levels for the existence and the early manifestation of coronary artery disease by systematically recording cardiovascular risk factors in diagnostic coronary angiographies in a larger group of patients, whereby particular attention was paid to sex-specific differences. In 1011 consecutive patients who underwent coronary angiography (731 men, 280 women, mean age 59 +/- 10 years), fasting blood samples were taken immediately before the angiographies to determine the levels of cholesterol, low density lipoprotein-, high density lipoprotein-cholesterol, triglycerides and lipoprotein (a). In addition, further risk factors were qualitatively recorded. The data evaluation was carried out using the SPSSx software package univariately and multivariately with stepwise discriminant analysis. In 231 patients (144 men, 87 women) either no or only discrete coronary findings appeared, while in 780 cases (587 men, 193 women) coronary artery disease with stenoses > 50% were found. Women with coronary artery disease were significantly older than men and demonstrated higher lipoprotein levels. Women as well as men with coronary artery disease differed from healthy controls by having higher levels of lipoprotein (a) and other lipoproteins, lipoprotein (a) having the smallest error probability (P < 0.0005). The early manifestation of coronary artery disease (below the 18th age percentile) in men (< 50 years) was connected with significantly higher levels of cholesterol, triglycerides and lipoprotein (a), which emphasized their atherogenic significance in the general view. The most striking finding was that in young women (< 53 years), compared to older women with coronary artery disease--corresponding to the age-determined prevalence--significantly lower concentrations of cholesterol, triglycerides and lipoprotein (a) were found. Possible explanations include later manifestation of coronary artery disease, a steeper increase of the lipids with age, particularly of lipoprotein (a), but also a different valence of the risk factors in women.     

Plasma lipoprotein abnormalities in type 1 (insulin-dependent) diabetes mellitus

Lipoprotein abnormalities may well contribute to the increased risk of coronary heart disease, cerebrovascular disease and peripheral vascular disease observed in type 1 (insulin-dependent) diabetes mellitus. The spectrum of diabetes-associated changes in lipoprotein metabolism is discussed. The plasma levels of lipoprotein cholesterol and triglycerides are largely influenced by the degree of glycaemic control. With poor metabolic control, plasma cholesterol and triglycerides are frequently elevated. In contrast, in well-regulated patients without micro- and macrovascular complications lipid levels are generally normal or even favourable, although lipoprotein composition abnormalities can persist despite intensified insulin treatment. With the development of diabetic nephropathy the cardiovascular risk increases markedly and this complication is associated with increased concentrations of cholesterol and of the atherogenic lipoprotein species, lipoprotein(a), and low levels of high-density lipoprotein cholesterol. The rationale for treatment of lipid disorders in diabetes mellitus is based upon results of trials conducted primarily in non-diabetic populations. It is hoped that with increased recognition of dyslipidaemia and aggressive therapeutic measures the overkill in diabetes mellitus from macrovascular diseases will be reduced.     

Sex differences in lipoprotein metabolism and dietary response: Basis in hormonal differences and implications for cardiovascular disease

The transport of fat in the blood stream is approximately twice as fast in women as men. Disease states such as obesity and diabetes are associated with greater lipoprotein abnormalities in women compared with men. A greater increment in cardiovascular disease risk in women is linked to these abnormalities. A greater change in triglyceride level and a lesser change in lowdensity lipoprotein are observed in women than men with high-carbohydrate or high-fat feeding. Most consistent are greater changes in high-density lipoprotein (HDL), HDL2, and apolipoprotein A-I levels in women compared with men with high-carbohydrate or highfat feeding. Dietary fat restriction in women appears to have a less beneficial lipoprotein effect than in men. Dietary fat restriction for heart disease prevention may be less ideal in women than in men.     

Relatively more atherogenic coronary heart disease risk factors in prediabetic women than in prediabetic men

Summary Men with non-insulin-dependent diabetes mellitus (NIDDM) have a twofold increased risk of coronary heart disease and women with NIDDM have a fourfold increased risk. The reasons for this higher relative risk in NIDDM women than in NIDDM men is not completely understood. Since some studies suggest that duration of clinical diabetes and degree of hyperglycaemia have only a modest effect on coronary heart disease risk, we hypothesized that women who eventually convert to NIDDM might have a more atherogenic pattern of lipids and blood pressure relative to subjects who do not convert than male converters, even in the prediabetic period. We examined this issue in Mexican-American subjects in the 8-year follow-up of the San Antonio Heart Study. Seventy-nine out of 801 men converted to NIDDM compared to 133 out of 1131 women. In both men and women, conversion to NIDDM was significantly associated with increased body mass index, fasting insulin and glucose, higher triglyceride and blood pressure and lower high density lipoprotein (HDL) cholesterol. The relative differences between converters and non-converters was significantly greater for women than for men; this interaction term for gender by conversion status was statistically significant for fasting insulin, triglyceride, HDL cholesterol and diastolic blood pressure. Thus, the higher relative risk for coronary heart disease in women with NIDDM relative to men with NIDDM may be partially due to their greater burden of cardiovascular risk factors even prior to the onset of diabetes. [Diabetologia (1997) 40: 711–717] Received: 7 November 1996 and in revised form: 11 March 1997     

Gender differences in lipoprotein metabolism and dietary response: Basis in hormonal differences and implications for cardiovascular disease

The transport of fat in the blood stream is approximately twice as fast in women as men. Disease states such as obesity and diabetes are associated with greater lipoprotein abnormalities in women compared with men. A greater increment in cardiovascular disease risk in women is linked to these abnormalities. A greater change in triglyceride level and a lesser change in low-density lipoprotein are observed in women than men with high-carbohydrate or high-fat feeding. Most consistent are greater changes in high-density lipoprotein (HDL), HDL₂, and apolipoprotein A-I levels in women compared with men with high-carbohydrate or high-fat feeding. Dietary fat restriction in women appears to have a less beneficial lipoprotein effect than in men. Dietary fat restriction for heart disease prevention may be less ideal in women than in men.     

Obesity, diabetes, and risk of cardiovascular disease in the elderly

There is an age-related increase in total body fat and visceral adiposity until age 65 years that often is accompanied by diabetes or impaired glucose tolerance. The prevalence of type 2 diabetes increases progressively with age, peaking at 16.5% in men and 12.8% in women at age 75-84 years. Over age 65, diabetes or glucose intolerance was present in 30%-40% of Framingham Study subjects. There has been an alarming increase, of epidemic proportions, in both obesity and diabetes in the general population. Type 2 diabetes and obesity are both associated with a clustering of atherogenic risk factors, and when three or more are present it generally signifies an insulin resistance syndrome. This is promoted by weight gain and visceral adiposity. The risk of macrovascular disease is increased before glucose levels reach the diagnostic threshold for "diabetes," and 25% of newly diagnosed diabetics already have overt cardiovascular disease. In the Framingham Study, increased risk of cardiovascular disease was two-fold in men and three-fold in women, eliminating the female advantage over men for all outcomes except stroke. Coronary disease is the most common and lethal sequela, and unrecognized myocardial infarctions are three times more common in diabetic than nondiabetic men. Following a myocardial infarction, diabetes imposes a high rate of recurrence, heart failure, and death, more so in women than men. The risk of cardiovascular sequelae in diabetics is variable, the majority of events occurring in those with two or more additional risk factors. Because of the variable risk of cardiovascular disease in either the diabetic or obese person, risk stratification is necessary to determine the hazard of impending cardiovascular disease. This is readily accomplished with Framingham cardiovascular risk formulations. For persons with diabetes or obesity, the chief goal is to avoid the common cardiovascular sequelae. Comprehensive care should include not only normalization of the blood sugar, but also weight reduction, dietary fat restriction, strict blood pressure and lipid control, exercise, and avoidance of tobacco. Trial data indicate that preventive measures benefit obese diabetics even more than nondiabetics.     

Does statin monotherapy address the multiple lipid abnormalities in type 2 diabetes?

Lipid abnormalities, which are common in type 2 diabetes, predispose to a greatly increased risk of coronary heart disease. This characteristic dyslipidaemia includes decreased concentrations of high-density lipoprotein cholesterol (HDL-C), elevated triglycerides, and a small, dense, atherogenic form of low-density lipoprotein cholesterol (LDL-C). Insulin resistance and obesity, which is commonly present in type 2 diabetes, act in concert to disrupt normal lipoprotein metabolism; reverse cholesterol transport in particular. The proatherogenic changes, which result from this process include enrichment of very-low-density lipoprotein with cholesteryl esters and enrichment of LDL with triglycerides. Results from both the Pravastatin Pooling Project and the Heart Protection Study demonstrate that, although people with diabetes obtain the same relative risk reduction with statin therapy, the absolute benefit derived is much lower than for comparable individuals without diabetes. In order to achieve improved outcomes in diabetes patients, it will be important to address other abnormalities in their lipid profiles, including elevated triglycerides and low HDL-C.     

Epidemiology of coronary heart disease in women

Cardiovascular disease (CVD) is the leading cause of mortality in women and a major cause of morbidity. Coronary heart disease (CHD) accounts for nearly half of all CVD deaths. Gender differences in CHD include a later age of onset for women, a greater prevalence of comorbid diseases, and differences in the initial manifestations of the disease. Traditional risk factors for CHD include tobacco use, hypertension, diabetes mellitus, dyslipidemia, obesity, sedentary lifestyle, and atherogenic diet. More recently identified risk factors in women include high sensitivity C-reactive protein (hsCRP), homocysteine, and lipoprotein (a). Appropriate management of risk factors is associated with a reduced incidence of CHD, yet poor implementation in women is widely documented. Barriers to optimal risk factor management in women should be identified and overcome in an effort to maximize the cardiovascular health of women.     

Small LDL and its clinical importance as a new CAD risk factor: a female case study

The underlying metabolic cause of coronary heart disease in many patients is not high blood cholesterol. In fact, the Framingham study has reported that 80% of individuals who go on to have coronary artery disease have the same total blood cholesterol values as those who do not go on to have a cardiovascular event. The most common metabolic contributor to coronary artery disease is the atherogenic lipoprotein profile, characterized by an abundance of highly atherogenic small, dense low-density lipoprotein particles and a deficiency of the high-density lipoprotein (HDL) subtype most associated with coronary artery disease protection (HDL(2b)). This trait is present in 50% of men with coronary artery disease and is not reflected by total or low-density lipoprotein cholesterol values. While fasting triglycerides tend to he higher, and HDL cholesterol lower in patients with the atherogenic lipoprotein profile, the majority have triglyceride and HDL cholesterol values generally accepted to be in the "normal" range. An abundance of basic science and clinical trial evidence convincingly indicates that the presence of an atherogenic lipoprotein profile signifies a three-fold increased risk for a cardiovascular event and rapid arteriographic progression, but it also identifies a group of patients who respond particularly well to specific therapeutic interventions. Often the most effective interventions are the least expensive.