Long-term cardiovascular risk with protease inhibitors and management of the dyslipidemia

This report reviews current data pertaining to the development of dyslipidemia during treatment with protease inhibitors and the associated risk for cardiovascular disease in patients who have the human immunodeficiency virus. Most protease inhibitors used to manage the human immunodeficiency virus and the acquired immunodeficiency syndrome are associated with prompt, marked, and sustained increases in serum lipid levels that are consistent with an increased 10-year risk for coronary heart disease as determined in the Framingham Heart Study. Management of lipid elevations in patients who use protease inhibitors is discussed. Novel protease inhibitors, which have minimal effects on lipid profiles, may have a role in the long-term management of the human immunodeficiency virus.     

Coronary heart disease risk in people 65 years of age and older

Evidence from epidemiologic studies indicates that the same factors that are associated with increased risk of coronary heart disease (CHD) in middle-aged people are relevant in older adults (i.e., those aged >or=65). The relative risk associated with some risk factors decreases with advancing age but this is offset by greater incidence of CHD among older adults. A growing body of evidence from clinical trials indicates that risk factor modification in older adults reduces CHD risk as effectively as it does in middle-aged adults. Multivariable risk assessment can be used to effectively target intervention to those at significant risk for an initial CHD event and to avoid over-treatment. It is important to appreciate that the average remaining life expectancy after achieving 80 years is about 8 years.     

Clinical-electrocardiographic correlates of newly acquired left bundle branch block: the Framingham Study

To determine whether any associated electrocardiographic findings in persons with newly acquired complete left bundle branch block (LBBB) correlate with the prevalence of associated clinically apparent cardiovascular abnormalities, electrocardiograms (ECGs) from all 55 members of the Framingham Study cohort in whom LBBB developed during 18 years of routine prospective biennial examinations were reviewed. A QRS axis left of or equal to 0 degrees, left atrial conduction delay and an inverted T wave in lead V6 on the first ECG with LBBB, and an abnormal ECG in the Framingham examination preceding the appearance of LBBB each correlated with the prevalence of systemic hypertension, cardiomegaly, coronary heart disease and congestive heart failure. However, neither the PR interval nor the duration of the QRS complex on the first ECG with LBBB correlated with the prevalence of any of the associated cardiovascular abnormalities. The 8 patients with neither left atrial conduction delay nor a QRS axis left of or equal to 0 degrees on the first Framingham ECG with LBBB nor an abnormal ECG on the examination preceding the appearance of LBBB were 6 times more likely to remain free of all of the clinical cardiovascular abnormalities than the 47 patients with 1 or more of these 3 electrocardiographic findings (p less than 0.001).     

Obesity and lipoprotein cholesterol in the Framingham offspring study

This study examines the relationship between obesity and low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and very-low-density lipoprotein (VLDL) cholesterol in 4260 young adult men and women. The strongest association between obesity and LDL cholesterol was found in 20–29 yr-old males, the weakest in 40–49-yr-old males. Conversely, in women the relationship between LDL cholesterol and obesity was modest except in the oldes (40–49 yr) age group. An inverse relationship between obesity and HDL cholesterol was of similar shape and strength in all sex and age-specific groups. When the ratio of total cholesterol (TCHOL) to HDL cholesterol was compared in lean and grossly obese 20–29-yr-old males, substantial differences were found. Since other data show this index of the lipoprotein profile to be the single best indicator of CHD risk, it would appear that the atherogenic potential of obesity is greater than would be suggested by the relatively weak association between obesity and TCHOL or any single lipoprotein cholesterol. These data also suggest that the impact of obesity as a risk factor for CHD may have been underestimated. The paucity of lean males 40–49-yr-old prevents firm conclusions about the CHD risk in such a group. Indirect evidence indicates that lean 40–49-yr-old men would have a markedly more favorable lipoprotein profile and consequently a much lower risk of CHD.     

Overall and coronary heart disease mortality rates in relation to major risk factors in 325,348 men screened for the MRFIT. Multiple Risk Factor Intervention Trial

The influence of risk factors on CHD and all-cause mortality rates in 35- to 57-year-old men is examined by means of data on 325,348 white men who were screened for the MRFIT. This large data set permits an unusually detailed analysis of factors associated with the 6968 deaths, including 2426 ascribed to CHD, that were detected in the Social Security Administration data set during 6 years of follow-up. Simple cross classification of the data confirms the independent effect of serum cholesterol concentration, diastolic blood pressure, and cigarette smoking as risk factors for CHD and all-cause mortality rates. A distinct escalation of risk is noted for combinations of these risk factors. The strength of the association of each of the risk factors with CHD and all-cause mortality rates diminished with increasing age, although the number of excess deaths attributable to the risk factors increased because of the higher death rates in older men. Comparison of these findings with those observed in the five populations studied in the Pooling Project revealed an overall similarity in the risk relationships. It is estimated that elimination of these risk factors has the potential for reducing the CHD mortality rate by two thirds in 35- to 45-year old men, and by one half in 46- to 57-year-old men.     

Probability of stroke: a risk profile from the Framingham Study

A health risk appraisal function has been developed for the prediction of stroke using the Framingham Study cohort. The stroke risk factors included in the profile are age, systolic blood pressure, the use of antihypertensive therapy, diabetes mellitus, cigarette smoking, prior cardiovascular disease (coronary heart disease, cardiac failure, or intermittent claudication), atrial fibrillation, and left ventricular hypertrophy by electrocardiogram. Based on 472 stroke events occurring during 10 years' follow-up from biennial examinations 9 and 14, stroke probabilities were computed using the Cox proportional hazards model for each sex based on a point system. On the basis of the risk factors in the profile, which can be readily determined on routine physical examination in a physician's office, stroke risk can be estimated. An individual's risk can be related to the average risk of stroke for persons of the same age and sex. The information that one's risk of stroke is several times higher than average may provide the impetus for risk factor modification. It may also help to identify persons at substantially increased stroke risk resulting from borderline levels of multiple risk factors such as those with mild or borderline hypertension and facilitate multifactorial risk factor modification.