Low high-density lipoprotein cholesterol and what to do about it.
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Cholesterol, HDL↗
Biomedical subjects
W B Kannel
Publications and source records attributed to W B Kannel.
Predictors of smoking cessation: the Framingham Study.
The relation of demographic, behavioral, and health-related variables to smoking cessation was studied in 1,178 women and 1,506 men cigarette smokers enrolled in the Framingham Heart Study. Smoking cessation was defined as abstinence from all tobacco products for at least 1 year. Proportional hazard models were used to identify baseline variables associated with long-term cessation. In order to identify factors predictive of cessation in the following 2 years, logistic regression models on person-examination data were used. Recent hospitalization and development of coronary heart disease were predictive of smoking cessation, while diagnosis of cancer or changes in pulmonary function were not. Overall, women were as likely to quit as men; however, women who smoked heavily were the least likely to quit. Secular trends were noted in men only; men were more likely to quit after the release of the 1964 Surgeon General's report on smoking. The relation of illness development and sex to smoking cessation should be considered in developing smoking cessation programs.
Coronary Disease↗
White blood cell count and cardiovascular disease. Insights from the Framingham Study.
OBJECTIVE: To examine the relation of white blood cell (WBC) count to the development of cardiovascular disease (CVD), including coronary heart disease, stroke, peripheral arterial disease, and cardiac failure. Traditional CVD risk factors, hematocrit, and vital capacity were considered. DESIGN: Prospective cohort analysis with one baseline examination of relevant risk factors and 12 years of follow-up for CVD. PARTICIPANTS AND METHODS: A community-based sample (Farmingham Offspring Study) of 1393 men and 1401 women who were free of CVD at the onset of the study and who were between the ages of 30 and 59 years at baseline. Time-dependent multiple variable logistic regression methods were used. RESULTS: There were 180 CVD events in men and 80 in women. The WBC count was correlated most strongly with the number of cigarettes smoked per day, hematocrit, and vital capacity. Among nonsmoking men with WBC counts within the normal range, the age-adjusted WBC count was significantly associated with CVD and coronary heart disease incidence. For each 1.0 x 10(9)/L-cell difference in WBC count, the CVD risk increased 32%. In women, each 1.0 x 10(9)/L-cell increment in WBC count was associated with a 17% increase in CVD risk, but only in smokers, and the relationship was not statistically significant after adjustment for relevant risk factors. CONCLUSIONS: The degree of elevation of WBC count within the normal range is a marker for increased risk of CVD that is partially explained by cigarette smoking. Future studies should include differential WBC determinations to assess their association with CVD.
Adult↗
A comparison between lovastatin and gemfibrozil in the treatment of primary hypercholesterolemia.
A randomized, multicenter, double-blind, prospective, 18-week comparison of lovastatin with gemfibrozil was performed to compare their efficacy and tolerability in adults with types IIa and IIb primary hypercholesterolemia. Sixty men and 44 women aged 24 to 78 years participated in the trial. Each treatment group of 52 patients was closely matched by the randomization procedure. All participants met national cholesterol education program guidelines for evaluation and treatment. In all, 94 (90%) completed the 18 weeks of study. After 18 weeks of diet-plus-active treatment, lovastatin decreased serum total cholesterol and low-density lipoprotein (LDL) cholesterol significantly better than gemfibrozil (adjusted mean decreases were 63 vs 35 mg/dl for total cholesterol and 67 vs 28 mg/dl for LDL; p = 0.0001). Gemfibrozil was more effective than lovastatin in increasing high-density lipoprotein (HDL) cholesterol (8 vs 5 mg/dl adjusted mean HDL cholesterol increases; p = 0.0086) after 18 weeks. No significant differences in the adjusted mean ratio of total to HDL cholesterol were noted, but the lovastatin group had a significantly greater adjusted mean reduction in the ratio of LDL to HDL cholesterol (1.8 vs 1.3; p = 0.0013). The gemfibrozil group achieved significantly greater reductions in very low density lipoprotein (VLDL) cholesterol and triglycerides compared with the lovastatin group (adjusted mean decreases were 14 vs 1 mg/dl for VLDL cholesterol and 71 vs 15 mg/dl for triglycerides). After 18 weeks of lovastatin therapy, 49% of patients achieved goal LDL cholesterol, whereas only 9% of those who took gemfibrozil achieved this goal (p = 0.0001).
Adult↗
Efficacy of lipid profiles in prediction of coronary disease.
National guidelines in the United States and Europe have stimulated interest in controlling blood lipid levels to prevent CHD. In this review, the efficiency of lipid profiles in predicting CHD has been examined, and total cholesterol, HDL and LDL cholesterol, and triglyceride values have been compared on the basis of 12 to 14 years of surveillance in the Framingham Study. The average value of total cholesterol and LDL cholesterol in patients who had coronary disease was at or below values that are considered dangerous, which indicates the need for more specific and sensitive lipid profiles. Measurement of LDL cholesterol levels predicted CHD only marginally better than measurement of serum total cholesterol. Measurement of triglyceride levels was the weakest predictor. The total cholesterol to HDL cholesterol ratio was the most efficient predictor both in those with apparently safe and those with abnormal cholesterol values. Measurement of HDL cholesterol was the best single lipid predictor and use of this measurement avoids needlessly alarming or falsely reassuring persons at risk for CHD who have high total cholesterol values. Since the risk associated with any serum cholesterol value varies over a 10-fold range depending on coexistent cardiovascular risk factors, these lipid factors must be taken into account in judging the hazards and efficacy of treatment needed. Evidence is available that controlling elevated cholesterol by diet and administration of pharmaceutical agents can reduce the rate of coronary events, slow progression of angiographically visualized lesions, and regress xanthomata.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Pulling it all together: changing the cardiovascular outlook.
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Adult↗
Family patterns of coronary heart disease mortality: the Framingham Longevity Study.
Family patterns for age at death were examined in a 40 year follow-up of 5209 men and women (2900 deceased, 2309 living) in the Framingham Study and their parents. Age at death of both mothers and fathers was significantly older for surviving offspring when compared to decreased offspring (p less than 0.0001). When longevity was assessed according to cause of death in the offspring, parental age at death was a significant predictor of death by coronary heart disease (CHD), but not for stroke or cancer. Multiple regression analysis for offspring with sudden CHD death revealed that mother's age at death was a significant predictor of age at sudden CHD death (p less than 0.0003) whereas father's age at death was a significant predictor of age at death in non-sudden CHD death (p less than 0.004). Life table analysis showed longest survival rates associated with both parents surviving to age 75 or older followed by mother only surviving to age 75 or older, then father only, and shortest survival with neither parent surviving to age 75. Longevity appears to be more strongly associated with maternal death age than parental death age. Proportional hazards analysis of risk factors associated with CHD revealed that systolic blood pressure, sex of the individual, and cigarette smoking were the most significant predictors of death age. These findings suggest that familial similarities for death age may be mediated primarily through shared CHD risk factors within families, either genetic or non-genetic.
Adult↗
Update on fibrinogen as a cardiovascular risk factor.
Mounting data support a causal connection between high-normal fibrinogen levels and atherosclerotic cardiovascular disease. There is clearly a thrombogenic component to atherosclerosis and the onset of clinical manifestations. This offers the possibility to better identify high-risk candidates and also to protect them by reducing blood fibrinogen concentration or blocking its action. The relationship of antecedent fibrinogen to the subsequent development of cardiovascular disease is examined, based on 18 years of surveillance of a cohort of 1274 men and women aged 47 to 79 years who participated in the Framingham Study. The association with the development of peripheral arterial disease and cardiac failure is now examined in addition to previously studied relationships to coronary heart disease and stroke. In men and women, there is a significant age-adjusted relationship of fibrinogen level to coronary heart disease and to cardiovascular disease in general. In women, a significant relationship to cardiac failure and peripheral arterial disease, but not to stroke, was also found. These data on women are unique as they are not available elsewhere. Age-adjusted cardiovascular, all-cause, and coronary heart disease mortality were all related to fibrinogen in both sexes. In men, fibrinogen impact was the greatest for stroke and the least for peripheral arterial disease. For women, the impact on coronary heart disease was greatest. The absolute risk for an elevated fibrinogen level was greatest for coronary heart disease in both sexes. Average fibrinogen values are higher in women and in persons with other risk factors, including hypertension, cigarette smoking, diabetes, obesity, and elevated hematocrit. However, there is an independent contribution of fibrinogen to cardiovascular disease in general and coronary disease in particular, on adjustment for coexistent risk factors. Fibrinogen enhances the risk of cardiovascular disease in hypertensives, diabetics, and cigarette smokers. About half the cardiovascular risk of cigarette smoking appears due to the higher fibrinogen values. Now, five prospective studies document the excess incidence of cardiovascular events in persons with elevated fibrinogen levels within the "normal range." Each standard deviation increase in fibrinogen is associated with a 30% increment of coronary heart disease in men and a 40% increase in women. Fibrinogen should be added to the list of major cardiovascular risk factors. Trials of intervention to lower fibrinogen in high-risk coronary candidates are needed.
Age Factors↗
Left ventricular hypertrophy as a risk factor in arterial hypertension.
Data on the evolution and prognostic implications of left ventricular hypertrophy (LVH) determined by ECG, chest X-ray and echocardiogram in the Framingham Study are reviewed. Echocardiographic examination provides the most sensitive and specific measure of left ventricular hypertrophy, providing a quantitative evaluation of the anatomical condition. Chest X-ray evaluation is also more sensitive than the ECG, but less specific than the echocardiogram. When ECG-LVH is present, X-ray and echocardiographic LVH are often found; but, when negative, the ECG clearly does not exclude anatomical LVH. The incidence of each variety of LVH increases with age, weight and blood pressure. Although it may also appear following coronary heart disease (CHD), valvular deformity and congenital cardiac defects, the former are the major determinants of LVH in the general population. Each contributes independently to the occurrence of LVH. LVH has emerged as a powerful non-invasive indicator of increased vulnerability to the occurrence of major cardiovascular disease outcomes in hypertension. It appears that X-ray and echocardiographic LVH measure anatomical hypertrophy, whereas the ECG variety is also indicative of ischaemic myocardial involvement when repolarization abnormality is present. Hypertension clearly predisposes to both anatomical and ECG-LVH which cannot be taken as an incidental compensatory feature since at any blood pressure those with ECG-LVH, X-ray or echo LVH are distinctly more prone to cardiovascular sequelae. ECG-LVH carries a greater risk than anatomical (X-ray) LVH. ECG-LVH with repolarization abnormality is more dangerous than that with voltage alone. The latter appears to reflect chiefly the severity and duration of accompanying hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)
Coronary Disease↗
Potency of vascular risk factors as the basis for antihypertensive therapy.
Hypertension is a powerful predisposing risk factor for cardiovascular disease at all ages and in both sexes. Epidemiological assessment indicates the largest risk ratios for stroke and congestive heart failure (CHF), but coronary heart disease (CHD) is the most common and most lethal sequela of hypertension. Examination of the risk of cardiovascular sequelae in the hypertensive population indicates that this is not uniform and varies over a 10-fold range, depending on the associated risk factors. Systolic pressure merits greater consideration than the diastole pressure because isolated systolic hypertension is a powerful cardiovascular risk at all ages. Furthermore, recent trials have indicated the benefit of therapy for systolic-based hypertension in the elderly, even using a diuretic, for coronary disease as well as stroke. Persons with hypertension have a high prevalence of associated cardiovascular risk factors, including elevated cholesterol, reduced HDL-C, diabetes, left ventricular hypertrophy (LVH), and obesity. About 9% under the age of 65 years have an associated overt cardiovascular disease; above age 65 about 30% are so afflicted. Each of these risk factors can double the risk associated with hypertension. Because they are so common, a large fraction of the disease sequelae of hypertension is attributable to these associated risk factors. The high risk of coronary disease in hypertensive patients is concentrated in those with a high total/HDL-cholesterol ratio, impaired glucose tolerance, high fibrinogen, ECG abnormalities, and cigarette smokers. Stroke risk in hypertensive persons is concentrated in those with cardiovascular disease, diabetes, atrial fibrillation, LVH and cigarette smoking.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Left ventricular hypertrophy and mortality--results from the Framingham Study.
Data on the prognostic implications of left ventricular hypertrophy (LVH) in the Framingham Study based on routine ECG, echocardiogram (ECHO) and X-ray determination with 36 years of follow-up indicate that LVH has emerged as a powerful indicator of rapidly evolving lethal atherosclerotic disease, whether determined by ECG, ECHO or X-ray. Cardiovascular morbidity and mortality increase progressively with left ventricular muscle mass from lowest to highest values. The ECG and X-ray versions of LVH each independently contribute to the risk of cardiovascular events; each adds to the risk associated with the other, and those with both are at greater risk than those with either alone. Risk ratios associated with ECG-LVH are substantial and are greatest for cardiac failure and stroke, but coronary disease is the commonest and most lethal sequela. LVH is reversible, the anatomical variety more so than ECG-LVH, and reversal of this toward normal appears to confer greater benefit for the anatomical rather than the ECG manifestation of LVH. The risk of cardiovascular disease associated with LVH is not uniform, varying widely depending not only on whether there is concomitant ECG and anatomical evidence of hypertrophy but also on the associated hypertension, glucose intolerance, lipid profile and cigarette smoking habit. This suggests that there is much to be gained in correcting those associated risk factors which also promote the development of LVH.
Adult↗
Secular trends in stroke incidence and mortality. The Framingham Study.
BACKGROUND: The reduction in US stroke mortality has been attributed to declining stroke incidence. However, evidence is accumulating of a trend in declining stroke severity. METHODS: We examined secular trends in stroke incidence, prevalence, and fatality in Framingham Study subjects aged 55-64 years in three successive decades beginning in 1953, 1963, and 1973. RESULTS: No significant decline in overall stroke and transient ischemic attack incidence or prevalence occurred. In women, but not men, incidence of completed ischemic stroke declined significantly. Stroke severity, however, decreased significantly over time. Stroke with severe neurological deficit decreased in later decades, with a fall in rates of severe stroke cases in which patients were unconscious on admission to the hospital. There was no substantial change in the case mix of infarcts and hemorrhages and no decline in hemorrhage to account for the decline in severity. The proportion of isolated transient ischemic attacks increased significantly over the 30 years studied, yielding an apparent and significant decline in case-fatality rates in men only. CONCLUSIONS: Secular trends in stroke incidence and fatality did not follow a clear or definite pattern of decline. While a significant decline in stroke severity occurred over three decades, incidence of infarction fell only in women. The decline in total case fatality rates occurred only in men and resulted largely from an increased incidence of isolated transient ischemic attacks. The severity of completed stroke was significantly lower in the later decades under study.
Adult↗
Inferences from secular trend analysis of hypertension control.
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Cause of Death↗
Long- and short-term risk of sudden coronary death.
The long- and short-term relation of risk factors to sudden cardiac death (SCD) is examined in the Framingham heart study of 2,011 men and 2,534 women aged 35-70 at the fourth biennial exam. Risk factor measurements over the first four biennial exams were averaged and analyzed as predictors of the long-term occurrence of SCD over the ensuing 28 years using Kaplan-Meier survival curves and the Cox proportional hazards method. The relation of risk factors to the short-term risk of SCD was examined by relating risk factors at each biennium to incidence over the ensuing 2 years, using pooled logistic regression analyses. Over the 28 years of follow-up, 171 men and 80 women experienced SCDs. Women had a lower incidence than men at all ages, and even after adjusting for known risk factors, their SCD rate was only 32% of that in men. In the short term, women have an SCD rate that is 23% of that in men. Most of the modifiable or constitutional risk factors, including glucose intolerance, systolic blood pressure, body mass index, and cigarette smoking have a greater long-term than short-term net effect. This is less apparent in women. Electrocardiographic abnormalities such as left ventricular hypertrophy, intraventricular block, and nonspecific repolarization abnormality were better short-term predictors. In men, preexisting coronary heart disease conferred a 3.3-fold (risk factor-adjusted) increased long-term risk of SCD and 5.3-fold increased short-term risk. In women, the long-term risk is 1.9 and short-term risk is 2.8.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Epidemiology of cardiovascular disease in the elderly: an assessment of risk factors.
The major risk factors apply in the elderly as well as the young, including hypertension, dyslipidemia, impaired glucose tolerance, physical indolence, and [table: see text] cigarette smoking. These risk factors are highly prevalent in the elderly and are not inevitable consequences of aging and genetic makeup. With aging, there is a longer exposure to risk factors and diminished capacity to cope with them, resulting in a doubled incidence of cardiovascular sequelae at any level of risk factors compared with younger candidates for cardiovascular disease. The predisposing modifiable risk factors for coronary disease, stroke, cardiac failure, and peripheral arterial disease are virtually the same in younger and older candidates for cardiovascular disease. Multivariate cardiovascular risk profiles predict cardiovascular disease as efficiently in the elderly as in the young. There is also evidence that recurrent cardiovascular events are influenced by the same risk factors that predispose to initial events. Although proof of the efficacy of modifying risk factors in older persons is limited to hypertension control, recent declines in coronary and stroke mortality in the United States have included the elderly. This justifies extrapolations of data from the middle aged until sorely needed data become available on the efficacy of modifying risk factors in the elderly.
Aged↗
Serum cholesterol as a prognostic factor after myocardial infarction: the Framingham Study.
OBJECTIVE: To determine the relation between serum cholesterol levels and the long-term risk for reinfarction, death from coronary heart disease, and all-cause mortality in persons who recover from myocardial infarction. DESIGN: Prospective, longitudinal study. SETTING: A geographically defined population-based cohort of adults participating in the Framingham Heart Study. PATIENTS: Men (n = 260) and women (n = 114), 33 to 88 years of age (mean age, 62 years), who had a history of myocardial infarction. MEASUREMENTS: A complete physical examination, including electrocardiographic evaluation, blood pressure measurement, height and weight measurements, determination of smoking habits, and casual determinations of blood glucose and serum cholesterol, was done approximately 1 year after recovery from initial myocardial infarction. Patients were followed after infarction for the occurrence of reinfarction or death (mean follow-up, 10.5 years; range, 0.8 to 31.6 years). MAIN RESULTS: The mean cholesterol level after infarction was 5.21 mmol/L (242.8 mg/dL); 20% of patients had levels below 5.17 mmol/L (200 mg/dL), and 22% had levels of 7.11 mmol/L (275 mg/dL) or more. Compared with patients who had cholesterol levels below 5.17 mmol/L, patients with levels of 7.11 mmol/L or more were at increased risk for reinfarction (relative risk, 3.8; 95% Cl, 1.6 to 8.7), death from coronary heart disease (relative risk, 2.6; Cl, 1.4 to 4.8), and all-cause mortality (relative risk, 1.9; Cl, 1.2 to 2.9) based on multivariate Cox regression analyses adjusted for other coronary risk factors. Intermediate cholesterol levels (5.17 mmol/L to 7.11 mmol/L) were generally not associated with increased risk. The association between elevated serum cholesterol and increased risk was strongest in men; however, elevated cholesterol levels were found to be most strongly related to death from coronary disease and to all-cause mortality in persons who were 65 years of age or more. CONCLUSIONS: Patients who have recovered from a myocardial infarction and who have high cholesterol levels are at an increased long-term risk for reinfarction, death from coronary heart disease, and all-cause mortality. Our results confirm the prognostic value of cholesterol levels measured after myocardial infarction and support the role of lipid management in this population.
Adult↗
Relation of low diastolic blood pressure to coronary heart disease death in presence of myocardial infarction: the Framingham Study.
OBJECTIVE: To examine the hypothesis that a J curve relation between blood pressure and death from coronary heart disease is confined to high risk subjects with myocardial infarction. DESIGN: Cohort longitudinal epidemiological study with biennial examinations since 1950. SETTING: Framingham, Massachusetts, USA. SUBJECTS: 5209 subjects in the Framingham study cohort followed up by a person examination approach. MAIN OUTCOME MEASURES: Coronary heart disease deaths and non-cardiovascular disease deaths in men and women with or without myocardial infarction relative to blood pressure. RESULTS: Among subjects without myocardial infarction non-cardiovascular disease deaths were twice to three times as common as coronary heart disease deaths. Furthermore, there was no significant relation between non-cardiovascular disease death and diastolic or systolic blood pressure. Also coronary heart disease deaths were linearly related to diastolic and systolic blood pressures. Among high risk patients (that is, people with myocardial infarction but free of congestive heart failure) death from coronary heart disease was more common than non-cardiovascular disease death. There was a significant U shaped relation between coronary heart disease death and diastolic blood pressure. Although there was an apparent U shaped relation between coronary heart disease death and systolic blood pressure, it did not attain statistical significance when controlling for age and change in systolic blood pressure from the pre-myocardial infarction level. None of the above conclusions changed when adjustments were made for risk factors such as serum cholesterol concentration, antihypertensive treatment, and left ventricular function. The U shaped relation between diastolic blood pressure and high risk subjects existed for both those given antihypertensive treatment and those not. CONCLUSIONS: These data suggest that an age and sex independent U curve relation exists for diastolic blood pressure and coronary heart disease deaths in patients with myocardial infarction but not for low risk subjects without myocardial infarction. The relation seems to be independent of left ventricular function and antihypertensive treatment.
Adult↗
The impact of obesity on left ventricular mass and geometry. The Framingham Heart Study.
OBJECTIVE: --To determine the relationship of varying degrees of obesity with left ventricular mass and geometry. DESIGN: --Survey. SETTING: --Population-based epidemiologic study. PARTICIPANTS AND METHODS: --M-mode echocardiograms, which were adequate for estimation of left ventricular mass, were obtained in 3922 healthy participants of the Framingham Heart Study. Measured height and weight were used to calculate body-mass index, a measure of obesity. RESULTS: --Body-mass index was strongly correlated with left ventricular mass. After adjusting for age and blood pressure, body-mass index remained a strong independent predictor of left ventricular mass, left ventricular wall thickness, and left ventricular internal dimension (P less than .01 for all). Body-mass index was associated with prevalence of echocardiographic left ventricular hypertrophy, particularly in subjects with a body-mass index exceeding 30 kg/m2. CONCLUSIONS: --Obesity is significantly correlated with left ventricular mass, even after controlling for age and blood pressure. The increase in left ventricular mass associated with increasing adiposity reflects increases in both left ventricular wall thickness and left ventricular internal dimension.
Adult↗