Erythrocyte sedimentation rate and coronary heart disease: the NHANES I Epidemiologic Follow-up Study

Erythrocyte sedimentation rate (ESR) is a simple and relatively inexpensive laboratory test. Data were examined to determine whether elevated ESR was a predictor of CHD incidence and death in a large U.S. national sample of persons aged 45-74 at baseline. In the NHANES I Epidemiologic Follow-up Study cohort, white men aged 45-64 years with ESR in the upper quintile at baseline had increased incidence of CHD (RR = 1.73, 95% CL 1.12, 2.68) over a 15 year follow-up after controlling multiple risk factors compared to white men with ESR in the lowest quintile. Furthermore, men aged 45-64 with ESR in the upper quintile had more than twice the risk of CHD death (RR = 2.73, 95% CL 1.21, 6.15) of men with ESR in the lowest quintile after adjusting other risk factors. No significant associations were seen in white women. The mechanism of this association is unclear. Further studies are needed to replicate this finding and elucidate the mechanism for this association in longitudinal studies in which plasma fibrinogen, HDL cholesterol, as well as ESR are measured.     

Population versus clinical view of case fatality from acute coronary heart disease: results from the WHO MONICA Project 1985-1990. Multinational MONItoring of Trends and Determinants in CArdiovascular Disease

BACKGROUND: The clinical view of case fatality (CF) from acute myocardial infarction (AMI) in those reaching the hospital alive is different from the population view. Registration of both hospitalized AMI cases and out-of-hospital coronary heart disease (CHD) deaths in the WHO MONICA Project allows both views to be reconciled. The WHO MONICA Project provides the largest data set worldwide to explore the relationship between CHD CF and age, sex, coronary event rate, and first versus recurrent event. METHODS AND RESULTS: All 79,669 events of definite AMI or possible coronary death, occurring from 1985 to 90 among 5,725,762 people, 35 to 64 years of age, in 29 MONICA populations are the basis for CF calculations. Age-adjusted CF (percentage of CHD events that were fatal) was calculated across populations, stratified for different time periods, and related to age, sex, and CHD event rate. Median 28-day population CF was 49% (range, 35% to 60%) in men and 51% (range, 34% to 70%) in women and was particularly higher in women than men in populations in which CHD event rates were low. Median 28-day CF for hospitalized events was much lower: in men 22% (range, 15% to 36%) and in women 27% (range, 19% to 46%). Among hospitalized events CF was twice as high for recurrent as for first events. CONCLUSIONS: Overall 28-day CF is halved for hospitalized events compared with all events and again nearly halved for hospitalized 24-hour survivors. Because approximately two thirds of 28-day CHD deaths in men and women occurred before reaching the hospital, opportunities for reducing CF through improved care in the acute event are limited. Major emphasis should be on primary and secondary prevention.     

Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: results of AFCAPS/TexCAPS. Air Force/Texas Coronary Atherosclerosis Prevention Study

CONTEXT: Although cholesterol-reducing treatment has been shown to reduce fatal and nonfatal coronary disease in patients with coronary heart disease (CHD), it is unknown whether benefit from the reduction of low-density lipoprotein cholesterol (LDL-C) in patients without CHD extends to individuals with average serum cholesterol levels, women, and older persons. OBJECTIVE: To compare lovastatin with placebo for prevention of the first acute major coronary event in men and women without clinically evident atherosclerotic cardiovascular disease with average total cholesterol (TC) and LDL-C levels and below-average high-density lipoprotein cholesterol (HDL-C) levels. DESIGN: A randomized, double-blind, placebo-controlled trial. SETTING: Outpatient clinics in Texas. PARTICIPANTS: A total of 5608 men and 997 women with average TC and LDL-C and below-average HDL-C (as characterized by lipid percentiles for an age- and sex-matched cohort without cardiovascular disease from the National Health and Nutrition Examination Survey [NHANES] III). Mean (SD) TC level was 5.71 (0.54) mmol/L (221 [21] mg/dL) (51 st percentile), mean (SD) LDL-C level was 3.89 (0.43) mmol/L (150 [17] mg/dL) (60th percentile), mean (SD) HDL-C level was 0.94 (0.14) mmol/L (36 [5] mg/dL) for men and 1.03 (0.14) mmol/L (40 [5] mg/dL) for women (25th and 16th percentiles, respectively), and median (SD) triglyceride levels were 1.78 (0.86) mmol/L (158 [76] mg/dL) (63rd percentile). INTERVENTION: Lovastatin (20-40 mg daily) or placebo in addition to a low-saturated fat, low-cholesterol diet. MAIN OUTCOME MEASURES: First acute major coronary event defined as fatal or nonfatal myocardial infarction, unstable angina, or sudden cardiac death. RESULTS: After an average follow-up of 5.2 years, lovastatin reduced the incidence of first acute major coronary events (1 83 vs 116 first events; relative risk [RR], 0.63; 95% confidence interval [CI], 0.50-0.79; P<.001), myocardial infarction (95 vs 57 myocardial infarctions; RR, 0.60; 95% CI, 0.43-0.83; P=.002), unstable angina (87 vs 60 first unstable angina events; RR, 0.68; 95% CI, 0.49-0.95; P=.02), coronary revascularization procedures (157 vs 106 procedures; RR, 0.67; 95% CI, 0.52-0.85; P=.001), coronary events (215 vs 163 coronary events; RR, 0.75; 95% CI, 0.61-0.92; P =.006), and cardiovascular events (255 vs 194 cardiovascular events; RR, 0.75; 95% CI, 0.62-0.91; P = .003). Lovastatin (20-40 mg daily) reduced LDL-C by 25% to 2.96 mmol/L (115 mg/dL) and increased HDL-C by 6% to 1.02 mmol/L (39 mg/dL). There were no clinically relevant differences in safety parameters between treatment groups. CONCLUSIONS: Lovastatin reduces the risk for the first acute major coronary event in men and women with average TC and LDL-C levels and below-average HDL-C levels. These findings support the inclusion of HDL-C in risk-factor assessment, confirm the benefit of LDL-C reduction to a target goal, and suggest the need for reassessment of the National Cholesterol Education Program guidelines regarding pharmacological intervention.     

Intake of fatty acids and risk of coronary heart disease in a cohort of Finnish men. The Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study

The relation of intakes of specific fatty acids and the risk of coronary heart disease was examined in a cohort of 21,930 smoking men aged 50-69 years who were initially free of diagnosed cardiovascular disease. All men participated in the Finnish Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study and completed a detailed and validated dietary questionnaire at baseline. After 6.1 years of follow-up from 1985-1988, the authors documented 1,399 major coronary events and 635 coronary deaths. After controlling for age, supplement group, several coronary risk factors, total energy, and fiber intake, the authors observed a significant positive association between the intake of trans-fatty acids and the risk of coronary death. For men in the top quintile of trans-fatty acid intake (median = 6.2 g/day), the multivariate relative risk of coronary death was 1.39 (95% confidence interval (CI) 1.09-1.78) (p for trend = 0.004) as compared with men in the lowest quintile of intake (median = 1.3 g/day). The intake of omega-3 fatty acids from fish was also directly related to the risk of coronary death in the multivariate model adjusting also for trans-saturated and cis-monounsaturated fatty acids (relative risk (RR) = 1.30, 95% CI 1.01-1.67) (p for trend = 0.06 for men in the highest quintile of intake compared with the lowest). There was no association between intakes of saturated or cis-monounsaturated fatty acids, linoleic or linolenic acid, or dietary cholesterol and the risk of coronary deaths. All the associations were similar but somewhat weaker for all major coronary events.     

Do cardiovascular risk factors explain the relation between socioeconomic status, risk of all-cause mortality, cardiovascular mortality, and acute myocardial infarction?

Much remains to be understood about how low socioeconomic status (SES) increases cardiovascular disease and mortality risk. Data from the Kuopio Ischemic Heart Disease Risk Factor Study (1984-1993) were used to estimate the associations between acute myocardial infarction and income, all-cause mortality, and cardiovascular mortality in a population-based sample of 2,272 Finnish men, with adjustment for 23 biologic, behavioral, psychologic, and social risk factors. Compared with the highest income quintile, those in the bottom quintile had age-adjusted relative hazards of 3.14 (95% confidence interval (CI) 1.77-5.56), 2.66 (95% CI 1.25-5.66), and 4.34 (95% CI 1.95-9.66) for all-cause mortality, cardiovascular mortality, and AMI, respectively. After adjustment for risk factors, the relative hazards for the same comparisons were 1.32 (95% CI 0.70-2.49), 0.70 (95% CI 0.29-1.69), and 2.83 (95% CI 1.14-7.00). In the lowest income quintile, adjustment for risk factors reduced the excess relative risk of all-cause mortality by 85%, that of cardiovascular mortality by 118%, and that of acute myocardial infarction by 45%. These data show how the association between SES and cardiovascular mortality and all-cause mortality is mediated by known risk factor pathways, but full "explanations" for these associations will need to encompass why these biologic, behavioral, psychologic, and social risk factors are differentially distributed by SES.     

Relation of Helicobacter pylori infection to 13-year mortality and incident ischemic heart disease in the caerphilly prospective heart disease study

BACKGROUND: Associations have been suggested between Helicobacter pylori seropositivity, cardiovascular risk factors, and ischemic heart disease (IHD). The effect of this common infection on mortality is uncertain. METHODS AND RESULTS: Plasma specimens collected during 1979 to 1983 from 1796 men in Caerphilly, South Wales, were analyzed for IgG antibodies to H pylori. Cause of death and occurrence of incident IHD events were ascertained over an average of 13.7 years from death certificates, hospital records, and ECG changes at 5-yearly follow-up examinations. Seventy percent of men were seropositive. The prevalence of IHD at entry was similar in men with and without H pylori antibodies (odds ratio [OR], 1.10; 95% CI, 0.87 to 1.40). Seropositivity was significantly (P<0.05) associated with poorer socioeconomic status currently and in childhood, shorter stature, and poorer ventilatory function at entry but not with age, smoking, body mass index, blood pressure, total cholesterol, HDL cholesterol, LDL cholesterol, fibrinogen, plasma viscosity, or heat shock protein antibodies. Thirteen-year incidence of IHD was not significantly associated with H pylori (OR, 1.05; 95% CI, 0.80 to 1.39), but there was a stronger relationship with all-cause mortality (OR, 1.46; 95% CI, 1.12 to 1.92) and fatal IHD (OR, 1.54; 95% CI, 1.03 to 2.30). After adjustment for cardiovascular risk factors and both adult and childhood socioeconomic status, ORs were slightly reduced and lost statistical significance (OR=1.32 [95% CI, 0.99 to 1.78] for all-cause mortality and OR=1.52 [95% CI, 0.99 to 2.34] for fatal IHD). CONCLUSIONS: H pylori infection is unlikely to be as strong a risk factor for IHD as some previous studies have suggested, but its relationship to mortality, including fatal IHD, deserves further investigation. The mechanism underlying these associations is unlikely to involve hypertension, circulating lipid profile, fibrinogen, or cross-reacting antibodies to bacterial heat shock proteins.     

Stroke was predicted by dimensions of quality of life in treated hypertensive men

BACKGROUND AND PURPOSE: Psychosocial factors have been suggested as risk factors for atherosclerotic disease. The purpose of the present study was to examine whether quality of life predicted strokes and acute coronary events in a prospective study. METHODS: The study included 412 treated hypertensive men, aged 50 to 72 years, with >/=1 of the following: serum cholesterol >/=6.5 mmol/L, smoking, or diabetes mellitus. The Minor Symptoms Evaluation Profile (MSEP) was used to estimate quality of life at entry. Incidences of stroke and acute coronary events were recorded during follow-up. The median follow-up time was 6.6 years. RESULTS: Sixty-four patients had an acute coronary event, and 37 had a stroke during the follow-up period. The Cox regression analyses revealed that the 3 dimensions of MSEP at entry were significant predictors of stroke. The relationship between low contentment at entry and the incidence of stroke during follow-up remained significant (relative risk=1.04; 95% CI, 1.01 to 1.06; P=0.003) even after adjustment for other potential cardiovascular risk factors. Vitality also remained an independent predictor for stroke after adjustment for these potential cardiovascular risk factors (relative risk=1.04; 95% CI, 1. 02 to 1.06; P<0.0001). There was no relationship between MSEP score at entry and myocardial infarction during follow-up. CONCLUSIONS: An independent and significant association between reduced well-being at entry and future stroke was observed in hypertensive men at high cardiovascular risk. The causal relationship is not known, however.     

Risk of coronary heart disease and activation of factor XII in middle-aged men

Increased activity is known to be present in the extrinsic, intrinsic, and final common pathways of the hemostatic system in men at high risk of coronary heart disease (CHD), but the status of the contact system of coagulation in this condition is uncertain. Plasma levels of activated factor XII (XIIa), the initial product of contact activation, have therefore been measured by ELISA in 2464 men aged 51 to 62 years, clinically free of CHD, who were taking part in a prospective cardiovascular survey based in general medical practices. Statistically significant, independent, and positive associations of XIIa were found with serum cholesterol and triglyceride concentrations, blood pressure, body mass index, factor VII activity, plasma fibrinogen concentration, and tobacco smoking, all associated with CHD. Plasma XIIa also increased with recent alcohol intake. Men in the highest quintile of risk according to their conventional risk factors had a mean XIIa of 2.07 ng/mL (95% confidence interval 1.99-2.16), 31% higher than that of men in the lowest quintile (1.58; 95% confidence interval 1.51-1.65). Thus, the contact system of coagulation appears to be activated when CHD risk is increased. Furthermore, the independent associations of XIIa with the major conventional CHD risk factors and its broad range of values in the general population (0.1 to 12.5 ng/mL), combined with a relatively low day-to-day variability in individuals (the within-person component of its total variation being 14.7%), suggest its potential usefulness as a marker of atherosclerotic vascular damage.     

Cardiovascular events and mortality in newly and chronically depressed persons > 70 years of age

The role of duration of depressed mood in the prediction of cardiovascular disease (CVD) requires further study, as it has been suggested that emerging depressive symptoms may be a better predictor than persistent depressive symptoms. This prospective cohort study of 3,701 men and women aged > 70 years uses 3 measurement occasions of depressive symptomatology (Center for Epidemiologic Studies-Depression Scale) during a 6-year period to distinguish persons who were newly (depressed at baseline but not at 3 and 6 years before baseline) and chronically depressed (depressed at baseline and at 3 or 6 years before baseline). Their risk of subsequent CVD events and all-cause mortality was compared with that of subjects who were never depressed during the 6-year period. Outcome events were based on death certificates and Medicare hospitalization records. During a median follow-up of 4.0 years, there were 732 deaths (46.2/1,000 person-years) and 933 new CVD events (64.7/1,000 person-years). In men, but not in women, newly depressed mood was associated with an increased risk of CVD mortality (relative risk 1.75, 95% confidence interval [CI] 1.00 to 3.05), new CVD events (relative risk 2.07, 95% CI 1.44 to 2.96), and new coronary heart disease events (relative risk 2.03, 95% CI 1.28 to 3.24) after adjustment for traditional CVD risk factors. The association between newly depressed mood and all-cause mortality was smaller (relative risk 1.40, 95% CI 0.95 to 2.07). Chronic depressed mood was not associated with new CVD events or all-cause mortality. Our findings suggest that newly depressed older men, but not women, were approximately twice as likely to have a CVD event than those who were never depressed. In men, recent onset of depressed mood is a better predictor of CVD than long-term depressed mood.     

Increased plasma viscosity during an air pollution episode: a link to mortality?

BACKGROUND: Air pollution episodes have been consistently associated with increased mortality, and most strikingly with mortality due to cardiovascular disease. One hypothesis to explain this association is that inflammation of the peripheral airways caused by pollution might increase blood coagulability. We have tested this hypothesis in a cross-sectional study by comparing measurements of plasma viscosity during a severe episode of air pollution during 1985 with those made on less polluted days. METHODS: Plasma viscosity was measured as part of the MONICA Augsburg survey during the winter of 1984-85 in 3256 randomly selected men and women aged 25-64 years. Daily mean concentrations of air pollutants and meteorological variables were measured in Augsburg as part of the automated Bavarian air-quality network. We compared measurements of plasma viscosity made in 324 people who attended for screening during the pollution episode and in 2932 people screened during the remainder of the survey period. FINDINGS: In January, 1985, high concentrations of sulphur dioxide (mean 200 micrograms/m3) and total suspended particles (mean 98 micrograms/m3) were recorded during a 13-day period in Augsburg. In men, the odds ratio for plasma viscosity above the 95th percentile of the distribution (1.38 mPa s) was 3.6 (95% CI 1.6-8.1) comparing measurements during the air pollution episode with non-episode measurements after adjustment for cardiovascular risk factors and meteorological variables. The corresponding odds ratio for women (95th percentile of plasma viscosity 1.37 mPa s) was 2.3 (1.0-5.3). High concentrations of carbon monoxide were also associated with increased plasma viscosity in women. INTERPRETATION: During the 1985 air pollution episode, an increased risk of extreme values of plasma viscosity was observed in both men and women. Altered blood rheology due to inflammatory processes in the lung that induce an acute-phase reaction might therefore be part of the pathological mechanisms linking air pollution to mortality.     

Intake of trans fatty acids and risk of coronary heart disease among women

Trans isomers of fatty acids, formed by the partial hydrogenation of vegetable oils to produce margarine and vegetable shortening, increase the ratio of plasma low-density-lipoprotein to high-density-lipoprotein cholesterol, so it is possible that they adversely influence risk of coronary heart disease (CHD). To investigate this possibility, we studied dietary data from participants in the Nurses' Health Study. We calculated intake of trans fatty acids from dietary questionnaires completed by 85,095 women without diagnosed CHD, stroke, diabetes, or hypercholesterolaemia in 1980. During 8 years of follow-up, there were 431 cases of new CHD (non-fatal myocardial infarction or death from CHD). After adjustment for age and total energy intake, intake of trans isomers was directly related to risk of CHD (relative risk for highest vs lowest quintile 1.50 [95% Cl 1.12-2.00], p for trend = 0.001). Additional control for established CHD risk factors, multivitamin use, and intakes of saturated fat, monounsaturated fat, and linoleic acid, dietary cholesterol, vitamins E or C, carotene, or fibre did not change the relative risk substantially. The association was stronger for the 69,181 women whose margarine consumption over the previous 10 years had been stable (1.67 [1.05-2.66], p for trend = 0.002). Intakes of foods that are major sources of trans isomers (margarine, cookies [biscuits], cake, and white bread) were each significantly associated with higher risks of CHD. These findings support the hypothesis that consumption of partially hydrogenated vegetable oils may contribute to occurrence of CHD.     

Video laparoscopic adrenalectomy

BACKGROUND: A majority of all myocardial infarctions occur in patients who are 65 years of age or older and have average cholesterol levels, but little information is available on whether cholesterol lowering in such patients reduces the rate of recurrent cardiovascular disease. OBJECTIVE: To determine whether pravastatin reduces the rate of recurrent cardiovascular events in older patients. DESIGN: Subset analysis of a randomized, controlled trial. SETTING: 80 hospitals and affiliates in the United States and Canada. PATIENTS: 1283 patients aged 65 to 75 years who had had myocardial infarction and had a plasma total cholesterol level less than 6.2 mmol/L (240 mg/dL) and a low-density lipoprotein cholesterol level of 3.0 to 4.5 mmol/L (115 to 174 mg/dL). INTERVENTION: Pravastatin, 40 mg/d, or placebo. MEASUREMENTS: Five-year event rates of major coronary events (coronary death, nonfatal myocardial infarction, angioplasty, or bypass surgery) and stroke. RESULTS: Major coronary events occurred in 28.1% of placebo recipients and 19.7% of pravastatin recipients (difference, 9.0 percentage points [95% CI, 4 to 13 percentage points]; relative risk reduction, 32%; P < 0.001). Coronary death occurred in 10.3% of the placebo group and in 5.8% of the pravastatin group (difference, 4.6 percentage points [CI, 1.9 to 6.5 percentage points]; relative risk reduction, 45%; P = 0.004). Stroke incidence was 7.3% in the placebo group and 4.5% in the pravastatin group (absolute reduction, 2.9 percentage points [CI, 0.3 to 4.5 percentage points]; relative reduction, 40%; P = 0.03). The numbers of older patients needed to treat for 5 years were 11 (CI, 8 to 24) to prevent a major coronary event and 22 (CI, 15 to 53) to prevent a coronary death. For every 1000 older patients treated, 225 cardiovascular hospitalizations would be prevented compared with 121 hospitalizations in 1000 younger patients. CONCLUSIONS: In older patients with myocardial infarction and cholesterol levels in the average range, pravastatin is associated with a clinically important reduction in risk for major coronary events and stroke. Given the high cardiovascular event rate in older patients, the potential for absolute benefit in this age group is substantial.     

Increased coronary heart disease in Japanese-American men with mutation in the cholesteryl ester transfer protein gene despite increased HDL levels

Plasma high density lipoprotein (HDL) levels are strongly genetically determined and show a general inverse relationship with coronary heart disease (CHD). The cholesteryl ester transfer protein (CETP) mediates the transfer of cholesteryl esters from HDL to other lipoproteins and is a key participant in the reverse transport of cholesterol from the periphery to the liver. A high prevalence of two different CETP gene mutations (D442G, 5.1%; intron 14G:A, 0.5%), was found in 3,469 men of Japanese ancestry in the Honolulu Heart Program and mutations were associated with decreased CETP (-35%) and increased HDL chol levels (+10% for D442G). However, the overall prevalence of definite CHD was 21% in men with mutations and 16% in men without mutations. The relative risk (RR) of CHD was 1.43 in men with mutations (P < .05); after adjustment for CHD risk factors, the RR was 1.55 (P = .02); after additional adjustment for HDL levels, the RR was 1.68 (P = .008). Similar RR values were obtained for the D442G mutation alone. Increased CHD in men with mutations was primarily observed for HDL chol 41-60 mg/dl; for HDL chol > 60 mg/dl men with and without mutations had low CHD prevalence. Thus, genetic CETP deficiency appears to be an independent risk factor for CHD, primarily due to increased CHD prevalence in men with the D442G mutation and HDL cholesterol between 41 and 60 mg/dl. The findings suggest that both HDL concentration and the dynamics of cholesterol transport through HDL (i.e., reverse cholesterol transport) determine the anti-atherogenicity of the HDL fraction.     

Blood viscosity and risk of cardiovascular events: the Edinburgh Artery Study

We examined the relationships of whole blood viscosity and its major determinants to incident cardiovascular events (ischaemic heart disease and stroke) in a prospective study of a random population sample of 1592 men and women aged 55-74 years (the Edinburgh Artery Study). 272 fatal and non-fatal cardiovascular events occurred during 5 years of follow-up (cumulative incidence 17.1%). Age and sex adjusted mean levels of blood viscosity (3.70 v 3.55 mPa.s), haematocrit (46.2 v 45.7%), haematocrit-corrected blood viscosity (3.57 v 3.48 mPa.s), plasma viscosity (1.35 v 1.33 mPa.s) and fibrinogen (2.88 v 2.67 g/l) were significantly higher in subjects who experienced events than in subjects who did not. The relationships of these rheological variables to cardiovascular events were at least as strong as those of conventional risk factors (smoking habit, diastolic blood pressure, and low-density lipoprotein cholesterol). After adjustment for these conventional risk factors, the associations of blood viscosity and haematocrit remained significant for stroke, but not for total events; whereas the associations of plasma viscosity and fibrinogen remained significant for total events and for stroke. These findings suggest that increased blood viscosity may be one plausible biological mechanism through which increases in haematocrit and fibrinogen may promote ischaemic heart disease and stroke. Randomized controlled trials of viscosity reduction in the prevention of cardiovascular events (e.g. by lowering high levels of haematocrit or plasma fibrinogen) are suggested.     

Fasting insulin and apolipoprotein B levels and low-density lipoprotein particle size as risk factors for ischemic heart disease

CONTEXT: Epidemiological studies have established a relationship between cholesterol and low-density lipoprotein cholesterol (LDL-C) concentrations and the risk of ischemic heart disease (IHD), but up to half of patients with IHD may have cholesterol levels in the normal range. OBJECTIVE: To assess the ability to predict the risk of IHD using a cluster of nontraditional metabolic risk factors that includes elevated fasting insulin and apolipoprotein B levels as well as small, dense LDL particles. DESIGN: Nested case-control study. SETTING: Cases and controls were identified from the population-based cohort of the Quebec Cardiovascular Study, a prospective study conducted in men free of IHD in 1985 and followed up for 5 years. PARTICIPANTS: Incident IHD cases were matched with controls selected from among the sample of men who remained IHD free during follow-up. Matching variables were age, smoking habits, body mass index, and alcohol consumption. The sample included 85 complete pairs of nondiabetic IHD cases and controls. MAIN OUTCOME MEASURES: Ability of fasting insulin level, apolipoprotein B level, and LDL particle diameter to predict IHD events, defined as angina, coronary insufficiency, nonfatal myocardial infarction, and coronary death. RESULTS: The risk of IHD was significantly increased in men who had elevated fasting plasma insulin and apolipoprotein B levels and small, dense LDL particles, compared with men who had normal levels for 2 of these 3 risk factors (odds ratio [OR], 5.9; 95% confidence interval [CI], 2.3-15.4). Multivariate adjustment for LDL-C, triglycerides, and high-density lipoprotein cholesterol (HDL-C) did not attenuate the relationship between the cluster of nontraditional risk factors and IHD (OR, 5.2; 95% CI, 1.7-15.7). On the other hand, the risk of IHD in men having a combination of elevated LDL-C and triglyceride levels and reduced HDL-C levels was no longer significant (OR, 1.4; 95% CI, 0.5-3.5) after multivariate adjustment for fasting plasma insulin level, apolipoprotein B level, and LDL particle size. CONCLUSION: Results from this prospective study suggest that the measurement of fasting plasma insulin level, apolipoprotein B level, and LDL particle size may provide further information on the risk of IHD compared with the information provided by conventional lipid variables.     

Prospective blinded study of the relationship between plasma homocysteine and progression of symptomatic peripheral arterial disease

PURPOSE: An elevated plasma homocysteine level is an established risk factor for atherosclerotic coronary heart disease (CHD), cerebrovascular disease (CVD), and lower extremity occlusive disease (LED). An elevated plasma homocysteine level can be reduced by therapy with folate and vitamins B6 and B12. An accurate evaluation of the role of vitamin therapy requires knowledge of the influence of plasma homocysteine levels on the progression of CHD, CVD, and LED. METHODS: The Homocysteine and Progression of Atherosclerosis Study is a blinded prospective study of the influence of homocysteine and of other atherosclerotic risk factors on the progression of disease in patients with symptomatic CVD, LED, or both. This study is set in a university hospital vascular surgery clinic and the General Clinical Research Center. Consecutive patients with stable symptomatic CVD or LED underwent baseline clinical, laboratory, and vascular laboratory testing for homocysteine and other risk factors and were examined every 6 months. The primary endpoints were ankle brachial pressure index, duplex scan-determined carotid stenosis, and death. The secondary endpoints were the clinical progressions of CHD, LED, and CVD. The hypothesis that was tested was whether the progression of symptomatic CVD or LED was more frequent or more rapid in patients with elevated plasma homocysteine levels. plasma homocysteine levels. RESULTS: After a mean follow-up period of 37 months (range, 1 to 78 months) for deaths from all causes (>14 micromol/L; elevated, 18.6%; normal, 9.4%; P = .022), deaths from cardiovascular disease (elevated, 12.5%; normal, 6.3%; P = .05) and the clinical progression of CHD (highest 20% of homocysteine levels, 80%; lowest 20% of homocysteine levels, 39%; P = .007) were significantly more frequent or more rapid by life-table analysis when the homocysteine levels were elevated. Multivariate Cox proportional hazards regression model showed a significant independent and increasing relationship between the plasma homocysteine levels and the time to death (relative risk for highest one third of homocysteine values, 1.6; 95% confidence interval [CI], 1.04 to 2.56; P = 029; and relative risk for highest one fifth of homocysteine values, 3.13; 95% CI, 1.69 to 6.64; P = .0001). After an adjustment for age, smoking, hypertension, diabetes, cholesterol, and the vascular laboratory progression of CVD or LED, each 1.0 micromol/L increase in the plasma homocysteine levels resulted in a 3.6% increase (95% CI, 0.0% to 6.6%; P = .06) in the risk of death (all causes) at 3 years and a 5.6% increase (95% CI, 2.2% to 8.5%; P = .003) in the risk of death from cardiovascular disease. CONCLUSION: We conclude that elevated plasma homocysteine levels are associated significantly with death, with death from cardiovascular disease, and with the progression of CHD in patients with symptomatic CVD or LED. These results strongly mandate clinical trials of homocysteine-lowering vitamin therapy in such patients.     

Association of coronary heart disease incidence with carotid arterial wall thickness and major risk factors: the Atherosclerosis Risk in Communities (ARIC) Study, 1987-1993

Few studies have determined whether greater carotid artery intima-media thickness (IMT) in asymptomatic individuals is associated prospectively with increased risk of coronary heart disease (CHD). In the Atherosclerosis Risk in Communities Study, carotid IMT, an index of generalized atherosclerosis, was defined as the mean of IMT measurements at six sites of the carotid arteries using B-mode ultrasound. The authors assessed its relation to CHD incidence over 4-7 years of follow-up (1987-1993) in four US communities (Forsyth County, North Carolina; Jackson, Mississippi; Minneapolis, Minnesota; and Washington County, Maryland) from samples of 7,289 women and 5,552 men aged 45-64 years who were free of clinical CHD at baseline. There were 96 incident events for women and 194 for men. In sex-specific Cox proportional hazards models adjusted only for age, race, and center, the hazard rate ratio comparing extreme mean IMT (> or = 1 mm) to not extreme (< 1 mm) was 5.07 for women (95% confidence interval 3.08-8.36) and 1.85 for men (95% confidence interval 1.28-2.69). The relation was graded (monotonic), and models with cubic splines indicated significant nonlinearity. The strength of the association was reduced by including major CHD risk factors, but remained elevated at higher IMT. Up to 1 mm mean IMT, women had lower adjusted annual event rates than did men, but above 1 mm their event rate was closer to that of men. Thus, mean carotid IMT is a noninvasive predictor of future CHD incidence.     

Serum cholesterol level and mortality due to suicide and trauma in the Honolulu Heart Program

BACKGROUND: Recent results from cholesterol level-lowering trials and some, but not all, observational studies support an intriguing link between low or lowered serum cholesterol levels and violent death. The reasons behind this relationship are far from clear. METHODS: In this report, we further investigate this issue by assessing the relationship of baseline serum cholesterol levels with long-term risk of mortality due to trauma and suicide in a cohort of 7309 middle-aged Japanese-American men. RESULTS: After 23 years of follow-up, a total of 75 traumatic fatalities and 24 deaths by suicide were documented. Rather than an inverse relation, a positive association between serum cholesterol level and risk of suicide death was observed. After controlling for potential confounders, the relative risk of suicide associated with an increment of 0.98 mmol/L (38 mg/dL) in serum cholesterol level (1 SD) was 1.46 (95% confidence interval, 1.04 to 2.05; P = .02). Multivariate analysis of traumatic mortality failed to detect a relation with serum cholesterol level (relative risk = 0.89; 95% confidence interval, 0.70 to 1.13; P = .44). Heavy alcohol consumption (> 1200 mL of alcohol per month, top quintile) was an independent risk factor for trauma death relative to abstinence (relative risk = 1.86; 95% confidence interval, 1.07 to 3.22; P = .02). CONCLUSIONS: These findings contradict the hypothesis of an inverse relation between serum cholesterol level and suicide, but they support the hypothesis that heavy alcohol consumption is a risk factor for traumatic fatal events.     

Depression and risk of coronary heart disease in elderly men and women: New Haven EPESE, 1982-1991. Established Populations for the Epidemiologic Studies of the Elderly

BACKGROUND: Results of several recent studies suggest that depression is predictive of incident coronary disease. However, few studies have examined this relationship in the elderly, the age at which most coronary heart disease (CHD) becomes clinically manifest. METHODS AND RESULTS: Data are from the New Haven, Conn, cohort (N = 2812) of the Established Populations for the Epidemiologic Studies of the Elderly project. Baseline information on depressive symptoms and CHD risk factors was collected during an in-person interview in 1982. Nonfatal myocardial infarctions were identified through monitoring of admissions to local hospitals and were validated by medical chart review. Cause of death was obtained from death certificates for all deceased participants. Outcomes were defined as CHD deaths (n = 255) and total incident CHD events (n = 391) between January 1, 1982, and December 31, 1991. There was no association between depressive symptoms and CHD outcomes in men. Among women, depressive symptoms were associated with an age-adjusted relative risk of 1.03 (per unit increase on the symptom scale) for CHD mortality (P=.001) and total CHD incidence (P=.002). These associations were largely unaffected by adjustment for established CHD risk factors but were reduced to nonsignificant levels after additional adjustment for impaired physical function. Additional analysis showed a significant association for depressive symptoms among women who had no physical function impairments or who survived at least 3 years without an event. CONCLUSION: Depressive symptoms may not be independent risk factors for CHD outcomes in elderly populations in general but may increase risk among relatively healthy older women.     

Effects of age, gender, and menopausal status on plasma low density lipoprotein cholesterol and apolipoprotein B levels in the Framingham Offspring Study

Plasma low density lipoprotein (LDL) cholesterol, non-high density lipoprotein (HDL) cholesterol, and apolipoprotein (apo) B, the major protein constituent of LDL, were measured in 1,533 men (mean age 49 +/- 10 years) and 1,597 women (mean age 49 +/- 10 years) participating in the 3rd examination cycle of the Framingham Offspring Study. Mean plasma levels of LDL cholesterol and apoB were higher in men than in women (136 versus 132 mg/dl, P < 0.0001; and 109 versus 95 mg/dl, P < 0.0001, respectively). Increased age was associated with higher plasma LDL cholesterol and apoB levels, especially in women. After adjustment for age and body mass index, LDL cholesterol and apoB levels were still significantly higher in postmenopausal than in premenopausal women, indicating a hormonal effect on LDL metabolism. The associations between coronary heart disease (CHD) and LDL cholesterol, non-HDL cholesterol, apoB, and other plasma lipid and lipoprotein parameters were examined by dividing participants in four groups, based on approximate quartiles for these parameters. Elevated LDL cholesterol levels were not significantly associated with CHD in men, but were in women. This result, at variance with that of several longitudinal studies, is likely due to the cross-sectional design of our analysis. Elevated non-HDL cholesterol and apoB levels were significantly associated with the presence of CHD, in both males and females. A plasma apoB value > or = 125 mg/dl may be associated with an increased risk for CHD. Low plasma levels of HDL cholesterol were also significantly associated with CHD. Plasma triglyceride levels, age and body mass index were strong determinants of LDL cholesterol, non-HDL cholesterol, and apoB levels in men and women. In women, postmenopausal status and elevated blood pressure were also significantly associated with elevated levels of these parameters.