Lloyd E. Chambless

Neighborhood of Residence and Incidence of Coronary Heart Disease

BACKGROUND Where a person lives is not usually thought of as an independent predictor of his or her health, although physical and social features of places of residence may affect health and health-related behavior. METHODS Using data from the Atherosclerosis Risk in Communities Study, we examined the relation between characteristics of neighborhoods and the incidence of coronary heart disease. Participants were 45 to 64 years of age at base line and were sampled from four study sites in the United States: Forsyth County, North Carolina; Jackson, Mississippi; the northwestern suburbs of Minneapolis; and Washington County, Maryland. As proxies for neighborhoods, we used block groups containing an average of 1000 people, as defined by the U.S. Census. We constructed a summary score for the socioeconomic environment of each neighborhood that included information about wealth and income, education, and occupation. RESULTS During a median of 9.1 years of follow-up, 615 coronary events occurred in 13,009 participants. Residents of disadvantaged neighborhoods (those with lower summary scores) had a higher risk of disease than residents of advantaged neighborhoods, even after we controlled for personal income, education, and occupation. Hazard ratios for coronary events in the most disadvantaged group of neighborhoods as compared with the most advantaged group--adjusted for age, study site, and personal socioeconomic indicators--were 1.7 among whites (95 percent confidence interval, 1.3 to 2.3) and 1.4 among blacks (95 percent confidence interval, 0.9 to 2.0). Neighborhood and personal socioeconomic indicators contributed independently to the risk of disease. Hazard ratios for coronary heart disease among low-income persons living in the most disadvantaged neighborhoods, as compared with high-income persons in the most advantaged neighborhoods were 3.1 among whites (95 percent confidence interval, 2.1 to 4.8) and 2.5 among blacks (95 percent confidence interval, 1.4 to 4.5). These associations remained unchanged after adjustment for established risk factors for coronary heart disease. CONCLUSIONS Even after controlling for personal income, education, and occupation, we found that living in a disadvantaged neighborhood is associated with an increased incidence of coronary heart disease.

Ankle brachial index combined with Framingham risk score to predict cardiovascular events and mortality - A meta-analysis

CONTEXT Prediction models to identify healthy individuals at high risk of cardiovascular disease have limited accuracy. A low ankle brachial index (ABI) is an indicator of atherosclerosis and has the potential to improve prediction. OBJECTIVE To determine if the ABI provides information on the risk of cardiovascular events and mortality independently of the Framingham risk score (FRS) and can improve risk prediction. DATA SOURCES Relevant studies were identified. A search of MEDLINE (1950 to February 2008) and EMBASE (1980 to February 2008) was conducted using common text words for the term ankle brachial index combined with text words and Medical Subject Headings to capture prospective cohort designs. Review of reference lists and conference proceedings, and correspondence with experts was conducted to identify additional published and unpublished studies. STUDY SELECTION Studies were included if participants were derived from a general population, ABI was measured at baseline, and individuals were followed up to detect total and cardiovascular mortality. DATA EXTRACTION Prespecified data on individuals in each selected study were extracted into a combined data set and an individual participant data meta-analysis was conducted on individuals who had no previous history of coronary heart disease. RESULTS Sixteen population cohort studies fulfilling the inclusion criteria were included. During 480,325 person-years of follow-up of 24,955 men and 23,339 women, the risk of death by ABI had a reverse J-shaped distribution with a normal (low risk) ABI of 1.11 to 1.40. The 10-year cardiovascular mortality in men with a low ABI (< or = 0.90) was 18.7% (95% confidence interval [CI], 13.3%-24.1%) and with normal ABI (1.11-1.40) was 4.4% (95% CI, 3.2%-5.7%) (hazard ratio [HR], 4.2; 95% CI, 3.3-5.4). Corresponding mortalities in women were 12.6% (95% CI, 6.2%-19.0%) and 4.1% (95% CI, 2.2%-6.1%) (HR, 3.5; 95% CI, 2.4-5.1). The HRs remained elevated after adjusting for FRS (2.9 [95% CI, 2.3-3.7] for men vs 3.0 [95% CI, 2.0-4.4] for women). A low ABI (< or = 0.90) was associated with approximately twice the 10-year total mortality, cardiovascular mortality, and major coronary event rate compared with the overall rate in each FRS category. Inclusion of the ABI in cardiovascular risk stratification using the FRS would result in reclassification of the risk category and modification of treatment recommendations in approximately 19% of men and 36% of women. CONCLUSION Measurement of the ABI may improve the accuracy of cardiovascular risk prediction beyond the FRS.

Trends in the incidence of myocardial infarction and in mortality due to coronary heart disease, 1987 to 1994.

BACKGROUND AND METHODS To clarify the determinants of contemporary trends in mortality from coronary heart disease (CHD), we conducted surveillance of hospital admissions for myocardial infarction and of in-hospital and out-of-hospital deaths due to CHD among 35-to-74-year-old residents of four communities of varying size in the United States (a total of 352,481 persons in 1994). Between 1987 and 1994, we estimate that there were 11,869 hospitalizations for myocardial infarction (on the basis of 8572 hospitalizations sampled) and 3407 fatal coronary events (3023 sampled). RESULTS The largest average annual decrease in mortality due to CHD occurred among white men (change in mortality, -4.7 percent; 95 percent confidence interval, -2.2 to -7.1 percent), followed by white women (-4.5 percent; 95 percent confidence interval, -0.7 to -8.2 percent), black women (-4.1 percent; 95 percent confidence interval, -10.3 to +2.5 percent), and black men (-2.5 percent; 95 percent confidence interval, -6.9 to +2.2 percent). Overall, in-hospital mortality from CHD fell by 5.1 percent per year, whereas out-of-hospital mortality declined by 3.6 percent per year. There was no evidence of a decline in the incidence of hospitalization for a first myocardial infarction among either men or women; in fact, such hospital admissions increased by 7.4 percent per year (95 percent confidence interval for the change, +0.5 to +14.8 percent) among black women and 2.9 percent per year (95 percent confidence interval, -3.6 to +9.9 percent) among black men. Rates of recurrent myocardial infarction decreased, and survival after myocardial infarction improved. CONCLUSIONS From 1987 to 1994, we observed a stable or slightly increasing incidence of hospitalization for myocardial infarction. Nevertheless, there were significant annual decreases in mortality from CHD. The decline in mortality in the four communities we studied may be due largely to improvements in the treatment and secondary prevention of myocardial infarction.

Prospective Study of Hemostatic Factors and Incidence of Coronary Heart Disease The Atherosclerosis Risk in Communities (ARIC) Study

BACKGROUND Although hemostatic factors contribute to acute coronary syndromes and atherogenesis, few studies have prospectively evaluated the association between multiple hemostatic factors and coronary heart disease incidence. METHODS AND RESULTS The Atherosclerosis Risk in Communities Study recruited 14,477 adults from 45 to 64 years of age who were initially free of coronary heart disease. Coronary disease risk factors and several plasma hemostatic factors were measured, and incidence of coronary heart disease was ascertained during an average follow-up of 5.2 years. Age-, race-, and field center-adjusted relative risks of coronary heart disease were significantly elevated (P < or = .05) per higher value of fibrinogen (relative risk: men, 1.76; women, 1.54), white blood cell count (men, 1.68; women, 2.23), factor VIII coagulant activity (women, 1.25), and von Willebrand factor antigen (men, 1.20; women, 1.18). Adjustment for other risk factors attenuated these associations for fibrinogen (adjusted relative risk: men, 1.48; women, 1.21), and it eliminated the white blood cell count, factor VIII, and von Willebrand factor associations, consistent with the other risk factors either confounding or partly operating through their effects on the hemostatic variables. Adjusted standardized relative risks of total mortality, ranging from 1.13 to 1.37, were also elevated (P < .05) in relation to these four factors. There was no association of coronary disease incidence with factor VII, protein C, antithrombin III, or platelet count. CONCLUSIONS Elevated levels of fibrinogen, white blood cell count, factor VIII, and von Willebrand factor are risk factors and may play causative roles in coronary heart disease. However, their measurement in healthy adults appears to add little to prediction of coronary events beyond that of more established risk factors.

Carotid artery intimal-medial thickness distribution in general populations as evaluated by B-mode ultrasound. ARIC Investigators.

Background and Purpose B-mode ultrasound is a widely used technique for the clinical and epidemiological assessment of carotid atherosclerosis. This article provides a description of the distribution of carotid atherosclerosis in the general population. Methods Intimal-medial arterial wall thickness was measured by B-mode real-time ultrasound as an index of atherosclerotic involvement in the extracranial carotid arteries as part of the population-based Atherosclerosis Risk in Communities (ARIC) study. The distribution was described by race-sex strata, in which 759 to 4952 individuals were imaged depending on strata and location in the carotid system. Results Median wall thickness ranged between 0.5 and 1 mm at all ages; fewer than 5% of ARIC participants had values exceeding 2 mm. Individuals tended to have a larger wall thickness in the carotid bifurcation than in the common carotid artery. Internal carotid artery values were more variable, with higher proportions of both large and small wall thicknesses than in the common carotid. The proportion of individuals with a large wall thickness was greatest at the bifurcation and smallest at the common carotid artery. Men had uniformly larger wall thickness than women. Cross-sectional analysis suggests that age-related increases in wall thickness average approximately 0.015 mm/y in women and 0.018 mm/y in men in the carotid bifurcation, 0.010 mm/y for women and 0.014 mm/y for men in the internal carotid artery, and 0.010 mm/y in both sexes in the common carotid artery. Conclusions Estimates provided for wall thickness percentiles can serve as “nomograms” by age, race, and sex.

Stroke Incidence and Survival Among Middle-Aged Adults 9-Year Follow-Up of the Atherosclerosis Risk in Communities (ARIC) Cohort

BACKGROUND AND PURPOSE Although stroke mortality rates in the United States are well documented, assessment of incidence rates and case fatality are less well studied. METHODS A cohort of 15 792 men and women aged 45 to 64 years from a population sample of households in 4 US communities was followed from 1987 to 1995, an average of 7. 2 years. Incident strokes were identified through annual phone contacts and hospital record searching and were then validated. RESULTS Of the 267 incident definite or probable strokes, 83% (n=221) were categorized as ischemic strokes, 10% (n=27) were intracerebral hemorrhages, and 7% (n=19) were subarachnoid hemorrhages. The age-adjusted incidence rate (per 1000 person-years) of total strokes was highest among black men (4.44), followed by black women (3.10), white men (1.78), and white women (1.24). The black versus white age-adjusted rate ratio (RR) for ischemic stroke was 2.41 (95% CI, 1.85 to 3.15), which was attenuated to 1.38 (95% CI, 1.01 to 1.89) after adjustment for baseline hypertension, diabetes, education level, smoking status, and prevalent coronary heart disease. There was a tendency for the adjusted case fatality rates to be higher among blacks and men, although none of the case fatality comparisons across sex or race was statistically significant. CONCLUSIONS After accounting for established baseline risk factors, blacks still had a 38% greater risk of incident ischemic stroke compared with whites. Identification of new individual and community-level risk factors accounting for the elevated incidence of stroke requires further investigation and incorporation into intervention planning.

Cardiac Troponin T Measured by a Highly Sensitive Assay Predicts Coronary Heart Disease, Heart Failure, and Mortality in the Atherosclerosis Risk in Communities Study

Background— We evaluated whether cardiac troponin T (cTnT) measured with a new highly sensitive assay was associated with incident coronary heart disease (CHD), mortality, and hospitalization for heart failure (HF) in a general population of participants in the Atherosclerosis Risk in Communities (ARIC) Study. Methods and Results— Associations between increasing cTnT levels and CHD, mortality, and HF hospitalization were evaluated with Cox proportional hazards models adjusted for traditional CHD risk factors, kidney function, high-sensitivity C-reactive protein, and N-terminal pro–B-type natriuretic peptide in 9698 participants aged 54 to 74 years who at baseline were free from CHD and stroke (and HF in the HF analysis). Measurable cTnT levels (≥0.003 &mgr;g/L) were detected in 66.5% of individuals. In fully adjusted models, compared with participants with undetectable levels, those with cTnT levels in the highest category (≥0.014 &mgr;g/L; 7.4% of the ARIC population) had significantly increased risk for CHD (hazard ratio=2.29; 95% confidence interval, 1.81 to 2.89), fatal CHD (hazard ratio=7.59; 95% confidence interval, 3.78 to 15.25), total mortality (hazard ratio=3.96; 95% confidence interval, 3.21 to 4.88), and HF (hazard ratio=5.95; 95% confidence interval, 4.47 to 7.92). Even minimally elevated cTnT (≥0.003 &mgr;g/L) was associated with increased risk for mortality and HF (P<0.05). Adding cTnT to traditional risk factors improved risk prediction parameters; the improvements were similar to those with N-terminal pro–B-type natriuretic peptide and better than those with the addition of high-sensitivity C-reactive protein. Conclusions— cTnT detectable with a highly sensitive assay was associated with incident CHD, mortality, and HF in individuals from a general population without known CHD/stroke.

Associations of ankle-brachial index with clinical coronary heart disease, stroke and preclinical carotid and popliteal atherosclerosis:: the Atherosclerosis Risk in Communities (ARIC) Study

The resting ankle-brachial index (ABI) is a non-invasive method to assess the patency of the lower extremity arterial system and to screen for the presence of peripheral occlusive arterial disease. To determine how the ABI is associated with clinical coronary heart disease (CHD), stroke, preclinical carotid plaque and far wall intimal-medial thickness (IMT) of the carotid and popliteal arteries, we conducted analyses in 15 106 middle-aged adults from the baseline examination (1987-1989) of the Atherosclerosis Risk in Communities (ARIC) Study. The prevalence of clinical CHD, stroke/transient ischemic attack (TIA) and preclinical carotid plaque increased with decreasing ABI levels, particularly at those of < 0.90. Individuals with ABI < 0.90 were twice as likely to have prevalent CHD as those with ABI > 0.90 (age-adjusted odds ratio (OR) ranging from 2.2 (95% CI: 1.0-5.1) in African-American men to 3.3 (95% CI: 2.1-5.0) in white men). Men with ABI < 0.90 were more than four times as likely to have stroke/TIA as those with ABI > 0.90 (age-adjusted OR: 4.2 (95% CI: 1.8-9.5) in African-American men and 4.9 (95% CI: 2.6-9.0) in white men). In women the association was weaker and not statistically significant. Among those free of clinical cardiovascular disease, individuals with ABI < or = 0.90 had statistically significantly higher prevalence of preclinical carotid plaque compared to those with ABI > 0.90 (age-adjusted ORs ranging from 1.5 (95% CI: 1.0-1.9) in white women to 2.6 (95% CI: 1.0-6.6) in african-american men). The ABI was also inversely associated with far wall IMT of the carotid arteries (in both men and women) and the popliteal arteries (in men only). The associations of ABI with clinical CHD, stroke, preclinical carotid plaque and IMT of the carotid and popliteal arteries were attenuated and often not statistically significant after further adjustment for LDL cholesterol, cigarette smoking, hypertension and diabetes. These data demonstrate that low ABI levels, particularly those of < 0.90, are indicative of generalized atherosclerosis.

Arterial stiffness and the development of hypertension. The ARIC study.

Decreased elasticity in large and medium-sized arteries has been postulated to be associated with cardiovascular diseases. We prospectively examined the relation between arterial elasticity and the development of hypertension over 6 years of follow-up in a cohort of 6992 normotensive men and women aged 45 to 64 years at baseline from the biracial, population-based Atherosclerosis Risk in Communities (ARIC) Study. Arterial elasticity was measured from high-resolution B-mode ultrasound examination of the left common carotid artery as adjusted arterial diameter change (in micrometers, simultaneously adjusted for diastolic blood pressure, pulse pressure, pulse pressure squared, diastolic arterial diameter, and height), Petersons elastic modulus (in kilopascals), Youngs elastic modulus (in kilopascals), and beta stiffness index. Incident hypertension (n=551) was defined as systolic blood pressure >/=160 mm Hg, diastolic blood pressure >/=95 mm Hg, or the use of antihypertensive medication at a follow-up examination conducted every 3 years. The age-, ethnicity-, center-, gender-, education-, smoking-, heart rate-, and obesity-adjusted means (SE) of baseline adjusted arterial diameter change, Petersons elastic modulus, Youngs elastic modulus, and beta stiffness index were 397 (5), 148 (2.0), 787 (12.7), and 11.43 (0.16), respectively, in persons who developed hypertension during follow-up, in contrast to 407 (1), 124 (0.6), 681 (3.7), and 10.34 (0.05), respectively, for persons who did not. The similarly adjusted cumulative incident rates of hypertension from the highest to the lowest quartiles of arterial elasticity were 6.7%, 8.0%, 7.3%, and 9.6%, respectively, when measured by adjusted arterial diameter change (P<0.01). One standard deviation decrease in arterial elasticity was associated with 15% greater risk of hypertension, independent of established risk factors for hypertension and the level of baseline blood pressure. These results suggest that lower arterial elasticity is related to the development of hypertension.

Relation of carotid artery wall thickness to diabetes mellitus, fasting glucose and insulin, body size, and physical activity. Atherosclerosis Risk in Communities (ARIC) Study Investigators.

Background and Purpose We tested the hypothesis that body mass, waist-to-hip circumference ratio, physical inactivity, diabetes, hyperglycemia, and fasting insulin are each positively associated with asymptomatic carotid artery wall thickness. Methods Average intimal-medial carotid wall thickness (an indicator of atherosclerosis) was measured noninvasively by B-mode ultrasonography in cross-sectional samples of 45- to 64-year-old adults, both blacks and whites, free of symptomatic cardiovascular disease, in four US communities. Results Sample mean carotid wall thickness was approximately 0.7 mm in women (n=7956) and 0.8 mm in men (n=6474). Body mass, waist-to-hip ratio, work physical activity, diabetes, and fasting insulin were associated (P < .05) with carotid wall thickness in the hypothesized direction. Adjusted for age, race, smoking, body mass index, artery depth, and Atherosclerosis Risk in Communities field center, mean wall thickness was greater by 0.02 mm in women and 0.03 mm in men for a 0.07-unit (one SD) larger waist-to-hip ratio. Adjusted mean wall thickness was about 0.07 mm thicker in participants with diabetes mellitus and 0.02 mm thicker in participants with hyperglycemia (fasting glucose 6.4 to 7.7 mmol/L) than in subjects with fasting glucose <6.4 mmol/L. Adjusted mean wall thickness increased by about 0.02 mm with an increase of 100 mmol/L in fasting serum insulin. Conclusions Abdominal adiposity, physical inactivity, and abnormal glucose metabolism are associated positively with carotid intimal-medial wall thickness, suggesting these factors contribute to atherogenesis.