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BackgroundThe ankle brachial index (ABI) is related to risk of cardiovascular events independent of the Framingham risk score (FRS). The aim of this study was to develop and evaluate a risk model for cardiovascular events incorporating the ABI and FRS.DesignAn analysis of participant data from 18 cohorts in which 24,375 men and 20,377 women free of coronary heart disease had ABI measured and were followed up for events.MethodsSubjects were divided into a development and internal validation dataset and an external validation dataset. Two models, comprising FRS and FRS + ABI, were fitted for the primary outcome of major coronary events.ResultsIn predicting events in the external validation dataset, C-index for the FRS was 0.672 (95% CI 0.599 to 0.737) in men and 0.578 (95% CI 0.492 to 0.661) in women. The FRS + ABI led to a small increase in C-index in men to 0.685 (95% CI 0.612 to 0.749) and large increase in women to 0.690 (95% CI 0.605 to 0.764) with net reclassification improvement (NRI) of 4.3% (95% CI 0.0 to 7.6%, p = 0.050) and 9.6% (95% CI 6.1 to 16.4%, p

Objective: Elevated fasting glucose level is associated with increased carotid intima-media thickness (IMT), a measure of subclinical atherosclerosis. It is unclear if this association is causal. Using the principle of Mendelian randomization, we sought to explore the causal association between circulating glucose and IMT by examining the association of a genetic risk score with IMT.Research Design and Methods: The sample was drawn from the Atherosclerosis Risk in Communities (ARIC) study and included 7,260 nondiabetic Caucasian individuals with IMT measurements and relevant genotyping. Components of the fasting glucose genetic risk score (FGGRS) were selected from a fasting glucose genome-wide association study in ARIC. The score was created by combining five single nucleotide polymorphisms (SNPs) (rs780094 [GCKR], rs560887 [G6PC2], rs4607517 [GCK], rs13266634 [SLC30A8], and rs10830963 [MTNR1B]) and weighting each SNP by its strength of association with fasting glucose. IMT was measured through bilateral carotid ultrasound. Mean IMT was regressed on the FGGRS and on the component SNPs, individually.Results: The FGGRS was significantly associated (P = 0.009) with mean IMT. The difference in IMT predicted by a 1 SD increment in the FGGRS (0.0048 mm) was not clinically relevant but was larger than would have been predicted based on observed associations between the FFGRS, fasting glucose, and IMT. Additional adjustment for baseline measured glucose in regression models attenuated the association by about one third.Conclusions: The significant association of the FGGRS with IMT suggests a possible causal association of elevated fasting glucose with atherosclerosis, although it may be that these loci influence IMT through nonglucose pathways. [ABSTRACT FROM AUTHOR]

Objective: To determine the burden of chronic obstructive pulmonary disease (COPD) on all-cause mortality in Blacks and Whites from four US communities.Methods: We determined prospectively the risk of death through December 2004 in relation to baseline (1987-1989) COPD status in 10,333 Black and White participants of the Atherosclerosis Risk in Communities (ARIC) study.Results: Over a mean follow-up of 15 years (maximum 18 years), 462 deaths occurred in Blacks and 1221 deaths occurred in Whites. Hazard ratios for all-cause mortality among Blacks and Whites were similar (hazard ratio [HR] = 1.74 in Blacks and HR = 1.59 in Whites), indicating a 59%-74% greater risk of mortality for those with COPD. However, for both those with and without COPD, crude death rates were approximately double in Blacks compared to Whites.Conclusions: Our findings suggest that given COPD, Blacks and Whites have the same proportionate increase in mortality and that the difference in death rates between Blacks and Whites cannot be explained by COPD status. The public health burden of COPD is enormous, and strategies to reduce COPD and smoking could have a large impact on total mortality rates of both Blacks and Whites. [ABSTRACT FROM AUTHOR]

The authors sought to examine the relation between serum or dietary magnesium and the incidence of ischemic stroke among blacks and whites. Between 1987 and 1989, 14,221 men and women aged 45-64 years took part in the first examination of the Atherosclerosis Risk in Communities Study cohort. The incidence of stroke was ascertained from hospital records. Higher serum magnesium levels were associated with lower prevalence of hypertension and diabetes mellitus at baseline. During the 15-year follow-up, 577 ischemic strokes occurred. Serum magnesium was inversely associated with ischemic stroke incidence. The age-, sex-, and race-adjusted rate ratios of ischemic stroke for those with serum magnesium levels of or=1.8 mEq/L were 1.0, 0.78 (95% confidence interval (CI): 0.62, 0.96), 0.70 (95% CI: 0.56, 0.88), and 0.75 (95% CI: 0.59, 0.95) (P(trend) = 0.005). After adjustment for hypertension and diabetes, the rate ratios were attenuated to nonsignificant levels. Dietary magnesium intake was marginally inversely associated with the incidence of ischemic stroke (P(trend) = 0.09). Low serum magnesium levels could be associated with increased risk of ischemic stroke, in part, via effects on hypertension and diabetes. [ABSTRACT FROM AUTHOR]

Background: Little is known about the role of diet in the development of venous thromboembolism (VTE). We explored the prospective relation of dietary patterns, food groups, and nutrients to incident VTE in older women.Methods: In 1986, Iowa women aged 55 to 69 years completed a mailed survey, including a 127-item food frequency questionnaire. These data were linked to Medicare data from 1986 to 2004, and International Classification of Diseases discharge codes were used to identify hospitalized VTE cases. Cox regression analyses evaluated relations of 2 principal components-derived dietary patterns, 11 food groups, and 6 nutrients to VTE, adjusted for age, education, smoking status, physical activity, and energy intake.Results: Over 19 years of follow-up, 1,950 of the 37,393 women developed VTE. Women consuming alcohol daily were at 26% (95% CI 11%-38%) lower risk of VTE as compared to nonconsumers. All alcoholic beverages types were in the direction of lower risk; however, only beer and liquor were statistically significant. After basic adjustments, coffee was inversely related to VTE, and diet soda and fish positively related. However, these associations were confounded and became nonsignificant after adjustment for body mass index and diabetes. No associations were observed with consumption of 'Western' or 'Prudent' dietary patterns, fruit, vegetables, dairy, meat, refined grains, whole grains, regular soda, vitamins E, vitamin B6, vitamin B12, folate, omega-3 fatty acids, or saturated fat.Conclusions: In this cohort of older women, greater intake of alcohol was associated with a lower risk of incident VTE. No other independent associations were seen between diet and VTE. [ABSTRACT FROM AUTHOR]

Background: Inflammation and hemostasis may increase the risk of kidney function decline; however, data from prospective studies are sparse.Study Design: The Atherosclerosis Risk in Communities (ARIC) Study, a prospective observational cohort.Setting& Participants: We used data from 14,854 middle-aged adults from 4 different US communities.Predictor: Markers of inflammation and hemostasis were examined.Outcomes& Measurements: The risk of kidney function decrease associated with these markers was studied. Glomerular filtration rate (GFR) was calculated from serum creatinine levels using the 4-variable Modification of Diet in Renal Disease (MDRD) Study equation. Chronic kidney disease (CKD) was defined as: (1) a decrease in estimated GFR to less than 60 mL/min/1.73 m2 from greater than 60 mL/min/1.73 m2 at baseline, or (2) a hospitalization discharge or death coded for CKD. Serum creatinine was measured at baseline and the 3- and 9-year follow-up visits. Hazard ratios (HRs) of CKD associated with increased levels of inflammatory and hemostatic variables were estimated by using multivariate Cox proportional hazards regression.Results: 1,787 cases of CKD developed between 1987 and 2004. After adjusting for demographics, smoking, blood pressure, diabetes, lipid levels, prior myocardial infarction, antihypertensive use, alcohol use, year of marker measurement, and baseline renal function using estimated GFR, the risk of incident CKD increased with increasing quartiles of white blood cell count (HR quartile 4 versus quartile 1, 1.30; 95% confidence interval [CI], 1.12 to 1.50; P trend = 0.001), fibrinogen (HR, 1.25; 95% CI, 1.09 to 1.44; P < 0.001), von Willebrand factor (HR, 1.46; 95% CI, 1.26 to 1.68; P < 0.001), and factor VIIIc (HR, 1.39; 95% CI, 1.20 to 1.60; P < 0.001). A strong inverse association was found between serum albumin level and risk of CKD (HR, 0.63; 95% CI, 0.55 to 0.72; P < 0.001). No independent association was found with factor VIIc level.Limitations: Although we lacked a direct measure of kidney function, associations were robust to case definitions.Conclusions: Markers of inflammation and hemostasis are associated with greater risk of kidney function decrease. Findings suggest that inflammation and hemostasis are antecedent pathways for CKD. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to determine whether a variation in the transcription factor 7-like 2 (TCF7L2) gene, which influences diabetes risk, is associated with incidence of cancers.Research Design and Methods: We related diabetes and TCF7L2 variation with occurrence of several common cancers in a prospective cohort study of 13,117 middle-aged adults initially free of cancer in 1987-1989. We assessed five single nucleotide polymorphisms (SNPs) in TCF7L2 including the putative SNP (rs7903146) for diabetes. We identified incident cancers through 2000 via cancer registries, supplemented by hospital records.Results: Diabetes was associated marginally inversely with incidence of prostate cancer but not with incidence of colorectal, colon, lung, or breast cancer. The T allele of rs7903146 (frequency 30%) was associated with increased risk of colorectal cancer and, more specifically, colon cancer, with adjusted hazard ratios (95% CI) of 1.0 for CC, 1.25 (0.85-1.83) for CT, and 2.15 (1.27-3.64) for TT genotypes (P(trend) = 0.009). TCF7L2 variation also was associated with lung cancer incidence in whites but not blacks, but residual confounding by smoking may be present.Conclusions: Subjects who were initially cancer-free and carrying certain genetic variants of TCF7L2, most notably the T allele of rs7903146, have an increased risk of colon cancer. This association appears to be an independent gene effect not explained by diabetes. Because the T allele of rs7903146 is common, if a causal link is established, this variant could account for a sizable proportion ( approximately 17% here) of cases of colon cancer in the general population. [ABSTRACT FROM AUTHOR]

BACKGROUND: Few studies have examined the relation between lung function and ischemic stroke incidence; none have studied African Americans. METHODS: We followed 13,842 middle-aged adults initially free of stroke and coronary heart disease and observed 472 incident ischemic strokes over 13 years. Quartiles of FEV(1) as a percentage of predicted value (FEV(1)PP) and FVC as a percentage of a predicted value (FVCPP) were used as the indicators of lung function. RESULTS: In the age-, race-, gender-, and education-adjusted models, both lung function measures were significantly inversely related to ischemic stroke incidence (linear trend for FEV(1)PP, p < 0.01; linear trend for FVCPP, p < 0.01), but adjustment for possible confounders attenuated these relations. For white subjects, a significant inverse relation remained even after full adjustment (relative hazards [RH] across FEV(1)PP quartiles (lowest to highest) were 1.59, 1.52, 1.26, and 1.00; and for FVCPP quartiles were 1.56, 1.80, 1.09, and 1.00 [trend for both, p < 0.05]). There was no association for African Americans (RH across FEV(1)PP and FVCPP quartiles were 0.74, 0.89, 0.73, 1.00 [linear trend, p = 0.27] and 0.81, 1.07, 0.61, 1.00 [linear trend, p = 0.75], respectively). An inverse relation between lung function and ischemic stroke was also observed among white subjects who never smoked (FEV(1)PP) or had no respiratory symptoms (both FEV(1)PP and FVCPP) but not among their African-American counterparts. CONCLUSIONS: Among white subjects, participants with impaired lung function have a modestly higher risk of ischemic stroke even if they have never smoked nor had respiratory symptoms. [ABSTRACT FROM AUTHOR]

The authors analyzed data from a prospective, community-based cohort to assess the risk of incident type 2 diabetes mellitus associated with coffee and sweetened beverage consumption. They included 12,204 nondiabetic, middle-aged men and women in the Atherosclerosis Risk in Communities (ARIC) Study (1987-1999). Consumption of each beverage was assessed by food frequency questionnaire and classified into categories of cups per day. They found an inverse association, after adjusting for potential confounders, between increased coffee consumption and risk of type 2 diabetes mellitus in men (for >/=4 cups (>/=0.95 liter)/day compared with almost never: hazard ratio = 0.77, p(trend) = 0.02) with no significant association in women (hazard ratio = 0.89, p(trend) = 0.32) using a combination of self-report of physician-diagnosed diabetes, diabetes treatment, and a fasting or nonfasting blood glucose test. When self-reported diabetes or diabetes treatment alone was used, a stronger and significant inverse association was seen in men and women. Sweetened beverage consumption (men: hazard ratio = 1.03, p(trend) = 0.94; women: hazard ratio = 1.01, p(trend) = 0.58) showed no consistent association with the incidence of type 2 diabetes mellitus. In summary, increased coffee consumption was significantly associated with a decreased risk of diagnosed type 2 diabetes mellitus in community-based US adults. [ABSTRACT FROM AUTHOR]

PURPOSE: The aim of the study is to describe the association between apolipoprotein E (apoE) genotype and gallbladder disease incidence.METHODS: Cases of incident hospitalized gallbladder disease were ascertained in nearly 13,000 middle-aged men and women participating in the Atherosclerosis Risk in Communities (ARIC) Study, a prospective cohort study in four US communities.RESULTS: Between the ARIC baseline examination (1987 to 1989) and December 31, 2001, a total of 639 participants were hospitalized for gallbladder disease. After adjustment for age, sex, race, obesity, plasma lipid level, and diabetes, the relative risk for hospitalized gallbladder disease associated with the presence of an E4 allele (i.e., genotypes E4/4, E3/4, and E2/4 versus other genotypes) was 0.72 (95% confidence interval [CI], 0.60-0.87). Stratification by race showed that the inverse association with E4 was stronger in whites (relative risk, 0.69; 95% CI, 0.56-0.85) than African Americans (relative risk, 0.86; 95% CI, 0.58-1.30). The presence of the other rare isoform, E2 (i.e., genotypes E2/2, E2/3, and E2/4 versus others) was associated with a modest increased risk for gallbladder disease (relative risk, 1.28; 95% CI, 1.05-1.57).CONCLUSIONS: These results suggest that independent of traditional risk factors, apoE genotype may influence gallbladder disease risk, particularly in whites. The exact biologic mechanism for such an association remains unclear and requires further investigation. [ABSTRACT FROM AUTHOR]

With the growing number of epidemiologic publications on the relation between dietary factors and cancer risk, pooled analyses that summarize results from multiple studies are becoming more common. Here, the authors describe the methods being used to summarize data on diet-cancer associations within the ongoing Pooling Project of Prospective Studies of Diet and Cancer, begun in 1991. In the Pooling Project, the primary data from prospective cohort studies meeting prespecified inclusion criteria are analyzed using standardized criteria for modeling of exposure, confounding, and outcome variables. In addition to evaluating main exposure-disease associations, analyses are also conducted to evaluate whether exposure-disease associations are modified by other dietary and nondietary factors or vary among population subgroups or particular cancer subtypes. Study-specific relative risks are calculated using the Cox proportional hazards model and then pooled using a random- or mixed-effects model. The study-specific estimates are weighted by the inverse of their variances in forming summary estimates. Most of the methods used in the Pooling Project may be adapted for examining associations with dietary and nondietary factors in pooled analyses of case-control studies or case-control and cohort studies combined. [ABSTRACT FROM AUTHOR]

Objective: To develop and evaluate clinical rules to predict risk for diabetes in middle-aged adults.Research Design and Methods: The Atherosclerosis Risk in Communities is a cohort study conducted from 1987-1989 to 1996-1998. We studied 7,915 participants 45-64 years of age, free of diabetes at baseline, and ascertained 1,292 incident cases of diabetes by clinical diagnosis or oral glucose tolerance testing.Results: We derived risk functions to predict diabetes using logistic regression in a random half of the sample. Rules based on these risk functions were evaluated in the other half. A risk function based on waist, height, hypertension, blood pressure, family history of diabetes, ethnicity, and age was performed similarly to one based on fasting glucose (area under the receiver-operating characteristic curve [AUC] 0.71 and 0.74, respectively; P = 0.2). Risk functions composed of the clinical variables plus fasting glucose (AUC 0.78) and additionally including triglycerides and HDL cholesterol (AUC 0.80) performed better (P < 0.001). Evaluation of scores based on the metabolic syndrome as defined by the National Cholesterol Education Program or with slight variations showed AUCs of 0.75 and 0.78, respectively. Rules based on all these approaches, while identifying 20-56% of the sample as screen positive, achieved sensitivities of 40-87% and specificities of 50-86%.Conclusions: Rules derived from clinical information, alone or combined with simple laboratory measures, can characterize degrees of diabetes risk in middle-aged adults, permitting preventive actions of appropriate intensity. Rules based on the metabolic syndrome are reasonable alternatives to rules derived from risk functions. [ABSTRACT FROM AUTHOR]

Variations in the validity of hospital discharge diagnoses can complicate the assessment of trends in incidence of acute myocardial infarction (AMI). To clarify trends in the validity of discharge codes, the authors compared event classification based on published Atherosclerosis Risk in Communities (ARIC) Study criteria with the presence or absence of an International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) hospital discharge code for AMI (code 410). Between 1987 and 2000, 154,836 coronary heart disease events involving hospitalization in the four ARIC communities had ICD-9-CM codes screened for AMI. The sensitivity of ICD-9-CM code 410 for classifying AMI in men (sensitivity = 0.65, 95% confidence interval (CI): 0.63, 0.66) was statistically significantly greater than that found for women (sensitivity = 0.60, 95% CI: 0.58, 0.62) and was greater in Whites (sensitivity = 0.67, 95% CI: 0.65, 0.68) than in Blacks (sensitivity = 0.50, 95% CI: 0.47, 0.53). The ethnic difference was related to a greater frequency of hypertensive heart disease and congestive heart failure codes encompassing AMI among Blacks as compared with Whites. The authors found that although the validity of ICD-9-CM code 410 to identify AMI was generally stable from 1987 through 2000, differences between Blacks and Whites and across geographic locations support investment in validation efforts in ongoing surveillance studies. [ABSTRACT FROM AUTHOR]

Coronary artery calcification assessed by computed tomography is an emerging marker of coronary atherosclerosis. The authors examined the association of coronary calcium scores with traditional and nontraditional cardiovascular risk factors. In 1999-2000, they measured coronary artery calcium in 360 participants free of known coronary artery disease who had participated in 2 centers of the Atherosclerosis Risk in Communities (ARIC) Study. They related coronary calcium scores to risk factors measured in 1987-1989. Most traditional risk factors were associated with the coronary calcium score. For example, the multivariately adjusted odds ratio for an elevated score (> or = 100 versus < 100) was 3.5-fold greater per 10 years of age, 3.2-fold greater in men than in women, 3.1-fold greater with diabetes (statistically nonsignificant), and 1.4- to 1.7-fold greater per standard deviation greater increments of plasma cholesterol and pack-years of cigarettes smoked. Carotid artery intima-media thickness also was positively associated with coronary calcification. In contrast, a wide variety of hemostatic and inflammatory markers and serum chemistry values were unrelated to calcium scores. These findings reaffirmed the established role of traditional risk factors in the etiology of coronary artery disease, as assessed by computed tomography, but did not identify any important nontraditional risk factors. [ABSTRACT FROM AUTHOR]

The authors evaluated the relation between consumption of alcoholic beverages and incidence of coronary heart disease in White and African-American participants in the Atherosclerosis Risk in Communities Study. The average duration of follow-up was 9.8 years between 1987 and 1998. The association was analyzed by means of Cox proportional hazards regression models. The authors found a positive association between ethanol consumption and incident coronary heart disease for Black men (for a 13-g/day increment in ethanol consumption, adjusted hazard ratio (HR) = 1.13, 95% confidence interval (CI): 1.01, 1.28) and an inverse association for White men (HR = 0.88, 95% CI: 0.79, 0.99). There was an inverse association of coronary heart disease with rare drinking (HR = 0.47, 95% CI: 0.28, 0.80) and with consumption of > or =70 g of ethanol per week (HR = 0.49, 95% CI: 0.24, 0.98) in White women and with consumption of > or =210 g/week (HR = 0.56, 95% CI: 0.33, 0.95) in White men. In Black men, the association was positive for consumption of 140-<210 g/week (HR = 2.61, 95% CI: 1.11, 6.17). The contrasting findings in Whites and Black men in this cohort raise the question of whether the cardioprotective effect of alcohol is real or may be confounded by lifestyle characteristics of drinkers. [ABSTRACT FROM AUTHOR]

We examined associations among colon cancer incidence and dietary intake of heme iron, a possible prooxidant, zinc, a possible antioxidant, and alcohol, a disruptor of iron homeostasis. During 15 years of follow-up, 34 708 postmenopausal women, aged 55-69 years at baseline who completed a food-frequency questionnaire for the Iowa Women's Health Study, were followed for incident colon cancer. After adjusting for each micronutrient, the relative risks for proximal colon cancer increased more than twofold across categories of heme iron intake (P(trend) =.01) and the corresponding relative risks decreased more than 50% across categories for zinc intake (P(trend) =.01). The positive association with heme iron and the inverse association with zinc intake were stronger among women who consumed alcohol than among those who did not. Zinc intake was also associated with a decreased risk of distal colon cancer (P(trend) =.03), regardless of alcohol or heme iron consumption. Our results suggest that intake of dietary heme iron is associated with an increased risk of proximal colon cancer, especially among women who drink, but that intake of dietary zinc is associated with a decreased risk of both proximal and distal colon cancer. [ABSTRACT FROM AUTHOR]