Retinal arteriolar narrowing and left ventricular hypertrophy in African Americans. the Atherosclerosis Risk in Communities (ARIC) study

BACKGROUND: Whether microvascular disease contributes to the development of left ventricular hypertrophy (LVH) is unclear. We examined the relationship of retinal microvascular signs with LVH in an African-American population. METHODS: A population-based, cross-sectional study of 1,439 middle-aged African-American participants in Jackson, Mississippi. A retinal photograph of one randomly selected eye was obtained and graded for presence of retinal microvascular signs (focal arteriolar narrowing, arterio-venous (AV) nicking, and retinopathy) according to standardized protocols. Retinal vessel diameter was measured from a computer-assisted technique to define generalized arteriolar narrowing. LVH was defined from standardized echocardiography. RESULTS: In age and gender-adjusted models, retinal microvascular signs (except non-diabetic retinopathy) were significantly associated with LVH, with an odds ratio (OR) of 1.64 (95% confidence interval (CI) 1.29-2.09) for generalized arteriolar narrowing, OR 1.82 (95% CI 1.33-2.50) for focal arteriolar narrowing, and OR 1.35 (95% CI 1.02-1.79) for AV nicking. With further adjustment for cardiovascular (serum total cholesterol, fasting glucose, diabetes, diabetes duration, smoking, body mass index (BMI), waist-to-hip ratio, and exercise level) and hypertension-related factors (mean arterial blood pressure (MABP) at the time of retinal photography and antihypertensive medication use), associations were attenuated but remained significant for generalized and focal arteriolar narrowing, with OR 1.35 (95% CI 1.02-1.78) and OR 1.66 (95% CI 1.16-2.38), respectively. CONCLUSIONS: Middle-aged African Americans with generalized and focal retinal arteriolar narrowing were more likely to have LVH. This association was explained only partly by cardiovascular risk factors and hypertension.     

Pulmonary function and left ventricular mass in African Americans: the Atherosclerosis Risk in Communities (ARIC) study

Purpose: Impaired pulmonary function has been associated with increased cardiovascular disease incidence and mortality. The objective of this study was to investigate associations between pulmonary function and left ventricular (LV) mass. Methods: Participants were African American women (n = 1,069) and men (n = 555) aged 49–73 years, from the Atherosclerosis Risk in Communities study. Mean pulmonary function values at the first (1987–1989) and second (1990–1992) examinations were used. Echocardiograms were performed at the third and early in the fourth examinations (1993–1996). Analysis of covariance and linear regression were used to assess associations. Results: Mean levels of LV mass decreased with increasing quintiles of forced expiratory volume in one second (FEV₁) among female never smokers (P = 0.039). Forced vital capacity (FVC) showed stronger associations than FEV₁ with LV mass. Among men, LV mass was positively associated with FEV₁ among current and never smokers, and with FVC among never smokers. Additional analyses among never smokers revealed significant inverse associations between LV mass and FVC among women with waist‐to‐hip ratios of >0.85 and those with no history of diabetes. In contrast, significant positive associations between LV mass and FVC were seen among male never smokers with body mass index (BMI) of ≤24.9 kg/m², waist‐to‐hip ratios of ≤0.95, no history of hypertension or diabetes, and ≤60 years old. BMI and waist‐to‐hip ratio significantly modified associations among men. Conclusions: Among never smokers, LV mass and pulmonary function were inversely associated among women and positively associated among men. Further studies are warranted. (Echocardiography 2012;29:131‐139)     

Optimal threshold value for left ventricular hypertrophy in blacks: the Atherosclerosis Risk in Communities study

The distribution of echocardiographic left ventricular (LV) mass differs among ethnicities. Because ethnic-specific echocardiographic criteria for LV hypertrophy (LVH) are not established, we determined whether threshold values derived from overwhelmingly white populations are appropriate for blacks, a subgroup having more LVH. Between 1992 and 1994, LV mass was measured echocardiographically in the Jackson, Mississippi, black cohort of the Atherosclerosis Risk in Communities study. Participants free of prevalent cardiovascular disease (CVD) (n=1616; mean+/-SD, age 59+/-5.7; 65% women and 57% with hypertension) were included. The optimal LVH threshold value was selected from the continuum of LV mass index (LVMI=LV mass/height(2.7)) using 3 methods: (1) the best operating point from the area under the resulting receiver-operating characteristic (ROC) curve predicting incident CVD; (2) the value with the smallest probability value associated with incident CVD; and (3) visual inspection of functions of LVMI and CVD in the general additive model (GAM) plot. At a median follow-up of 6.8 years, there were 192 events (coronary heart disease=87, stroke=62, and congestive heart failure=43; incidence=17.6/1000 person-years). The best operating point from the resulting ROC analysis was 51.2 g/m(2.7) for sensitivity (53.4%) and specificity (61.5%). The Cox and GAM models adjusted for age, gender, systolic blood pressure, hypertension, diabetes, smoking, total cholesterol-to-high-density lipoprotein ratio, LVH by ECG criterion, and socioeconomic status found 50 to 51 g/m(2.7) as the optimal threshold for LVH in middle-aged blacks, corresponding to a minimum probability value and to a log-hazard ratio of zero, respectively. Because these values are close to the 51 g/m(2.7) established from predominantly white populations, this cutpoint is appropriate for both groups.     

Anemia as a risk factor for cardiovascular disease in The Atherosclerosis Risk in Communities (ARIC) study

OBJECTIVES: We investigated whether the presence of anemia is a risk factor for cardiovascular disease (CVD) outcomes in the general population. BACKGROUND: Chronic anemia is a risk factor for CVD outcomes in patients with kidney disease and in patients with heart failure, but has not been evaluated as a risk factor in the general population. METHODS: The Atherosclerosis Risk in Communities (ARIC) study was used to evaluate the relationship of anemia, defined by hemoglobin <13 g/dl in men and <12 g/dl in women, to CVD. Cox proportional hazards regression was used to adjust the relationship between anemia and CVD outcomes for other covariates in the entire study cohort, as well as in subgroups of men, women, African Americans and whites. RESULTS: A total of 14,410 subjects (6,267 men and 8,143 women) without CVD at baseline had hemoglobin levels measured. Three hundred men (4.8%) and 1,058 women (13.0%) were anemic. During an average follow-up of 6.1 years there was a total of 549 (3.8%) CVD events. The presence of anemia was independently associated with an increased risk of CVD (hazard ratio [95% confidence interval] of 1.41 [1.01, 1.95]) in the entire study cohort. In subgroup analyses the hazard ratios were in the same direction, although not statistically significant in all cases. CONCLUSIONS: Anemia is an independent risk factor for CVD outcomes in the ARIC cohort, a community cohort of subjects between the ages of 45 and 64 years.     

Glycated haemoglobin and cognitive decline: the Atherosclerosis Risk in Communities (ARIC) study

Aims/hypothesis  

This study aimed to examine the association between diabetes and hyperglycaemia—assessed by HbA_1c—and change in cognitive function in persons with and without diabetes.     

Metabolic and lifestyle determinants of postprandial lipemia differ from those of fasting triglycerides: The Atherosclerosis Risk In Communities (ARIC) study

Despite the reported association of lipoprotein responses to a fatty meal with atherosclerosis, little is known about the determinants of these responses. Plasma triglyceride, retinyl palmitate, and apolipoprotein B-48 responses to a standardized fatty meal containing a vitamin A marker were measured in 602 Atherosclerosis Risk in Communities (ARIC) study participants. To focus on postprandial responses specifically, which have been reported to be related to atherosclerosis independently of fasting triglycerides, analyses for determinants of postprandial responses were adjusted for fasting triglycerides. Major determinants of fasting triglycerides, namely, diabetes, obesity, other factors related to insulin resistance, and male sex, were not independently associated with postprandial responses. Fasting triglycerides were the strongest predictor of postprandial lipids, but independent of triglycerides, the predictors of postprandial responses were smoking, diet, creatinine, and alcohol. Smokers had substantially increased retinyl palmitate and apolipoprotein B-48 responses, indicators of chylomicrons and their remnants. Persons who consume more calories or omega3 fatty acids had reduced chylomicron responses. Triglyceride responses were associated positively with serum creatinine levels and negatively with moderate alcohol consumption. Thus, determinants of fasting and postprandial lipids differ. The independent atherogenic influence of postprandial lipids may relate more to smoking and diet than to obesity and insulin resistance.     

Arterial stiffness and contralateral differences in blood pressure: The Atherosclerosis Risk in Communities (ARIC) study

A large interarm difference in brachial systolic blood pressure (SBP) (≥10 or ≥15 mmHg) is strongly associated with elevated cardiovascular events and mortality. Evidence demonstrating whether such contralateral differences in SBP occur in ankle blood pressure and its association with arterial stiffness is scarce. The aims of this study were to characterize arm and ankle contralateral SBP differences in a sample of community‐dwelling older adults (5077), and to determine whether this difference is associated with arterial stiffness assessed by pulse wave velocity (PWV) between the heart and ankle (haPWV), femoral artery and ankle (faPWV), and brachial artery and ankle (baPWV) in the right and left sides. Prevalence of interarm SBP differences ≥10 and ≥15 mmHg was 5.1% and .7%, respectively; the corresponding prevalence for interankle SBP was 24.9% and 12.0%. Higher BMI and lower ankle‐brachial index (ABI) were significantly correlated with greater interarm SBP differences. Increased age, higher BMI, lower ABI, and greater contralateral differences in haPWV, faPWV, and baPWV were significantly correlated to greater interankle SBP differences. Interankle SBP difference ≥15 mmHg was significantly associated with contralateral differences of >80 cm/s in haPWV (OR = 1.94 [95% CI = 1.52–2.49]), >165 cm/s in faPWV (OR = 1.64 [95% CI = 1.27–2.12]), and >240 cm/s in baPWV (OR = 2.43 [95% CI = 1.94–3.05]). The associations remained significant after adjustment for age, sex, race, BMI, smoking status, and ABI. Compared with interarm differences, interankle differences in SBP are common in older adults. The magnitude of interankle, but not interarm, differences in SBP is associated with various measures of arterial stiffness.     

Trait anger and arterial stiffness: results from the Atherosclerosis Risk in Communities (ARIC) study

The cross-sectional association between trait anger and stiffness of the left common carotid artery was examined in 10,285 black or white men or women, 48-67 years of age, from the Atherosclerosis Risk in Communities (ARIC) study cohort. Trait anger was assessed using the 10-item Spielberger Trait Anger Scale. Arterial stiffness was assessed by pulsatile arterial diameter change (PADC) derived from echo-tracking ultrasound methods; the smaller the PADC, the stiffer the common carotid artery. In men, trait anger was significantly associated with PADC, independent of the established cardiovascular disease risk factors (p=0.04). PADC decreased from the first (lowest anger group) to the second quintile of anger, but there was no progressive decrease thereafter. Also observed was a 13-microm (95% confidence interval [CI], 1-25) difference in the magnitude of PADC from the lowest to the uppermost quintile of anger (PADC [standard error], 421 [4] microm vs. 408 [5] microm). In women, the association was marginally significant (p=0.07). The low-high difference in the magnitude of PADC (PADC [standard error], 397 [3] microm vs. 406 [4] microm) was inverse (-9 microm 95% CI, -19 to 2). Conclusions indicate that very high trait anger is associated with arterial stiffness in men.     

Ankle-brachial index and hemostatic markers in the Atherosclerosis Risk in Communities (ARIC) study cohort

To determine whether elevated levels of hemostatic and inflammatory markers [von Willebrand factor (vWF), fibrinogen, D-dimer, factor VII, factor VIII, PAI-1, tPA, beta-thromboglobulin (beta-TG), CRP, and WBC count] are associated with increased peripheral arterial disease (PAD) prevalence, measured by low ABI, we studied 13,778 participants from the ARIC study in a cross-sectional analysis after adjustment for major cardiovascular risk factors. PAD was positively associated with fibrinogen, vWF, factor VIII, WBC count, D-dimer, beta-TG, and CRP (p for trend <0.05) but not with the other markers. Adjusted odds ratios for the highest versus the lowest quartile of fibrinogen in men and women, respectively, were 3.49 (95% CI 1.68-7.26) and 2.44 (95% CI 1.58-3.77); for vWF 2.36 (95% CI 1.36-4.07) and 1.45 (95% CI 1.00-2.10); for factor VIII 2.31 (95% CI 1.36-3.94) and 1.68 (95% CI 1.14-2.48). In a smaller subset, the sex and risk factor adjusted odds ratio for the highest versus the lowest quartile of D-dimer was 2.70 (95% CI 1.56-4.65), for beta-TG was 1.80 (95% CI 1.12-2.88), and for CRP was 1.57 (95% CI 0.84-2.95). Plasma levels of hemostatic and inflammatory markers are elevated in PAD, suggesting these processes are involved in the pathophysiology of PAD.     

Association of the Lewis genotype with cardiovascular risk factors and subclinical carotid atherosclerosis: the Atherosclerosis Risk in Communities (ARIC) study

OBJECTIVES: To evaluate the relationship of Lewis genotypes with major cardiovascular risk factors and the intima-media thickness (IMT) of carotid arteries. Lewis genotyping included four major mutations of the Lewis (FUT3) gene at nucleotide positions 59, 1067, 202 and 314. DESIGN: Two complementary population-based cross-sectional studies. SETTING: The Atherosclerosis Risk in Communities (ARIC) Study. SUBJECTS: The relationship between Lewis genotype and major cardiovascular risk factors was studied in 761 men and women aged 45-64 years without known clinical atherosclerotic disease; 577 were Caucasians and 184 were African-Americans. The association of Lewis genotype and subclinical carotid atherosclerosis was studied in 419 individuals with, and 819 controls without carotid IMT of >1.0 mm, measured by B-mode ultrasound. MAIN OUTCOME MEASURES: Mean values of cardiovascular risk factors by Lewis genotype. Lewis genotype frequencies in subclinical carotid atherosclerosis cases and controls. RESULTS: Individuals with Lewis genotypes consistent with lack of alpha(1,3/1,4)-fucosyltransferase activity (i.e. Lewis-negative genotype) had statistically significantly lower fasting glucose, factor VIIIc, von Willebrand factor and diastolic blood pressure compared with their counterparts with Lewis-positive genotypes. The distribution of Lewis genotypes and haplotypes was not significantly different between individuals with carotid IMT of >1.0 mm (cases) and their controls. The odds of carotid atherosclerosis in carriers of the Lewis-negative genotype was 1.23 (95% confidence interval 0.70-2.16) compared to individuals with Lewis-positive genotype, controlling for age, gender and race/ARIC field centre. CONCLUSION: The lack of a statistically significant association between Lewis 'genotype' and subclinical atherosclerosis in our data suggests that earlier studies reporting associations at the 'phenotypic' level may reflect aspects of the biology of the Lewis system other than an inherent genetic property.     

Metabolic syndrome and left ventricular hypertrophy in the prediction of cardiovascular events: the Strong Heart Study

Background and aimsMetabolic syndrome (MetS) is associated with increased prevalence of echocardiographic LV hypertrophy (LVH), a potent predictor of cardiovascular (CV) outcome. Whether MetS increases risk of CV events independently of presence of LVH has never been investigated. It is also unclear whether LVH predicts CV risk both in the presence and absence of MetS.Methods and resultsParticipants in the 2nd Strong Heart Study examination without prevalent coronary heart disease, congestive heart failure or renal insufficiency (plasma creatinine >2.5 mg/dL) were studied (n = 2758; 1746 women). MetS was defined by WHO criteria. Echocardiographic LV hypertrophy was defined using population-specific cut-point value for LV mass index (>47.3 g/m^2.7). After controlling for age, sex, LDL-cholesterol, smoking, plasma creatinine, diabetes, hypertension and obesity, participants with MetS had greater probability of LVH than those without MetS (OR = 1.55 [1.18–2.04], p < 0.002). Adjusted hazard of composite fatal and non-fatal CV events was greater when LVH was present, in participants without (HR = 2.03 [1.33–3.08]) or with MetS (HR = 1.64 [1.31–2.04], both p < 0.0001), with similar adjusted population attributable risk (12% and 14%). After adjustment for LVH, risk of incident CV events remained 1.47-fold greater in MetS (p < 0.003), an effect, however, that was not confirmed when diabetic participants were excluded.ConclusionLVH is a strong predictor of composite 8-year fatal and non-fatal CV events either in the presence or in the absence of MetS and accounts for a substantial portion of the high CV risk associated with MetS.     

C-reactive protein and incident coronary heart disease in the Atherosclerosis Risk In Communities (ARIC) study

Background Recent evidence implicates inflammation in the pathogenesis of coronary heart disease (CHD). C-reactive protein, a plasma marker of inflammation, is a marker of CHD risk but has been studied in few prospective investigations of the general population. Methods and Results We prospectively examined the association of CRP with incident CHD among middle-aged adults in the Atherosclerosis Risk In Communities (ARIC) study. With the use of a nested case-cohort approach, we measured CRP in stored, baseline blood samples of 2 groups of subjects in whom CHD developed during follow-up (242 incident cases from 1987 to 1993 and 373 from 1990 to 1995) and, for comparison, 2 stratified random samples of noncases. In analyses adjusted for demographic variables and traditional CHD risk factors, the relative risk of CHD across quintiles of CRP was 1.0, 0.8, 1.6, 1.9, and 1.5 for events from 1987 to 1995 (P for trend = .01). As expected, inclusion of fibrinogen, intracellular adhesion molecule-1, and white blood cell count (other potential markers of the inflammatory reaction) attenuated the association of CRP with CHD incidence. In a supplemental cross-sectional analysis, CRP was not associated with carotid intima-media thickness after adjustment for major risk factors. Conclusions C-reactive protein is a moderately strong marker of risk of CHD in this cohort of middle-aged adults, consistent with the role of inflammation in the pathogenesis of CHD events. The association was not specific to CRP because other markers of inflammation could largely account for the finding. (Am Heart J 2002;144:233-8.)     

The ARIC (Atherosclerosis Risk In Communities) Study: JACC Focus Seminar 3/8

ARIC (Atherosclerosis Risk In Communities) initiated community-based surveillance in 1987 for myocardial infarction and coronary heart disease (CHD) incidence and mortality and created a prospective cohort of 15,792 Black and White adults ages 45 to 64 years. The primary aims were to improve understanding of the decline in CHD mortality and identify determinants of subclinical atherosclerosis and CHD in Black and White middle-age adults. ARIC has examined areas including health disparities, genomics, heart failure, and prevention, producing more than 2,300 publications. Results have had strong clinical impact and demonstrate the importance of population-based research in the spectrum of biomedical research to improve health.