Risk prediction of coronary heart disease based on retinal vascular caliber (from the Atherosclerosis Risk In Communities [ARIC] Study)

Recent studies showed that such retinal vascular signs as quantitative retinal vascular caliber were associated with increased risk of incident coronary heart disease (CHD), but whether these retinal vascular signs add to the prediction of CHD over and above traditional CHD risk factors was not addressed. Whether these signs add to the prediction of CHD over and above the Framingham risk score in people (n = 9,155) without diabetes selected from the ARIC Study was investigated. Incident CHD was ascertained using standardized methods, and retinal vascular caliber and other retinal signs were measured from retinal photographs. After a mean of 8.8 years of follow-up, there were 700 incident CHD events. Women with wider retinal venular caliber (hazard ratio 1.27/1-SD increase, 95% confidence interval 1.08 to 1.50) and narrower retinal arteriolar caliber (hazard ratio 1.31/1-SD decrease, 95% confidence interval 1.10 to 1.56) had a higher risk of incident CHD after adjusting for Framingham risk score variables. Area under the receiver operator characteristic curve increased from 0.695 to 0.706 (1.7% increase) with the addition of retinal vascular caliber to the Framingham risk model. Risk prediction models with and without retinal vascular caliber both fitted the data and were well calibrated for women. In men, retinal vascular caliber was not associated with CHD risk after adjustment. Other retinal vascular signs were not associated with 10-year incident CHD in men or women. In conclusion, although retinal vascular caliber independently predicted CHD risk in women, the incremental predictive ability over that of the Framingham model was modest and unlikely to translate meaningfully into clinical practice.     

Usefulness of ventricular premature complexes to predict coronary heart disease events and mortality (from the Atherosclerosis Risk In Communities cohort)

The clinical relevance of ventricular premature complexes (VPCs) in apparently healthy patients is not clear and is typically not considered when evaluating risk. We conducted a prospective longitudinal study of the population-based Atherosclerosis Risk In Communities (ARIC) study of 15,070 Caucasians and African-Americans, 45 to 64 years of age, to assess the risks of coronary heart disease (CHD) events and mortality associated with VPCs among participants with and without prevalent CHD at baseline. VPCs on a single 2-minute electrocardiogram were identified in 940 participants (6.2%). After a follow-up of >10 years, 1,762 participants died, with 366 deaths related to CHD, and 1,736 had cardiac events. The percentage of participants with CHD mortality was >3 times greater for those with VPCs compared with those without VPCs. After controlling for cardiovascular risk factors and therapy with proportional hazards regression, participants with VPCs were >2 times as likely to die due to CHD than were those without VPCs. Increased risk was found for participants with and without baseline CHD. In conclusion, a clinical finding of VPCs on electrocardiography of even apparently healthy patients may warrant a heightened awareness of and attention to cardiovascular risk assessment and management.     

Relation of atrial and/or ventricular premature complexes on a two-minute rhythm strip to the risk of sudden cardiac death (the Atherosclerosis Risk in Communities [ARIC] study)

Ventricular premature complexes (VPCs) and atrial premature complexes (APCs) are common findings on routinely obtained electrocardiograms. Despite their common occurrence, the significance of these irregular beats is unclear, especially with regard to risk of sudden cardiac death (SCD). In this study, we examined the prospective relation between baseline VPCs or APCs and SCD, myocardial infarction, and fatal coronary heart disease (CHD) in a population-based sample of subjects from the Atherosclerosis Risk in Communities (ARIC) study excluding participants with known history of CHD or stroke. Baseline examination was conducted from 1987 to 1989, with follow-up data regarding clinical cardiac events collected until December 2002. The total study population was 14,574 subjects. Kaplan-Meier curves and computed univariate and multivariate Cox proportional hazard models were employed to estimate the effect of VPC and APC occurrences on incident cardiac events. During the follow-up period, there were 130 incident cases of SCD, 1,657 incident cases of CHD cases, and 288 cases of fatal CHD. Participants with VPC were 2 times as likely to have SCD (hazard ratio [HR] 2.09, 95% confidence interval [CI] 1.22 to 3.56) compared to those without VPC. Presence of APC was not significantly associated with SCD (HR 1.15, 95% CI 0.56 to 2.39). Compared to subjects without VPC and APC, risk of SCD in subjects with VPC and APC was significantly increased (HR 6.39, 95% CI 2.58 to 15.84). In conclusion, our study shows that subjects with VPCs are significantly more likely to die from SCD, despite not having any known history of cardiovascular disease. This effect appears to be additive when APCs occur concurrently.     

Left ventricular architecture and survival in African-Americans free of coronary heart disease (from the Atherosclerosis Risk in Communities [ARIC] study)

Published studies of the prognostic value of left ventricular (LV) hypertrophy and LV geometric pattern in African-Americans were based on referred or hospitalized patients with hypertension or coronary heart disease. All-cause mortality rates and survival associated with LV geometric pattern were determined using echocardiography in a population-based sample of middle-aged and elderly African-American men and women. During the third (1993 to 1995) visit of the ARIC Study, echocardiography was performed at the Jackson, Mississippi, field center on the cohort of 2,445 African-Americans aged 49 to 75 years. M-Mode LV echocardiographic measurements were available for 1,722 persons. Mortality data were available through December 31, 2003. During the follow-up period (median 8.8 years, maximum 10.4), 160 deaths were identified. In men, multivariable-adjusted hazard ratios for all-cause mortality (compared with men with normal LV geometry) were 1.75 (95% confidence interval [CI] 0.71 to 4.33) in those with concentric LV hypertrophy, 0.38 (95% CI 0.08 to 1.88) in those with eccentric LV hypertrophy, and 0.79 (95% CI 0.41 to 1.54) in those with concentric remodeling. In women, multivariable-adjusted hazard ratios for all-cause mortality (compared with women with normal LV geometry) were 1.17 (95% CI 0.48 to 2.84) in those with concentric LV hypertrophy, 1.23 (95% CI 0.46 to 3.28) in those with eccentric LV hypertrophy, and 1.17 (95% CI 0.60 to 2.28) in those with concentric remodeling. In conclusion, in this population-based cohort of middle-aged and elderly African-Americans free of coronary heart disease, adjustment for baseline differences in cardiovascular disease risk factors and LV mass greatly attenuated the strength of the association between LV pattern and all-cause mortality risk in women. In men, an association between concentric LV hypertrophy and mortality risk remained.     

Usefulness of high-sensitivity C-reactive protein to predict mortality in patients with atrial fibrillation (from the Atherosclerosis Risk In Communities [ARIC] Study)

High-sensitivity C-reactive protein (hs-CRP) is a marker for the risk of cardiovascular and overall mortality. However, information about the association between hs-CRP and mortality in patients with atrial fibrillation is scarce. A total of 293 participants of the Atherosclerosis Risk In Communities study with a history of AF and hs-CRP levels available were studied. During a median follow-up of 9.4 years, 134 participants died (46%). The hazard ratio of all-cause mortality associated with the highest versus the lowest tertile of hs-CRP was 2.52 (95% confidence interval 1.49 to 4.25) after adjusting for age, gender, history of cardiovascular diseases, and cardiovascular risk factors. A similar trend was observed for cardiovascular mortality (57 events; hazard ratio 1.90, 95% confidence interval 0.81 to 4.45). The Congestive heart failure, Hypertension, Age >75 years, Diabetes, and previous Stroke or transient ischemic attack (CHADS2) score was also associated with all-cause and cardiovascular mortality, with an adjusted hazard ratio of 3.39 (95% confidence interval 1.91 to 6.01) and 8.71 (95% confidence interval 2.98 to 25.47), respectively, comparing those with a CHADS2 score >2 versus a CHADS2 score of 0. Adding hs-CRP to a predictive model including the CHADS2 score was associated with an improvement of the C-statistic for total mortality (from 0.627 to 0.677) and for cardiovascular mortality (from 0.700 to 0.718). In conclusion, high levels of hs-CRP constitute an independent marker for the risk of mortality in patients with atrial fibrillation.     

Electrocardiographic predictors of new-onset heart failure in men and in women free of coronary heart disease (from the Atherosclerosis in Communities [ARIC] Study)

We compared the prognostic value of 12 electrocardiographic (ECG) variables in predicting risk of new-onset heart failure (HF) in a subgroup of 13,555 participants of the Atherosclerosis Risk in Communities (ARIC) study who were considered free of coronary heart disease at the onset of the study. Cox proportional hazards models were used to evaluate risk of HF for the highest decile of the distribution of each ECG variable (lowest decile for ST and T amplitudes in lead V(5)), with the remaining deciles as reference groups. Risk models were adjusted for demographic and clinical variables. In univariate Cox regression models, in men 11 and in women 8 of the 12 ECG variables were significant, strong predictors of risk of new-onset HF. Subsequently, 8 ECG variables with low mutual correlations were entered simultaneously into a multivariate Cox regression model. In men, large left ventricular mass by electrocardiogram, QT prolongation, and increased heart rate were the strongest independent predictors of new-onset HF, each with a twofold increased risk. Other independent predictors in men were ST depression in lead V(5), wide QRS/T angle, and old (silent) myocardial infarction, each with a >50% increased risk of incident HF. In women, QRS nondipolar voltage was associated with an 87% increased risk of incident HF, and other independent predictors, as in men, were wide QRS/T angle and increased heart rate. In conclusion, several ECG abnormalities are manifestations of evolving HF in men and women considered free of coronary heart disease.     

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.     

Association of serum uric acid with incident atrial fibrillation (from the Atherosclerosis Risk in Communities [ARIC] study)

Atrial fibrillation (AF) is one of the most common arrhythmias seen in clinical practice. Current evidence suggests that serum uric acid (SUA) could be a marker of oxidative damage, a factor reported as a part of the mechanisms of AF. The purpose of the present study was to evaluate whether SUA predicted AF in the Atherosclerosis Risk In Communities (ARIC) study. The present analysis included 15,382 AF-free black and white men and women, aged 45 to 64 years, from the ARIC study, a population-based prospective cohort in the United States. SUA was determined using the uricase-peroxidase method at baseline. The primary outcome was the incidence of AF, defined as the occurrence of AF detected using hospital discharge codes, scheduled study electrocardiograms, and/or death certificates during the follow-up period (1987 to 2004). We identified 1,085 cases of incident AF. In Cox proportional hazards models adjusted for age, gender, race, center, education, body mass index, serum glucose, systolic and diastolic blood pressure, low-density lipoprotein cholesterol, alcohol use, prevalent coronary heart disease and heart failure, serum creatinine, diuretics, and P-wave duration on the electrocardiogram (as a measure of left atrial size) at baseline, the hazard ratio of AF associated with a SD increment in SUA was 1.16 (95% confidence interval 1.06 to 1.26). The association of SUA with AF risk differed by race and gender (p for interaction <0.01). In conclusion, elevated SUA is associated with a greater risk of AF, particularly among blacks and women. Additional studies should replicate this association and explore potential mechanisms.     

Prospective study of fibrinolytic factors and incident coronary heart disease: the Atherosclerosis Risk in Communities (ARIC) Study

The fibrinolytic system may play a role in the pathogenesis of coronary heart disease (CHD), but existing prospective studies have not consistently shown an independent association between fibrinolytic factors and CHD. None has reported an association between plasminogen and CHD incidence. In the prospective Atherosclerosis Risk in Communities (ARIC) Study of middle-aged adults, we examined the association of incident CHD with several fibrinolytic factors: tissue plasminogen activator antigen, plasminogen activator inhibitor-1, plasminogen, and fibrin fragment D-dimer as well as a marker of coagulation activation (prothrombin fragment F1.2). We measured these in stored baseline plasma samples of 326 subjects who developed CHD and, for comparison, a stratified random sample of the entire cohort (n=720). Tissue plasminogen activator and plasminogen activator inhibitor-1 antigen levels were associated positively with CHD incidence in analyses adjusted for age, race, and sex but were not associated with CHD after adjustment for other risk factors. Plasminogen and D-dimer levels were associated positively and independently with CHD incidence; the multivariable-adjusted relative risks (95% CIs) for the highest versus lowest quintiles were 2.20 (1.2 to 4.2) for plasminogen and 4.21 (1.9 to 9.6) for D-dimer. F1.2 was not associated with CHD incidence. Our findings lend support for a link between fibrinolytic factors and CHD incidence. A positive association between plasminogen and CHD is seemingly opposite the direction expected but may reflect a compensatory response to impaired plasminogen activation in subjects prone to CHD.