Atherosclerosis Risk In Communities Study Cohort Research Articles

Associations of psychosocial factors and cardiovascular health measured by Life's Essential 8: The Atherosclerosis Risk in Communities (ARIC) study.

Few studies investigate whether psychosocial factors (social isolation, social support, trait anger, and depressive symptoms) are associated with cardiovascular health, and none with the American Heart Association's new definition of cardiovascular health, Life's Essential 8 (LE8). Therefore, we assessed the cross-sectional associations of psychosocial factors with Life's Essential 8 and individual components of Life's Essential 8. We included 11,311 Atherosclerosis Risk in Communities cohort participants (58% females; 23% Black; mean age 57 (standard deviation: 6) years) who attended Visit 2 (1990-1992) in this secondary data analysis using cross-sectional data from the ARIC cohort study. Life's Essential 8 components included diet, physical activity, nicotine exposure, sleep quality, body mass index, blood lipids, blood glucose, and blood pressure. Life's Essential 8 was scored per the American Heart Association definition (0-100 range); higher scores indicate better cardiovascular health. Associations of categories (high, moderate, and low) of each psychosocial factor with continuous Life's Essential 8 score and individual Life's Essential 8 components were assessed using multivariable linear regressions. 11% of participants had high Life's Essential 8 scores (80-100), while 67% and 22% had moderate (50-79) and low Life's Essential 8 scores (0-49) respectively. Poor scores on psychosocial factor assessments were associated with lower Life's Essential 8 scores, with the largest magnitude of association for categories of depressive symptoms (low β = Ref.; moderate β = -3.1, (95% confidence interval: -3.7, -2.5; high β = -8.2 (95% confidence interval: -8.8, -7.5)). Most psychosocial factors were associated with Life's Essential 8 scores for diet, physical activity, nicotine, and sleep, but psychosocial factors were not associated with body mass index, blood lipids, blood glucose, or blood pressure. Less favorable measures of psychosocial health were associated with lower Life's Essential 8 scores compared better measures of psychosocial health among middle-aged males and females.

Abstract 12533: Heart Failure Diagnostic Classification Criteria in Hospitalized Patients Are Associated With Increased Mortality Risk: The Atherosclerosis Risk in Communities (ARIC) Study

Introduction: Multiple diagnostic HF classification have been used to identify heart failure (HF) events. Whether these classification criteria can be used for estimating prognosis is unknown. Research Question: This study compares multiple research-derived HF classification criteria for predicting mortality in the ARIC study cohort with validated hospitalized acute decompensated heart failure (ADHF) events. Methods: There were 1,954 ARIC cohort members with hospitalized HF events from 2005-2019, validated as ADHF by ARIC study classification/adjudication. These HF events were also classified as HF present/absent at the time of hospitalization by other HF classification criteria - Framingham, Modified Boston, NHANES, and Gothenburg. Hazard ratios (HRs) for all-cause mortality at 30 days, 1 year, and 5 years were calculated using logistic regression for all included HF classification criteria compared to ARIC, stratified by ejection fraction (EF), and adjusted for demographics and comorbidities. Results: For all ADHF events, Framingham, NHANES, and Gothenburg were prognostic for survival, but not modified Boston criteria (Table). ADHF patients who were also classified as HF by Framingham criteria had a 30% or more increased mortality at 30-day, 1-year, and 5-years regardless of EF, compared to those who were not classified as HF by Framingham (p<0.05). Framingham criteria were prognostic for 30-day survival for those with HFrEF, and also for 1-year and 5-year survival for those with HFpEF. Conclusion: The presence of HF as defined using different published criteria is associated with elevated risk of all-cause mortality. To our knowledge, this is a novel study comparing multiple research-derived HF classification criteria for clinical prognostication of mortality in ADHF. More studies are needed to assess the utility of these HF classification criteria for prognostication for HF morbidity and rehospitalization and by HF type.

Abstract 16776: Recurrent Admission of Acute Decompensated Heart Failure Among Patients With and Without PAD and Its Significance in the CKD Population: The ARIC Cohort Study

Introduction: Peripheral artery disease (PAD) and chronic kidney disease (CKD) are common comorbidities in patients with heart failure (HF). Importantly, CKD is associated with a greater risk of incident PAD and is a known risk factor for worse outcomes in HF patients. However, it is unclear whether the concomitant existence of PAD and CKD increases the risk of recurrent hospitalization for acute decompensated heart failure (ADHF). Methods: Since 2005, the Atherosclerosis Risk in Communities (ARIC) study has conducted hospital surveillance of ADHF with events verified by physician review. Demographics, comorbidities, laboratory data, and medications were abstracted from medical record by trained personnel. Hazard ratios of ADHF readmissions were analyzed using repeat-events Cox regression. Models were adjusted for age, race, sex, year and hospital of admission, coronary artery disease (CAD), COPD, and diabetes mellitus. CKD was defined by glomerular filtration rate [GFR] ≤60 mL/min/1.73m 2 . Results: From 2005-2018, there were 1049 index hospitalizations for ADHF (mean age 77 years, 66% white) with measured creatinine, who were discharged alive. Of these, 155 (15%) had a diagnosis of PAD and 66% had CKD stage 3a or worse (GFR ≤60 mL/min/1.73m 2 ). Patients with PAD had a greater prevalence of smoking, CAD, myocardial infarction, and stroke. The 1-year ADHF readmission rate tended to be higher in patients with PAD, irrespective of CKD stage, compared to those without PAD ( Figure 1 ). After adjustments, PAD was associated with greater hazards of 1-year ADHF readmissions, both in patients with CKD stage 3a or worse (HR, 1.71; 95% CI: 1.25 - 2.32) and without CKD (HR, 1.84; 95% CI: 1.07-3.15). Conclusion: Patients with ADHF and concomitant PAD have a higher prevalence of cardiovascular comorbidities and higher likelihood of 1-year ADHF readmission, irrespective of the CKD status. Focused strategies to prevent ADHF readmission in this high-risk group are warranted.

Abstract 16832: Biomarker Enhanced Risk Prediction of Incident Heart Failure in Low-Risk Patients: The Atherosclerosis Risk in Communities (ARIC) Study

Background: Primary prevention strategies to reduce heart failure (HF) burden are urgently warranted. The Pooled Cohort equations to Prevent HF (PCP-HF) risk score is a validated risk tool that integrates readily available parameters obtained in primary care setting to estimate the 10-year risk for incident HF. Although PCP-HF performs well for high-risk individuals, the model’s predictive utility for low-risk individuals may potentially be enhanced by integration of biomarkers. Methods: In this study, the PCP-HF risk score was derived from data collected at visit 5 (2011-2013) of the ARIC cohort study and its 5-year predictive accuracy was investigated using surveillance data up to 2019. Participants with <10% PCP-HF risk probability of incident HF were classified as low-risk. Incremental improvement in predicting incident HF by including laboratory and imaging-based biomarkers in the low-risk population was analyzed by logistic regression, by calculating the area under the curve (AUC) from receiver operating characteristics. Results: Of 4980 study participants with 5 years of follow up, 47% had a low PCP-HF risk score (mean age 73 years, 71% women, 32% Black). Of these, 3% developed HF within 5 years. Compared to those with a high PCP-HF risk score, individuals with low PCP-HF risk score were younger, more often female and Black; had lower left ventricular (LV) mass index and left atrial volume index, higher magnitude of LV global longitudinal strain, and lower levels of NT-proBNP and hs-TnT. On further analysis, the model incorporating laboratory and imaging-based biomarkers exhibited greater predictive accuracy for incident HF compared to the original PCP-HF risk score in this low-risk population (AUC: 0.85 vs 0.62). Conclusion: The integration of laboratory and imaging-based biomarkers with the PCP-HF risk score enhances the predictive accuracy of risk modeling for incident HF, especially in individuals identified as low-risk by the 10-year risk prediction tool.

Association of Childhood and Midlife Neighborhood Socioeconomic Position With Cognitive Decline

Early-life socioeconomic adversity may be associated with poor cognitive health over the life course. To examine the association of childhood and midlife neighborhood socioeconomic position (nSEP) with cognitive decline. This cohort study included 5711 men and women enrolled in the community-based Atherosclerosis Risk in Communities (ARIC) Study with repeated cognitive data measured over a median 27.0 years (IQR, 26.0-27.9 years) (1990-2019). Statistical analysis was performed from December 2022 through March 2023. Residence addresses for ARIC Study cohort participants were obtained at midlife (1990-1993) and as recalled addresses at 10 years of age (childhood). A composite nSEP z score was created as a sum of z scores for US Census-based measures of median household income; median value of owner-occupied housing units; percentage of households receiving interest, dividend, or net rental income; percentage of adults with a high school degree; percentage of adults with a college degree; and percentage of adults in professional, managerial, or executive occupations. Childhood nSEP and midlife nSEP were modeled as continuous measures and discretized into tertiles. A factor score for global cognition was derived from a battery of cognitive tests administered at 5 in-person visits from baseline to 2019. The rate of cognitive decline from 50 to 90 years of age was calculated by fitting mixed-effects linear regression models with age as the time scale and adjusted for race, sex, birth decade, educational level, and presence of the apolipoprotein E ε4 allele. Among 5711 ARIC Study participants (mean [SD] baseline age, 55.1 [4.7] years; 3372 women [59.0%]; and 1313 Black participants [23.0%]), the median rate of cognitive decline was -0.33 SDs (IQR, -0.49 to -0.20 SDs) per decade. In adjusted analyses, each 1-SD-higher childhood nSEP score was associated with a slower (β, -9.2%; 95% CI, -12.1% to -6.4%) rate of cognitive decline relative to the sample median. A comparable association was observed when comparing the highest tertile with the lowest tertile of childhood nSEP (β, -17.7%; 95% CI, -24.1% to -11.3%). Midlife nSEP was not associated with the rate of cognitive decline. In this cohort study of contextual factors associated with cognitive decline, childhood nSEP was inversely associated with trajectories of cognitive function throughout adulthood.

Association of socioeconomic status with arterial stiffness in older African American and White adults: The ARIC study cohort

ObjectiveTo examine the cross-sectional associations of individual measures of SES—educational attainment and household income—and the joint effects of SES with PWV, as well as the SES-race interaction, in a cohort of older African American and White adults. MethodsData from the Atherosclerosis Risk in Communities (ARIC) Study were used to evaluate the cross-sectional associations of individual and joint SES [education and income] and carotid femoral pulse wave velocity (cfPWV), a subclinical marker of arterial stiffness, and the interaction of SES and race using adjusted multivariable linear regression models in a cohort of 3342 men and women aged 67–89 years free of CVD in 2011–2013. ResultsParticipants were 64% female, 23% African American, mean cfPWV (12.3±3.5-African American and 11.6±3.9-White participants). Post-graduate education compared to less than high school was significantly associated with lower cfPWV (less stiffness) in African American (β = -1.28 m/s; 95% CI, -1.97, -0.59) but not in White (β = -0.69 m/s; 95% CI, -1.39, 0.01) participants. Income ≥$50K as compared to <$25K, was associated with lower cfPWV both in African American (β = -0.82 m/s; 95% CI, -1.42, -0.22) and White (β = -0.76 m/s; 95% CI, -1.19, -0.32) participants. The interaction of race and individual measures of SES on cfPWV in African American and White adults were not statistically significant (p-value >0.10). ConclusionsHigher SES was cross-sectionally associated with lower arterial stiffness in this cohort; the data did not support differences by race. Prospective studies of SES and cfPWV are needed to efficiently compare larger racially and regionally diverse populations with a wider range of socioeconomic profiles to better identify subgroup CVD risk.

Loneliness and its predictors among older adults prior to and during the COVID-19 pandemic: cross-sectional and longitudinal survey findings from participants of the Atherosclerosis Risk in Communities (ARIC) Study cohort in the USA

ObjectivesWe aimed to ascertain the prevalence of perceived loneliness among older adults following the onset of the COVID-19 pandemic and to examine factors contributing to the perception of loneliness.DesignCross-sectional and...

Association of Hypertension According to New American College of Cardiology/American Heart Association Blood Pressure Guidelines With Incident Dementia in the ARIC Study Cohort.

BackgroundThe impact of the new 2017 American College of Cardiology/American Heart Association (ACC/AHA) hypertension guideline on dementia risk at the population level has not been evaluated.Methods and ResultsWe studied dementia‐free participants in the ARIC (Atherosclerosis Risk in Communities) Study cohort in 1987 to 1989. Hypertension was defined by 2003 Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure and 2017 ACC/AHA guidelines using blood pressure measured at baseline. Dementia was defined using adjudicated consensus diagnoses, informant telephone interviews, and discharge codes from hospitalizations and death certificates. Cox regression estimated hazard ratios (HRs) for dementia and 95% CIs by hypertension categories, adjusting for confounders. Population attributable fraction of dementia was calculated by hypertension categories. Among 13 971 participants followed up for a median of 23 years, 1381 dementia cases were identified. Prevalence of hypertension was 34% and 48%, according to the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure and ACC/AHA criteria, respectively. HRs (95% CIs) compared with normal blood pressure, according to ACC/AHA categories, were 1.35 (1.12–1.61) for elevated blood pressure, 1.28 (1.07–1.52) for hypertension stage 1, and 1.36 (1.18–1.57) for hypertension stage 2. Population attributable fractions (95% CIs) of dementia from blood pressure categories were 3% (1%–5%), 3% (1%–5%), and 9% (4%–14%), respectively. Population attributable fractions (95% CIs) using the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure categories were 6% (3%–9%) for prehypertension, 0% (−2% to 2%) for hypertension stage 1, and 9% (5%–13%) for hypertension stage 2.ConclusionsRisk of dementia increased across hypertension categories defined by ACC/AHA guidelines. The population impact on dementia incidence using ACC/AHA categories was similar to the impact of the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure.

Operationalizing Frailty in the Atherosclerosis Risk in Communities Study Cohort.

Factors that may contribute to the development of frailty in late life have not been widely investigated. The Atherosclerosis Risk in Communities (ARIC) Study cohort presents an opportunity to examine relationships of midlife risk factors with frailty in late life. However, we first present findings on the validation of an established frailty phenotype in this predominantly biracial population of older adults. Among 6,080 participants, we defined frailty based upon the Cardiovascular Health Study (CHS) criteria incorporating measures of weight loss, exhaustion, slow walking speed, low physical activity, and low grip strength. Criterion and predictive validity of the frailty phenotype were estimated from associations between frailty status and participants' physical and mental health status, physiologic markers, and incident clinical outcomes. A total of 393 (6.5%) participants were classified as frail and 50.4% pre-frail, similar to CHS (6.9% frail, 46.6% pre-frail). In age-adjusted analyses, frailty was concurrently associated with depressive symptoms, low self-rated health, low medication adherence, and clinical biomarker levels (ie, cholesterol, hemoglobin A1c, white blood cell count, C-reactive protein, and hemoglobin). During 1-year follow-up, frailty was associated with falls, low physical ability, fatigue, and mortality. These findings support the validity of the CHS frailty phenotype in the ARIC Study cohort. Future studies in ARIC may elucidate early-life exposures that contribute to late-life frailty.

Abstract 133: Comparison of CMS Medicare Beneficiaries Enrolled in Fee-For-Service and Managed Care Programs. The Atherosclerosis Risk In Communities (ARIC) Study

Background: Healthcare utilization analyses often are conducted with Centers for Medicare and Medicaid (CMS) data from fee-for-service (FFS) Medicare beneficiaries. Although use of preventive care services is greater among beneficiaries in managed care programs compared with those in FFS care, evidence of the effect of managed care enrollment on health outcomes is mixed. We compared the health status of ARIC cohort participants enrolled in FFS to those enrolled in managed care. Methods: Data for participants of the ARIC Study cohort were linked with CMS Medicare claims for the years 1991-2012 (N=14,695). Participants missing coverage start date or enrolled prior to 1991 were excluded from analyses (N=2,513). Enrollment in FFS and managed care was ascertained at the start of CMS Medicare coverage. Switch from initial FFS enrollment to managed care was ascertained in follow-up through December 31, 2012. Demographics and comorbidities were ascertained from ARIC clinical examination and follow-up data up to the coverage start date. Mortality was ascertained from start date of CMS Medicare coverage through December 31, 2012; rates were modeled using Poisson regression adjusted for age at time of coverage start. Cox proportional hazard regression models, adjusted for demographic characteristics and comorbidities, were used to examine the hazard ratio of all-cause mortality among those in FFS compared to those enrolled in managed care. Results: At the start of Medicare coverage, 10,983 and 1,087 ARIC participants were enrolled in FFS and managed care, respectively. In comparison with managed care beneficiaries, those in FFS at the start of coverage were more likely to be white (91% vs. 73.5%), male (43% vs. 38.5%) and have less than a high school education (20.4 vs. 11.8%). Comorbidity burden was greater among those enrolled in FFS compared to those in managed care. The age-adjusted rate of mortality (per 100,000 person-years; median follow-up 11.2 years) was 5.9 (95% CI 5.7, 6.1) among those in FFS and 3.5 (95% CI 2.9, 4.1) among those in managed care. The mortality hazard ratio, comparing FFS to managed care beneficiaries was 1.29 (95% CI 1.08, 1.55). During the time from coverage start to end of follow-up, 4,200 beneficiaries switched from FFS to managed care. With the exception of gender, education and proportion with a history of cancer, demographic characteristics and comorbidities of beneficiaries who switched vs. those who remained in FFS were comparable. The mortality hazard ratio, assessed from start of coverage through December 31, 2012, was 1.59 (95%CI 1.46, 1.74) among those remaining in FFS, as compared to those who switched to managed care. Conclusion: Generalizability of inferences from FFS CMS Medicare data may be limited by a greater observed mortality rate among FFS beneficiaries compared to those in managed care. Further analyses are needed to confirm this finding.

Abundant local interactions in the 4p16.1 region suggest functional mechanisms underlying SLC2A9 associations with human serum uric acid.

Human serum uric acid concentration (SUA) is a complex trait. A recent meta-analysis of multiple genome-wide association studies (GWAS) identified 28 loci associated with SUA jointly explaining only 7.7% of the SUA variance, with 3.4% explained by two major loci (SLC2A9 and ABCG2). Here we examined whether gene–gene interactions had any roles in regulating SUA using two large GWAS cohorts included in the meta-analysis [the Atherosclerosis Risk in Communities study cohort (ARIC) and the Framingham Heart Study cohort (FHS)]. We found abundant genome-wide significant local interactions in ARIC in the 4p16.1 region located mostly in an intergenic area near SLC2A9 that were not driven by linkage disequilibrium and were replicated in FHS. Taking the forward selection approach, we constructed a model of five SNPs with marginal effects and three epistatic SNP pairs in ARIC—three marginal SNPs were located within SLC2A9 and the remaining SNPs were all located in the nearby intergenic area. The full model explained 1.5% more SUA variance than that explained by the lead SNP alone, but only 0.3% was contributed by the marginal and epistatic effects of the SNPs in the intergenic area. Functional analysis revealed strong evidence that the epistatically interacting SNPs in the intergenic area were unusually enriched at enhancers active in ENCODE hepatic (HepG2, P = 4.7E−05) and precursor red blood (K562, P = 5.0E−06) cells, putatively regulating transcription of WDR1 and SLC2A9. These results suggest that exploring epistatic interactions is valuable in uncovering the complex functional mechanisms underlying the 4p16.1 region.

Secular changes in rates of coronary heart disease, fatal coronary heart disease, and out-of-hospital fatal coronary heart disease

Secular changes in rates of coronary heart disease, fatal coronary heart disease, and out-of-hospital fatal coronary heart disease

Properties of Local Interactions and Their Potential Value in Complementing Genome-Wide Association Studies

Local interactions between neighbouring SNPs are hypothesized to be able to capture variants missing from genome-wide association studies (GWAS) via haplotype effects but have not been thoroughly explored. We have used a new high-throughput analysis tool to probe this underexplored area through full pair-wise genome scans and conventional GWAS in diastolic and systolic blood pressure and six metabolic traits in the Northern Finland Birth Cohort 1966 (NFBC1966) and the Atherosclerosis Risk in Communities study cohort (ARIC). Genome-wide significant interactions were detected in ARIC for systolic blood pressure between PLEKHA7 (a known GWAS locus for blood pressure) and GPR180 (which plays a role in vascular remodelling), and also for triglycerides as local interactions within the 11q23.3 region (replicated significantly in NFBC1966), which notably harbours several loci (BUD13, ZNF259 and APOA5) contributing to triglyceride levels. Tests of the local interactions within the 11q23.3 region conditional on the top GWAS signal suggested the presence of two independent functional variants, each with supportive evidence for their roles in gene regulation. Local interactions captured 9 additional GWAS loci identified in this study (3 significantly replicated) and 73 from previous GWAS (24 in the eight traits and 49 in related traits). We conclude that the detection of local interactions requires adequate SNP coverage of the genome and that such interactions are only likely to be detectable between SNPs in low linkage disequilibrium. Analysing local interactions is a potentially valuable complement to GWAS and can provide new insights into the biology underlying variation in complex traits.

The Socio-Geography of Heart Failure

Morbidity and mortality rates from heart failure are staggering and continue to pose daunting challenges to patients, providers, researchers, and the health care system. As populations age, the increasing burden of cardiovascular disease portends a humbling future, particularly for heart failure. Despite advances in medical care, heart failure prevalence, hospitalizations, and mortality rates have not declined; in 2007, more than 250 000 Americans died of heart failure, and the number of heart failure hospitalizations has tripled from about 1.3 million in 1979 to nearly 4 million in 2004.1,2 The burden of heart failure admissions and frequent readmissions are also costly to the health care system. Corresponding to the projected increase in heart failure prevalence, real medical costs for heart failure are projected to increase by ≈200% over the next 20 years.3 Articles see p 308 and 317 Reports from the Agency for HealthCare Research and Quality (AHRQ) recognize geographic variation in heart failure hospitalizations.4 Regional variations have been associated with number of primary care physicians per population, regional income level, and the proportion of Medicare payment.5 The mere presence of this variation implies that some, maybe even most, heart failure rehospitalizations are avoidable. Potential contributors to admission may include barriers at the system or individual level such as difficulties accessing primary or outpatient medical care services, poor quality of this care when accessed, or lack of patient adherence.5 However, optimal outpatient care may reduce avoidable hospitalizations and medical expenditures and improve quality of life, suggesting a potential opportunity.5 ### Geography Matters In this issue of Circulation: Heart Failure , two reports highlight associations of geography with heart failure service utilization and outcomes, …

Association of the platelet GPIIb/IIIa polymorphism with atherosclerotic plaque morphology: The Atherosclerosis Risk in Communities (ARIC) Study

Objectives Platelet activation and aggregation play an important role in the pathogenesis of cardiovascular disease. We examined the association of a single nucleotide polymorphism (SNP) in the GPIIIa platelet glycoprotein (Leu33Pro) with carotid artery plaque morphology and with expression of platelet markers using data from the Atherosclerosis Risk in Communities (ARIC) Carotid MRI study.Methods The study sample consisted of 1202 Caucasian members of the ARIC study cohort recruited in 2004–2005 to participate in the Carotid MRI Substudy under stratified sampling based on maximum carotid artery wall thickness. The Leu33Pro polymorphism was identified as SNP rs5918 in the ITGB3 gene. Plaque visualization was accomplished with contrast enhanced MRI examination of the thickest segment of the carotid artery. Expression of platelet markers was measured using fasting whole blood flow cytometry.Results This cross-sectional analysis based on age and gender adjusted weighted linear regression models suggests that those homozygous for the Leu33Pro risk allele (C) have decreased mean and minimum fibrous cap thickness. We did not observe differences in plaque lipid volume or maximum carotid artery wall thickness across SNP rs5918 genotypes. Carriers of the Leu33Pro polymorphism, as compared to major allele homozygotes, had greater percent of platelets expressing P-selectin, a platelet glycoprotein indicating activation status. Prevalent coronary heart disease did not affect estimates of fibrous cap thickness or of platelet activation.Conclusion Our results suggest that individuals with Leu33Pro polymorphism of the GPIIIa glycoprotein may be predisposed to increased risk of atherosclerotic plaque rupture.

The Decline of Ischaemic Heart Disease Mortality in the ARIC Study Communities

Age-adjusted, population-weighted mortality rates of ischaemic heart disease (1968-78) and all cardiovascular diseases (1962-82) are presented for the four study communities investigated by the Atherosclerosis Risk in Communities (ARIC) Study. Temporal trends in mortality rates and differences by gender, race and study community are discussed. There is an overall pattern of decline in ischaemic heart disease and cardiovascular disease mortality in the four study areas, but the onset and the magnitude of the decline differ markedly by study community, race and gender. Preliminary data on population levels of selected cardiovascular risk factors measured in the ARIC Study cohort participants are also presented.