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Background: Several cardiovascular risk factors have been associated with the risk of atrial fibrillation (AF). Limited and inconsistent evidence exists on the association of blood lipid levels and lipid-lowering medication use with AF risk.Methods and Results: We analyzed 13 969 participants (25% African American, 45% men) free of AF at baseline from the Atherosclerosis Risk in Communities study. Fasting high-density lipoprotein cholesterol (HDLc), low-density lipoprotein cholesterol (LDLc), triglycerides, and total cholesterol were measured at baseline (1987-1989) and each of 3 follow-up visits. The incidence of AF was ascertained through 2007. The association of the use of statins and other lipid-lowering medications with AF was estimated in 13 044 Atherosclerosis Risk in Communities participants attending visit 2 (1990-1992), adjusting for covariates from the previous visit. During a median follow-up of 18.7 years, there were 1433 incident AF cases. Multivariable hazard ratios (HRs) and 95% CIs of AF associated with a 1-SD increase in lipid levels were as follows: HDLc, 0.97 (0.91-1.04); LDLc, 0.90 (0.85-0.96); total cholesterol, 0.89 (0.84-0.95); and triglycerides, 1.00 (0.96-1.04). Participants taking lipid-lowering medications had an adjusted HR (95% CI) of AF of 0.96 (0.82-1.13) compared with those not taking medications, whereas those taking statins had an adjusted HR of 0.91 (0.66-1.25) compared with those taking other lipid-lowering medications.Conclusions: Higher levels of LDLc and total cholesterol were associated with a lower incidence of AF. However, HDLc and triglycerides were not independently associated with AF incidence. No association was found between the use of lipid-lowering medications and incident AF. [ABSTRACT FROM AUTHOR]

Gender differences in the association of blood and urine cadmium concentrations with peripheral arterial disease (PAD) were evaluated by using data from 6,456 US adults aged >=40 years who participated in the 1999-2004 National Health and Nutrition Examination Survey. PAD was defined as an ankle-brachial blood pressure index of <0.9 in at least one leg. For men, the adjusted odds ratios for PAD comparing the highest with the lowest quintiles of blood and urine cadmium concentrations were 1.82 (95% confidence interval (CI): 0.82, 4.05) and 4.90 (95% CI: 1.55, 15.54), respectively, with a progressive dose-response relation and no difference by smoking status. For women, the corresponding odds ratios were 1.19 (95% CI: 0.66, 2.16) and 0.56 (95% CI: 0.18, 1.71), but there was evidence of effect modification by smoking: among women ever smokers, there was a positive, progressive dose-response relation; among women never smokers, there was a U-shaped dose-response relation. Higher blood and urine cadmium levels were associated with increased prevalence of PAD, but women never smokers showed a U-shaped relation with increased prevalence of PAD at very low cadmium levels. These findings add to the concern of increased cadmium exposure as a cardiovascular risk factor in the general population. [ABSTRACT FROM AUTHOR]

OBJECTIVE: We sought to examine the relation of diabetic retinopathy to incident coronary heart disease (CHD). RESEARCH DESIGN AND METHODS: A population-based, prospective cohort study consisting of 1,524 middle-aged individuals with type 2 diabetes without prevalent CHD and stroke at baseline was conducted. Diabetic retinopathy signs were graded from retinal photographs according to the Early Treatment for Diabetic Retinopathy Study severity scale. Incident CHD events (myocardial infarction, fatal CHD, or coronary revascularization) were identified and validated following standardized protocols. RESULTS: In our study, 214 (14.7%) participants had diabetic retinopathy. Over an average follow-up of 7.8 years, there were 209 (13.7%) incident CHD events. After controlling for age, sex, race, study center, fasting glucose, A1C, duration of diabetes, blood pressure, antihypertensive treatment, cigarette smoking, BMI, and lipid profile, the presence of diabetic retinopathy was associated with a twofold higher risk of incident CHD events (hazard rate ratio [HR] 2.07 [95% CI 1.38-3.11]) and a threefold higher risk of fatal CHD (3.35 [1.40-8.01]). Further adjustments for inflammatory markers, carotid artery intima-media thickness, or nephropathy had minimal impact on the association. The increased risk of CHD was significant in both men (1.89 [1.08-3.31]) and women (2.16 [1.16-4.02]) with diabetic retinopathy. CONCLUSIONS: In individuals with type 2 diabetes, the presence of retinopathy signifies an increased CHD risk, independent of known risk factors. Our data support the role of microvascular disease in the pathogenesis of CHD in diabetes. [ABSTRACT FROM AUTHOR]

Associations between findings on cranial magnetic resonance imaging (MRI) and retinal photographs have been described mostly in middle-aged people. In the Cardiovascular Health Study, 1,717 elderly participants underwent MRI and retinal photography between 1991 and 1999. Associations were sought between MRI findings and four findings of retinal microvascular disease: retinopathy, focal arteriolar narrowing, arteriovenous nicking, and the arteriovenous ratio--the last based upon semiautomated measurements of arterioles and venules. After controlling for age and gender, the authors found associations between MRI findings and the smaller arteriovenous ratio (per standard deviation decrease): prevalent infarcts (odds ratio = 1.18, 95% confidence interval: 1.05, 1.34; p = 0.007), white matter grade (regression coefficient, 0.093; p = 0.011), incident infarct (odds ratio = 1.26, 95% confidence interval: 1.09, 1.46; p = 0.002), and worsening white matter grade (odds ratio = 1.12, 95% confidence interval: 0.98, 1.29; p = 0.09). Arteriovenous nicking was also associated with prevalent (odds ratio = 1.84, 95% confidence interval: 1.23, 2.76; p = 0.003) and incident (odds ratio = 1.84, 95% confidence interval: 1.15, 2.94; p = 0.011) infarcts. Adjustment for hypertension and diabetes had minimal effect. Evidence of small vessel disease in the retina increases the likelihood of finding it in the brain. Associations were less prominent in this elderly population than have been described in middle-aged people. [ABSTRACT FROM AUTHOR]

Background: Age-related macular degeneration (AMD) affects 7 million persons 40 years of age and older in the United States. Risk factors for the disease are similar to those for stroke.Objective: To determine what relationship, if any, exists between AMD and incident clinical stroke.Design: Prospective cohort study.Setting: The population-based Atherosclerosis Risk in Communities Study, which was conducted in Minnesota, Maryland, Mississippi, and North Carolina.Patients: 10 405 persons between 49 and 73 years of age who had no history of stroke or coronary heart disease.Measurements: Participants had retinal photographs taken between 1993 and 1995. A standardized protocol was used to evaluate the photographs for the presence of drusen and other signs of AMD. Incident stroke events were identified and validated by reviewing case records.Results: There were 498 early-stage and 10 late-stage cases of AMD in the cohort (n = 508). Over a 10-year period, 241 persons had an incident stroke event. After adjusting for age, sex, ethnicity, and site, the authors found that persons with early-stage AMD had a higher cumulative incidence of stroke than those without the disease (4.08% vs. 2.14%). The presence of early-stage AMD was associated with a higher adjusted risk for stroke (hazard ratio, 1.87 [95% CI, 1.21 to 2.88]). Further adjustment for systolic blood pressure, diabetes, cigarette smoking, and use of antihypertensive medications did not substantially alter this association (hazard ratio, 1.85 [CI, 1.19 to 2.87]). The authors found that the association between early-stage AMD and stroke varied by study site and patient ethnicity. Multivariable-adjusted hazard ratios were 3.15 and 1.07 in samples of white patients in Minnesota and Maryland, respectively; 3.77 in a sample of African-American patients in Mississippi; and 0.33 in a sample of mostly white patients (91%) in North Carolina. No site included sufficient numbers of both African-American and white patients to determine whether ethnicity contributed to the observed differences by study site.Limitations: There were few cases of late-stage AMD, and the cohort assembly method prohibited full understanding of variation by ethnicity and site.Conclusion: Middle-aged persons with signs of early-stage AMD have a higher risk for stroke independent of traditional stroke risk factors. [ABSTRACT FROM AUTHOR]

Objective: To assess the relation between HbA(1c) (A1C) and incident peripheral arterial disease (PAD) in a community-based cohort of diabetic adults from the Atherosclerosis Risk in Communities (ARIC) study. A second aim was to investigate whether the association was stronger for severe, symptomatic disease compared with PAD assessed by low ankle-brachial index (ABI).Research Design and Methods: This was a prospective cohort study of 1,894 individuals with diabetes using ARIC visit 2 as baseline (1990-1992) with follow-up for incident PAD through 2002. We assessed the relation between A1C and incident PAD, defined by intermittent claudication, PAD-related hospitalization, or a low ABI (<0.9).Results: During a mean follow-up of 9.8 years, the crude incidence rates were 2.1 per 1,000 person-years for intermittent claudication (n = 41), 2.9 per 1,000 person-years for PAD-related hospitalization (n = 57), and 18.9 per 1,000 person-years for low ABI at visit 3 or 4 (n = 123). The relative risk (RR) (95% CI) of an incident PAD event comparing the second and third tertiles of A1C to the first, respectively, after adjustment for cardiovascular risk factors was strongest for severe, symptomatic forms of disease, e.g., PAD-related hospitalization (RR = 4.56 [1.86-11.18] for the third A1C tertile compared with the first, P trend <0.001) than for low ABI (RR = 1.64 [0.94-2.87], P trend = 0.08).Conclusions: We found a positive, graded, and independent association between A1C and PAD risk in diabetic adults. This association was stronger for clinical (symptomatic) PAD, whose manifestations may be related to microvascular insufficiency, than for low ABI. Our results suggest that efforts to improve glycemic control in persons with diabetes may substantially reduce the risk of PAD. [ABSTRACT FROM AUTHOR]

Background: Narrowing of the small arterioles has been hypothesized to contribute to the pathogenesis of hypertension, but prospective clinical data are lacking.Objective: To examine the relation of retinal arteriolar narrowing to incident hypertension in healthy middle-aged persons.Design: Prospective cohort study.Setting: The population-based Atherosclerosis Risk in Communities Study, conducted in 4 U.S. communities.Participants: 5628 persons 49 to 73 years of age without preexisting hypertension.Measurements: Diameters of retinal vessels were measured from digitized retinal photographs. A summary arteriole-to-venule ratio was computed as an indicator of generalized arteriolar narrowing; a lower ratio indicated greater narrowing. Areas of focal arteriolar narrowing were defined from photographs by using a standard protocol. Incident hypertension, defined as systolic blood pressure of 140 mm Hg or higher, diastolic blood pressure of 90 mm Hg or higher, or use of antihypertensive medication, was identified from the cohort.Results: After 3 years of follow-up, 811 (14.4%) persons had developed hypertension. The incidence of hypertension was higher in persons with lower arteriole-to-venule ratios (incidence of 8.9%, 12.3%, 13.7%, 14.3%, and 22.3%, comparing decreasing quintiles of the ratio) and in persons with focal arteriolar narrowing than in those without focal arteriolar narrowing (25.1% vs. 13.0%). After the authors controlled for the average systolic and diastolic blood pressures over the preceding 6 years, body mass index, waist-to-hip ratio, and other risk factors, the odds of developing hypertension were approximately 60% higher in persons with lower arteriole-to-venule ratios (odds ratio, 1.62 [95% CI, 1.21 to 2.18] comparing lowest to highest quintile; P = 0.006 for trend) and focal arteriolar narrowing (odds ratio, 1.61 [CI, 1.27 to 2.04]; P < 0.001).Conclusions: Smaller retinal arteriolar diameters are independently associated with incident hypertension, which suggests that arteriolar narrowing may be linked to the occurrence and development of hypertension. [ABSTRACT FROM AUTHOR]

Context: The value of exercise testing in women has been questioned.Objective: To determine the prognostic value of exercise testing in a population-based cohort of asymptomatic women followed up for 20 years.Design and Setting: Near-maximal Bruce-protocol treadmill test data from the Lipid Research Clinics Prevalence Study (1972-1976) with follow-up through 1995.Participants: A total of 2994 asymptomatic North American women, aged 30 to 80 years, without known cardiovascular disease.Main Outcome Measures: Cardiovascular and all-cause mortality.Results: There were 427 (14%) deaths during 20 years of follow-up, of which 147 were due to cardiovascular causes. Low exercise capacity, low heart rate recovery (HRR), and not achieving target heart rate were independently associated with increased all-cause and cardiovascular mortality. There was no increased cardiovascular death risk for exercise-induced ST-segment depression (age-adjusted hazard ratio, 1.02; 95% confidence interval [CI], 0.57-1.80; P =.96). The age-adjusted hazard ratio for cardiovascular death for every metabolic equivalent (MET) decrement in exercise capacity was 1.20 (95% CI, 1.18-1.30; P<.001); for every 10 beats per minute decrement in HRR, the hazard ratio was 1.36 (95% CI, 1.19-1.55; P<.001). After adjusting for multiple other risk factors, women who were below the median for both exercise capacity and HRR had a 3.5-fold increased risk of cardiovascular death (95% CI, 1.57-7.86; P =.002) compared with those above the median for both variables. Among women with low risk Framingham scores, those with below median levels of both exercise capacity and HRR had significantly increased risk compared with women who had above median levels of these 2 exercise variables, 44.5 and 3.5 cardiovascular deaths per 10 000 person-years, respectively (hazard ratio for cardiovascular death, 12.93; 95% CI, 5.62-29.73; P<.001).Conclusion: The prognostic value of exercise testing in asymptomatic women derives not from electrocardiographic ischemia but from fitness-related variables. [ABSTRACT FROM AUTHOR]

Context: Microvascular processes have been hypothesized to play a greater role in the development of coronary heart disease (CHD) in women than in men; however, prospective clinical data are limited.Objective: To examine the association between retinal arteriolar narrowing, a marker of microvascular damage from hypertension and inflammation, and incident CHD in healthy middle-aged women and men.Design, Setting, and Participants: The Atherosclerosis Risk in Communities Study, an ongoing prospective, population-based cohort study in 4 US communities initiated in 1987-1989. Retinal photographs were taken in 9648 women and men aged 51 to 72 years without CHD at the third examination (1993-1995). To quantify retinal arteriolar narrowing, the photographs were digitized, individual arteriolar and venular diameters were measured, and a summary arteriole-to-venule ratio (AVR) was calculated.Main Outcome Measure: Risk of CHD associated with retinal arteriolar narrowing.Results: During an average 3.5 years of follow-up, 84 women and 187 men experienced incident CHD events. In women, after controlling for mean arterial blood pressure averaged over the previous 6 years, diabetes, cigarette smoking, plasma lipid levels, and other risk factors, each SD decrease in the AVR was associated with an increased risk of any incident CHD (relative risk [RR], 1.37; 95% confidence interval [CI], 1.08-1.72) and of acute myocardial infarction (RR, 1.50; 95% CI, 1.10-2.04). In contrast, AVR was unrelated to any incident CHD in men (RR, 1.00; 95% CI, 0.84-1.18) or to acute myocardial infarction (RR, 1.08; 95% CI, 0.85-1.38).Conclusion: Retinal arteriolar narrowing is related to risk of CHD in women but not in men, supporting a more prominent microvascular role in the development of CHD in women than in men. Future work is needed to confirm these findings. [ABSTRACT FROM AUTHOR]

Purpose: To examine the effect of correcting coronary heart disease (CHD) risk factors for long-term within-person variation on CHD risk.Methods: By using 5533 men and 7301 women from the Atherosclerosis Risk in Communities (ARIC) study, we compared models incorporating risk factors measured at a single visit and models incorporating additional measurements for systolic blood pressure, total cholesterol, and high-density lipoprotein cholesterol taken 3 years before baseline.Results: The largest change away from null was observed for systolic blood pressure, ie, hazard ratio (HR) 1.38 to 1.69 (+81%) in women and HR 1.26 to 1.41 (+56%) in men. HRs also decreased for age (-32% in women, -9% in men), race (-67% in women), the presence of diabetes (-13% in men and women), and medication use for hypertension (-27% in women, -26% in men) and cholesterol (-97% in women, HR 1.06-0.93 in men). The area under the ROC curve did not improve significantly in men or women, whereas reclassification was only significant in women (net reclassification improvement 5.4%, p = 0.016).Conclusions: Modeling long-term variation in CHD risk factors had a substantial impact on HR estimates, with new effect estimates further from the null for some risk factors and closer for others including age and medication use, but only improved risk classification in women. [ABSTRACT FROM AUTHOR]

Background: Type 2 diabetes mellitus and atherosclerotic cardiovascular disease have common antecedents. Since markers of inflammation predict coronary heart disease and are raised in patients with type 2 diabetes, we investigated whether they predict whether people will develop type 2 diabetes.Methods: 12,330 men and women, aged 45-64 years, were followed up for a mean of 7 years. We analysed the association between different markers of acute inflammation and subsequent diagnosis of diabetes. In a subgroup of 610 individuals selected originally for an unrelated atherosclerosis case-control study, we also investigated diabetes associations with total sialic acid and orosomucoid, haptoglobin, and alpha1-antitrypsin.Findings: 1335 individuals had a new diagnosis of diabetes. Adjusted odds ratios for developing diabetes for quartile extremes were 1.9 (95% CI 1.6-2.3) for raised white-cell count, 1.3 (1.0-1.5) for low serum albumin, and 1.2 (1.0-1.5) for raised fibrinogen. In the subgroup analysis, individuals with concentrations of orosomucoid and sialic acid of more than the median had odds ratios of 7.9 (2.6-23.7) and 3.7 (1.4-9.8), respectively. Adjustment for body-mass index and waist-to-hip ratio lessened the associations; those for white-cell count (1.5 [1.3-1.8]), orosomucoid (7.1 [2.1-23.7]), and sialic acid (2.8 [1.0-8.1]) remained significant.Interpretation: Markers of inflammation are associated with the development of diabetes in middle-aged adults. Although autoimmunity may partly explain these associations, they probably reflect the pathogenesis of type 2 diabetes. [ABSTRACT FROM AUTHOR]

Importance: Plasma biomarkers show promise for identifying Alzheimer disease (AD) neuropathology and neurodegeneration, but additional examination among diverse populations and throughout the life course is needed., Objective: To assess temporal plasma biomarker changes and their association with all-cause dementia, overall and among subgroups of community-dwelling adults., Design, Setting, and Participants: In 1525 participants from the US-based Atherosclerosis Risk in Communities (ARIC) study, plasma biomarkers were measured using stored specimens collected in midlife (1993-1995, mean age 58.3 years) and late life (2011-2013, mean age 76.0 years; followed up to 2016-2019, mean age 80.7 years). Midlife risk factors (hypertension, diabetes, lipids, coronary heart disease, cigarette use, and physical activity) were assessed for their associations with change in plasma biomarkers over time. The associations of biomarkers with incident all-cause dementia were evaluated in a subpopulation (n = 1339) who were dementia-free in 2011-2013 and had biomarker measurements in 1993-1995 and 2011-2013., Exposure: Plasma biomarkers of amyloid-β 42 to amyloid-β 40 (Aβ42:Aβ40) ratio, phosphorylated tau at threonine 181 (p-tau181), neurofilament light (NfL), and glial fibrillary acidic protein (GFAP) were measured using the Quanterix Simoa platform., Main Outcomes and Measures: Incident all-cause dementia was ascertained from January 1, 2012, through December 31, 2019, from neuropsychological assessments, semiannual participant or informant contact, and medical record surveillance., Results: Among 1525 participants (mean age, 58.3 [SD, 5.1] years), 914 participants (59.9%) were women, and 394 participants (25.8%) were Black. A total of 252 participants (16.5%) developed dementia. Decreasing Aβ42:Aβ40 ratio and increasing p-tau181, NfL, and GFAP were observed from midlife to late life, with more rapid biomarker changes among participants carrying the apolipoprotein E epsilon 4 (APOEε4) allele. Midlife hypertension was associated with a 0.15-SD faster NfL increase and a 0.08-SD faster GFAP increase per decade; estimates for midlife diabetes were a 0.11-SD faster for NfL and 0.15-SD faster for GFAP. Only AD-specific biomarkers in midlife demonstrated long-term associations with late-life dementia (hazard ratio per SD lower Aβ42:Aβ40 ratio, 1.11; 95% CI, 1.02-1.21; per SD higher p-tau181, 1.15; 95% CI, 1.06-1.25). All plasma biomarkers in late life had statistically significant associations with late-life dementia, with NfL demonstrating the largest association (1.92; 95% CI, 1.72-2.14)., Conclusions and Relevance: Plasma biomarkers of AD neuropathology, neuronal injury, and astrogliosis increase with age and are associated with known dementia risk factors. AD-specific biomarkers' association with dementia starts in midlife whereas late-life measures of AD, neuronal injury, and astrogliosis biomarkers are all associated with dementia.