scholarly journals Association of FMO3 Variants with Blood Pressure in the Atherosclerosis Risk in Communities Study

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Tyler S. Bryant ◽  
Priya Duggal ◽  
Bing Yu ◽  
Alanna C. Morrison ◽  
Tariq Shafi ◽  
...  
Keyword(s):  
Blood Pressure ◽  
African Americans ◽  
Exome Sequencing ◽  
Meta Analysis ◽  
African Ancestry ◽  
Low Frequency ◽  
Atherosclerosis Risk In Communities ◽  
European Americans ◽  
Atherosclerosis Risk ◽  
Nitrogen Containing Compounds

Flavin containing monooxygenase 3 [FMO3] encodes dimethylaniline monooxygenase [N-oxide-forming] 3, which breaks down nitrogen-containing compounds, and has been implicated in blood pressure regulation. Studies have reported conflicting results of the association of a common nonsynonymous variant, E158K (rs2266782), with hypertension. We examined the associations of E158K, along with rare and low frequency exonic variants (minor allele frequency [MAF]<5%) in FMO3 with hypertension, systolic blood pressure (SBP), and diastolic blood pressure (DBP). We included 7,350 European Americans and 2,814 African Americans in the Atherosclerosis Risk in Communities (ARIC) study with exome sequencing of FMO3. The association of FMO3 variants with SBP and DBP was tested using single variant and gene-based tests followed by the replication or interrogation of significant variants in ancestry-specific cohorts based on Bonferroni corrected thresholds. E158K had significant association with higher SBP in African Americans in ARIC (p=0.03), and two low frequency variants had significant association with higher SBP in African Americans (rs200985584, MAF 0.1%, p=0.0003) and European Americans (rs75904274, MAF 1.7%, p=0.006). These associations were not significant with additional samples: E158K in a meta-analysis of SBP of African ancestry (N=30,841, p=0.43) that included ARIC participants and the two low frequency variants in an independent ancestry-specific exome sequencing study of blood pressure (rs200985584, p=0.94; rs75904274, p=0.81). Our study does not support the association of E158K and low frequency variants in FMO3 with blood pressure and demonstrates the importance of replication in genetic studies.

Abstract 033: Epigenetic Clocks And Incident Heart Failure: The Atherosclerosis Risk In Communities (aric)

Circulation ◽  
2021 ◽  
Vol 143 (Suppl_1) ◽  
Author(s):  
Steven Nguyen ◽  
Carin A Northuis ◽  
Weihua Guan ◽  
Jan Bressler ◽  
Megan Grove ◽  
...  
Keyword(s):  
Heart Failure ◽  
African American ◽  
African Americans ◽  
Risk Prediction ◽  
European American ◽  
Cvd Risk ◽  
Atherosclerosis Risk In Communities ◽  
European Americans ◽  
Atherosclerosis Risk

Background: DNA methylation (DNAm)-based measures of aging, termed epigenetic clocks (EC), are associated with aging-related outcomes including cardiovascular disease (CVD) and all-cause mortality. Associations of ECs with heart failure (HF) are unclear. We tested whether ECs were positively associated with risk of incident HF in the Atherosclerosis Risk in Communities (ARIC) study and evaluated whether adding ECs to Pooled Cohort Equation (PCE) variables improved risk prediction. Methods: We measured DNAm in peripheral blood leukocytes in 2,263 African American (mean age=56.3 years) and 925 European American (mean age=59.5 years) participants using the Illumina HM450K and calculated 7 ECs: Horvath, Hannum, extrinsic (EEAA) and intrinsic (IEAA) epigenetic age acceleration, Hannum, PhenoAge, and GrimAge. HF was ascertained by ICD- 9 code 428 and adjudication by an expert panel. We carried out race stratified proportional hazards regression to test associations ECs with incident HF, adjusting for PCE variables: age, sex, smoking, total cholesterol, HDL, systolic blood pressure (SBP), antihypertensive medication use, and diabetes. We calculated area under the curve (AUC) and integrated discrimination index (IDI) to evaluate improvement in risk prediction when adding the ECs to PCE variables. Results: The number of incident HF events and mean follow-up time in African Americans and European Americans were 640 (189 in the first 10 years) and 19.3 years, and 191 and 21.7 years, respectively. All 7 ECs were positively associated with HF in both African Americans and European Americans. In African Americans with follow-up restricted to the first 10 years, the HR for a one SD increment in GrimAge (5.64 years) was 1.57 (95% CI=1.31, 1.88), comparable to that for a one-SD (5.82 years) increment in age (HR=1.58, 95% CI=1.36, 1.83) and greater than that for a one-SD (20.2mmHg) increment in SBP (HR=1.33, 95% CI=1.18, 1.51). In European Americans across the entire follow-up period, the HR for a one-SD increment in GrimAge (6.13 years) was 1.22 (95% CI=1.06, 1.41), smaller than that for a one-SD (5.50 years) increment in age (HR=1.93, 95% CI=1.63, 2.29) and larger than that for a one-SD (17.9 mmHG) increment in SBP (HR=1.13, 95% CI=0.98, 1.30). In African Americans with follow-up restricted to the first 10 years, adding GrimAge to PCE variables increased AUC by 0.019 (95% CI=0.003, 0.035) and the IDI was 0.010 (95% CI=0.002, 0.019). In European Americans, adding GrimAge did not change AUC appreciably (0.004, 95% CI=-0.006, 0.014) and the IDI was 0.002 (95% CI=0.000, 0.005). Conclusion: ECs are positively associated with HF in African American and European American participants independent of traditional CVD risk factors. GrimAge modestly improved heart failure risk prediction in African Americans. HF-specific DNAm-based measures should be developed and evaluated for improvement in risk prediction.

Abstract 03: Projected impact of shifting categories of hypertension on rates of coronary heart disease, heart failure and stroke: the Atherosclerosis Risk in Communities Study (ARIC)

Circulation ◽  
2014 ◽  
Vol 129 (suppl_1) ◽  
Author(s):  
Shakia T Hardy ◽  
Laura R Loehr ◽  
Kenneth R Butler ◽  
Patricia P Chang ◽  
Aaron R Folsom ◽  
...  
Keyword(s):  
Heart Failure ◽  
Blood Pressure ◽  
Coronary Heart Disease ◽  
Heart Disease ◽  
African Americans ◽  
Population Distribution ◽  
Blood Pressure Reduction ◽  
Atherosclerosis Risk In Communities ◽  
Atherosclerosis Risk ◽  
The Impact

Introduction: Despite indications that blood pressure is positively related to vascular disease, with no evidence of a threshold, recommendations for population improvements in cardiovascular health are largely focused on populations with hypertension or prehypertension. Here we compare the impact of meeting the Healthy People 2020 goal of a 10% reduction in the proportion of adults with hypertension, with a 2 mm Hg reduction in population-wide levels of systolic blood pressure (SBP) on the incidence of heart failure (HF), coronary heart disease (CHD), and stroke. Methods: In the biracial Atherosclerosis Risk in Communities Study (n=15,744) cohort, blood pressure was measured at baseline (1987-1989) using standardized methodology. Thresholds to define prehypertension (SBP=120-139 or DBP=80-89 mm Hg) and hypertension (SBP ≥140 or DBP ≥ 90) were from JNC7. A first hospitalization with discharge diagnosis code of ‘428’ defined incident HF. Incident hospitalized (definite or probable) CHD and stroke was classified by physician panel. We used multivariable regression to estimate incidence rate differences (IRD) for HF, CHD, and stroke that could be associated with a 10% reduction in the proportion of individuals with prehypertension and hypertension, as compared to a population-wide 2 mm Hg decrease in SBP. Results: At baseline, there were 31% African Americans and 13% Caucasians with hypertension, and 38% African Americans and 33% Caucasians with prehypertension. Over a mean of 18.7 years of follow up, age-adjusted incidence rates for HF, CHD, and stroke were higher among African Americans than Caucasians. After adjusting for covariates measured at study baseline, a hypothetical 10% reduction in the proportions of individuals with hypertension and pre-hypertension was associated with a larger estimated effect for HF compared with CHD and stroke. For the 10% reduction in those with hypertension, we estimated 2/100,000 person-years (PY) and 8/100,000 PY fewer incident HF hospitalizations in Caucasians and African Americans, respectively. In contrast, a population-wide blood pressure reduction approach of 2 mm Hg was associated with an estimated 24/100,000 PY and 39/100,000 PY fewer incident HF events in Caucasians and African Americans, respectively. When extrapolated to the 2010 US population aged greater than 45 years, hypothetical interventions that shift the population distribution of SBP by 2 mm Hg potentially result in an additional reduction of 22,000 HF hospitalizations, 17,000 CHD events, and 11,000 stroke events annually when compared to a primary prevention approach aimed at populations with hypertension and pre-hypertension. Conclusion: Modest, population-wide shifts in SBP may produce greater reductions in HF, CHD, and stroke events than can be achieved by only targeting reductions for those with hypertension, particularly among African Americans.

Abstract MP013: Strong Inverse Relation between Physical Activity and Incidence of Cardiovascular Disease in African Americans: the Atherosclerosis Risk in Communities Study

Circulation ◽  
2012 ◽  
Vol 125 (suppl_10) ◽  
Author(s):  
Elizabeth J Bell
Keyword(s):  
Physical Activity ◽  
Heart Failure ◽  
Cardiovascular Disease ◽  
Coronary Heart Disease ◽  
Heart Disease ◽  
African Americans ◽  
Risk Reduction ◽  
Atherosclerosis Risk In Communities ◽  
Baseline Visit ◽  
Atherosclerosis Risk

Introduction: Although there is substantial evidence that physical activity reduces risk of cardiovascular disease (CVD), the few studies that included African Americans offer inconclusive evidence and did not study stroke and heart failure separately. Objective: We examined, in African Americans and Caucasians in the Atherosclerosis Risk in Communities study (ARIC), the association of physical activity with CVD incidence (n=1,039) and its major components - stroke (n=350), heart failure (n=633), and coronary heart disease (n=442) - over a follow-up period of 21 years. Methods: ARIC is a population-based biracial cohort study of 45– to 64-yr-old adults at the baseline visit in 1987–89. Physical activity was assessed using the modified Baecke physical activity questionnaire and categorized by the American Heart Association’s ideal CVD health guidelines: poor, intermediate, and ideal physical activity. An incident CVD event was defined as the first occurrence of 1) heart failure, 2) definite or probable stroke, or 3) coronary heart disease, defined as a definite or probable myocardial infarction or definite fatal coronary heart disease. Results: We included 3,707 African Americans and 10,018 Caucasians free of CVD at the baseline visit. After adjustment for age, sex, cigarette smoking, alcohol intake, hormone therapy use, education, and ‘Western’ and ‘Prudent’ dietary pattern scores, higher physical activity was inversely related to CVD, heart failure, and coronary heart disease incidence in African Americans and Caucasians (p-values for trend tests <.0001), and with stroke in African Americans. Hazard ratios (95% confidence intervals) for CVD for intermediate and ideal physical activity, respectively, compared to poor, were similar by race: 0.65 (0.56, 0.75) and 0.59 (0.49, 0.71) for African Americans, and 0.74 (0.66, 0.83) and 0.67 (0.59, 0.75) for Caucasians (p-value for interaction = 0.38). Physical activity was also associated similarly in African Americans and Caucasians for each of the individual CVD outcomes (coronary heart disease, heart failure, and stroke), with an approximate one-third reduction in risk for intermediate and ideal physical activity versus poor physical activity- this reduction was statistically significant. Conclusions: In conclusion, our findings reinforce public health recommendations that regular physical activity is important for CVD risk reduction, including reductions in stroke and heart failure. They provide strong new evidence that this risk reduction applies to African Americans as well as Caucasians and support the idea that some physical activity is better than none.

Abstract MP77: Projected Impact of Shifting Population Distributions of Blood Pressure on Rates of Coronary Heart Disease, Heart Failure and Stroke: The Atherosclerosis Risk in Communities Study

Circulation ◽  
2013 ◽  
Vol 127 (suppl_12) ◽  
Author(s):  
Shakia T Hardy ◽  
Laura R Loehr ◽  
Kenneth R Butler ◽  
Patricia P Chang ◽  
Aaron R Folsom ◽  
...  
Keyword(s):  
Heart Failure ◽  
Blood Pressure ◽  
Coronary Heart Disease ◽  
African American ◽  
Heart Disease ◽  
Population Distribution ◽  
The United States ◽  
Incidence Rates ◽  
Atherosclerosis Risk In Communities ◽  
Atherosclerosis Risk

Introduction: Rates of cerebrovascular disease, heart failure (HF), and coronary heart disease (CHD), increase progressively as blood pressure rises. Several authors have estimated the theoretical effects of shifting the population distribution of blood pressure; however few studies have examined the degree to which modest decrements in blood pressure affect HF incidence, or included a racially diverse population. Methods: Incident HF was identified by a first hospitalization with discharge diagnosis code of 428.X. Incident hospitalized (definite or probable) CHD and stroke were classified according to protocol. We used multivariable regression to estimate incidence rate differences (IRD) for HF, CHD, and stroke that could be associated with a two mm Hg reduction in systolic blood pressure (SBP) in 15,744 participants from the Atherosclerosis Risk in Communities Study. Results: Over a mean of 18.3 years of follow up, age-adjusted incidence rates for HF, CHD, and stroke were higher among African American than Caucasians (Table 1). After adjusting for antihypertensive use, gender, and age, a two mm Hg decrement in SBP across the total population was associated with an estimated 24/100,000 person-years (PY) and 39/100,000 PY fewer incident HF events in Caucasians and African Americans, respectively. The projected disease reductions were of smaller absolute magnitude for incident CHD and incident stroke. Extrapolation to the African American and Caucasian U.S. populations age greater than 45 years suggests that a two mmHg decrement in SBP could result in approximately 22,000 fewer incident HF events, 15,000 fewer incident CHD events, and 5,000 fewer incident stroke events annually. Conclusion: Our results suggest that modest shifts in SBP, consistent with what could theoretically be achieved through population level lifestyle interventions, could substantially decrease the incidence of HF, stroke, and CHD in the United States, especially among African American populations.

scholarly journals Hemodynamic Correlates of Blood Pressure in Older Adults: The Atherosclerosis Risk in Communities (ARIC) Study

2016 ◽  
Vol 18 (12) ◽  
pp. 1222-1227 ◽  
Author(s):  
Hirofumi Tanaka ◽  
Gerardo Heiss ◽  
Elizabeth L. McCabe ◽  
Michelle L. Meyer ◽  
Amil M. Shah ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Older Adults ◽  
Atherosclerosis Risk In Communities ◽  
Atherosclerosis Risk ◽  
Aric Study

Abstract P002: Evidence For Smoking Dependent Genetic Effects on C-reactive Protein Levels in a Multi-ethnic Cohort Setting: The Care Consortium.

Circulation ◽  
2012 ◽  
Vol 125 (suppl_10) ◽  
Author(s):  
Jaclyn Ellis ◽  
Jeremy Walston ◽  
Josee Dupuis ◽  
Emma Larkin ◽  
Maja Barbalic ◽  
...  
Keyword(s):  
African Americans ◽  
Candidate Gene ◽  
Meta Analysis ◽  
Cardiovascular Health Study ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
European Americans ◽  
Heart Study ◽  
Study Results ◽  
Never Smokers

INTRODUCTION: C-reactive protein (CRP) is a heritable biomarker of systemic inflammation and a predictor of cardiovascular disease (CVD). Cigarette smoking is a major risk factor in the development of CVD and has been shown to affect circulating levels of CRP. Therefore, we sought to determine how this important environmental exposure may influence genetic associations with CRP in a multi-ethnic setting. METHODS: Using the ITMAT Broad-CARe (IBC) SNP array, a custom 50,000 SNP gene-centric array having dense coverage of over 2,000 candidate genes for CVD pathways, we performed a meta-analysis of up to 26,065 participants of European descent and 7,584 participants of African descent for association with log-CRP level within smoking status stratum. The 2 smoking strata were: never smokers and ever smokers (comprising of current and former smokers). We conducted IBC-wide association scans for CRP within cohort-, race- and smoking-stratum and meta-analyzed by race. Samples were from the Candidate gene Association Resource (CARe) cohorts (Atherosclerosis Risk in Communities Study, Framingham Heart Study, Cardiovascular Health Study, Cleveland Family Study , Coronary Artery Risk Development in Young Adults Study, Jackson Heart Study, and Multi-Ethnic Study of Atherosclerosis Study). Results were considered to be panel wide statistically significant if p<2.2×10−6. RESULTS: The overall sample size for ever smokers (never smokers) was 11,698 (10,344) in European Americans and 3,448 (4,330) in African Americans. The per-allele beta coefficients for genes previously established to be associated with CRP and present on the IBC chip ( CRP, APOE, GCKR, IL6R, LEPR, HNF1A, NLRP3 ) were very similar in magnitude between smoking strata in European Americans. However, in the African Americans, the estimated per-allele CRP and IL6R betas were 2-times larger for the ever smokers as compared to the never smokers. In the European American analysis, one gene not previously reported for association with CRP reached IBC-wide significance for a CRP-lowering effect in the never smokers ( GSTT1 , p=4.8E-07 for SNP rs405597 ), but not in the ever smokers (p=0.078). CONCLUSION: This large scale candidate gene based meta-analysis identified one novel locus for CRP ( GSTT1 ) associated with serum CRP levels in those reporting having never regularly smoked. Polymorphisms in GSTT1 , which plays a role in detoxification, have previously been reported to interact with smoking for other phenotypes including birth weight and colorectal cancer. We also observed evidence that smoking modifies the effects for previously established loci CRP and IL6R in African Americans. These results may identify important context genetic specific effects that influence chronic inflammation.

Abstract P250: Incidence of Hospitalized Peripheral Arterial Disease and Critical Limb Ischemia: The Atherosclerosis Risk in Communities (ARIC) Study

Circulation ◽  
2012 ◽  
Vol 125 (suppl_10) ◽  
Author(s):  
Corey A Kalbaugh ◽  
Anna Kucharska-Newton ◽  
Laura Loehr ◽  
Elizabeth Selvin ◽  
Aaron R Folsom ◽  
...  
Keyword(s):  
Risk Factors ◽  
African Americans ◽  
Peripheral Arterial Disease ◽  
Lower Extremity ◽  
Limb Ischemia ◽  
Arterial Disease ◽  
Atherosclerosis Risk In Communities ◽  
Atherosclerosis Risk ◽  
Baseline Characteristics ◽  
Peripheral Arterial

Introduction: Lower extremity peripheral arterial disease (PAD) affects between 12% and 20% of Americans over the age of 65. PAD compromises quality of life, contributes a high burden of disability and its related health care costs exceed $4 billion/year, yet this preventable CVD outcome remains understudied. Aims: Assess the incidence of hospitalized PAD, and of the most severe form of PAD, critical limb ischemia (CLI), in middle-aged men and women, and evaluate their risk factors in a bi-ethnic, population-based cohort. We hypothesized that incidence of hospitalized PAD and CLI are higher in African Americans, and that modifiable atherosclerosis risk factors in middle age predict these sequelae of PAD. Methods: We analyzed data from 13,865 participants from the Atherosclerosis Risk in Communities Study aged 45–64 without PAD at baseline (1987–89). Incident PAD and CLI events were identified using ICD-9 codes from active surveillance of all hospitalizations among cohort participants from 1987 through 2008. All estimates are incidence rates per 10,000 person-years; nominal statistical significance was achieved for all baseline characteristic comparisons reported. Results: There were 707 incident hospitalized PAD during a median of 18 years of follow-up (249,570 person-years). The overall age-adjusted incidence of PAD and limb-threatening CLI were 26.0 and 9.6 per 10,000 person-years, respectively. Incidence of hospitalized PAD was higher in African Americans than whites (34.7 vs. 23.2) and in men compared to women (32.4 vs. 26.7). Baseline characteristics associated with age-adjusted incident PAD (per 10,000 person-years) compared to their referent groups were diabetes (91.2 vs. 19.0), history of smoking (33.6 vs. 16.2), hypertension (42.6 vs. 18.6), coronary heart disease (81.4 vs. 24.1), and obesity (41.5 vs. 20.2). Incidence of CLI also was higher among African Americans (21.0 vs. 5.9) and in men (10.5 vs. 8.9 per 10,000 person-years). Baseline characteristics associated with incident CLI were similar to those for PAD. Conclusions: The absolute risk of hospitalized lower extremity PAD in this community-based cohort is of a magnitude similar to that of heart failure and of stroke. As modifiable factors are strongly predictive of the long-term risk of hospitalized PAD and CLI, particularly among African Americans, our results highlight the need for effective risk factor prevention and control.

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