Incident Heart Research Articles

Abstract 11250: Historical Neighborhood Redlining and Cardiovascular Risk in Patients With Chronic Kidney Disease: Results From Chronic Renal Insufficiency Cohort

Background: Neighborhood redlining was established by the government-sanctioned Home Owners' Loan Corporation (HOLC) in the 1930s aimed to develop neighborhood risk assessment for mortgage applications in the United States. Redlining has resulted in residential segregation and has contributed to persistent systemic racism. Objectives: We sought to investigate the association between redlining and prevalent and incidence cardiovascular disease (CVD) in patients with chronic kidney disease (CKD). Methods: We linked participants from the Chronic Renal Insufficiency Cohort (patients with mild to moderate CKD enrolled 2003-2008 and followed prospectively) with historical redlining risk groups using participant residential address at enrollment. HOLC groups neighborhoods into risk groups (A-D, with A being lowest risk and D being highest risk). We examined the association between redlining groups with prevalent and incident cardiovascular events Results: A total of 1720 participants were included: 109 (6.3%) in group A, 305 (18%) in group B, 753 (44%) in group C, and 553 (32.2%) in group D. Overall, increasing neighborhood HOLC risk was associated with increased proportion of Black and Hispanic residents, younger age, proteinuria, higher systolic BP, and high sensitivity troponin levels (all P<0.01). In multivariable models, group B (Odds Ratio [OR] 2.34 (95% CI: 1.32-4.15), P=0.003), group C (OR 2.31 (1.34-3.98), P=0.003) and group D (OR 2.10 (1.21-3.65), P=0.009) were associated with increased CVD at baseline (vs group A). Among 1118 participants without baseline CVD, group D was associated with increased risk for HF or all-cause death (adjusted HR 2.63 (1.31-5.28), P=0.006) which remained unchanged after further adjustment for BNP and high-sensitivity troponins (D vs A: HR 2.55 (1.27-5.13), P=0.008). Conclusions: Historical neighborhood redlining is associated with prevalent CVD and incident heart failure/death in a contemporary cohort of patients with CKD, enrolled more than 6 decades after the redlining practices were abolished. Future studies should focus on investigating the mechanisms of this relationship and the impact of residential segregation on cardiovascular health.

Abstract 5303: Cardiovascular disease risk associated with breast cancer chemotherapy drugs: The Pathways Heart Study

Abstract Purpose: Chemotherapy drugs to treat breast cancer (BC) are cardiotoxic, but few studies have examined the effects of specific chemotherapy combinations on cardiovascular disease (CVD). We examined the additive effects of combinations of BC chemotherapy drugs associated with incident CVD events among women with a history of BC compared to those without. Methods: The Pathways Heart Study is a cohort study within Kaiser Permanente Northern California (KPNC) examining incident CVD events and risk factors in women with BC. Eligibility criteria included invasive BC diagnosis from 11/2005 to 3/2013, age≥21 years, and KPNC membership≥12 months at BC diagnosis. Controls without BC were matched 5:1 on birth year and race/ethnicity. KPNC electronic health records were used to collect demographic, clinical, and treatment characteristics. Chemotherapy drugs identified from clinical data included anthracyclines, cyclophosphamides, taxanes, and trastuzumab. Mutually exclusive groups were created according to the types of chemotherapy drugs received. Outcomes identified from ICD9/10 diagnosis codes included incident ischemic heart disease, heart failure (HF)/cardiomyopathy and stroke. Multivariable Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) of the CVD outcome by chemotherapy drug combinations received relative to matched controls. Results: A total of 6,761 women with BC who received chemotherapy were identified and were matched to 33,801 controls. On average, women were 55.2 years old (standard deviation (SD)=10.9) and were followed for 7.1 years (SD=3.6). Four groups of women with distinct chemotherapy combinations were identified: anthracyclines + cyclophosphamide (AC, 10.5%), AC + taxanes (39.0%), AC + taxanes + trastuzumab (8.8%), and cyclophosphamide + taxanes (20.7%). Women who received AC had a 2.00 (95% CI: 1.27-3.14) increased risk of incident HF/cardiomyopathy relative to matched controls without BC. When taxanes were added to this combination, risk was similar (HR=1.88; 95% CI: 1.44-2.47). However, when trastuzumab was further added, risk of HF/cardiomyopathy increased more than 1.5-fold (HR=3.18; 95% CI: 1.91-5.30). The combined receipt of cyclophosphamide and taxanes was associated with a 1.42 (95% CI: 1.05-1.92) increased risk of developing stroke, but including anthracyclines with this combination inversed the association for stroke (HR: 0.73, 95% CI: 0.54- 0.99). No combinations examined were associated with incidence of ischemic heart disease. Conclusion: Findings suggest specific chemotherapy drug combinations may differentially affect the risk of incident HF/cardiomyopathy and stroke in BC survivors. Future work will examine dosage and duration of chemotherapy exposure, comparisons of the groups’ characteristics to account for possible confounding by indication, and competing risk analysis. Citation Format: Hanjie Shen, Eileen Rillamas-Sun, Carlos Iribarren, Richard Cheng, Jamal S. Rana, Mai Nguyen-Huynh, Cecile A. Laurent, Valerie S. Lee, Janise M. Roh, Dawn L. Hershman, Lawrence H. Kushi, Marilyn L. Kwan, Heather Greenlee. Cardiovascular disease risk associated with breast cancer chemotherapy drugs: The Pathways Heart Study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5303.

Abstract MP26: Replacing Sedentary Behavior Time With Various Daily-life Physical Activities And Structured Exercises, Recommended Physical Activity, And Incident Coronary Heart Disease

Introduction: While excessive sedentary behavior time has been associated with cardiovascular diseases, it is largely unknown to what extend substituting sedentary behaviors with various physical activities may offset the risk of coronary heart disease (CHD). Hypothesis: We hypothesize that reallocating time from sedentary behavior to various daily-life physical activities and structured exercises might be associated with lower risk of CHD. We particularly examined such reallocations according to whether or not the participants meet the recommended physical activity level. Method: A total of 468,960 UK Biobank participants free of CHD were included. Sedentary behavior time was quantified by summing up the time spent on television watching, computer use (not at work), and driving. Physical activities were categorized as daily-life activities (walking for pleasure, light DIY, and heavy DIY) and structured exercise (strenuous sports and other exercises). We used iso-temporal substitution model to estimate the effect of replacing sedentary behavior with each type of physical activity for the same amount of time. Results: During a median follow-up of 11 years, 7,982 incident CHD cases were documented. Sedentary behavior time was significantly associated with a higher risk of CHD, independent of physical activity. In comparison of the extreme categories (≥6 vs. <2 h/d), the HR for CHD was 1.31 (95% CI: 1.18-1.46). Replacing 30 minutes of sedentary behavior per day with an equal time of various physical activities was significantly associated with a 3%-12% risk reduction of CHD. Replacing 1 hour of sedentary behaviors with different types of physical activities was associated with a 6%-23% risk reduction of CHD. Sedentary behavior-to-strenuous sports reallocations showed the largest reduction in CHD risk when replacing sedentary behavior. Moreover, reallocations of sedentary behavior to various physical activities showed particularly greater benefits among those who did not meet the physical activity recommendations. Conclusion: Our study indicates that replacing sedentary behavior time with various daily-life activities or structured exercise was associated with significant reductions in CHD risk.

Abstract P228: Social Networks And Cardiovascular Disease Events Among Men And Women From The Jackson Heart Study

Background: Cardiovascular disease (CVD) burden disproportionately affects African-American adults in the United States. Greater social networks, or social integration, may lower CVD risk among African-American adults. Objective: To determine the association of social networks and incident coronary heart disease (CHD), stroke, and heart failure (HF) and test whether there are differences by sex. Methods: Among participants of the Jackson Heart Study without CVD at baseline (mean age: 54.4 years, n=3,053 women, n=1684 men), we used the Social Networks Index at baseline (2000-2004) to develop a continuous social networks score in standard deviation units (range 0-5) and binary categories (high vs. low relative to the median). Surveillance of CHD, stroke, and HF events occurred after exam 1 (2005 for HF) until 2016. We utilized Cox proportional hazards regression to estimate hazard ratios (HR 95% confidence interval-CI) of each CVD event by levels of social networks, adjusting for demographics, education, behaviors, risk factors and depressive symptoms. Interaction terms by sex were used to evaluate sex differences. Results: There were 262 CHD events, 213 stroke events, and 331 HF events that occurred by 2016. P-values for interaction terms by sex were statistically significant for stroke and HF ( p <0.05). After full adjustment, a 1-SD unit increase in social networks was associated with a lower hazard of CHD and HF among women (HR 0.80, 95% CI 0.72, 0.90 and HR 0.81 95% CI 0.69, 0.98, respectively). Men had a lower hazard of CHD with every 1-SD unit increase in social networks (HR 0.88, 95% CI 0.79, 0.99) after full adjustment. High vs. low social networks was associated with a lower hazard of stroke (HR 0.58, 95% CI 0.35, 0.98) and HF (HR 0.61, 95% CI 0.39, 0.94) among women after full adjustment. Conclusion: Men and women who reported greater social networks were less likely to have a CHD event, but women with greater social networks were less likely to have stroke and HF.

Abstract MP76: Association Of Elevated High-sensitive Cardiac Troponin T And Low Ankle-brachial Index With Incident Cardiovascular Events. The Multi-ethnic Study Of Atherosclerosis And The Cardiovascular Health Study

Introduction: Elevated high-sensitive cardiac troponin T (hs-cTnT>14 ng/L) and low ankle-brachial index (ABI < 0.9) are known to be associated with cardiovascular diseases (CVD) but their joint effect on the risk of CVD events is unknown. Methods: We used data from the MESA and CHS among 10,900 participants free of CVD events at baseline (mean age 66.3 years, 44.7% males). Incident coronary heart disease (CHD) was defined as fatal or non-fatal myocardial infarction or revascularization and incident CVD was defined as CHD, transient ischemic attack, stroke, or atrial fibrillation. Hazard ratio (HR) and 95% CI was calculated from a Cox regression model. Interaction on the additive scale was assessed using relative excess risk due to interaction (RERI) and interaction on the multiplicative scale was assessed by Likelihood ratio (LR) test. Results: At baseline (2000-2002 for MESA and 1989-1990 for CHS), 10.2% of participants had elevated hs-cTnT and 7.5% had low ABI. During 26.1 years of total follow-up (median follow-up 18.4 years), there were 3,911 incident CVD events. The risk of CHD and CVD was higher in participants with both elevated hs-cTnT and low ABI [CHD HR: 2.1 (1.5, 2.9), CVD HR: 2.1 (1.7, 2.5)], only elevated hs-cTnT [CHD HR: 1.7 (1.4, 2.0), CVD HR: 1.6 (1.5, 1.8)], and only low ABI [CHD HR: 1.8 (1.5, 2.2), CVD HR: 1.5 (1.3, 1.7)] than those with unelevated hs-cTnT and normal ABI. Interaction on the multiplicative scale was observe in both adjusted and unadjusted models for CHD (unadjusted LR test p-value=0.002, adjusted LR test p-value=0.042) and only in unadjusted model for CVD (LR test p-value=0.001). No significant additive interaction was detected for both CHD and CVD (RERI p-value≥0.25 for unadjusted and adjusted models). Conclusion: Having both elevated cTnT and low ABI was associated more strongly with CVD events than only elevated cTnT or low ABI. Antagonistic multiplicative interaction was found indicating the observed joint effect of elevated cTnT and low ABI was smaller than the expected combined individual effects.

Trends in myocarditis incidence, complications and mortality in Sweden from 2000 to 2014

Investigate trends in myocarditis incidence and prognosis in Sweden during 2000–2014. Little data exist concerning population-trends in incidence of hospitalizations for myocarditis and subsequent prognosis. Linking Swedish National Patient and Cause of Death Registers, we identified individuals ≥ 16 years with first-time diagnosis of myocarditis during 2000–2014. Reference population, matched for age and birth year (n = 16,622) was selected from Swedish Total Population Register. Among the 8 679 cases (75% men, 64% < 50 years), incidence rate/100,000 inhabitants rose from 6.3 to 8.6 per 100,000, mostly in men and those < 50 years. Incident heart failure/dilated cardiomyopathy occurred in 6.2% within 1 year after index hospitalization and in 10.2% during 2000–2014, predominantly in those ≥ 50 years (12.1% within 1 year, 20.8% during 2000–2014). In all 8.1% died within 1 year, 0.9% (< 50 years) and 20.8% (≥ 50 years). Hazard ratios (adjusted for age, sex) for 1-year mortality comparing cases and controls were 4.00 (95% confidence interval 1.37–11.70), 4.48 (2.57–7.82), 4.57 (3.31–6.31) and 3.93 (3.39–4.57) for individuals aged < 30, 30 to < 50, 50 to < 70, and ≥ 70 years, respectively. The incidence of myocarditis during 2000–2014 increased, predominantly in men < 50 years. One-year mortality was low, but fourfold higher compared with reference population.

Abstract 13245: Cardiovascular Risk Burden in Relation to Dementia and Brain Structural Imaging Markers: A Study From UK Biobank

Introduction: Cardiovascular risk burden is associated with higher all-cause dementia risk. However, the roles of cardiovascular disease (CVD) and genetic background, and the associations of cardiovascular risk burden with dementia subtypes and brain structure, need to be examined. Hypothesis: We hypothesized that the Framingham General Cardiovascular Risk Score (FGCRS) would be associated with all-cause and subtypes of dementia and brain structure. Methods: We conducted a prospective study among 354,654 participants free of CVD and dementia at baseline (2006-2010, mean age 56.4 years) within UK Biobank. CVD risk burden was evaluated by baseline FGCRS. Dementia case was identified from hospital inpatient records and death register data. Brain MRI volume markers were available for 15,104 participants since 2014. Logistic and linear regression models were used for dementia risk and brain volumes, respectively. Results: During a median 12.0 years of follow-up, 3,996 all-cause dementia cases were identified. Higher FGCRS was associated with an increased all-cause dementia risk after adjusting for demographic, major lifestyle, clinical factors, and polygenic risk score (PRS) of Alzheimer’s disease (AD). Comparing the high vs. low tertile of FGCRS, the odds ratios (ORs) and 95% CIs were 1.26 (1.12, 1.42) for all-cause dementia, 1.67 (1.33, 2.09) for AD, and 1.53 (1.08, 2.17) for vascular dementia (all P trend &lt; 0.05). Incident stroke and coronary heart disease accounted for 13% (95% CI: 9%, 19%) of the association of FGCRS with all-cause dementia. Interaction was not detected for FGCRS and PRS on risk of all-cause or any subtype of dementia (all P for interaction &gt; 0.05). We observed an 83% (95% CI: 47%, 128%) higher all-cause dementia risk comparing the high-high vs. low-low for FGCRS-PRS category. For standardized brain volumes, higher FGCRS was associated with greater log-transformed white matter hyperintensities, smaller cortical volume, and smaller grey matter volume. Conclusions: Cardiovascular risk burden was associated with higher dementia risk and neurodegeneration-related brain volume markers. The association of cardiovascular risk burden with all-cause dementia was partly explained by CVD onset and independent of dementia genetic risk.

Educational Level Inequalities in Cardiovascular Outcomes and All-Cause Mortality in Turkey: A Cohort

Abstract Background Recent decades witnessed an increase in the burden of non-communicable diseases including adverse cardiovascular outcomes in low- and middle income countries and the burden was not equal across socioeconomic strata. This study aimed to define educational level inequalities in cardiovascular outcomes and all-cause mortality in a six-years cohort in Turkey. Methods Non-communicable Diseases and Risk Factors Cohort randomly sampled two adults (&amp;gt;14) from each of the registered family physicians in Turkey in July 2011 (n = 18,477). The family physicians collected demographic data. Incident coronary heart disease (CHD), cardiovascular and all-cause deaths were obtained from electronic health records in the end of 2017. Ridit score transformation was applied to the educational level by gender (illiterate, primary school, secondary school, high school or higher) and then Relative Index of Inequalities by educational level were estimated using Poisson Regression for morbidity and Cox Regression for mortality. Results There were 17,847 participants in CHD and 18,461 in the mortality cohort. During six-years 1,026 cases were diagnosed with CHD, 185 cardiovascular and 769 all-cause deaths occurred respectively. The inequalities were not significant for all outcomes however Relative Index of Inequalities were close to be significant for CHD incidence among men and all-cause mortality among women (0.721 (0.507 to 1.025) and 1.721 (0.969 to 3.057), respectively). Conclusions This is the first-ever cohort in Turkey with the aim to define educational level inequalities in cardiovascular outcomes and all-cause mortality. The inequalities may not have been observed due to the low number of outcomes. Key messages In Turkey, there were no educational level inequalities in our cohort. The possible inverse inequalities among men and inequalities among women may arise with a longer follow up.

Early Chronic Kidney Disease (G1-G3a) in Combination with Steatosis as a Predictor of Incident Ischemic Heart Disease: A Longitudinal Study in Non-Diabetic Koreans.

Hepatic steatosis and chronic kidney disease (CKD) in the advanced stages are closely related to cardiovascular diseases. Despite the potential connection between early CKD (G1-G3a) and hepatic steatosis on cardiometabolic risks, few studies have revealed their causal link to ischemic heart disease (IHD). We prospectively investigated the combined effect of CKD in earlier stages and hepatic steatosis on incident IHD risk in large-scale, non-diabetic Koreans. Data were assessed from 16,531 participants without diabetes from the Health Risk Assessment Study (HERAS) and Korea Health Insurance Review and Assessment (HIRA) data. We divided the study population into four groups according to the existence of early CKD and hepatic steatosis: controls, early CKD only, hepatic steatosis only, and both early CKD and hepatic steatosis. We prospectively assessed hazard ratios (HRs) with 95% confidence intervals (CIs) for IHD using multivariate Cox proportional-hazard regression models over a 50-month period. During the follow-up period, 326 (2.0%) patients developed IHD. HRs of IHD in the four groups were 1.00 (controls), 1.26 (95% CI 0.72–2.19), 1.19 (95% CI 0.90–1.57) and 1.76 (95% CI 1.04–2.97), respectively, after adjusting for potential confounding variables. Even less than stage 3A, CKD could precede and predict IHD in patients with hepatic steatosis.

Weight change and risk of cardiovascular disease among adults with type 2 diabetes: more than 14\xa0years of follow-up in the Tehran Lipid and Glucose Study

BackgroundTo examine the impact of weight change on incident cardiovascular disease and coronary heart disease (CVD/CHD) among an Iranian population with type 2 diabetes mellitus (T2DM).MethodsThe study population included 763 participants with T2DM aged ≥ 30 years without a history of CVD and cancer at baseline. Two weight measurements done at baseline and about 3 years later. Based on their weight change, they categorized into: > 5% loss, 3–5% loss, stable (± < 3%), 3–5% gain, > 5% gain. Participants were then followed for incident CVD/CHD annually up to 20 March 2018. Multivariable Cox proportional hazard models, adjusted for age, sex, body mass index, educational level, current smoking, glucose-lowering drug use, family history of CVD, hypertension, hypercholesterolemia, chronic kidney disease, and fasting plasma glucose (FPG) were applied to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) of weight change categories for incident CVD/CHD, considering stable weight as reference.ResultsAfter the weight change measurement, during a median follow-up of 14.4 years, 258 CVD and 214 CHD occurred. Over 5% weight gain was associated with reduced risks of CVD and CHD development by the HRs of 0.70 [95% CI 0.48–1.01; P-value: 0.058] and 0.61 [0.40–0.93], respectively, in multivariable analysis. After further adjustment for FPG change, the HRs of weight gain > 5% were attenuated to 0.75 [0.51–1.10; P-value: 0.138] and 0.66 [043–1.01; P-value: 0.053] for incident CVD and CHD, respectively. The effect of weight loss > 5% was in opposite direction among those older versus younger than 60 years; with suggestive increased risk (not statistically significant) of incident CHD/CVD for the older group. Moreover, weight gain > 5% significantly reduced the risk of CHD only among those older than 60 years (P-value for interaction < 0.2). Furthermore, weight gain > 5% had an association with lower risk of CVD and CHD among sulfonylurea users (0.56 [0.32–0.98] for CVD and 0.54 [0.29–0.99] for CHD).ConclusionsOur results with a long-term follow-up showed that weight gain > 5% was associated with better CVD/CHD outcomes among Iranian participants with T2DM, especially older ones. Moreover, we did not find an unfavorable impact on incident CVD/CHD for sulfonylurea-induced weight gain.

Prevalence and correlates of suicidal behaviour among adults in Malawi: a nationally representative cross-sectional survey in 2017

BackgroundThe study aimed to assess the prevalence and associated factors of suicidal behaviour (SB) among adults in Malawi.MethodsData were analysed from 4187 persons aged 18–69 years (median age: 32 years) that took part in the nationally representative cross-sectional “2017 Malawi STEPS survey.”ResultsThe prevalence of ever suicide attempt was 0.8%, and the prevalence of SB (ideation, plan and/or attempt) in the past year was 7.9% (6.0% among men and 9.6% among women). In adjusted logistic regression analysis, among men, being 30 years and older and having an alcohol family problem were positively and obesity was negatively associated with SB in the past year. Moreover, in univariate analysis, early smoking initiation was positively and not using active transportation was negatively associated with SB in the past year. Among women, having an alcohol family problem, death from suicide of a close family member, having a cardiovascular incident (heart attack, stroke, or angina) and not using active transportation increased the odds of SB in the past year. In addition, in univariate analysis, low systolic blood pressure (< 100 mmHg), not taking antihypertensive medication, and current alcohol use were associated with past year SB.ConclusionAlmost one in ten participants engaged in SB in the past year and several associated factors were identified that can inform intervention programmes.

992-P: Early Menopause and Cardiovascular Disease Risk in Women with and without Diabetes

Background: Early menopause may be associated with higher cardiovascular disease (CVD) risk due to the early cessation of estrogens protection. The presence of diabetes (DM) coupled with early menopause may result in even greater CVD risk in postmenopausal women. We compared CVD risk in women with early vs. normal age menopause with and without DM. Methods: We pooled data from the Atherosclerosis Risk in Communities Study, the Multi-Ethnic Study of Atherosclerosis, and the Jackson Heart Study. Women with data on menopausal status, age at menopause and DM (yes/no) were included. We excluded pre- or peri-menopausal women, those with hysterectomy/oophorectomy or prevalent CVD. Outcomes were incident coronary heart disease (CHD), ischemic or hemorrhagic stroke, heart failure (HF), and a composite CVD outcome (CHD, stroke or HF). Cox models examined the risk associated with early (&amp;lt;45 yrs) vs. normal age (≥45 yrs) menopause. Covariates included baseline age, race, education, BMI, blood pressure, cholesterol, smoking, alcohol consumption, and hormone therapy use. Results: During a median follow-up of 15 yrs for 5964 postmenopausal women, 684 CHD, 434 stroke, 962 HF and 1535 CVD events occurred. In adjusted models, women with early menopause had elevated risk of CHD (Hazard ratio 1.12, 95% CI 1.03-1.22), stroke (1.09, 1.01-1.18) and HF (1.09, 1.00-1.19) compared to those with normal age menopause. DM was a significant effect modifier to the relationship between early menopause and CHD, stroke or CVD (P for interaction ≤0.05). HRs for early menopause and the outcomes were greater in diabetic than nondiabetic women (CHD 1.34, 1.02-1.78 vs. 1.10, 1.00-1.20; stroke 1.26, 0.98-1.61 vs. 1.07, 0.98-1.16; CVD 1.41, 1.01-1.95 vs. 1.04, 0.94-1.14). Conclusion: Early menopause increases risk for CVD in postmenopausal women; DM places this group at even higher CVD risk. Attention to CVD risk monitoring and management in women with early menopause, with and without diabetes, should be considered. Disclosure Y. Yoshida: None. Z. Chen: None. R. L. Baudier: None. M. Krousel-wood: None. A. H. Anderson: None. V. Fonseca: Consultant; Self; Abbott Diabetes, Asahi Kasei Corporation, Bayer Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Intarcia Therapeutics, Inc., Novo Nordisk, Pfizer Inc., Sanofi-Aventis, Stock/Shareholder; Self; Amgen Inc., Bravo4health, Mellitus Health. F. Mauvais-jarvis: None. Funding National Institutes of Health (K12HD043451)

Abstract P137: Association Of Equol Producing Capacity With Aortic Calcification In Middle-aged Japanese Men

Background: Soy isoflavones (ISFs) are regularly consumed in Japan and other Asian countries where some studies showed a significant inverse association of ISFs intake with incident coronary heart disease (CHD). However, a US randomized clinical trial did not find ISFs as anti-atherogenic. This discrepancy may be due to the higher capacity of people in Japan than in the US to produce equol, a metabolite of ISF by the gut microbiome. Equol may have greater anti-atherogenic properties than ISFs. It is unknown whether equol producers (EP), people who produce equol after consuming ISF, have lower aortic calcification (AC), a biomarker of atherosclerosis, as compared to non-EP. Aim: To determine the association between equol producing status and AC in Japanese men. Method: This cross-sectional, population-based study included 302 Japanese men aged 40-49, free of CHD. EP was defined as participants with serum levels of equol ≥20 nM. AC was measured in the entire aorta and quantified by the Agatston method. The presence of AC was defined as AC score ≥10. We analyzed the association between equol producing status and AC using the Tobit and the logistic regressions. Result: We observed 125 participants as EP. In multivariable analyses, EP had non-significantly lower AC score by 147 (95% confidence interval (CI): -386, 92) units and an odds ratio of 0.71 (95% CI: 0.40, 1.26) for the AC presence as compared to non-EP. As significant interaction of equol producing status with age was present, we stratified the analyses by the median age. In men aged 45-49 years, EP had non-significantly lower AC score by 246 units and a non-significant 0.62 times the odds of AC presence as compared to non-EP; the corresponding values in men aged 40-44 were 12 units and 0.91 times (Table). Such an association was not observed with serum ISFs (data not shown). Conclusion: Japanese middle-aged men who were EP had non-significantly lower AC than non-EP and such association was stronger in men aged 45-49 than 40-44 years. Further study with much larger sample size is warranted.

Association of Mid- to Late-Life Blood Pressure Patterns With Risk of Subsequent Coronary Heart Disease and Death.

Background: The elevated blood pressure (BP) at midlife or late-life is associated with cardiovascular disease and death. However, there is limited research on the association between the BP patterns from middle to old age and incident coronary heart disease (CHD) and death.Methods: A cohort of the Atherosclerosis Risk in Communities (ARIC) Study enrolled 9,829 participants who attended five in-person visits from 1987 to 2013. We determined the association of mid- to late-life BP patterns with incident CHD and all-cause mortality using multivariable-adjusted Cox proportional hazards models.Results: During a median of 16.7 years of follow-up, 3,134 deaths and 1,060 CHD events occurred. Compared with participants with midlife normotension, the adjusted hazard ratio for all-cause mortality and CHD was 1.14 (95% CI, 1.04–1.25) and 1.28 (95% CI, 1.10–1.50) in those with midlife hypertension, respectively. In further analyses, compared with a pattern of sustained normotension from mid- to late-life, there was no significant difference for the risk of incident death (HR, 1.15; 95% CI, 0.96–1.37) and CHD (HR, 1.33; 95% CI, 0.99–1.80) in participants with a pattern of midlife normotension and late-life hypertension with effective BP control. A higher risks of death and CHD were found in those with pattern of mid- to late-life hypertension with effective BP control (all-cause mortality: HR, 1.24; 95% CI, 1.08–1.43; CHD: HR, 1.65; 95% CI 1.30–2.09), pattern of midlife normotension and late-life hypertension with poor BP control (all-cause mortality: HR, 1.27; 95% CI, 1.12–1.44; CHD: HR, 1.53; 95% CI, 1.23–1.92), and pattern of mid- to late-life hypertension with poor BP control (all-cause mortality: HR, 1.49; 95% CI, 1.30–1.71; CHD: HR, 1.87; 95% CI, 1.48–2.37).Conclusions: The current findings underscore that the management of elderly hypertensive patients should not merely focus on the current BP status, but the middle-aged BP status. To achieve optimal reductions in the risk of CHD and death, it may be necessary to prevent, diagnose, and manage of hypertension throughout middle age.

Abstract 13711: Coronary Artery Calcium, Ankle-brachial Index, High Sensitivity C-reactive Protein, and a Family History of Coronary Artery Disease as Predictors of Incident Cardiovascular Events at Different Stages of Hypertension: The Multi-ethnic Study of Atherosclerosis

Background: Coronary artery calcium (CAC), ankle-brachial index (ABI), high-sensitivity CRP (hsCRP), and family history (FHx) of coronary artery disease (CAD) are used as complementary aids in cardiac risk stratification. The 2017 ACC/AHA hypertension guideline’s new Stage I hypertension group has created uncertainty regarding intensity of blood pressure (BP) treatment in this group. We evaluated the comparative utility of CAC, ABI, hsCRP and FHx CAD as risk predictors of cardiovascular (CVD) events within different BP strata. Methods: The MESA cohort was followed for a median of 13 years with regards to incident coronary heart disease (CHD) and CVD events. BP was categorized per ACC/AHA guideline: normal- &lt;120/&lt;80, elevated 120-129/&lt;80, stage I 130-139/80-89, and stage II ≥140/≥90. Participants on BP medications were assigned stage II. Cox regression was used to compare prediction of CHD and CVD events by CAC&gt;300, CAC&gt;75 t h %, ABI&lt;0.9, hsCRP&gt;2 mg/L and FHx CAD, stratifying by BP groups after adjusting for demographics, CVD risk factors and use of BP and cholesterol medications. Results: Of 6268 persons, 539 incident CHD events and 572 incident CVD events were noted. CAC&gt;300 and CAC&gt;75 th % predicted an increased CHD event risk throughout all BP groups. ABI&lt;0.9 was predictive of CHD events in stage I and II, while hsCRP was not predictive in any group. CAC&gt;300 predicted a 2-fold increased CVD risk in all BP groups after adjustment. In the Stage I group, CAC&gt;300, CAC&gt;75 th % and ABI&lt;0.9 showed additive predictive value in incident CHD and CVD events. Using the adjusted model to predict CHD survival, CAC&gt;300 had a consistently higher C-statistic throughout all BP categories compared to other risk markers. Conclusion: CAC&gt;300 was associated with increased CHD and CVD risk in all BP groups and demonstrated superior prognostic utility compared to other risk markers. CAC&gt;300, CAC&gt;75 th % and ABI&lt;0.9 showed potential as risk modifiers in the new Stage I hypertension group.

Abstract 13944: Biracial Proteomic Profiling Reveals Novel Candidate Pathways in Left Ventricular Hypertrophy and Incident Heart Failure Specific to Black Individuals

Background: Increased left ventricular (LV) mass is associated with future adverse cardiovascular events including heart failure (HF). Both increased LV mass and HF disproportionately affect black individuals. To understand the mechanisms that drive disease, particularly in black individuals, we undertook a proteomic screen in a black cohort and compared it to a white cohort. Methods: We measured 1305 plasma proteins using an aptamer-based proteomic platform (SOMAscan™) in 1772 black participants in the Jackson Heart Study (JHS) with available baseline LV mass as assessed by 2D echocardiography, as well as 1600 free of HF with follow-up assessment of incident cases. Mean follow-up time was 11 years; 152 cases of incident HF hospitalization were identified. Models were adjusted for age, sex, body mass index, estimated glomerular filtration rate (as calculated by CKD-EPI equation), systolic blood pressure, hypertension treatment, presence of diabetes, total/HDL cholesterol, prevalent coronary disease, and current smoking status. Incident HF models were also adjusted for incident coronary heart disease. We then compared protein associations in JHS to those observed in whites from the Framingham Heart Study (FHS) to examine significant differences. Results: In JHS, there were 112 proteins associated with LV mass and 10 proteins associated with incident HF hospitalization with FDR &lt;5%. Several proteins showed expected associations with both LV mass and HF, including N-terminal pro-BNP (β = 0.04 [0.02, 0.05], p = 1.0 x 10 -8 , HR = 1.46 [1.20, 1.79], p = 0.0002). The strongest association with LV mass was more novel: leukotriene A4 hydrolase (LKHA4) (β = 0.05 [0.04, 0.06], p = 2.6 x 10 -15 ). Conversely, Fractalkine/CX3CL1 showed a novel association with incident HF (HR = 1.32 [1.14, 1.54], p = 0.0003). While proteins like Cystatin C and N-terminal pro-BNP showed consistent effects in FHS, LKHA4 and Fractalkine were significantly different. Conclusions: We identify several novel biological pathways specific to black individuals hypothesized to contribute to the pathophysiologic cascade of LV hypertrophy and incident HF including LKHA4 and Fractalkine. Further studies are needed to validate these results and elucidate the detailed underlying mechanisms.

Abstract 14635: The Fib-4 Index is a Risk Factor for Incident Cardiovascular Disease in Urban Male Residents: The Suita Study

Introduction: The fibrosis index based on four factors (FIB-4 index) is a score that predicts liver fibrosis easily, quickly, and inexpensively, but there is little evidence of its relationship with the onset of cardiovascular disease in general population in Japan. Therefore, we examined the relationship between incident cardiovascular disease (CVD) by the FIB-4 index level in urban area residents. Methods: We studied 5,333 follow-up Japanese individuals (2,478 men, 2,855 women) with no history of CVD in the Suita Study. The platelet count was measured at the time of medical examination. The FIB-4 index was calculated using age (yrs), alanine aminotransferase (ALT, IU/L), aspartate aminotransferase (AST, IU/L), and platelet count (PLT, 10^9/L) as follow: FIB-4 index = (AST x Age) / (PLT x (square root of ALT)). The primary endpoint was CVD events, including stroke or ischemic heart disease. The risk of CVD was analyzed by the FIB-4 index level using the Cox proportional hazards model adjusted by the components of the ischemic heart disease risk score in the Suita Study. Results: The percentage of the FIB-4 index ≥2.67 in the 30s to 80s at the baseline survey was 0%, 1%, 2%, 7,%, 21%, 43% for men, and 0%, 0%, 1%, 5%, 16%, 39% for women, respectively. During the mean follow-up period of 9.3 years, 195 strokes and 137 ischemic heart diseases were observed. Based on men with FIB-4 index &lt;1.30, the adjusted hazard ratio (95% confidence interval) for incident CVD in men with FIB-4 index ≥2.67 was 1.91 (1.05-3.47), those for incident ischemic heart disease in men with FIB-4 index 1.30-2.66 and ≥2.67 were 2.49 (1.33-4.64) and 3.29 (1.32-8.16), respectively. Conclusion: The FIB-4 index was considered to be useful as a predictor of ischemic heart disease in urban men in Japan.

Abstract 13514: Gender-Stratified Difference in the Association Between Coronary Artery Calcium and Incident Peripheral Artery Disease: The Multi-Ethnic Study of Atherosclerosis

Introduction: Coronary artery calcium score (CACs) measured by non-contrast cardiac CT has a strong correlation with coronary atherosclerotic burden. Although CACs predicts incident coronary heart disease, its gender-specific association with incident peripheral artery disease (PAD) is not clear. Methods: The multi-ethnic study of atherosclerosis (MESA) is a prospective population-based cohort consisting of 6814 men and female free of overt cardiovascular disease at enrollment. In this study we included MESA participants with baseline CACs and at least one ankle brachial index (ABI) measured at follow up exams. We excluded participants with baseline ABI≤ 0.9 or&gt; 1.4. Incident PAD was defined as a follow up ABI≤ 0.9 and decline of ≥15%. Multivariable logistic regression models were deployed to evaluate the association between baseline CACs and incident PAD in female and male. Results: The mean age (SD) was 61.29 (9.96) years and 52.6% (3013/5725) were female. Female had lower baseline ABI [1.10 (0.08) vs 1.15 (0.09); p &lt; 0.001]. Over a median (IQR) of 9.23 (8.22-9.60) years, 113(4%) female and 85(3%) male developed PAD. Every one unit increase in log (CACs+1) was associated with 1.11-fold higher odds of incident PAD in male (p=0.001). This association remained significant after adjustment for demographics, traditional cardiovascular risk factor and baseline ABI. Male participants with CACs&gt;300 showed 1.94-fold higher odds of incident PAD compared to participant with CACs=0 (p=0.005). In female there was no statistically significant association between CACs and incident PAD in multivariable analysis. Conclusions: Baseline CACs is associated with future PAD independent of traditional cardiovascular risk factors in male participants of a multi-ethnic cohort. Disclaimer statement: The views expressed in this abstract are those of the authors and do not necessarily represent the views of the National Heart, Lung, and Blood Institute; the National Institutes of Health; or the U.S. Department of Health and Human Services.

Sex differences in the rates of incident and recurrent coronary heart disease and all-cause mortality

Abstract Background Women have lower age-specific rates of incident coronary heart disease (CHD) than men. However, it remains unclear whether women maintain the same advantage once they have had a cardiac event. Purpose To assess whether sex differences in the rates of cardiac events and all-cause mortality among individuals without a history of CHD persist following a myocardial infarction (MI). Methods We identified 171,897 women and 167,993 men &amp;lt;65 years of age with commercial health insurance and ≥66 years of age with government health insurance through Medicare who had a MI hospitalization between 2015 and 2016 in the US. These beneficiaries were matched to 687,588 women and 671,972 men without a history of CHD based on age and calendar year. Beneficiaries were followed until December 2017 for the occurrence of MI, CHD, heart failure, and all-cause mortality (Medicare only). Results The age-standardized rates of MI per 1,000 person-years were 4.5 in women and 5.7 in men without a history of CHD (multivariable-adjusted hazard ratio [HR] [95% confidence interval] of female sex: 0.64 [0.62; 0.67]) and 60.2 in women and 59.8 in men with a history of MI (HR: 0.94 [0.92, 0.96]) (Figure 1). Rates of CHD events in women vs. men were 6.3 vs. 10.7 among those without CHD (HR: 0.53 [0.51, 0.54]) and 84.5 vs. 99.3 among those with MI (HR: 0.87 [0.85, 0.89]). Heart failure hospitalization rates in women vs. men were 9.3 vs. 6.6 for those without CHD (HR: 0.93 [0.90, 0.96]) and 114.9 vs. 97.9 among those with MI (HR: 1.02 [1.00, 1.04]). All-cause mortality rates in women vs. men were 63.7 vs. 59.0 among those without CHD (HR: 0.72 [0.71; 0.73]) and 311.6 vs. 284.5 among those with a MI (HR: 0.90 [0.89, 0.92]). Conclusion The women advantage against MI, CHD, heart failure and all-cause mortality is considerably attenuated following a MI, suggesting that a prior MI puts women at almost the same high-risk of subsequent events as men. Figure 1 Funding Acknowledgement Type of funding source: Private company. Main funding source(s): This work was funded by an industry/academic collaboration between Amgen Inc. and University of Alabama at Birmingham.

Genome-wide association meta-analysis in 652,134 participants identifies 9 novel susceptibility loci for aortic stenosis

Abstract Background Aortic stenosis (AS) is the most common form of incident valvular heart disease. While valve replacement is effective, the absence of an approved medical therapy provides no alternatives to patients with contraindications or mild disease. An improved understanding of the genetics of AS could identify targets for pharmacological intervention. Methods An inverse variance-weighted, fixed effects meta-analysis of the association of 11,591,806 variants with AS was undertaken using data from 10 European cohorts totalling 652,134 participants (13,758 cases of AS). We queried publicly available datasets to characterize the functional consequences of genome-wide significant variants, conducted a phenome-wide association study to assess their association with other outcomes, and constructed polygenic risk scores to examine their association with AS. We also performed gene- and gene-set enrichment analyses, estimated genetic correlation with cardiovascular traits, and assessed whether five lipid or immunological biomarkers were causally associated with AS using Mendelian randomization. Results Eighteen independent variants at 16 loci attained genome-wide significance in the meta-analysis, including variants at all seven previously reported loci. Many of the significant variants were intronic or intergenic, and the phenome-wide association study revealed extensive pleiotropy with apolipoprotein B, C-reactive protein, and other cardiovascular and immunological traits. A weighted polygenic risk score composed of the 18 variants was strongly associated with AS (adjusted OR per SD, 1.38; 95% CI, 1.33 to 1.44; p=4.6×10–57), and improved the discriminatory ability for AS when added to a model that contained clinical risk factors (difference in the area under the curve p=2.0×10–11). Gene-based approaches indicated higher IL6R expression in the blood among AS cases compared to controls (p=3.1×10–6), and the association of LDLR with AS (p=2.3×10–10). Gene set analyses revealed that genes bound by the transcription factor TCF7 or micro-RNAs miR-21, miR-219, miR-491, and miR-19 were differentially expressed in the liver depending on AS status (p≤5.7×10–4), suggesting disease development may be mediated by tissue-specific transcriptional and post-transcriptional regulation. Mendelian randomization supported a causal association of five lipid and immunological biomarkers with AS, including low-density lipoprotein cholesterol (OR per mmol/L, 1.61; 95% CI, 1.48 to 1.75; p=1.3×10–30). Conclusions Evidence from large-scale genetic analyses indicate that lipid metabolism, inflammation, and calcification are key contributors to AS. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): Canadian Institutes of Health Research, National Institutes of Health