Incident Heart Research Articles

Dipeptidyl peptidase-4 inhibitor compared with sulfonylurea in combination with metformin: cardiovascular and renal outcomes in a propensity-matched cohort study

BackgroundTo determine the impact of dipeptidyl peptidase-4 inhibitor (DPP4i) on the risk of major cardiocerebrovascular and renal outcomes compared with sulfonylurea (SU) combined with metformin in patients with type 2 diabetes from a population-based cohort.MethodsFrom a nationwide cohort in Korea (2008–2013), 23,674 patients with type 2 diabetes treated with DPP4i plus metformin or SU plus metformin were selected and matched by propensity score. Composite cardiocerebrovascular events including incident ischemic heart disease (IHD), ischemic stroke (IS), hospitalization for heart failure (HHF), and cardiocerebrovascular death, as well as renal events including incident end-stage renal disease or initiation of renal-replacement therapy were assessed by Cox proportional-hazards models.ResultsDuring a median follow-up of 19.6 months (interquartile range 7.2–36.4), 762 composite cardiocerebrovascular events and 17 end-stage renal events occurred. There was no significant difference in the risk of IHD (hazard ratio [HR], 1.00; 95% CI 0.81–1.23), IS (HR, 0.95; 95% CI 0.74–1.23), or cardiocerebrovascular death (HR, 0.74; 95% CI 0.46–1.18) in the DPP4i group compared to that in the SU group. Likewise, DPP4i therapy was not associated with the risk of end-stage renal outcomes (HR, 1.23; 95% CI 0.41–3.62). However, the risk of HHF was significantly higher in the DPP4i group than in the SU group (HR, 1.47; 95% CI 1.07–2.04).ConclusionsThis real-world database analysis showed that DPP4i therapy did not increase the overall risk of major cardiovascular and renal outcomes compared to SU therapy. However, the DPP4i-associated risk of HHF remained significant.

Abstract P032: Soluble CD14 Level is a Coronary Heart Disease Risk Factor in Younger-aged Black Adults of the Reasons for Geographical and Racial Differences in Stroke (REGARDS) Study

Introduction: CD14 plays an important role in the innate immune response and promotes inflammation. Soluble CD14 (sCD14) is produced during an acute phase response and following cleavage from immune cell surfaces upon activation. Higher sCD14 may be a risk factor for cardiovascular disease, however prospective studies evaluating sCD14 with incident coronary heart disease (CHD) events are limited. We examined the association of sCD14 levels with incident CHD in black and white REGARDS participants. Methods: REGARDS enrolled 30,239 participants from across the contiguous U.S. in 2003-07. The cohort was 55% female and 41% black by design. In a nested case-cohort study, sCD14 levels were measured by ELISA in 612 participants with incident CHD and 856 in a cohort random sample; all were free of CHD at baseline. Using Cox proportional hazards models we calculated the hazards ratio (HR) of CHD for increasing sCD14, and studied interactions of sCD14 with age, sex, or race. Results: In models adjusted for Framingham risk factors, interaction terms for sCD14-by-race (p-interaction=0.02) and sCD14-by-age (p-interaction=0.02) were statistically significant but not for sCD14-by-sex (p=0.21). Stratified by race and age, each 1-SD higher sCD14 (442 ng/mL) was associated with an increased CHD risk in blacks but not whites (Table). Relationships were stronger in younger than older black participants. SCD14 was not significantly associated with CHD risk among white participants, but there was a trend for stronger relationships at younger ages. Conclusions: Higher sCD14 is associated with risk of CHD in blacks with greater risk at younger ages. These findings suggest sCD14 may be an important CHD risk factor among younger black adults.

Abstract P347: Lower Optimism is Associated With Heart Failure Readmissions

Introduction: Heart failure is one of the most common reasons for hospitalizations in the U.S. and within 30 days of discharge, nearly one in four patients have been readmitted. While optimism is associated with favorable cardiovascular outcomes, including incident coronary heart disease events and readmission post coronary artery bypass surgery, no data exist for the role of optimism in heart failure patients. Hypothesis: We assessed the hypothesis that optimism is associated with 30 day hospital readmission in heart failure patients. Methods: Optimism is measured using the revised Life Orientation Test (LOT-R) a brief, well-validated scale of optimism. This test was administered by convenience sampling to hospitalized adult (>18 years) heart failure patients to determine if low LOT-R scores (less optimistic) were associated with 30 day hospital readmission. Results: Patients in the lower quartile of optimism scores (or pessimistic) had a higher rate of all cause 30 day readmission compared with those in the highest quartile (p=0.0290). Conclusion: In a single center series of hospitalized heart failure patients, those patients with low optimism scores had a significantly higher all-cause 30 day readmission rate compared with those in the highest quartile of optimism scores. Optimism is trait-like yet may be modifiable, thus presenting an opportunity for intervention in heart failure.

Abstract P202: Serum Values of Branched-chain Amino Acids Predict High Triglycerides Among People Free of Diabetes. The Brazilian Longitudinal Study of Adult Health (ELSA-Brasil)

Introduction: Branched-chain amino acids (isoleucine, leucine, and valine) are associated with new-onset diabetes and incident coronary heart disease and stroke. However, the impact of elevated serum branched-chain amino acids on lipids and lipoproteins remains a matter of investigation. Hypothesis: branched-chain amino acids are independent predictors of dyslipidemia among people free of diabetes. Methods: We tested this hypothesis among 5060 men and women aged 35 to 74 years-old enrolled in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) with a 4-year follow-up. The variable of exposure was serum branched-chain amino acids measured in serum by proton nuclear magnetic resonance (1H NMR) spectroscopy at (LabCorp; Raleigh, NC). The outcome variables were LDL-C greater than 130 mg/dl; HDL-C lower than 40 mg/dl; triglycerides higher than 150 mg/ dl during the reappraisal examination. We excluded participants with any type of dyslipidemia at time of baseline, people who sustained a cardiovascular event, and those receiving lipid-lowering therapy or who had a diagnosis of diabetes. The definition of diabetes was self-reported or use of medicines for diabetes or plasma fasting glucose greater than 126 mg/Dl or 2-hour load plasma glucose greater than 200 mg/dl or glycated hemoglobin greater than 6.5 %. We applied Poisson regression to determine prevalence ratios for dyslipidemia according to a 1-standard deviation of branched-chain amino acids. The final model included age, sex, race, body mass index, waist circumference, a 4-year weight change, insulin resistance (measured by the product of fasting plasma glucose * serum insulin divided by 405), and glycated hemoglobin. Results: During the 4-year follow-up, 1373 participants met the criteria of study (median age 47 years; 67% women, 59% white), and 736 (53.6%) developed new-onset dyslipidemia: high triglycerides (120; 8.7%), low HDL-C (332; 24.2%), or high LDL-C (284; 20.7%) The combination of incident high triglycerides and low HDL-C was observed in 44 (3.2%) of participants. After the full adjustment for the covariates, the prevalence ratios (and 95% Confidence Interval) of new-onset dyslipidemia for 1-Standard Deviation (1-SD) of serum branched-chain amino acids were for high triglycerides = 1.25 (1.04 to 1.50), low-HDL-C = 1.08 (0.98 to 1.20), and for high LDL-C = 1.02 (0.91-1.14). The association between 1-SD of branched-chain amino acids and high triglycerides was present for women [1.27 (1.02 to 1.58), but not for men [1.18 (0.90 to 1.53)]. Analyzing separately for the amino acid, the prevalence ratio for high triglycerides for 1-SD of leucine was 1.34 (1.13 to 1.62); for 1-SD of isoleucine was 1.07 (0.90 to 1.28), and for 1-SD of valine was 1.16 (0.96 to 1.38). Conclusion: Serum values of branched chain amino acids are associated with incident hypertriglyceridemia among people free of diabetes.

Abstract 17237: Physical Inactivity, Mortality and Incident Coronary Heart Disease in Blacks: The Jackson Heart Study

Introduction: Despite reductions in overall mortality in recent decades, blacks continue to have higher death rates compared to whites. According to a recent CDC report, blacks were more likely to have a higher prevalence of unhealthy behaviors such as physical inactivity/sedentariness compared to whites. We assessed the associations between physical activity (PA) and incident coronary heart disease (CHD) and overall mortality in blacks in the Jackson Heart Study (JHS). Methods: Among the 5306 participants enrolled in JHS at baseline (2000-2004), we examined overall mortality through 2016, and among 3507 participants without prevalent CHD at baseline, clinically adjudicated incident CHD events (CHD hospitalizations and fatal myocardial infarction). Based on participant responses and the American Heart Association’s Life’s Simple 7 metrics, participants were classified as having poor (0 minutes/week), intermediate (&rt;0 and <75 minutes/week) or ideal (<=150 minutes/week) PA based on number of minutes of moderate of vigorous PA per week. Cox proportional hazard ratios (HR) were used to assess the relationships between PA categories and incident CHD and overall mortality. Results: Through 2016, there were 992 deaths (18.7% mortality rate) with higher rates in men (21.5%) compared with women (17.1%, p<0.0001). After adjustment for age, sex, education, systolic blood pressure, hypertension medications, diabetes, cholesterol, alcohol use and current smoking at baseline, poor PA was associated with increased mortality (HR 1.53, 95% CI 1.18, 1.98) compared to those with ideal PA. However, there was no significant difference in incident CHD events between those with ideal and poor PA (HR 1.05, 95% CI 0.66, 1.67). Compared with ideal PA, there was no significant difference in mortality in those with intermediate PA (HR 1.23, 95% CI 0.93, 1.62). Conclusions: In a large community-based cohort of blacks, lower PA was associated with higher overall mortality but was not associated with increased risk of incident CHD events.

Abstract P298: Combination of Systolic Blood Pressure and Non-HDL Cholesterol Categories Increased the Risk of Incident Latent Heart Failure: The Suita Study

Objective: There are few population based prospective studies on heart failure (HF) in non-Western populations. We hypothesized that the combination of systolic blood pressure (SBP) and non-HDL cholesterol (non-HDLC) categories affect the risk of incident latent HF (LHF) in a general Japanese population. Methods: We prospectively followed-up 2,774 Suita Study subjects (average age 66.7±10.4 years, initially free of LHF) for incident LHF. BP were taken as the average of the first and second measurements. Each subject was classified into an SBP category: normal SBP, <120 mmHg; systolic prehypertension (preHT), 120-139 mmHg; or systolic hypertension (HT), ≥140 mmHg or antihypertensive drug use. The subjects' non-HDLC levels were calculated by subtracting the HDLC from the total cholesterol. B-type natriuretic peptide (BNP) was measured by the CLEIA method. LHF was defined as BNP ≥100 pg/mL or HF medication from medical records. Each subject’s health status and BNP were checked in biannual medical examinations, and all subjects completed annual questionnaires. The endpoint of the follow-up period for incident LHF was whichever occurred first: the date of the first diagnosis of LHF, the date of the last examination, or December 31, 2017. We analyzed Cox proportional hazard ratios (HRs) and 95% confidence intervals (CIs) for incident LHF after adjusting for cardiovascular risk factors. Results: In 18,134 person-years of follow-up, 294 incident LHF events occurred. Compared to the normal SBP subjects, the adjusted HR (95% CIs) of incident LHF in the systolic HT subjects was 1.64 (1.16-2.30). The adjusted HR (95% CIs) of incident LHF per 20 mmHg of SBP was 1.18 (1.04-1.34). Compared to the normal non-HDLC (130-179 mg/dL) subjects, the adjusted HR (95% CIs) of incident LHF in the low non-HDLC (<130 mg/dL) subjects was 1.47 (1.15-1.88). Compared to the normal non-HDLC subjects with normal SBP, the adjusted HRs (95% CIs) of incident LHF in the normal non-HDLC subjects with systolic HT and low non-HDLC subjects with systolic preHT and HT were 1.53 (1.01-2.31), 1.76 (1.02-3.04), and 2.44 (1.58-3.76), respectively. Conclusion: This is the first demonstration that systolic preHT and low non-HDLC were positively associated with incident LHF in a general Japanese population.

Reduced risk of heart failure with intensified multifactorial intervention in individuals with type 2 diabetes and microalbuminuria: 21\xa0years of follow-up in the randomised Steno-2 study

Aims/hypothesisIn type 2 diabetes mellitus, heart failure is a frequent, potentially fatal and often forgotten complication. Glucose-lowering agents and adjuvant therapies modify the risk of heart failure. We recently reported that 7.8 years of intensified compared with conventional multifactorial intervention in individuals with type 2 diabetes and microalbuminuria in the Steno-2 study reduced the risk of cardiovascular disease and prolonged life over 21.2 years of follow-up. In this post hoc analysis, we examine the impact of intensified multifactorial intervention on the risk of hospitalisation for heart failure.MethodsOne hundred and sixty individuals were randomised to conventional or intensified multifactorial intervention, using sealed envelopes. The trial was conducted using the Prospective, Randomised, Open, Blinded Endpoints (PROBE) design. After 7.8 years, all individuals were offered intensified therapy and the study continued as an observational follow-up study for an additional 13.4 years. Heart-failure hospitalisations were adjudicated from patient records by an external expert committee blinded for treatment allocation. Event rates were compared using a Cox regression model adjusted for age and sex.ResultsEighty patients were assigned to each treatment group. Ten patients undergoing intensive therapy vs 24 undergoing conventional therapy were hospitalised for heart failure during follow-up. The HR (95% CI) was 0.30 (0.14, 0.64), p = 0.002 in the intensive-therapy group compared with the conventional-therapy group. Including death in the endpoint did not lead to an alternate overall outcome; HR 0.51 (0.34, 0.76), p = 0.001. In a pooled cohort analysis, an increase in plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) during the first two years of the trial was associated with incident heart failure.Conclusions/interpretationIntensified, multifactorial intervention for 7.8 years in type 2 diabetic individuals with microalbuminuria reduced the risk of hospitalisation for heart failure by 70% during a total of 21.2 years of observation.Trial registration:ClinicalTrials.gov NCT00320008.

N-terminal pro-B-type natriuretic peptide and microsize myocardial infarction risk in the reasons for geographic and racial differences in stroke study

BackgroundN-terminal pro B-type peptide (NT-proBNP) has been associated with risk of myocardial infarction (MI), but less is known about the relationship between NT-proBNP and very small non ST-elevation MI, also known as microsize MI. These events are now routinely detectable with modern troponin assays and are emerging as a large proportion of all MI. Here, we sought to compare the association of NT-proBNP with risk of incident typical MI and microsize MI in the REasons for Geographic and Racial Differences in Stroke (REGARDS) Study.MethodsThe REGARDS Study is a national cohort of 30,239 US community-dwelling black and white adults aged ≥ 45 years recruited from 2003 to 2007. Expert-adjudicated outcomes included incident typical MI (definite/probable MI with peak troponin ≥ 0.5 μg/L), incident microsize MI (definite/probable MI with peak troponin < 0.5 μg/L), and incident fatal CHD. Using a case-cohort design, we estimated the hazard ratio of the outcomes as a function of baseline NT-proBNP. Competing risk analyses tested whether the associations of NT-proBNP differed between the risk of incident microsize MI and incident typical MI as well as if the association of NT-proBNP differed between incident non-fatal microsize MI and incident non-fatal typical MI, while accounting for incident fatal coronary heart disease (CHD) as well as heart failure (HF).ResultsOver a median of 5 years of follow-up, there were 315 typical MI, 139 microsize MI, and 195 incident fatal CHD. NT-proBNP was independently and strongly associated with all CHD endpoints, with significantly greater risk observed for incident microsize MI, even after removing individuals with suspected HF prior to or coincident with their incident CHD event.ConclusionNT-proBNP is associated with all MIs, but is a more powerful risk factor for microsize than typical MI.

Abstract 23: Lower Heart Rate Variability Associated With Incident Coronary Heart Disease and Death in Post-Menopausal Women

Rationale: Lower heart rate variability (HRV) has been associated with increased all-cause mortality and adverse cardiovascular events including sudden death. The role of HRV in post-menopausal women is understudied. Therefore, we tested the hypothesis of a significant association between HRV and incident coronary heart disease (CHD) and CHD death in post-menopausal women. Methods: This is an analysis of prospective data collected during the Women’s Health Initiative (WHI) clinical trials. A total of 57,061 post-menopausal women were included. HRV was quantified using two variables; standard deviation of all normal-to-normal RR intervals (SDNN, milliseconds), and the root mean square of successive differences in normal-to-normal RR intervals (RMSSD, milliseconds). We used Cox proportional hazards models to test the association between HRV and incident CHD, hard CHD (including myocardial infarction and fatal CHD), and total CHD death. We controlled for age, race, alcohol use, physical activity, depression, BMI, smoking, diabetes, hypertension, lipid disorders, and family history of CHD. Results: The results are as highlighted for incident and hard CHD in table 1 and for CHD death in table 2. There were statistically significant associations between lower HRV (as a continuous variable and as quartiles) and higher levels of incident CHD. Conclusion: In post-menopausal women, lower HRV was associated with a modestly higher, but statistically significant, risk for incident cardiovascular events, including fatal and non-fatal myocardial infarction. Factors associated with lower HRV and cardiac autonomic impairment may be candidates for reducing CHD risk, such as better glycemic control and improved physical activity.

Abstract P039: Longitudinal measures of serial plasma phospholipid de novo lipogenesis fatty acids and incident congestive heart failure in older adults: The Cardiovascular Health Study

Introduction: De novo lipogenesis (DNL) is an endogenous pathway for converting excess carbohydrates and proteins into fatty acids (FAs). While elevated DNL is linked to several metabolic abnormalities, little is known about associations of longitudinal changes in DNL FAs with incident congestive heart failure (CHF), a growing condition in older adults. Methods: We investigated relations of longitudinal changes in DNL FAs, measured at year 0, year 6, and year 13, with incident CHF using serial measures of plasma phospholipid myristic acid (14:0), palmitic acid (16:0), 7-hexadecenoic acid (16:1n-9), palmitoleic acid (16:1n-7), stearic acid (18:0), oleic acid (18:1n-9), and cis-vaccenic acid (18:1n-7). Time-varying covariates were measured using standardized methods in 2,005 older adults with two or more FA measures and free of CHF at baseline. Incident CHF was centrally adjudicated using medical records. Risk was assessed by multivariable-adjusted Cox proportional hazards. Results: During 14,628 person-years, 553 CHF events occurred. After multivariate adjustment, serial changes in 16:0, 16:1n-9, and 18:1n-7 were positively associated with incident CHF, with HRs (95% CI) for each 30% change in levels of 2.84 (1.50, 5.37), 1.16 (1.00, 1.33), and 1.42 (1.15, 1.77), respectively ( Table ). Findings were similar in sensitivity analyses excluding individuals with prevalent coronary heart disease (not shown). In analyses evaluating absolute, rather than changes in, DNL FA levels, the associations of 16:0, 16:1n-9, and 18:1n-7 with incident CHF were no longer statistically significant although with consistent directions of association (not shown). Neither changes nor absolute levels of 14:0, 16:1n-7, 18:0, and 18:1n-9 were associated with CHF. Conclusion: Serial changes in plasma phospholipid 16:0, 16:1n-9, and 18:1n-7 were associated with an elevated risk of CHF in older adults. These results indicate that potential mechanisms of risk, especially related to DNL, deserve further investigation.

Abstract MP64: APOL1 Renal Risk Variants Associate With Heart Failure With Preserved Ejection Fraction in African-American Women

Introduction: African origin coding variants in APOL1 , encoding apolipoprotein L1, are strongly associated with various kidney diseases in African Americans, with odds ratio ranging from 7 to 89 for two renal risk allele carriers. APOL1 renal risk genotypes may influence risk for cardiovascular disease and mortality, but findings have been inconsistent. Hypothesis: Given that African-American aging women are at high risk for cardiovascular disease and stroke, we asked whether APOL1 risk genotypes affect these outcomes. Methods: We used data from 11,137 African-American postmenopausal women who participated in the Women’s Health Initiative prospective cohort, followed from enrollment (1993-1998) to 2014. APOL1 genotypes were obtained directly or by imputation from whole exome sequencing data. Adjudicated outcomes were incident coronary heart disease, stroke and subtypes, heart failure and subtypes, and overall and cause-specific mortality obtained from hospital records and death certificates. End-stage renal disease status (ESRD) was obtained from the US Renal Data System. We estimated incident rates for each outcome and used Cox proportional hazard to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the associations of APOL1 high and low risk groups with outcomes. Results: Mean age was 61.7 years. APOL1 high risk carriers (12.3% of participants) had higher prevalence of hypertension, use of cholesterol lowering medication, and reduced estimated glomerular filtration rate (eGFR), defined as &lt;60 mL/min/1.73 m 2 . After 11 years mean follow-up APOL1 high risk subjects had a higher incident rate of ESRD and hospitalized heart failure with preserved ejection fraction (HFpEF) than low risk carriers, but showed no difference in the incident rates of other outcomes. In adjusted models, there were a significant 43% increased hazard of ESRD (95% CI 1.01, 2.02), and a 58% increased hazard of hospitalized HFpEF (95% CI 1.03, 2.41) among high risk compared to low risk APOL1 carriers. In sensitivity analyses restricted to the genome-wide association sample and accounting for population stratification (n=7,797), the associations remained significant for HFpEF. These associations were no longer significant after adjusting for eGFR. Conclusions: We identified novel associations of APOL1 high risk status with hospitalization for HFpEF among postmenopausal women, which are likely mediated by APOL1 -induced chronic kidney disease. We also showed lack of association of APOL1 with incident coronary heart disease, stroke and mortality.

Abstract P046: Sex Hormone Levels and 10-Year Change in N-Terminal Pro-Brain Natriuretic Peptide Among Men and Post-Menopausal Women: The Multi-Ethnic Study of Atherosclerosis (MESA)

Background: The risk of cardiovascular disease (CVD) differs between men and women, and sex hormones are thought to play a key role. N-terminal pro-brain natriuretic peptide (NT-proBNP) is a sensitive biomarker of ventricular wall stress and a strong predictor of incident cardiovascular disease (CVD) and heart failure (HF). It can thus be seen as an early marker of CVD. We evaluated whether sex hormones levels were associated with change in NT-proBNP concentrations over 10 years in MESA. Methods: We studied 2348 men and 2041 post-menopausal women. Serum testosterone (T), estradiol, dehydroepiandrosterone (DHEA), and sex hormone binding globulin (SHBG) were measured at Exam 1 (2000-02); free T and bioavailable T were calculated. NT-proBNP was measured by Roche assay at Exam 1, plus Exam 3 (2004-05) and/or Exam 5 (2010-12). Multivariable-adjusted linear mixed effects models were used to study associations between sex hormone levels and change in NT-proBNP over an approximately 10-year period. Results: Mean (SD) age (years) at baseline was 65 (9) for women and 62 (10) for men. Women had higher NT-proBNP than men (median 76.6 vs 37.1 pg/ml). Among women, after adjusting for demographic, socioeconomic, and CVD risk factors, higher total T, bioavailable T, and free T were independently associated with a greater increase in NT-proBNP over 10 years, whereas estradiol and SHBG were inversely associated with change in NT-proBNP ( Table ). When sex hormones were analyzed together in the same model, total T was positively associated and SHBG was inversely associated with change in NT-proBNP. In men, higher estradiol was associated with greater 10-year increase in NT-proBNP. These associations were preserved after excluding individuals with ejection fraction &lt;50%. Conclusion: A more androgenic sex hormone profile in post-menopausal women and a more estrogenic profile in men were independently associated with 10-year change in NT-proBNP levels. Sex hormone patterns may thus explain in part sex differences in the development of CVD and HF.

Abstract P316: Multiple Vulnerabilities to Health Disparities and Incident Coronary Heart Disease in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study

Social determinants contribute to disparities in incident CHD but it is not known if they have an additive effect. We hypothesized that having more socially determined vulnerabilities to health disparities is associated with increased risk of incident CHD in the REGARDS study, a large biracial prospective cohort with physiological and survey measures. Experts adjudicated incident fatal and nonfatal CHD over 10 years of follow-up. Vulnerabilities included black race, low education, low income, and Southeastern US residence. The risks for CHD outcomes associated with 1, 2, and 3+ vs 0 vulnerabilities were calculated with Cox proportional hazards models adjusted for medical conditions, functional status, health behaviors, and physiologic variables. Of the 19,645 participants free of CHD at baseline (mean age 64 years, 57% women), 16% had 0 vulnerabilities, 36% had 1, 29% had 2, and 18% had 3+. Increasing numbers of vulnerabilities were associated with higher incidence (Figure) and risk of CHD that attenuated somewhat after multivariable adjustment (Table). These findings may provide a method of risk stratification useful for population health management.

Abstract 054: Diet Beverage Intake is Positively Associated With Incident Coronary Heart Disease in People With Type 2 Diabetes

Introduction: Diet beverages are calorie free beverages sweetened with non-nutritive sweeteners. People with diabetes are the highest per-capita consumers of diet beverages, tending to consume them as a replacement for dietary sources of sugar, especially in place of sugar sweetened beverages. This behavior is endorsed by dietetic and scientific organizations and diet beverages are marketed synonymously with better health, weight loss, and thus, are considered advantageous for diabetes control. The underlying public health concern is the lack of data to support or refute this concept. Hypothesis: Higher diet beverage intake is positively associated with incident Coronary Heart Disease (CHD) Methods: We pooled the data sets of the Atherosclerosis Risk in Communities (ARIC) study (1987-2014), Cardiovascular Health Study (CHS) (1989-2014), Framingham Offspring Study (FOS) (1995-2014), Jackson Heart Study (JHS) (2000-2012), and Multi-Ethnic Study of Atherosclerosis (MESA (2000-2013) to conduct a prospective examination of the association of diet beverage intake with the incidence of CHD among participants with clinically ascertained type 2 diabetes (T2D) without prevalent CHD and with valid dietary data (N=3,947). We carried out a 2-step meta-analysis using individual level, cohort-specific Cox regression analyses with identical adjustment for demographic, lifestyle, overall diet quality and clinical risk factors to generate effect estimates that were pooled together using fixed and random effects meta-analysis. Results: 1,046 participants developed adjudicated CHD during follow-up. There was a positive, graded association between diet beverage intake and risk of incident CHD (Table). Results were consistent by sex, race and age. Conclusions: Diet beverage intake is associated with increased risk of developing CHD in a population with T2D. These results suggest the need to further evaluate dietary recommendations related to diet beverages and consider their role in this high risk population.

Abstract P369: Relation of Breast Arterial Calcification With Ankle Brachial Index

Presence of breast arterial calcification (BAC) has been shown to be independently associated with increased risk of subclinical cardiovascular disease (CVD), angiographically-defined coronary disease and with incident coronary heart disease, stroke and heart failure. However, a relationship between BAC and peripheral vascular disease has not been established. The ankle brachial index (ABI) is an indicator of the severity of peripheral arterial disease (PAD) that predicts future CVD risk. We utilized cross-sectional data collected at the baseline examination (2012-15) of the MultIethNic Study of BrEast ARterial Calcium Gradation and CardioVAscular Disease (MINERVA Study), a cohort study of 5,145 post-menopausal women who were members of the Kaiser Permanente Medical Care Program of Northern California (KPNC) who were free of clinical CVD at baseline. Presence and gradation (in mg of calcium mass) of BAC in digital mammograms was ascertained with a validated densitometry method. ABI, the average of two ankle systolic pressure readings divided by the average of two brachial systolic pressure readings, was measured by trained and certified personnel after a ten-minute rest. A total of 3,693 women had complete data on all variables of interest; their mean (SD) age was 66 (4) years and 64% were white, 12% African-American, 14% Asian, 9% Latina and 1% mixed or other. While 28.2% presented with any detectable BAC (i.e., BAC mass &gt; 0 mg), 5.4% had an ABI &lt; 0.90. Three women had ABI&gt;1.40 and were excluded from analyses (none had BAC&gt;0). Prevalence of ABI &lt; 0.90 was 4.8% (27/2,653) in women with BAC=0 and 6.9% (72/1,040) in women with any detectable BAC. The Odds Ratio of ABI&lt;0.90 associated with any BAC was 1.39 (95% CI, 1.03-1.89) in a model adjusting for age and race/ethnicity, and was 1.38 (95% CI, 1.02-1.88) in a model with further adjustment for BMI, smoking status, diabetes, hypertension, LDL cholesterol, HDL cholesterol and hs-CRP. However, among women with any detectable BAC, standardized log_BAC mass (mg) was not significantly associated in bivariate linear regression analysis with ABI (slope=-0.0030 [SE=0.0031]; p=0.32). Our study demonstrates (for the first time) an independent association between presence of BAC and ABI indicative of PAD, with no apparent linear dose-response relationship.

Review and Hypothesis about Gout

The first identification about gout as clinical entity was made by the Egyptians in the year 2640 b.C. (Schwartz 2006). For many centuries it was not unveil the mystery of the origin of the illness. Gout is the unique pathology that belongs to the human race. When uric acid is deposited in the articulate tissue produce an intense inflammation, basic element in the development of gout. Interesting is the evidence of ultra sonographic signs of monosodium urate crystalline articulate deposits in 25% of clinically asymptomatic hyperuricaemic subjects (more than 8mg/ dL) [1], and approximately 9% of the joints without clinical signs of flogosis [2]. Large epidemiological studies have now demonstrated that gout is an independent risk factor for incident coronary heart disease, [3-6] heart failure, [7] stroke [8] peripheral artery disease [9] and death cardiovascular [10,11]. But, several meta-analyses have concluded that hyperuricaemia is an independent risk factor for coronary heart disease [12,13] and also, for the development of hypertension [14,15]. The standard diagnostic goal remains the identification of the typical birefringence of crystals of uric acid under polarized light microscope in the synovial fluid and in the aspirated material from the tophi [16,17]. Hyperuricaemia with or without urate deposit (modern denomination of the formerly called gout) is currently one of the most frequent dysmetabolic diseases.

Relation of Carotid Artery Plaque to Coronary Heart Disease and Stroke in Chinese Patients: Does Hyperglycemia Status Matter?

To examine the association of carotid artery plaque with the incident coronary heart disease and stroke events in Chinese patients and explore whether the association differs between patients with and without hyperglycemia. We evaluated plaque, and blood pressure, total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, fasting serum insulin, fasting plasma glucose, 2 h postprandial glucose and Homeostasis model assessment of insulin resistance in 253 Chinese patients. T-test and X2 test were used to compare the clinical characteristics and Binary logistic regression was applied to analyze the association of coronary heart disease and stroke between patients with and without hyperglycemia. Among 253 patients, 162 patients had hyperglycemia (i. e., diabetes, impaired glucose regulation and stress induced hyperglycemia) and 155 (61.3%) patients had plaque. Fasting plasma glucose, 2 h postprandial glucose and Homeostasis model assessment of insulin resistance, triglycerides, plaque were significantly higher in the hyperglycemia group than non-hyperglycemia. The incident coronary heart disease and stroke events in patients with plaque were 2.254 (95%CI,1.203-4.224) and 2.437 (95%CI,1.042-5.701) times higher than those without plaque, respectively. Among hyperglycemia subgroup, plaque was an independent risk factor for coronary heart disease (OR,3.075,95%CI,1.353-6.992) and stroke (OR,3.571,95%CI,1.460-8.737). The slopes (associations between coronary heart disease/stroke and plaque) were steeper in the hyperglycemia group than those in the non-hyperglycemia group (coronary heart disease OR,3.075 vs. 2.614; stroke OR,3.571 vs. 3.307). The incident coronary heart disease and stroke events in patients with plaque were higher than those without plaque, and this difference was more pronounced for patients with hyperglycemia vs. those without hyperglycemia.

Abstract 21023: Population Attributable Risk for Cardiovascular Disease Associated With Hypertension and Prehypertension in African Americans: The Jackson Heart Study

Introduction: African Americans are disproportionately affected by hypertension (HTN) and cardiovascular disease (CVD). Determining the population attributable risk (PAR) for CVD associated with HTN and prehypertension in African Americans can help inform policymakers and prioritize public health interventions. Methods: Among 3770 participants in the Jackson Heart Study without prevalent CVD, we used Cox-proportional hazard analysis adjusted for traditional CVD risk factors to determine the association of HTN and prehypertension with incident CVD and its components including coronary heart disease, heart failure, and stroke. The PAR was calculated as pd*(HR-1)/HR; where pd is the prevalence of the exposure and HR is the hazard ratio for the outcome associated with the exposure. HTN was defined as a systolic blood pressure (SBP) ≥140 mmHg, diastolic blood pressure (DBP) ≥90 mmHg, or self-reported antihypertensive medication use and prehypertension as SBP of 120 to 139 mmHg or DBP of 80 to 89 mmHg. Results: At baseline, 52.4% of the cohort had HTN and 77.1% had prehypertension or HTN. Over a median of 9.9 years follow-up, 349 (9.3%) participants developed CVD. The HR for CVD and PAR associated with HTN was 2.17 (95% CI 1.63, 2.89) and 0.28 (95% CI 0.20, 0.35), respectively (Table). The HR for CVD and PAR associated with HTN and prehypertension pooled together was 2.21 (95% CI 1.41, 3.47) and 0.42 (95% CI 0.25, 0.56), respectively. In the pooled group there were significant associations with incident coronary heart disease, heart failure, and stroke. Sex-specific sensitivity analysis demonstrated PAR for CVD associated with HTN and prehypertension was 0.40 (95% CI 0.07, 0.62) in men and 0.43 (95% CI 0.19, 0.61) in women. Conclusions: Approximately 40% of incident CVD is attributable to HTN and prehypertension among African Americans in the southeastern United States. Preventing HTN and prehypertension in this population is a major public health priority.

Long-Term Exposure to Road Traffic Noise and Nitrogen Dioxide and Risk of Heart Failure: A Cohort Study.

Background:Although air pollution and road traffic noise have been associated with higher risk of cardiovascular diseases, associations with heart failure have received only little attention.Objectives:We aimed to investigate whether long-term exposure to road traffic noise and nitrogen dioxide () were associated with incident heart failure.Methods:In a cohort of 57,053 people 50–64 y of age at enrollment in the period 1993–1997, we identified 2,550 cases of first-ever hospital admission for heart failure during a mean follow-up time of 13.4 y. Present and historical residential addresses from 1987 to 2011 were found in national registers, and road traffic noise () and were modeled for all addresses. Analyses were done using Cox proportional hazard model.Results:An interquartile range higher 10-y time-weighted mean exposure for and was associated with incidence rate ratios (IRR) for heart failure of 1.14 (1.08–1.21) and 1.11 (1.07–1.16), respectively, in models adjusted for gender, lifestyle, and socioeconomic status. In models with mutual exposure adjustment, IRRs were 1.08 (1.00–1.16) for and 1.07 (1.01–1.14) for . We found statistically significant modification of the –heart failure association by gender (strongest association among men), baseline hypertension (strongest association among hypertensive), and diabetes (strongest association among diabetics). The same tendencies were seen for noise, but interactions were not statistically significant.Conclusions:Long-term exposure to and road traffic noise was associated with higher risk of heart failure, mainly among men, in both single- and two-pollutant models. High exposure to both pollutants was associated with highest risk. https://doi.org/10.1289/EHP1272

P627Associations between very low concentrations of LDL-cholesterol and health outcomes in the reasons for geographical and racial differences in stroke (REGARDS) Study

Introduction: Recent findings have demonstrated the important contribution of inflammation to the risk of cardiovascular disease (CVD) in individuals with optimally managed low density lipoprotein cholesterol (LDL-C). We explored relationships between LDL-C, high sensitivity C-reactive protein (hsCRP) and clinical outcomes in a free-living US population. Methods: We used data from the REasons for Geographical And Racial Differences in Stroke (REGARDS), and selected individuals at “high risk” for coronary events with a Framingham Coronary Risk Score of >10% or atherosclerotic cardiovascular disease (ASCVD) risk >7.5% in order to explore relationships between low LDL-C ( 70 mg/dl [1.8 mmol/L]); hs-CRP <2 compared to ≥2 mg/L and clinical outcomes (all-cause mortality, incident coronary heart disease [CHD] and incident stroke). To assess the association between the LDL-C and hs-CRP categories and each outcome, a series of incremental Cox proportional hazards models were employed on complete cases. To account for missing observations, the most adjusted model was used to interrogate the data using multiple imputation with chained equations (MICE). Results: In this analysis, 6136 REGARDS high risk participants were included. In the MICE analysis, participants with high LDL-C (>70 mg/dl) and low hs-CRP (<2 mg/L) had a lower risk of incident stroke (hazard ratio [HR] 0.69, 0.47-0.997) incident CHD (HR 0.71, 0.53- 0.95) and CHD death (HR 0.70, 0.50-0.99) than those in the same LDL-C category high hs- CRP (≥2 mg/L). In participants with high hsCRP (≥2 mg/dL), low LDL-C (<70 mg/dL [1.8 mmol/L]) was not associated with additional risk reduction of any investigated outcome, but with the significant increase of all-cause mortality (HR 1.37, 1.07-1.74). Conclusions: In this high-risk population, we found that low hsCRP (<2mg/L) appeared to be associated with reduced risk of incident stroke, incident CHD and CHD death, whereas low LDL-C (<70 mg/dL) was not associated with protective effects. Thus, our results support other data with respect to the importance of inflammatory processes in the pathogenesis of CVD.