Incident Heart Research Articles

Abstract P042: Associations Between Echocardiographic Arterial Compliance and Incident Cardiovascular Disease in African Americans: The ARIC Study

Background: The stroke volume to pulse pressure ratio (SVPP), derived by echocardiography, is a validated estimate of arterial compliance. SVPP has been shown to predict fatal coronary disease in Europeans; however, its prognostic value in African Americans and associations with incident cardiovascular disease (CVD) are unknown. Methods: We analyzed a subset (N=2059) of African Americans (mean age 59 ± 6 years, 65% female) in the ARIC study, who were free of prevalent cardiovascular disease and imaged by echocardiography in 1993-1995. Echocardiographic arterial compliance was determined 2 ways: by the SVPP, and a simplified arterial compliance index (ACI). Stroke volume was calculated by multiplying the aortic velocity-time integral (VTI) with the cross-sectional area of the left ventricular outflow tract (CSA). Pulse pressure was derived by subtracting the diastolic from systolic blood pressure. SVPP = VTI*CSA /PP. The ACI was calculated using the VTI as a surrogate for stroke volume: ACI = VTI / PP, as 75% of echocardiograms were missing CSA. Cox regression was used to model associations between ACI and subsequent CVD (defined as first incident stroke, coronary event, or heart failure), after controlling for age, sex, body mass index, smoking, diabetes, hypertension, total cholesterol, and glomerular filtration rate. A complete-case sensitivity analysis of participants with measured CSA (N=519) was conducted, to compare ACI and SVPP hazard ratios of CVD. Finally, missing stroke volume measurements were imputed by Monte Carlo Markov Chains, and risks between simulated SVPP and CVD assessed. Results: Over a mean follow up of 13 ± 4 years, 544 participants (26%) developed CVD. The lowest (representing greater arterial stiffness) compared to highest ACI quartile was associated with increased CVD risk (HR=2.67, 95%CI: 1.97 - 3.63). For each 1-unit decrease in ACI quartile, the HR of CVD increased 39% (HR = 1.39, 95%CI: 1.26 - 1.53). In the complete case analysis, the CVD hazard ratio contrasting lowest to highest quartiles was 1.88 (95% CI: 1.12 - 3.17) for ACI, and 1.81 (95%CI: 1.10 - 2.99) for SVPP. Each 1-unit decrease in arterial compliance quartile increased HR of CVD by 30% (HR = 1.30, 95%CI: 1.10 - 1.54) for ACI, compared to 24% (HR = 1.24, 95%CI: 1.05 - 1.45) for SVPP. By multiple imputation, a 1-unit decrease in simulated SVPP quartile increased CVD risk 18% (HR = 1.18, 95%CI: 1.08 - 1.28). Conclusions: This is the first study to examine the prognostic value of echocardiography-derived arterial compliance in African Americans. We observed that the ACI and SVPP were associated with incident CVD in African Americans, after controlling for cardiac risk factors and anthropometry. Risks associated with SVPP, a validated measurement of arterial compliance, and the ACI, a novel simplified index, show close agreement in complete-case analyses of incident CVD in African Americans.

Abstract P346: Novel Protein Glycan Derived Marker of Systemic Inflammation is Associated with Incident Coronary Heart Disease and Ischemic Stroke

Background: Enzymatically glycosylated proteins participate in multiple cellular processes, with variations in their concentration implicated in innate immunity and chronic inflammation. In addition, most inflammatory proteins are enzymatically glycosylated. GlycA is a novel nuclear magnetic resonance (NMR) biomarker whose signal originates from the N-acetyl groups of N-acetylglucosmine and N-acetylgalatosamine moieties of protein glycans. We assessed the association of GlycA with both incident CHD and ischemic stroke and performed a comparative analysis with hsCRP. Method: GlycA was quantified by proton NMR spectroscopy (LipoScience, NC) and hsCRP by immunoturbidimetric assay (Denka Seiken) in 27 649 participants of the Women’s Health Study. During a median follow up of 17 years, 1 089 incident cases of CHD and 465 incident cases of ischemic stroke were confirmed. Results: GlycA correlated with LDL cholesterol (r = 0.17), HDL cholesterol (r = -0.27), triglycerides (r = 0.47), BMI (r = 0.41) and hsCRP (r = 0.61), all p<0.0001. Multivariable-adjusted HRs (95% CIs) for top versus bottom quartiles of GlycA were 1.78 (1.44-2.20) with CHD and 1.50 (1.11-2.03) with ischemic stroke respectively (p-trend for both ≤ 0.006); these associations were similar in magnitude to that obtained for hsCRP and were weakened but remained significant after adjustment for lipids. (Table) Further adjustment for hsCRP attenuated the associations which were no longer statistically significant (p-trend ≥0.40 for both CHD and ischemic stroke). Conclusion: A novel protein glycan derived biomarker, GlycA, was associated with a graded increase in the risk of both incident CHD and ischemic stroke in this prospective study of initially healthy women in a manner similar to hsCRP. Adjustment for hsCRP attenuated this association, consistent with a possible role for protein glycans in inflammation.

Abstract 11: Fructosamine and Glycated albumin with Risk of Coronary Heart Disease and Death

Background: HbA1c is the standard measure to monitor glucose control and is now used for diagnosis of diabetes. Fructosamine and glycated albumin are markers of short-term glycemic control that may add complementary information to HbA1c. However, the associations of fructosamine and glycated albumin with cardiovascular outcomes are uncharacterized. Methods: We measured glycated albumin and fructosamine in 11104 adult participants (792 with a history of diabetes) of the community-based ARIC Study without cardiovascular disease at baseline (1990-1992). We evaluated the associations of fructosamine and glycated albumin with incident coronary heart disease and total mortality. We compared these associations to those for HbA1c. Results: Baseline HbA1c was highly correlated with fructosamine (Pearson’s r =0.82) and glycated albumin (Pearson’s r=0.86). During over two decades of follow-up there were 1,032 new cases of coronary heart disease and 2,594 deaths. In Cox proportional hazards models adjusted for traditional cardiovascular risk factors, elevated baseline levels of fructosamine and glycated albumin were significantly associated with coronary heart disease and total mortality ( Figure ). After additional adjustment for HbA1c, the associations were attenuated but remained significant, particularly at diabetic levels of fructosamine and glycated albumin. The associations with death were J-shaped, with an elevation of risk also apparent at the lowest levels of each biomarker, as has been previously observed for HbA1c. Conclusions: The acceptance of new measures of hyperglycemia is partly dependent on establishing their association with long-term outcomes. We found that fructosamine and glycated albumin were associated with coronary heart disease and mortality and that these associations were similar to those observed for HbA1c. The elevated risk of death at very low levels of fructosamine, glycated albumin, and HbA1c deserves further examination.

O212 Predictive Value of Lipoprotein Parameters on the Risk of Chronic Kidney Disease in Patients with Coronary Heart Disease

R A L A B ST R A C T S contradictory results for the associations of sodium and potassium intake with CVD incidence, and these associations have not been investigated in patients with CKD. Objectives: To assess the prospective associations between urinary sodium and potassium excretion and CVD incidence among patients with CKD. Methods: The Chronic Renal Insufficiency Cohort Study (CRIC) is a prospective cohort study of 3,939 participants with CKD from seven locations in the United States. Dietary sodium and potassium intake are averaged from three 24-hour urine samples, and the ratios of sodium and potassium to urinary creatinine are used. Composite CVD is defined as incident myocardial infarction (MI), stroke, or congestive heart failure (CHF). CVD events are reported every six months and confirmed by medical record adjudication. Results: Over an average 6.5 years of follow-up, 660 CVD events occurred. The highest quartile (>199.5 mmol/1,374 mg) of the sodium-to-creatinine ratio had a hazard ratio (HR) of 1.58 (95% confidence interval 1.27, 1.97; p for trend across quartiles 69.8 mmol/1,374 mg) of the potassium-to-creatinine ratio had a HR of 1.61 (1.28, 2.03; p for trend across quartiles 0.0002) for composite CVD events compared to the lowest quartile ( 42.3 mmol/ 1,374 mg). When modeled continuously, every 100-mmol higher sodium to 1,374 mg creatinine ratio was associated with an increased HR of 1.23 (1.12, 1.35) for composite CVD events, 1.23 (1.11, 1.37) for CHF, 1.35 (1.11, 1.64) for stroke, and 1.12 (0.96, 1.32) for MI. In addition, every 50-mmol higher potassium to 1,374 mg creatinine ratio was associated with an increased HR of 1.27 (1.11, 1.44) for composite CVD events, 1.35 (1.17, 1.56) for CHF, 1.14 (0.82, 1.59) for stroke, and 1.03 (0.81, 1.32) for MI. Conclusion: Our study found that dietary sodium and potassium are both associatedwith an increased risk of CVD among patients with CKD. These findings suggest that reductions in dietary sodium and potassiummight reduce the incidence of CVD among patients with CKD. Disclosure of Interest: None Declared

Predictive value of midregional pro-adrenomedullin compared to natriuretic peptides for incident cardiovascular disease and heart failure in the population-based FINRISK 1997 cohort

Introduction. To examine whether midregional pro-adrenomedullin (MR-proADM) plasma concentrations predict incident cardiovascular outcomes in the general population. Natriuretic peptides (N-terminal pro-brain natriuretic peptide (NT-proBNP), B-type natriuretic peptide (BNP), and midregional pro-atrial natriuretic peptide (MR-proANP)) were analyzed for comparison.Material and methods. MR-proADM plasma concentrations and those of the natriuretic peptides were determined in 8444 individuals of the FINRISK 1997 cohort. Patients were followed for 14 years (median). Cox regression analyses, discrimination, and reclassification analyses adjusting for Framingham risk factors were performed to evaluate the additional benefit from MR-proADM.Results. MR-proADM concentrations significantly predicted all-cause death (hazard ratio highest quintile versus lowest 1.18, 95% confidence interval 1.08–1.28), stroke (1.20, 1.05–1.38), major adverse cardiac events (MACE) (1.27, 1.17–1.37), and heart failure (1.67, 1.49–1.87). MR-proADM remained associated with MACE, death, and heart failure even after additional adjustment for NT-proBNP and C-reactive protein. Adding MR-proADM to the Framingham risk factors significantly improved discrimination (P < 0.001 for C-statistics and integrated discrimination improvement) and risk reclassification for heart failure (net reclassification improvement 12.12%, P < 0.001).Conclusions. In a healthy general population sample of the FINRISK 1997 cohort MR-proADM significantly predicted all-cause death, MACE, and especially heart failure even beyond NT- proBNP. It also improved risk reclassification for heart failure.

Abstract P1-13-04: A comparison of cardiovascular outcomes in postmenopausal women treated with aromatase inhibitors versus tamoxifen in breast cancer

Abstract OBJECTIVE: Breast cancer treatment Phase III studies show that Aromatase Inhibitors (AI) provide a longer disease free survival period compared to tamoxifen although overall survival is not consistently improved. This suggests an increase in a competing risk. The purpose of this study is to determine if there is an increase in cardiovascular morbidity and mortality in postmenopausal women treated with AI versus those treated with tamoxifen. METHODS: Using a retrospective cohort study design all postmenopausal women with breast cancer from January 1, 2002 to December 31, 2010 were identified from the Manitoba Cancer Registry (MCR). Data from these patients was requested from the Manitoba Health administrative databases for exposure, comorbidity, and outcome variables. Specifically, Drug Program Information Network (DPIN) data from 2002 to the most recent data available to determine prescriptions filled for tamoxifen and AI as a measure of exposure to these drugs. Hospital separation abstracts, physician claims data, and DPIN were used to determine comorbidity as well as new events for cardiovascular disease. Four specific groups were identified for comparison with respect to the outcomes of interest: tamoxifen exposed, AI exposed, exposure to both and no exposure. The primary end point was cardiovascular outcomes, including incident coronary heart disease and stroke. RESULTS: There were 4729 postmenopausal women diagnosed with Stage I – III breast cancer within previously defined years. The numbers for those treated with AI, Tamoxifen or both were 1590, 1015 and 607 respectively. Excluding women with preexisting comorbidity of coronary heart disease (CHD) and stroke, a competing risk regression model found that tamoxifen at 1 year of use had a statistically significantly lower rate of CHD endpoints compared to AI (p 0.040). There was no difference in stroke incidence between the two groups. CONCLUSION: Tamoxifen appears to provide a protective affect against CHD. Aromatase Inhibitors may lead to an increase in cardiovascular morbidity and mortality which may explain the lack of overall survival benefits with it's use. In the future, Tamoxifen may be preferentially used in women with a significant cardiac history. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-13-04.

Change in Positive Affect During Outpatient Cardiac Rehabilitation Predicts Vital Exhaustion in Patients with Coronary Heart Disease

Vital exhaustion is an acknowledged psychosocial risk factor of incident coronary heart disease (CHD) and recurrent CHD events. Little is known about trajectories in vital exhaustion in patients with CHD and the factors predicting this change. We hypothesized that vital exhaustion would decrease during outpatient cardiac rehabilitation and that an increase in positive affect over time would be associated with decreased vital exhaustion at discharge from cardiac rehabilitation. We also explored the role of the patient's sex in this context. Vital exhaustion was reduced during outpatient cardiac rehabilitation, especially in patients who experienced an increase in positive affect over time (p < .001). This relationship was significant in men (p < .001) but not in women (p = .11).

Abstract P283: Associations of Adiponectin and Leptin with Incident Coronary Heart Disease and Ischemic Stroke in African Americans: The Jackson Heart Study

Background: In population studies leptin is directly associated with coronary heart disease (CHD) and ischemic stroke, but leptin’s proatherogenic properties in animal models are not clear. Opposite to leptin, adiponectin is atheroprotective in animal models but epidemiological investigations evaluating its role in cardiovascular disease (CVD) have been contradictory. Because the predictive significance of previously reported racial differences in adipokine levels remains unclear, we assessed the prospective association of the two adipokines with the risk of incident CVD events in African Americans (AA), known to have a high prevalence of cardiometabolic risk factors. Methods: Serum specimens from 5,108 AA Jackson Heart Study (JHS) participants without prevalent CVD at baseline examination (2000-2004) were analyzed by ELISA for adiponectin levels and by a radioimmunoassay method for leptin levels. Age-adjusted correlation coefficients and Cox proportional hazards regression models were used to estimate the associations of the two adipokines with incident CHD and incident ischemic stroke. Results: During 6.2 years average of follow-up, 164 incident CHD and 122 incident ischemic stroke events were documented. Among our study participants (63% women; mean age 54 ± 13 years), the mean (standard deviation, SD) was 6.14 (4.55) μg/mL in women and 4.19 (3.51) μg/mL in men for adiponectin and 37.54 (24.02) ng/mL in women and 11.30 (10.36) ng/mL in men for leptin. Adiponectin statistically significantly correlated with insulin resistance, as measured continuously by the homeostasis assessment model for insulin resistance, HOMA-IR (r = - 0.41 in women and r = - 0.30 in men) and with high-density lipoprotein cholesterol, HDL-cholesterol (r = 0.37 in women and r = 0.39 in men). Leptin significantly correlated with body mass index, BMI (r = 0.66 in women and r = 0.73 in men) and with HOMA-IR (r = 0.38 in women and r = 0.50 in men). After multivariate adjustment that included age, BMI, HDL-cholesterol, triglycerides, HOMA-IR, systolic blood pressure, hypertension medication, smoking and physical activity, adiponectin was marginally directly associated among women with incident CHD (HR = 1.27, 95% CI = 1.00 - 1.61 per 1 SD; p = 0.05), but not among men (p = 0.29). It was associated among women with incident stroke, HR = 1.36 (1.05 - 1.76) per 1 SD (p = 0.02), but not among men (p = 0.09). Leptin was not associated with incident CHD nor incident stroke. Conclusion: In the largest community-based cohort of African Americans, a higher adiponectin level was associated among women with a higher risk of incident stroke and marginally with a higher risk of incident coronary heart disease. Whether adiponectin harbors harmful properties, or it is produced in response to vascular inflammation to counter the atherosclerotic process, or the putative ’adiponectin resistance’ phenomenon acts, should be further investigated.

Abstract P316: Prehypertension and Incident Acute Coronary Heart Disease in the REasons for Geographic and Racial Differences in Stroke (REGARDS) Study

Objective: The independent prognostic value of prehypertension (preHTN) for incident coronary heart disease (CHD) remains unsettled. Using the REasons for Geographic And Racial Differences in Stroke (REGARDS) cohort study, we examined associations between preHTN and incident acute CHD and CVD death. Methods: REGARDS includes 30,239 black and white community-dwelling adults age 45 and older at baseline. Recruitment occurred from 2003-7, with baseline interviews and in-home data collection for physiologic measures. Follow-up is conducted by telephone every 6 months to detect events and deaths, which are adjudicated by experts. Systolic BP was categorized into &lt;120 mmHg (n=4385), 120-129 mmHg (n=4000), 130-139 (n=2066), and hypertension was categorized into controlled (&lt;140/90 mmHg on treatment) (n=8378), and uncontrolled (&gt;140/90 mmHg) (n=5364). Incident acute CHD was defined as definite or probable myocardial infarction (MI) or acute CHD death. CVD death was defined as acute CHD, stroke, heart failure or other cardiovascular disease related. Cox proportional hazards models estimated the hazard ratios (HR) for incident CHD by BP categories, adjusting for sociodemographics and CHD risk factors. Results: The 23,393 participants free of CHD at baseline were followed for a median of 4.4 years. Mean age was 64.1, 58% were women and 42% were black. There was a significant interaction between sex and BP categories, therefore analyses were stratified by sex. There were 252 non-fatal and fatal acute CHD events among women and 407 among men. Among women, compared with SBP&lt;120 mmHg, BP categories above SBP 120 mmHg were associated with incident CHD (adjusted HR for SBP120-129 mmHg=1.94 {95% CI 1.04-3.62]; SBP 130-139 mmHg=1.92 {0.95-3.87}; controlled HTN=2.16 {1.25-3.75}; uncontrolled HTN=3.25 {1.87-5.65}) in fully adjusted models. Among men, only uncontrolled HTN was associated with incident CHD (HR=1.55 {1.11-2.17}). Conclusion: In this sample, preHTN may be associated with incident CHD among women but not men.

Abstract 018: Egg Consumption and Risk of Cardiovascular Disease: Findings from Three Large Prospective US Cohort Studies of Men and Women

Background: Limiting dietary cholesterol intake is widely recommended for prevention of cardiovascular disease (CVD). Eggs are a major source of dietary cholesterol, but they also contain a variety of other nutrients. Several recent studies have examined egg intake and CVD with conflicting findings. Objective: To prospectively evaluate the association between egg intake and CVD risk in three large cohorts. Methods: Women and men from the Nurses’ Health Study (1980-2010; N=84,537), Nurses’ Health Study II (1991-2010; N=92,588), and Health Professionals Follow-up Study (1986-2010; N=42,815) were included if they were free of CVD and cancer at baseline. Egg intake was assessed every 4 years via validated food frequency questionnaire and evaluated in the following categories for frequency of consuming 1 egg: &lt;1/month (reference), 1-3/month, 1/week, 2-4/week, 5-6/week, 1+/day. Incident coronary heart disease (CHD) (nonfatal myocardial infarction (MI) and fatal coronary disease) and stroke cases were ascertained via self-report and confirmed with review of medical records. Relative risks (HR) and 95% confidence intervals (CI) for CVD risk across categories of egg intake were estimated using multivariate Cox proportional hazards models, adjusted for age, race, smoking, physical activity, BMI, family history of CVD, alcohol, red and processed meat, whole milk, and other dietary covariates. Individual cohort estimates were combined using fixed effects meta-analysis. Results: We identified 5,838 incident cases of CHD (nonfatal MI and fatal CHD) and 6,030 stroke cases. Consumption of up to 1+eggs/day was not significantly associated with risk of incident total CVD (CHD and stroke) after adjustment for several diet and lifestyle factors (HR (CI) by category: &lt;1/month: 1(reference); 1-3/month: 0.95(0.88, 1.02); 1/week: 0.85(0.79, 0.91); 2-4/week: 0.88(0.81, 0.96); 5-6/week: 0.96(0.84, 1.09); 1+/day: 0.99 (0.87, 1.13) (p-trend=0.77). When incident stroke and CHD were evaluated individually, egg intake was not associated with either endpoint (p-trend=0.09 for CHD and 0.52 for stroke). Conclusions: After controlling for lifestyle and dietary factors, egg intake (up to 1+/day) was not associated with increased risk of CVD in three prospective cohorts of men and women.

Abstract MP13: Circulating Long-chain Monounsaturated Fatty Acids and Cardiac Structure and Function

Background: We previously observed a prospective association of higher levels of plasma phospholipid long-chain monounsaturated fatty acids (LCMUFA, 22:1 and 24:1 fatty acids) with higher risk of incident congestive heart failure (CHF) in two independent cohorts: the Cardiovascular Health Study (CHS) and Atherosclerosis Risk in Communities Study. This is consistent with decades-old animal experiments demonstrating cardiotoxicity of LCMUFA, including cardiac lipid accumulation and dysfunction. However, relationships of LCMUFA to cardiac structure and function in humans are unknown. Aim: to evaluate associations of circulating LCMUFA with indices of cardiac structure and function including left-ventricular mass (LVM), LV hypertrophy (LVH), LV wall thickness, and systolic and diastolic function. Methods: We evaluated 2,220 CHS participants (age=74.6±5.0) in whom plasma phospholipid LCMUFA were measured in 1992 and M-mode echocardiography was performed in 1996. Primary outcomes were LVM index (LVM / height to the 2.7th power), LVH (LVM / height, &gt;143 g/m for men and &gt;102 g/m for women), LV wall thickness (average of posterior and septal wall thickness), systolic function (% fractional shortening), and diastolic function (ratio of early to atrial ventricular filling velocities, E/A ratio). Adjusting for sociodemographics, lifestyle factors, dietary factors, and prevalent cardiovascular diseases, we performed linear regression analyses to examine associations of 22:1 and 24:1 levels with each continuous outcome. For LVH (a common binary outcome), Poisson regression analysis was performed. Results: Mean±SD plasma phospholipid levels of 22:1 and 24:1 were 0.03±0.01 and 1.96±0.44 percent of total fatty acids. Across the interdecile range, higher levels of 22:1 and 24:1 were each associated with lower fractional shortening by 1.2% (95% confidence interval=0.1-2.3%, p=0.03) and 1.4% (0.2-2.7%, p=0.02), respectively. Higher levels of 22:1 and 24:1 were also associated with higher risk of LVH by 27% (0-62%, p=0.05) and 40% (5-86%, p=0.02), respectively. LCMUFA were not associated with LVM index, LV wall thickness, or E/A ratio (p&gt;0.1 each). Findings were similar after excluding 410 adults with prevalent coronary heart disease or CHF. Conclusions: Higher circulating levels of plasma phospholipid 22:1 and 24:1 were associated with two indices of lower systolic function and greater risk of LVH, but not with other indices. These findings, if replicated, suggest mechanistic pathways whereby LCMFUA exposure may increase CHF risk and potentially inform future prevention efforts.

Abstract MP87: Major Life Events and Social Strain are Associated with Incident Coronary Heart Disease: Results from the Women’s Health Initiative (WHI)

Background: Despite the longstanding notion that psychosocial stressors are associated with higher CHD risk, findings from epidemiologic studies are mixed. Recent research suggests positive associations may be driven by angina pectoris, a condition more susceptible to reporting bias, rather than MI. We assessed associations of major life events (MLE) and social strain with incident CHD defined as the first occurrence of clinical MI, definite silent MI, or death due to definite or possible CHD. We also examined whether these relationships were mediated by several health behaviors. Methods: WHI participants (baseline ages 50-79) with complete data on all covariates were included. Baseline MLE scores were calculated and broken into quartiles based on the occurrence of 11 different life events in the past year and the extent to which each event upset them. Baseline social strain was assessed with four questions and divided into tertiles. Mean follow-up time was 11.2 years. Cox proportional hazard models were used to separately estimate associations of MLE and social strain with incident CHD. Structural equation modeling was used to quantify mediation by health behaviors (current smoking, heavy alcohol use, poor diet, and physical activity) measured at baseline and Year 3. Results: Greater MLE and social strain were positively associated with incident CHD. Health behaviors accounted for 30.1% of the association between highest (vs. lowest) MLE category and incident CHD and 23.0% of the high (vs. low) strain-CHD relationship. Current smoking was the strongest mediator for both MLE (23.6%) and strain (16.3%), followed by physical activity (4.6% each) and poor diet (2.1% and 2.6%, respectively). Conclusions: We found MLE and social strain were both associated with incident CHD, and that these relationships were mediated by the same set of health behaviors. However, a substantial proportion of these associations were not explained by health behaviors alone, suggesting alternative pathways need to be explored.

Abstract P114: Association of Psychosocial Wtress with Incident Coronary Heart Disease and All-cause Mortality among Low and High Income Individuals in the REasons for Geographic and Racial Differences in Stroke (REGARDS) Study

Introduction: Stress may increase risk for coronary heart disease (CHD) and death, especially for individuals living in poverty. Few prospective studies have examined the relationships between stress, CHD and mortality among minorities, who are more likely to be poor. We studied the association of perceived stress with incident CHD and mortality in a large biracial cohort. Methods: REGARDS includes 30,239 community-dwelling black and white participants age &gt;45 years recruited from 2003-07. Recruitment oversampled the Stroke Belt and Buckle and included residents of 48 states. Participants were telephoned every 6 months for CVD endpoints, with retrieval of medical records, death certificates, interviews with next-of-kin, and expert adjudication. CHD was defined as definite or probable myocardial infarction or CHD death. Stress was assessed using the 4-item Cohen’s Perceived Stress Scale (PSS). Among participants free of CHD at baseline, Cox models estimated hazard ratios for incident CHD and all-cause mortality through 12/31/2009, adjusting for socioedemographic, clinical, and behavioral CHD risk factors, and testing for interactions by race and income. Results: The analytic sample included 24,439 subjects with mean age 64.1 years (SD+9.3), with 58% women and 42% blacks. Over a mean follow-up of 4.2 (maximum 6.9) years, there were 659 incident acute CHD events and 1320 deaths. Analyses were stratified by income (Table) due to significant interactions with stress; no significant interactions were found by race. The highest quartile of stress was associated with higher risk for incident CHD among those with low income (HR 1.36, {95% CI 1.04, 1.78}) but not high income (HR 0.82, {95% CI 0.57, 1.16}). This relationship was slightly attenuated with full adjustment. Each increasing quartile of stress was associated with increasingly higher risk of death for those with low but not high income. Conclusion: Stress may confer greater risks of CHD and death for individuals with low but not high income.

Abstract P050: Glycated Hemoglobin Versus Fasting Glucose in Defining Metabolic Syndrome and Prediction of Coronary Heart Disease

Introduction. Fasting glucose (FG) is part of the Adult Treatment Panel III (ATP III) criteria for defining the metabolic syndrome (MetS). Glycated hemoglobin (HbA1c) is a measure of 2-3 month endogenous glucose exposure and is now recommended for diabetes diagnosis and screening for high-risk individuals. The aim of this study was to evaluate if replacing FG with HbA1c to define MetS improves prediction of incident coronary heart disease (CHD) in the Atherosclerosis Risk in Communities (ARIC) cohort. Methods. We included 11,194 ARIC participants without diabetes (based on diagnosis, medication use, FG ≥126 mg/dL, or HbA1c ≥6.5%) or prevalent CHD at baseline (1990-92). Cox proportional hazards models (adjusted for age, race, and study center) were used to compare the association between MetS defined using HbA1c (5.7-6.4%) or FG (100-125 mg/dL, based on ATP III guidelines) and risk of CHD (defined by myocardial infarction or fatal CHD, event data available through 2009). Results. Study participants had a mean age at baseline of 57 years, 43% were male, and 79% were white; median follow-up time was 16 years. Thirty-four percent of the study population had both normal FG (&lt;100 mg/dL) and HbA1c (&lt;5.7%), 37% had elevated FG and normal HbA1c, 4% had normal FG and elevated HbA1c, and 25% had both elevated FG (100-125 mg/dL) and HbA1c (5.7-6.4%). The association of combined FG and HbA1c categories with incident CHD are shown in the Figure. The adjusted hazard ratio predicting for incident CHD from MetS status was 1.43 (95% CI: 1.25-1.63, c-statistic: 0.61) using FG in the definition of MetS and 1.69 (95% CI: 1.48-1.93, c-statistic: 0.62) in the model replacing FG with HbA1c. Conclusions. Incorporating HbA1c into the definition of the MetS may help in identifying individuals who should be targeted for aggressive CHD risk factor reduction. Additionally, HbA1c may be useful clinically and in research settings for identifying individuals with MetS in cases where FG measures are not available.

THE PRO-DIABETIC IMPAIRED FASTING GLUCOSE IN NON-DIABETIC PEOPLE IS “ATHEROPROTECTIVE”, ONLY TO BE MODIFIED BY METABOLIC SYNDROME

Whether impaired fasting glucose (IFG) confers modest cardiovascular risk is controversial and needs further exploration. A non-diabetic population-based sample was studied at 8.5 years follow-up for incident diabetes and coronary heart disease (CHD), using stratification by presence of metabolic

2224 – Assessment of depression and anxiety following myocardial infarction

Introduction Studies indicate that about 20% of patients experience depression after acute Myocardial infarction (MI) and that the presence of depression is associated with increased risk for recurrent hospitalization and death. Anxiety seemed to be an independent risk factor for incident Coronary heart disease (CHD) and cardiac mortality. CHD death rates vary with age, gender and socio-economic status. Heart attack patients feel a wide range of emotions including depression, fear and anger, for about two to six months post-MI. Objectives Examine a level of depression and anxiety in patients after acute MI compared to outpatient control group according to age, gender and education. Methods Patients (n = 60) were assessed on demographic and clinical variables and completed the Beck Depression Inventory (BDI). The State - Trait Anxiety Inventory for Adults (STAI) within the first week of hospital admission for acute MI. The STAI has forty questions with a range of four possible responses to each. Patients with a positive depression score should be interviewed more extensively to confirm or rule out depression. Results Significant anxiety and depressive symptoms were present in patients with MI compared to the healthy controls. Significant differences between anxiety and depression were found according to gender and age. According to education there were no substantive differences in either sample. Conclusion It appears that anxiety after MI a universal phenomenon. In future trials the cause effect relationships between depression, anxiety and adverse health behaviors in patients with coronary artery disease need to be clarified.

Abstract 469: Vitamin D Deficiency Potentiates Restenosis Following Coronary Angioplasty in Hypercholesterolemic Swine

Introduction: Vitamin D is a sectosteroid that functions through vitamin D receptor (VDR), a transcription factor, which regulates various downstream signaling pathways and controls the transcription of many targets genes. Vitamin D deficiency is associated increased risk of incident congestive heart failure, myocardial infarction, and cardiovascular disease mortality. However, most of the studies which identified an association between lower vitamin D intake or lower 25-hydroxyvitamin D and increased risk of cardiovascular disease are observational or cross-sectional studies. There has been no careful study evaluating the effect of vitamin D supplementation on coronary artery disease outcome following coronary intervention. Objective: The purpose of this study was to examine the effect of vitamin D deficiency and vitamin D supplementation on coronary artery restenosis following balloon angioplasty in hypercholesterolemic Yucatan microswine. Methods: Twelve female microswine were fed vitamin D-deficient or vitamin D-sufficient high cholesterol diet. At six months, animals underwent coronary angioplasty. Following coronary intervention swine in the vitamin D-sufficient high cholesterol diet group received supplementation of 1,000 IU or 3,000 IU of vitamin D3. Six months later, angiogram was performed followed by optical coherence tomography to monitor the development of intimal hyperplasia and restenosis. At the end of 12 months animals were euthanized, coronary arteries were harvested and morphological and histological studies were performed. Results: Findings from the optical coherence tomography and histomorphometric studies showed a significant decrease in neointimal hyperplasia, increase in in-segment lumen diameter, and decrease in the intima-media ratio in coronary arteries following balloon angioplasty in swine with vitamin D supplementation compared to the animals with vitamin D-deficient status. In the in-vitro studies, calcitriol inhibited proliferation of coronary artery smooth muscle cells. Conclusion: These data suggest that vitamin D deficiency increases intimal hyperplasia and restenosis following coronary balloon angioplasty in hypercholesterolemic swine. Since vitamin D inhibits smooth muscle cell proliferation, supplementation of non-secosteroidal VDR ligands prior to coronary intervention could help in preventing the neointimal formation and restenosis.

Abstract 166: Small Dense LDL Cholesterol Is Associated with Risk for Coronary Heart Disease: The Atherosclerosis Risk in Communities (ARIC) Study

Background— Evidence from in vitro studies indicates that small dense LDL (sd-LDL) is more atherogenic than large buoyant LDL. Previously, sd-LDL has been associated with risk for vascular disease. However, the lack of a standardized sd-LDL assay has hampered its clinical application. Objectives— We tested the hypothesis that elevated plasma sd-LDL-cholesterol (sd-LDL-C) level is associated with risk for incident coronary heart disease (CHD) and stroke in the ARIC cohort. Methods— Plasma sd-LDL-C was measured in 11,419 men and women of the biracial ARIC study using a newly developed automated homogeneous assay. A proportional hazards model was used to examine the relationship between sd-LDL-C, vascular risk factors, and risk for CHD events and stroke over a period of ≈10 years. Results— Mean plasma sd-LDL-C was higher in Caucasians than in African Americans (45.2 vs. 37.4 mg/dL, p&lt;0.0001). Plasma sd-LDL-C levels were strongly correlated with an atherogenic lipid profile and were higher in diabetics vs. non-diabetics (49.6 vs. 42.3 mg/dL, p&lt;0.0001, respectively). sd-LDL-C was associated with incident CHD in a basic model as well as a model that included traditional risk factors and hs-CRP with hazard ratios (HRs) of 1.99 (95%CI: 1.68-2.36) and 1.56 (95%CI: 1.26-1.93) for the highest vs. the lowest quartile, respectively (Table). We did not find a significant association of sd-LDL-C with risk for stroke (Table). Conclusions— sd-LDL-C is associated with incident CHD but does not predict risk for stroke in ARIC participants. Further studies will need to determine whether sd-LDL-C will add value beyond traditional risk factors to cardiovascular risk assessment in clinical practice.

Abstract 025: Multidetector Computed Tomography Adipose Tissue Depots and Incident Cardiovascular Disease

Introduction: Ectopic fat depots may play a role in obesity-mediated cardiovascular disease (CVD). We tested the association of several distinct fat depots and incident CVD in an asymptomatic community-based sample. Methods: Participants from the Framingham Heart Study (n=3086, 49% women, mean age 50.2 years, free of CVD at baseline) underwent volumetric assessment of multiple fat depots using multidetector computed tomography from 2002–2005, and were followed longitudinally for CVD events. Fat depots included subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), pericardial adipose tissue, intra-thoracic adipose tissue and thoracic periaortic adipose tissue (TAT). Adipose volumes were standardized within sex to a mean of 0 and a standard deviation of 1. Cardiovascular events included coronary heart disease (myocardial infarction, coronary insufficiency or angina), cerebrovascular disease (stroke or transient ischemic attack), intermittent claudication, heart failure or CVD death. Using Cox proportional hazards regression models, we examined the association of each fat depot with the risk of CVD after adjustment for age, sex, systolic blood pressure, hypertension treatment, diabetes, total cholesterol, high-density lipoprotein cholesterol, smoking, and then additionally for BMI. We additionally examined the association of pericardial fat and incident coronary heart disease. Results: During a mean follow-up of 4.7 years, 90 CVD events occurred. After multivariable adjustment, VAT, VAT/SAT ratio, intra-thoracic fat and TAT were significantly associated with incident CVD events. The hazard ratios (95% confidence intervals) per each standard deviation higher were 1.37 (1.10–1.71, p=0.006 [VAT]), 1.30 (1.05–1.60, p=0.02 [VAT/SAT ratio]), 1.28 (1.03–1.59, p=0.03 [intra-thoracic fat]), and 1.30 (1.03–1.67, p=0.03 [TAT]), respectively. We observed no association between BMI (HR 1.15, 0.92–1.43, p=0.21), SAT (HR 1.13, 0.90–1.42, p=0.28) or pericardial fat (HR 1.14, 0.95–1.37, p=0.15) and incident CVD. After additional adjustment for BMI, VAT, VAT/SAT ratio and TAT remained significantly associated with incident CVD events [HR 1.44 (1.08–1.92, p=0.01 [VAT]), 1.34 (1.08–1.65, p=0.007 [VAT/SAT ratio]), and 1.31 (1.03–1.67, p=0.03 [TAT])], respectively. Pericardial fat was also not associated with incident coronary heart disease, even when limiting our events to myocardial infarction or coronary heart disease death (HR 0.97, p=0.81). Conclusion: Several distinct ectopic fat depots, including VAT, VAT/SAT ratio, intra-thoracic fat, and TAT, but not generalized obesity, are significantly associated with CVD events after adjustment for risk factors in our community-based sample. These findings support the growing recognition of several potentially pathogenic ectopic fat depots.

Abstract 006: Relationship of Sedentary Behavior and Physical Inactivity to Incident Coronary Heart Disease: Results from the Women's Health Initiative

Background: Sedentary behavior, such as prolonged sitting, is becoming recognized as a distinct construct that may not merely reflect lack of leisure-time physical activity (PA), usually defined as physical inactivity. Our objective was to examine the independent and joint associations of sedentary time and physical inactivity with risk of incident coronary heart disease (CHD) in women. Methods: This study included 84,798 post-menopausal women, aged 50-79 and free of CHD at baseline, participating in the Women's Health Initiative Observational Study. At baseline, participants reported information on sedentary behavior, defined as hours of sitting and lying per day, and usual PA, defined as energy expenditure from recreational activity including walking, mild, moderate and strenuous PA. Participants were followed from the baseline visit through September 2010 for first occurrence of CHD (MI and CHD death). Cox regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for incident CHD according to tertiles of sedentary time (hrs/day) and physical activity (MET-hrs/wk). Results: Sedentary time ≥10 hrs/day was associated with increased CHD risk (HR=1.13, 95% CI 1.04,1.23) in age-adjusted models, but was non-significant in multivariable-adjusted models (HR=1.08, 95% CI 0.99,1.17). In multivariable-adjusted models, the HR of CHD comparing moderate (5.1 - 16.25 MET-hrs/wk) and low (≤ 5 MET-hrs/wk) levels of PA to high (&gt;16.25 MET-hrs/wk) levels were 1.10 (95%CI 1.01,1.21) and 1.21 (95%CI 1.11,1.32), respectively (P for trend &lt;.0001). When we cross-classified women by sedentary time and PA (P for interaction = 0.91), CHD risk was significantly increased only in women with low PA regardless of their sedentary behavior, with the greatest risk seen in women reporting low PA and ≥10 hrs/day of sedentary time. Conclusion: Physical inactivity is associated with increased CHD risk in a dose-response manner, whereas sedentary behavior was only modestly associated with CHD risk in this analysis. Physical Activity (MET-hours/week) Sedentary Time (hours/day) High (&gt; 16.25) Moderate (5.1 - 16.25) Low (≤ 5) ≤6 1.00 (Referent) 1.12 (0.96, 1.30) 1.17 (1.01, 1.36) 6.1-9.9 0.96 (0.82, 1.13) 1.09 (0.94, 1.27) 1.18 (1.02, 1.38) ≥10 1.08 (0.92, 1.27) 1.14 (0.99, 1.32) 1.32(1.15, 1.51) The multivariable model includes age, race, education, income, marital status, smoking, family history of MI, depression, alcohol intake, and history of diabetes, hypertension, or hypercholesterolemia