Traditional CVD Risk Factors Research Articles

Meta-Analysis of the Usefulness of Plasma Galectin-3 to Predict the Risk of Mortality in Patients With Heart Failure and in the General Population

Galectin-3 is an emerging biomarker of myocardial fibrosis, inflammation, and immune response. We sought to examine the relation of plasma galectin-3 with cardiovascular (CVD) mortality, all-cause mortality, and incident heart failure (HF). We performed a literature search for all relevant publications using Ovid MEDLINE, Google Scholar, and other databases up to January 2016. Two reviewers independently extracted data and assessed risk of bias. We extracted hazard ratios (HRs) from regression models that adjusted for age, gender, race, body mass index, smoking, hypertension, hyperlipidemia, diabetes, natriuretic peptides, and renal function, when available. A total of 18 studies with 32,350 participants (323,090 person-years of follow-up) met criteria for analysis. The mean age was 57.3years and 47.2% of participants were women, with a follow-up duration median of 5years, interquartile range: 2.9 to 10years. Of the 18 studies, 13 (72%) adjusted for N-terminal probrain natriuretic peptide and renal function in the multivariable adjusted models. Using a random-effects meta-analysis, we found an HR of 1.10 (95% CI 1.05 to 1.14) for all-cause mortality, 1.22 (95% CI 1.05 to 1.39) for CVD mortality, and 1.12 (95% CI 1.04 to 1.21) for HF risk for each 1 SD increase in galectin-3 level. In a subgroup analysis of CVD mortality, the HR was 1.44 (1.09 to 1.79) for patients with HF and 1.09 (0.91 to 1.27) for the general population. In conclusion, our results suggest that elevated plasma galectin-3 is associated with a higher risk of all-cause mortality, CVD mortality, and HF. It may add prognostic value beyond that provided by traditional CVD risk factors.

PP.07.01] MIR-483-5P ASSOCIATES WITH OBESITY AND INSULIN RESISTANCE AND INDEPENDENTLY PREDICTS NEW ONSET DIABETES MELLITUS AND CARDIOVASCULAR DISEASE

Objective: To identify circulating serum microRNAs (miRNAs) in healthy humans which predict future onset of both diabetes mellitus and cardiovascular disease. Design and method: In serum of 12 test subjects, we identified 48 miRNAs consistently detectable in all subjects out of a panel of 786 miRNAs well-conserved in mammals. The population-based Malmö Diet and Cancer Cardiovascular Cohort (n = 5400) (MDC-CC), underwent a baseline examination 1991–1994, where fasted blood was stored after which the population was followed for incidence of diabetes mellitus (DM) and cardiovascular disease (fatal and non-fatal myocardial infarction and stroke) (CVD). We measured the 48 miRNAs using a TaqMan quantitative real-time PCR Low Density Array (TLDA) based method in fasting serum of 553 healthy subjects from MDC-CC, including 155 incident cases of DM and 171 incident cases of CVD and used multivariate logistic regression to test individual miRNAs for association with incident DM and CVD. Results: After Bonferroni correction and adjustment for age and sex, each SD increment of log-transformed miR483-5p was significantly associated with both incident DM (OR = 1.48; 95% CI 1.18–1.84, P = 0.001) and CVD (OR = 1.40; 95% CI 1.15, 1.72, P = 0.001). In cross sectional analysis, MIR 483_5p was positively correlated with BMI (r = 0.162, P = 0.0001), fasting insulin (r = 0.156, P = 0.0002), HDL (r = -0.099, P = 0.02) and triglycerides (r = 0.11, P = 0.10). Adjustment for these metabolic risk factors, as well as traditional risk factors attenuated the miR-483-5p association with incident DM (OR = 1.28 95% CI 1.00–1.64, P = 0.049) whereas its association with incident CVD remained virtually unchanged (OR = 1.46 95% CI, 1.18-1.81, P = 0.0005). Conclusions: miR483–5p predicts development of both DM and CVD. The association with DM seems partly mediated by obesity and insulin resistance whereas the association with incident CVD is independent of these metabolic factors and traditional CVD risk factors. Previous studies (Ma et al. 2011, Mol Cell Endocrinol) suggest an underlying mechanism of our findings as miR-483-5p, which is co-expressed with its host gene Igf2, downregulates the expression of socs3 and thereby could mediate development of obesity and a state of high cardiometabolic risk.

Abstract P232: Psoriasis is Associated with Increased Arterial Stiffness: a Systematic Review and Meta-analysis

Background: Studies have shown that patients with psoriasis have higher risk of CVD, independent of traditional CVD risk factors. However, pathophysiology of the development of CVD in psoriasis is not well known. Arterial stiffness has been recognized as an independent predictor of cardiovascular risk. It is controversial whether psoriasis and arterial stiffness is associated. In this systematic review and meta-analysis, we sought to assess the hypothesis that patients with psoriasis have increased arterial stiffness compared with controls. Methods: Systematic literature search was performed using MEDLINE and EMBASE databases from inception to May 2016. We included original research publications that contained data on arterial stiffness and psoriasis. Aortic pulse wave velocity (aPWV) is the non-invasive marker for assessment of arterial stiffness. We compared aPWV between patients with psoriasis and controls and estimated the pooled mean difference (MD) and 95% confidence interval (CI) of aPWV using a random-effects model meta-analysis. Results: Data from five observational studies involving 438 participants (233 with psoriasis) were extracted and included in the meta-analysis. Pooled MD of aPWV was 1.17 m/sec higher in patients with psoriasis compared with controls (95% CI: 0.78-1.55, P-value<0.01, I 2 = 69%). There is no change in the direction or statistical significance of MD of aPWV after removing each study at a time in the sensitivity analysis. Conclusion: Psoriasis is associated with increased arterial stiffness. Assessment of arterial stiffness parameters may be important for early detection of cardiovascular deterioration in psoriasis patients.

Abstract P225: Calcification of the Splenic, Internal and External Iliac, and Breast Arteries and Risk of All-cause Mortality

Introduction: Prognostic consequences of and risk factors for coronary and aortic calcification are well known. Less is known about the consequences of and risk factors for calcification in other arteries. Hypothesis: We hypothesize that calcifications in the splenic, internal and external iliac, and breast arteries (in females) have different risk factor profiles, and that calcification in these beds is associated with mortality. Methods: We conducted a case cohort study from 5196 individuals who self-referred for whole body computed tomography (CT). We selected a random sub-cohort of 395 individuals. Our cases were 298 individuals who died during a median follow-up of 9.4 years. CT scans were scored for splenic, internal and external iliac, and, in females, breast artery calcification. The associations between risk factors and presence or absence of calcification in each vascular bed in the random sub-cohort was evaluated using logistic regression. Using both the sub-cohort and death cases, we used Prentice-weighted Cox proportional hazards models to assess associations of calcification in each bed with mortality. Results: Within the random sub-cohort, prevalence of calcification was 11.6% (46 of 395) in the splenic, 47.9% (187 of 390) in the internal iliac and 9.5% (37 of 390) in the external iliac arteries. Among the 163 women, 3.7% had breast artery calcification. In multivariable models, age (OR 1.62 [95%CI 1.04-2.54] per 10 years), diabetes (OR 5.80 [95%CI 1.37-24.61]), log-transformed abdominal aortic calcium (AAC) (OR 1.36 [95%CI 1.09-1.70]) and log-transformed CAC score (OR 1.38 [95%CI 1.13-1.68]) were independently associated with splenic artery calcification. Age (OR 1.60 [95%CI 1.09-2.33], male gender (OR 3.86 [95%CI 2.09-7.15]), AAC (OR 1.44 [95%CI 1.28-1.62]) and CAC score (OR 1.23 [95%CI 1.08-1.39]) were associated with internal iliac artery calcium. Smoking (current vs. never OR 9.87 [95%CI 2.24-43.61]) and AAC (OR 1.96 [95%CI 1.24-3.11]) were associated with external iliac artery calcium. For the breast arteries, numbers were too small to fit these multivariable models. Although calcification in the splenic, internal, and external iliac arteries were significantly associated with mortality in unadjusted models, these associations were attenuated and no longer statistically significant after adjusting for cardiovascular risk factors. Among women, breast artery calcification was associated with mortality independent of traditional CVD risk factors and a 0-5 score of the number of calcified vascular beds out of the carotids, coronaries, abdominal and thoracic aorta and common iliacs (HR 5.67 [95%CI 1.50-21.41]). Conclusions: Calcification in the splenic, internal and external iliac arteries was strongly associated with calcification in the abdominal aorta. In females, breast artery calcification was strongly and independently associated with mortality.

Psychosocial Factors Associated with Subclinical Atherosclerosis in South Asians: The MASALA Study

South Asians have the highest rates of premature atherosclerotic cardiovascular disease amongst all ethnic groups in the world; however this risk cannot be fully explained by traditional risk factors. Participants from the Mediators of Atherosclerosis in South Asians Living in America Study were included in this cross-sectional analysis. The purpose of this study was to investigate the association of psychosocial factors (including anger, anxiety, depressive symptoms, current and chronic stress, and everyday hassles) with carotid intima-media thickness (CIMT). Three multivariate models were examined to evaluate the association between the psychosocial factors and CIMT. Findings suggest that the impact of psychosocial factors on subclinical atherosclerosis is differential for South Asian men and women. For men, anxiety and depression were associated; while for women, stress was associated with common carotid intima media thickness, independent of traditional CVD risk factors, diet and physical activity.

The Prognostic Value of Family History for the Estimation of Cardiovascular Mortality Risk in Men: Results from a Long-Term Cohort Study in Lithuania.

AimTo evaluate the additional prognostic value of family history for the estimation of cardiovascular (CVD) mortality risk in middle-aged urban Lithuanian men.MethodsThe association between family history of CVD and the risk of CVD mortality was examined in a population-based cohort of 6,098 men enrolled during 1972–1974 and 1976–1980 in Kaunas, Lithuania. After up to 40 years of follow-up, 2,272 deaths from CVD and 1,482 deaths from coronary heart disease (CHD) were identified. Multivariate Cox proportional hazards models were used to estimate hazard ratios (HR) for CVD and CHD mortality.ResultsAfter adjustment for traditional CVD risk factors, the HR for CVD mortality was 1.24 (95% CI 1.09–1.42) and for CHD mortality 1.20 (1.02–1.42) in men with first-degree relatives having a history of myocardial infarction (MI), compared to men without positive family history. A significant effect on the risk of CVD and CHD mortality was also observed for the family history of sudden cardiac death and any CVD. Addition of family history of MI, sudden death, and any CVD to traditional CVD risk factors demonstrated modest improvement in the performance of Cox models for CVD and CHD mortality.ConclusionsFamily history of CVD is associated with a risk of CVD and CHD mortality significantly and independently of other risk factors in a middle-aged male population. Addition of family history to traditional CVD risk factors improves the prediction of CVD mortality and could be used for identification of high-risk individuals.

Pro-inflammatory dietary intake as a risk factor for CVD in men: a 5-year longitudinal study.

Convincing evidence has identified inflammation as an initiator of atherosclerosis, underpinning CVD. We investigated (i) whether dietary inflammation, as measured by the 'dietary inflammatory index (DII)', was predictive of 5-year CVD in men and (ii) its predictive ability compared with that of SFA intake alone. The sample consisted of 1363 men enrolled in the Geelong Osteoporosis Study who completed an FFQ at baseline (2001-2006) (excluding participants who were identified as having previous CVD). DII scores were computed from participants' reported intakes of carbohydrate, micronutrients and glycaemic load. DII scores were dichotomised into a pro-inflammatory diet (positive values) or an anti-inflammatory diet (negative values). The primary outcome was a formal diagnosis of CVD resulting in hospitalisation over the 5-year study period. In total, seventy-six events were observed during the 5-year follow-up period. Men with a pro-inflammatory diet at baseline were twice as likely to experience a CVD event over the study period (OR 2·07; 95 % CI 1·20, 3·55). This association held following adjustment for traditional CVD risk factors and total energy intake (adjusted OR 2·00; 95 % CI 1·03, 3·96). This effect appeared to be stronger with the inclusion of an age-by-DII score interaction. In contrast, SFA intake alone did not predict 5-year CVD events after adjustment for covariates (adjusted OR 1·40; 95 % CI 0·73, 2·70). We conclude that an association exists between a pro-inflammatory diet and CVD in Australian men. CVD clinical guidelines and public health recommendations may have to expand to include dietary patterns in the context of vascular inflammation.

Smoking cessation after an acute coronary syndrome: immediate quitters are successful quitters.

BackgroundCardiovascular disease (CVD) prevention guidelines stress the importance of smoking cessation and recommend intensive follow-up. To guide the development of such cessation support strategies, we analysed the characteristics that are associated with successful smoking cessation after an acute coronary syndrome (ACS).MethodsWe used data from the Randomised Evaluation of Secondary Prevention for ACS patients coordinated by Outpatient Nurse SpEcialists (RESPONSE) trial (n = 754). This was designed to quantify the impact of a nurse-coordinated prevention program, focusing on healthy lifestyles, traditional CVD risk factors and medication adherence. For the current analysis we included all smokers (324/754, 43 %). Successful quitters were defined as those who reported abstinence at 1 year of follow-up.ResultsThe majority of successful quitters quit immediately after the ACS event and remained abstinent through 1 year of follow-up, without extra support (128/156, 82 %). Higher education level (33 vs. 15 %, p < 0.01), no history of CVD (87 vs. 74 %, p < 0.01) and being on target for LDL-cholesterol level at 1 year (78 vs. 63 %, p < 0.01) were associated with successful quitting.ConclusionThe majority of successful quitters at 1 year stopped immediately after their ACS. Patients in this group showed that it was within their own ability to quit, and they did not relapse through 1 year of follow-up. Our study indicates that in a large group of patients who quit immediately after a life-threatening event, no relapse prevention program is needed.

Serum Soluble Klotho Level Is Associated with Abdominal Aortic Calcification in Patients on Maintenance Hemodialysis

Background: Klotho is a single transmembrane protein originally identified as an ‘aging suppressor'. Emerging evidence reveals that soluble Klotho (sKl) in the circulation plays important roles in anti-aging, anti-oxidation, anti-apoptosis and Wnt signaling. However, the role of serum sKl in the vascular calcification in hemodialysis patients is not clear. The aim of this study was to determine the associations of sKl with abdominal aortic calcification in patients on maintenance hemodialysis (MHD). Methods: 129 MHD patients were enrolled prospectively. Serum sKl level was detected by ELISA. Abdominal aortic calcification was measured by abdomen lateral plain radiograph, and the abdominal aorta calcification (AAC) score was calculated. The sKl levels were observed in patients with different degrees of calcification. Logistic regression analysis was used to determine the risk factor of abdominal aortic calcification in MHD patients. The diagnostic value of sKl for abdominal aortic calcification was assessed using receiver operator characteristic (ROC). Results: Abdominal aortic calcification was seen in 87 of 129 patients. The median AAC score was 4.0 (0.00, 11.00) and the median sKl level was 616.29 (378.19, 821.61) pg/ml. Serum sKl levels were inversely associated with AAC. When evaluated as AAC categories (<5, 5-15, >15) with ordinal logistic regression, each SD higher sKl was associated with 37.1% lower odds of AAC severity (proportional odds ratio: 0.629; 95% confidence interval: 0.413-0.959, p = 0.031) in models adjusted for demographic data, lifestyle factors, traditional CVD risk factors and uremic risk factors. Multivariate logistic regression analysis showed that serum sKl levels and smoking were independent risk factors for severe AAC. The area under the receiver-operating characteristic curve (AUC) of serum sKl for severe abdominal aortic calcification was 0.746 (0.612-0.880, p = 0.001), sensitivity was 0.885, and specificity was 0.562 for a cutoff value of 265.39 pg/ml. Conclusions: Lower serum sKl levels are independently associated with severe AAC. Serum sKl might have a diagnostic value for the severe AAC in MHD patients.

OP0163 Predictors of Heart Rate Recovery following Exercise in Patients with Rheumatoid Arthritis

BackgroundCardiovascular disease (CVD) is a major cause of death in rheumatoid arthritis patients (RA). The underlying mechanisms for the CVD increase risk in RA are not fully understood. However, poor...

Abstract P194: Fruit and Vegetable Slows Subclinical Atherosclerosis in Chinese Women

Objectives: This study aimed to investigate lifestyle factors, particularly fruit and vegetable intake in the protection against the progression of SA in early postmenopausal Chinese women. Methods: This is a community-based 5-year followup study on a cohort of 518 women recruited through random telephone dialing. All were aged 50-64y and within 10 years menopause. Lifestyle and dietary variables based on validated and structured questionnaires, clinical assessments and fasting blood samples were obtained at baseline (T 1 ) and 5-year followup (T 2 ). A 12.5-MHz linear probe of the HDI 5000 ultrasound scanner was used for measuring intima-media thickness (IMT) at the near and far walls of three 10-mm segments: distal common carotid, bifurcation, proximal internal carotid of both the left and right carotid arteries. The final IMT was the averages of maximum IMT free of atherosclerotic plaques measured at each of the 12 segments. Atherosclerotic plaques defined as a focal wall thickening of at least 1.5mm were also identified along the defined segments. Plaque was graded as: grade 0, no observable plaque; 1, one small plaque &lt;30% of vessel diameter; 2, one medium plaque between 30-50% of vessel diameter or multiple small plaques; 3, one large plaque &gt;50% vessel diameter or multiple plaques with at least one medium plaque. Repeated measurements of IMT and plaque were also obtained at T 2 . Plaque progression was computed by subtracting the plaque index at T 1 from the plaque index at T 2 . The within-sonographer intraclass correlations were 0.83-0.88 for IMT and 0.99 for plaque index, and between sonographer correlations were 0.81-0.88 for IMT, and 0.88- 0.99 for plaque index. Results: The five-year followup study of asymptomatic Chinese early postmenopausal women (mean age 61.5 years at T 2 ) has revealed a progression of IMT of 2.1 % (standard deviation =1.7) or a progression rate of 0.015 mm/year (standard deviation = 0.013). 25 % were found to have plaque progression (change of plaque index score of ≧1). Besides the traditional CVD risk factors (age, higher values of total cholesterol, systolic and diastolic blood pressure, LDL-cholesterol and triglyceride), multiple regression analysis showed that higher fruit and vegetable intake was a significant (p=0.001) and independent predictor of lower IMT at T 2 . Analysis of the followup data showed that maintenance of high intake of fruit and vegetable (&gt;median) at both T 1 and T 2 was associated with lower IMT at T 2 , even adjusted for the other significant predictors. Similar relationship with plaque progression was also observed. Conclusion: This population-based cohort study of Chinese asymptomatic midlife women has identified maintenance of high fruit and vegetable intake tended to reduce the risk of SA.

Abstract P335: The Number of Coronary Arteries with Calcified Plaque is Increased in Type 1 Diabetes

Adults with type 1 diabetes (T1D) have a higher risk for cardiovascular disease than non-diabetic (non-DM) adults. Coronary artery calcification (CAC) is a marker for subclinical atherosclerosis and the Agatston CAC score is the standard used today. The aim of our study was to look at the number of coronary arteries with calcified plaques to determine if more diffuse disease is present in adults with T1D for a given level of CAC. In addition, we examined risk factors associated with the number of coronary arteries with CAC, as this could be a novel way to risk-stratify individuals. This study consisted of 1169 participants (T1D n=535 and non-DM n =634) with a mean ± SD age of 39±9 years. CAC was measured by electron beam CT (EBCT) using two scans performed five minutes apart and the maximum number of coronary arteries with CAC was used in the analysis. CAC lesions were determined in the left main, left anterior descending, circumflex, and right coronary arteries, with a maximum number of arteries with CAC ranging from zero to four. Chi square analysis was used to compare the number of coronary arteries with CAC by diabetes group. Subjects were then divided into categories based on their CAC score (&gt;0-10, 10-100, &gt;100-300, &gt;300) and poisson regression was used in multivariable analysis to examine associated risk factors. Adults with T1D had a significantly higher number of coronary arteries with CAC lesions than the non-DM adults (p &gt; 0.0001). Among subjects with CAC&gt;300 (n=58), adults with T1D had more coronary arteries with CAC than the controls (p = 0.03), but there were no differences in number of arteries with CAC among the other Agatston score categories. In multivariable analysis, HDL and LDL cholesterol, BMI, and hypertension were all independently associated with the number of coronary arteries with CAC lesions when adjusting for age, diabetes and CAC score (p&lt;0.0001). There were no significant associations of number of arteries with CAC with smoking status or hemoglobin A1c. People with T1D were still significantly more likely to have more coronary arteries with CAC lesions than non-DM individuals after adjusting for the above factors. In conclusion, T1D patients have more diffuse subclinical atherosclerosis, as indicated by a greater number of coronary arteries with CAC compared with non-DM adults. The number of coronary arteries with calcified plaque was independently associated with traditional CVD risk factors, even when accounting for CAC score. These findings are important because traditionally just the Agatston CAC score is used to determine CVD risk, but the number of coronary arteries affected could indicate how diffuse the subclinical artherosclerosis is prompt for aggressive treatment of traditional risk factors.

Abstract MP25: Is Surgical Menopause Associated With Future Cardiovascular Risk Factors Independent Of Antecedent Levels? The Cardia Study

Objective: The aim of this study was to compare changes in selected CVD risk factors prior to and after natural or surgical (hysterectomy with or without bilateral oophorectomy) menopause. Methods: Data were obtained from women aged 18 to 30 years at baseline without hysterectomy enrolled in the Coronary Artery Risk Development in Young Adults (CARDIA) study and followed for 25 years. Piecewise linear mixed effects models were used to examine changes in waist circumference (WC) and HDL-cholesterol (HDL-c) from baseline to index visit (first visit after the date of natural or surgical menopause) and after index visit to the end of observation. Results: During follow up, 639 women reached natural menopause (NM), 304 reported hysterectomy with one or both ovaries conserved (HO) and 153 reported hysterectomy with bilateral oophorectomy (HBO). Baseline mean values of WC were 73.9, 76.4, 75.9 cm, p=0.005 for NM, HO, and HBO respectively while those for HDL-c were 57.6, 54.6, 54.2 mg/dL, p=0.001. After adjustment for race, education, field center, traditional CVD risk factors, lipid-lowering medication, age at and time since menopause, the mean values of WC at the index visit were 88.8, 92.4, 92.0 cm, p=0.001 for NM, HO, and HBO respectively while those for HDL-c were 61.5, 57.0, 57.8 mg/dL, p=0.006. Compared to women with natural menopause, surgically menopausal women (regardless of ovarian status) had higher annual rate of change for WC (0.74 vs. 0.63 cm, p=0.002) as well as lower rate of change for HDL-c (0.15 vs. 0.30 mg/dL, p=0.001) from baseline to index visit. No statistically significant differences in the annual rate of change after index visit to the end of follow up were observed between these two groups for either WC or HDL-c. Conclusion: While surgical menopause is commonly believed to worsen CVD risk, in this population-based sample, we found that women who undergo hysterectomy with or without bilateral oophorectomy had more adverse values for central adiposity and lipids at baseline compared to women with natural menopause. However, antecedent risk factor levels were strongly associated with postmenopausal levels in all women.

Abstract P325: Association of Risk Factors and Extra-coronary Atherosclerosis with Progression of Coronary Artery Calcification in the Framingham Heart Study

Background: Progression of coronary artery calcification (CAC) is associated with future incidence of adverse cardiovascular disease. However, the interplay of CAC progression and atherosclerosis in different vascular beds has been less studied. We tested for the association of risk factors and baseline abdominal aortic calcification (AAC) with CAC progression in a large community cohort. Methods: We determined risk factors, baseline AAC/CAC, and CAC progression in a sample of 1994 asymptomatic white participants from the Framingham Heart Study (FHS) who had undergone serial CT scanning within an average of 6.1 years. The primary outcomes were: (a) incident calcification (CAC &gt; 0) in participants free of CAC at baseline; and (b) absolute progression of CAC (CAC follow-up &gt; CAC baseline) in participants with detectable baseline CAC. To test the effect of risk factors and baseline AAC/CAC on CAC progression, we employed multivariable stepwise logistic and linear regression models of CAC progression with/without AAC, adjusted for traditional CVD risk factors. Results: There were 1118 participants free of CAC at the baseline scan, of which 18.8% developed CAC in the follow-up scan. Of the 776 participants with detectable CAC at baseline, 84.9% developed progression of baseline CAC. In both subsets, AAC was a highly significant predictor of CAC incidence or progression, independent of other risk factors. Of note, the stepwise model including baseline AAC as a candidate for entry resulted in the same set of non-AAC predictors of CAC incidence or progression as the model without AAC. Table 1 displays the final logistic regression results for the cohort free of CAC. The AUC improved to 0.738 compared to an AUC of 0.722 for the model without AAC (p=0.002). Conclusion: AAC is a strong independent predictor of CAC progression determined by incident CAC and CAC progression. Addition of AAC to the model that predicts incident CAC improves discrimination in a cohort free of baseline CAC.

Abstract MP69: Effect of Post Traumatic Stress Disorder and Combat Exposure on Carotid Intima-Media Thickness in Vietnam Era Veteran Twins

Introduction: Posttraumatic stress disorder (PTSD) is associated with an increased risk of ischemic heart disease, but the pathophysiologic mechanisms remains unclear. Genetic and shared familial and early environmental factors may confound this association. Carotid artery intima media thickness (cIMT) is a measure of atherosclerotic burden and is predictive of future cardiovascular events. In a study of Vietnam era twins, we assessed the hypothesis that PTSD and combat exposure are associated with cIMT after controlling for shared genetic and childhood environmental factors. Methods: We studied 465 middle-aged male twins from the Vietnam Era Twin Registry, who were part of the Emory Twin Studies, without a clinical history of cardiovascular disease. A diagnosis of PTSD was obtained with the Structured Clinical Interview for DSM-IV and combat exposure was measured using the Combat Exposure Scale. Carotid IMT was measured using B-mode ultrasound. Mixed effects regression models with a random effect for the twin pair were used to examine overall, between- and within-pair effects. Models were sequentially adjusting for traditional CVD risk factors, genetic and childhood environmental factors. Results: About 13% (60 out of 465) of participants met criteria for PTSD and 45% (209 out of 465) served in the Vietnam Theater. When twins were examined as individuals, PTSD was associated with 33.3 μm higher cIMT (p=0.03) after adjustment for potential confounders. In addition, the average cIMT for the twin pair increased by 43 μm for each additional twin affected by PTSD in the pair (p=0.04). However, there was no significant within-pair difference in cIMT comparing co-twins discordant for PTSD. Combat exposure showed a similar pattern of results but its association with cIMT weakened after adjusting for PTSD (unadjusted p=0.01, adjusted p=0.08). Conclusions: Among Vietnam era veterans, combat exposure and PTSD are both associated with cIMT, but such associations are largely mediated by shared familial or early environmental factors.

Abstract P032: Adiponectin is Significantly Associated with NT-pro BNP Levels: The Multi-Ethnic Study of Atherosclerosis

Background: Increasing adiposity results in an increase in intravascular volume, while natriuretic peptides increase in response to pressure and volume overload. Adiponectin and leptin are cytokines released from adipose tissue (adipokines) that have purportedly opposite associations with CVD and measures of left ventricular structure and function. Methods: Subjects were 1970 individuals enrolled in the Multi-Ethnic Study of Atherosclerosis who were without clinical CVD at baseline and evaluated by extensive survey information, relevant physical measurements and fasting venous blood that was analyzed for NT-pro BNP (proBNP) and the adipokines adiponectin and leptin. proBNP was assayed from two different study visits about 4 years apart. Results: At baseline, the mean age was 64.8 years and 48% were female. Forty-two percent were White, 26% Hispanic American, 18% African American and 14% Chinese American. Median values for adiponectin, leptin and proBNP were 17.3 μg/ml, 13.1 ng/ml and 66.7 pg/ml, respectively, while the median change in proBNP was 11.6 pg/ml. With adjustment for traditional CVD risk factors, adiposity, renin, aldosterone and LV mass and volume, a 1-SD increment in adiponectin was associated with a 13.7 pg/ml higher proBNP level (p &lt; 0.01), while, compared to the 1st quartile of adiponectin, the 2nd, 3rd and 4th quartiles were associated with 28, 45 and 67% higher proBNP levels (p &lt; 0.01 for all). For changes in proBNP over the follow-up period, and after multivariable adjustment including baseline proBNP, a 1-SD increment in adiponectin was associated with a 25 pg/ml increase in proBNP (p &lt; 0.01), while those in the 2nd, 3rd and 4th quartiles of adiponectin were associated increases of 5, 28 and 65 pg/ml (p = 0.74, 0.09 and &lt; 0.01, respectively). There were no significant multiplicative interactions by race or obesity status. However, there was a significant interaction between adiponectin and gender for proBNP, such that the associations detailed above were significantly stronger in men. Leptin was not associated with proBNP (data now shown). Conclusions: Higher adiponectin, but not leptin, is significantly associated with higher levels of proBNP, as well as significant longitudinal increases in proBNP. The findings appear to be stronger in men.

Gender differences in ghrelin association with cardiometabolic risk factors in arab population.

Ghrelin is a stomach produced hormone that has been shown to have protective role against development of CVD which is a leading cause of death in the Arab world. The objective of this study is to examine the gender difference in association between traditional CVD risk factors and plasma ghrelin among Arabs. 359 Arab residents in Kuwait participated in a cross-sectional survey (≥20 years old): 191 were females and 168 were males. Plasma level of ghrelin was assessed using Luminex-based assay. Ghrelin levels were significantly higher in females (935 ± 78 pg/mL) than males (763 ± 65 pg/mL) (P = 0.0007). Females showed inverse association with WC (r = −0.23, P = 0.001) and HbA1C (r = −0.19, P = 0.0102) as well as SBP (r = −0.15, P = 0.0383) and DBP (r = −0.16, P = 0.0230), respectively. Higher levels of ghrelin were shown to associate with increased insulin resistance, as measured by HOMAIR, in male Arab subjects (P-trend = 0.0202) but not in females. In this study we show that higher ghrelin level was negatively associated with measures of obesity, HbA1C, and blood pressure in females and positively associated with increased insulin resistance in Arab males.

Cardiovascular disease risk amongst African black patients with rheumatoid arthritis: the need for population specific stratification.

Rheumatoid arthritis (RA) enhances the risk of cardiovascular disease to a similar extent as diabetes. Whereas atherogenesis remains poorly elucidated in RA, traditional and nontraditional risk factors associate similarly and additively with CVD in RA. Current recommendations on CVD risk stratification reportedly have important limitations. Further, reported data on CVD and its risk factors derive mostly from data obtained in the developed world. An earlier epidemiological health transition is intrinsic to persons living in rural areas and those undergoing urbanization. It is therefore conceivable that optimal CVD risk stratification differs amongst patients with RA from developing populations compared to those from developed populations. Herein, we briefly describe current CVD and its risk factor profiles in the African black population at large. Against this background, we review reported data on CVD risk and its potential stratification amongst African black compared to white patients with RA. Routinely assessed traditional and nontraditional CVD risk factors were consistently and independently related to atherosclerosis in African white but not black patients with RA. Circulating concentrations of novel CVD risk biomarkers including interleukin-6 and interleukin-5 adipokines were mostly similarly associated with both endothelial activation and atherosclerosis amongst African black and white RA patients.

Effect of smoking and other traditional risk factors on the onset of coronary artery calcification: Results of the Heinz Nixdorf recall study

BackgroundCoronary artery calcium (CAC) indicates coronary atherosclerosis and can be present in very early stages of the disease. The conversion from no CAC to any CAC reflects an important step of the disease process as cardiovascular risk is increased in persons even with mildly elevated CAC. We sought to identify risk factors that determined incident CAC>0 in men and women from an unselected general population with a special focus on the role of smoking. MethodsAll 4814 persons that were initially studied in the Heinz Nixdorf Recall Study were invited to participate in the follow-up examination after 5.1 ± 0.3 years. All traditional Framingham risk factors were quantified using standard techniques. Smokers were categorized in never, former and present smokers. The CAC scores were measured from EBCT using the Agatston method. ResultsOverall, out of 342 men and 919 women with zero CAC at baseline, 107 (31.3%) men and 210 (22.9%) women had CAC>0 at second examination. In multivariable analysis, age (OR estimate per 5 years: 1.34 (95%CI: 1.21–1.47)), LDL cholesterol (per 10 mg/dL: 1.05 (95%CI: 1.01–1.10)), systolic blood pressure (per 10 mmHg: 1.19 (95%CI: 1.11–1.28)) and current smoking (1.49 (95%CI: 1.04–2.15)) were independent predictors of CAC onset. The probability of CAC onset steadily increased with age from 23.3% (men) and 15.3% (women) at age 45–49 years to 66.7% (men) and 42.9% (women) at age 70–74 years. The difference in age-dependent conversion rates was quantified by years between reaching a given level of CAC onset probability. We found a consistent pattern with respect to smoking status: presently (formerly) smoking middle-aged men convert to positive CAC 10 (5) years earlier than never smokers, for women (middle-aged to elderly) this time span is 8 (5) years. ConclusionSeveral traditional CVD risk factors are associated with CAC onset during 5 years follow-up. CAC onset is accelerated by approximately 10 (5) years for present (former) compared to never smokers.

Reduced CD14 expression on classical monocytes and vascular endothelial adhesion markers independently associate with carotid artery intima media thickness in chronically HIV-1 infected adults on virologically suppressive anti-retroviral therapy

HIV infection causes systemic immune inflammation, and increases the risk for cardiovascular (CVD) disease even among those on virologically suppressive anti-retroviral treatment (ART). We performed a biostatistical analysis and screen of candidate cellular and plasma biomarkers for association with carotid artery intima-media thickness (CIMT), independent of traditional CVD risk factors such as age, gender, systolic blood pressure (SBP), lipid levels, smoking and diabetes. We conducted a multi-stage analysis based on a cross-sectional study of CVD risk in HIV-infected subjects age >45 years on ART for >6 months. The goal of this analysis was to identify candidate cellular and plasma biomarkers of CIMT in HIV-1 infected adults. We further sought to determine if these candidate biomarkers were independent of traditional CVD risk factors previously identified in HIV negative adults. High-resolution B-mode ultrasound images of the right common carotid common artery (CCA) were obtained. Plasma soluble inflammatory mediators, cytokines and chemokines were detected. Monocytes were defined by CD14/CD16 expression, and CD8+ T-cell activation by CD38/HLA-DR expression. Subjects were a median of 49.5 years old, 87% male, had a CIMT of 0.73 mm, FRS of 6%, a median viral load of 48 copies/mL, and CD4+ T cell count of 479 cells/μL. Soluble VCAM-1, and expansion of CD14dimCD16− monocytes each associated with higher CIMT independently of age and SBP. These factors are distinct components of a shared atherogenic process; 1) vascular endothelial molecular expression and 2) vascular monocytes that enter into the vascular endothelium and promote atherosclerotic plaque.