Traditional Coronary Heart Disease Risk Factors Research Articles

Differential prediction performance between Caribbean- and Mainland-subgroups using state-of-the-art polygenic risk scores for coronary heart disease: Findings from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL).

Coronary heart disease (CHD) is a leading cause of death for Hispanic/Latino populations in the United States. We evaluated polygenic risk scores (PRS) with incident myocardial infarction (MI) in a Hispanic/Latino study sample. We leveraged data from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) to assess four CHD-PRS from the PGS catalog, derived using multiple methods (LDpred, AnnoPred, stacked clumping and thresholding, and LDPred2). We evaluated associations between each standardized PRS and time to adjudicated incident MI, adjusted for age, sex, first 5 principal components, and weighted for survey design. Concordance statistics (c-index) compared predictive accuracy of each PRS with, and in addition to, traditional risk factors (TRF) for CHD (obesity, hypercholesterolemia, hypertension, diabetes, and smoking). Analyses were stratified by self-reported Caribbean- (Puerto Rican, Dominican or Cuban) and Mainland- (those of Mexican, Central American, or South American) heritage subgroups. After 11 years follow-up, for 9055 participants (mean age (SD) 47.6(13.1), 62.2% female), the incidence of MI was 1.0% (n = 95). Each PRS was more strongly associated with MI among Mainland participants. LDPred2 + TRF performed best among the Mainland subgroup; HR=2.69, 95% CI [1.71, 4.20], c-index = 0.897, 95% CI [0.848, 0.946]; a modest increase over TRF alone, c-index = 0.880, 95% CI [0.827, 0.933]. AnnoPred + TRF performed best among the Caribbean sample; c-index = 0.721, 95% CI [0.647, 0.795]; however, was not significantly associated with rate of MI (HR=1.14, 95% CI [0.82, 1.60]). PRS performance for CHD is lacking for Hispanics/Latinos of Caribbean origin who have substantial proportions of African genetic ancestry, risking increased health disparities. AnnoPred, using functional annotations, outperformed other PRS in the Caribbean subgroup, suggesting a potential strategy for PRS construction in diverse populations. These results underscore the need to optimize cumulative genetic risk prediction of CHD in diverse Hispanic/Latino populations.

Abstract MP23: Circulating Gut Microbiota-Related Metabolites and Risk of Coronary Heart Disease: A Prospective, Multiethnic, Metabolomic Study

Introduction: Despite the importance of gut microbiota in human cardiometabolic health, the associations between circulating levels of gut microbiota-related metabolites and incident coronary heart disease (CHD) remain largely unexplored. Hypothesis: Certain circulating microbial metabolites are associated with incident CHD. Methods: This is a multi-stage and multiethnic metabolomics study. We first conducted a global, semi-quantitative assay for discovery among 900 incident CHD cases and 900 age-/sex-/race-matched controls (300 pairs of Black Americans, White Americans, and Chinese adults, respectively) selected from the Southern Community Cohort Study and Shanghai Men’s and Women’s Health Studies. We focused on 226 metabolites that were potentially related to gut microbiota and applied conditional logistic regression to estimate odds ratios (ORs) of CHD associated with a 1-SD increase of log-transformed metabolites adjusting for traditional CHD risk factors. Then, an in-silico validation was conducted using existing metabolites data of 9,264 participants from the Multi-Ethnic Study of Atherosclerosis and Atherosclerosis Risk in Communities Study. Results: In the discovery stage, we identified 73 named microbial metabolites related to incident CHD risk with a false discovery rate<0.10 or nominal p <0.05 and a large effect size (ORs >1.5 or <0.5). These metabolites were from super pathways of amino acids (n=28), lipids (n=24), nucleotides (n=6), carbohydrates (n=4), energy (n=4), xenobiotics (n=4), and cofactors/vitamins (n=3). Of them, 61 metabolites were available for the in-silico validation, and 30 showed a significant association ( p <0.05) with the same direction as the discovery results. After further adjustments for established CHD risk factors (e.g., glucose and LDL-cholesterol), 25 metabolites remained significant. A 14%-48% increased risk was observed for N-acetylglutamate (OR=1.48), sphingomyelin (1.42), imidazole propionate (1.37), hypoxanthine (1.29), guaiacol sulfate (1.28), glutamate (1.22), 2-hydroxyphenylacetate (1.20), 3-hydroxybutyrate (1.19), 3-hydroxy-2-ethylpropionate (1.17), 1-methyl-4-imidazoleacetate (1.16), urea (1.16), urate (1.16), 4-hydroxyphenylacetate (1.15), choline (1.15), isoleucine (1.14), and glycerol (1.14). Meanwhile, a significant inverse association was found for taurine (OR=0.64), asparagine (0.75), serotonin (0.78), histidine (0.79), threonine (0.81), glutamine (0.83), glycine (0.84), oxalate (0.85), and N-methylproline (0.89). Conclusions: Among ethnically and geographically diverse populations, we identified and validated some circulating gut microbiota-related metabolites as potential novel biomarkers for incident CHD. Targeted quantitative assays to confirm these results are ongoing, which are essential to inform potential clinical utility.

Cardiac biomarkers for cardiovascular risk prediction among women and men from the general population

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): the Erasmus Medical Center and Erasmus University Rotterdam; the Netherlands Organization for Health Research and Development (ZonMw); Purpose To evaluate the sex-specific predictive value of two cardiac biomarkers; N-terminal pro B-type natriuretic peptide (NT-proBNP) and high sensitivity cardiac troponin T (hs-cTnT), alongside traditional cardiovascular risk factors, for 10-year cardiovascular risk prediction in general population. Methods A total of 5430 participants (mean age 68.1 years; 59.9% women) free of cardiovascular disease (CVD), with blood sample measurements between 1997 and 2001 were included. We developed a ‘base’ model using cardiovascular risk factors used in the Pooled Cohort Equation (includes age, sex, systolic blood pressure, treatment of hypertension, total and high-density lipoprotein cholesterol levels, smoking, and diabetes) and then extended the ‘base’ model with NT-proBNP or hs-cTnT. These models were developed for coronary heart disease (CHD), stroke, and heart failure (HF) and also for composite CVD outcomes. To evaluate biomarkers’ added predictive value, c-statistic, and net reclassification improvement index (NRI) for events and non-events were calculated. NRI was calculated using cutoffs of 5%, 7.5% and 20% to categorize participants as low, borderline, intermediate, or high risk. Results Adding NT-proBNP to the ‘base’ model significantly improved c-statistic for all outcomes (increases ranged between 0.012-0.047), with the largest improvement in HF [0.026 (95% CI, 0.013, 0.040) for women and 0.047 (95% CI, 0.026, 0.069) for men]. Adding hs-TnT to ‘base’ model increased the c-statistic for CHD in women by 0.040 (95% CI, 0.013, 0.067) and for HF in men by 0.032 (95% CI, 0.005, 0.059). Improvments in reclassification by both biomarkers were mostly limited to modest improvemetns in reclassification of non-events [largest non-event NRI for global CVD in women (NT-proBNP: 11.8%; hs-cTnT: 10.5%) and for HF in men (NT-proBNP: 9.6%; hs-cTnT: 8.4%)]. Conclusion NT-proBNP improved model performance for prediction of all cardiovascular outcomes, in particular for HF, beyond traditional risk factors for both women and men. Hs-cTnT showed modest added predictive value beyond traditional risk factors for CHD among women and for HF among men. Imropovements in reclassification by both biomarkers were modest and not clinically relevant. Improvements of 10-year risk predictions Events Adding NT-proBNP Adding troponin T Delta c-statistic* Event NRI, % Non-event NRI, % Delta c-statistic* Event NRI, % Non-event NRI, % WomenASCVD Global CVD 0.012 (0.004, 0.020) 0.018 (0.010, 0.026) -1.7 (-5.0, 1.5)-0.8 (-3.8, 2.2) 5.4 (3.5, 7.2)11.8 (9.6, 14.1) 0.028 (0.009, 0.048)0.025 (0.009, 0.040) -0.4 (-7.1, 6.2)2.9 (-2.4, 8.3) 6.9 (3.9, 9.9)10.5 (7.3, 13.8) MenASCVD Global CVD 0.016 (0.005, 0.027)0.023 (0.012, 0.033) 0.7 (-2.3, 3.7)-0.3 (-3.0, 2.4) 5.2 (3.2, 7.2)7.2 (4.9, 9.4) 0.007 (-0.002, 0.016)0.011 (0.000, 0.021) -1.1 (-5.0, 2.7)-1.6 (-6.0, 2.8) 4.0 (1.2, 6.9)6.4 (3.1, 9.7) ASCVD comprises coronary heart disease and stroke; Global CVD comprises coronary heart disease, stroke and heart failure.

The association between bacterial infections and the risk of coronary heart disease in type 1 diabetes.

Diabetes increases the risk of infections and coronary heart disease (CHD). Whether infections increase the risk of CHD and how this applies to individuals with diabetes is unclear. To investigate the association between bacterial infections and the risk of CHD in type 1 diabetes. Individuals with type 1 diabetes (n=3781) were recruited from the Finnish Diabetic Nephropathy Study (FinnDiane), a prospective follow-up study. CHD was defined as incident events: fatal or nonfatal myocardial infarction, coronary artery bypass surgery or percutaneous coronary intervention, identified through national hospital discharge register data. Infections were identified through national register data on all antibiotic purchases from outpatient care. Register data were available from 1 January 1995 to 31 December 2015. Bacterial lipopolysaccharide (LPS) activity was measured from serum samples at baseline. Data on traditional risk factors for CHD were collected during baseline and consecutive visits. Individuals with an incident CHD event (n=370) had a higher mean number of antibiotic purchases per follow-up year compared to those without incident CHD (1.34 [95% CI: 1.16-1.52], versus 0.79 [0.76-0.82], P<0.001), as well as higher levels of LPS activity (0.64 [0.60-0.67], versus 0.58EUmL-1 [0.57-0.59], P<0.001). In multivariable-adjusted Cox proportional hazards models, the mean number of antibiotic purchases per follow-up year was an independent risk factor for incident CHD (HR 1.21, 95% CI: 1.14-1.29, P<0.0001). High LPS activity was a risk factor for incident CHD (HR 1.93 [1.34-2.78], P<0.001) after adjusting for static confounders. Bacterial infections are associated with an increased risk of incident CHD in individuals with type 1 diabetes.

Association of Low Socioeconomic Status With Premature Coronary Heart Disease in US Adults

Individuals with low socioeconomic status (SES) bear a disproportionate share of the coronary heart disease (CHD) burden, and CHD remains the leading cause of mortality in low-income US counties. To estimate the excess CHD burden among individuals in the United States with low SES and the proportions attributable to traditional risk factors and to other factors associated with low SES. This computer simulation study used the Cardiovascular Disease Policy Model, a model of CHD and stroke incidence, prevalence, and mortality among adults in the United States, to project the excess burden of early CHD. The proportion of this excess burden attributable to traditional CHD risk factors (smoking, high blood pressure, high low-density lipoprotein cholesterol, low high-density lipoprotein cholesterol, type 2 diabetes, and high body mass index) compared with the proportion attributable to other risk factors associated with low SES was estimated. Model inputs were derived from nationally representative US data and cohort studies of incident CHD. All US adults aged 35 to 64 years, stratified by SES, were included in the simulations. Low SES was defined as income below 150% of the federal poverty level or educational level less than a high school diploma. Premature (before age 65 years) myocardial infarction (MI) rates and CHD deaths. Approximately 31.2 million US adults aged 35 to 64 years had low SES, of whom approximately 16 million (51.3%) were women. Compared with individuals with higher SES, both men and women in the low-SES group had double the rate of MIs (men: 34.8 [95% uncertainty interval (UI), 31.0-38.8] vs 17.6 [95% UI, 16.0-18.6]; women: 15.1 [95% UI, 13.4-16.9] vs 6.8 [95% UI, 6.3-7.4]) and CHD deaths (men: 14.3 [95% UI, 13.0-15.7] vs 7.6 [95% UI, 7.3-7.9]; women: 5.6 [95% UI, 5.0-6.2] vs 2.5 [95% UI, 2.3-2.6]) per 10 000 person-years. A higher burden of traditional CHD risk factors in adults with low SES explained 40% of these excess events; the remaining 60% of these events were attributable to other factors associated with low SES. Among a simulated cohort of 1.3 million adults with low SES who were 35 years old in 2015, the model projected that 250 000 individuals (19%) will develop CHD by age 65 years, with 119 000 (48%) of these CHD cases occurring in excess of those expected for individuals with higher SES. This study suggested that, for approximately one-quarter of US adults aged 35 to 64 years, low SES was substantially associated with early CHD burden. Although biomedical interventions to modify traditional risk factors may decrease the disease burden, disparities by SES may remain without addressing SES itself.

Abstract 12: Skeletal Muscle Density, Not Size, is Beneficially Associated With Incident Coronary Heart Events: The Multi-Ethnic Study of Atherosclerosis

Introduction: Fat infiltration into muscle reduces muscle density and increases the risk for metabolic dysfunction, mobility disability and mortality. We assessed abdominal muscle density and muscle area in relation to incident coronary heart disease (CHD) events. Methods: Adults (mean age 64.6 ± 9.6) from the Multi-Ethnic Study of Atherosclerosis body composition ancillary study had computed tomography (CT)-derived measures of muscle density, muscle area and visceral fat at the L2-L4 spinal column levels between 2002-05 and were followed for incident events. Using sex-stratified Cox proportional hazards regression, associations of muscle density and muscle area (in the same model) with CHD events were assessed using restricted cubic splines with adjustment for confounders including visceral adiposity and BMI. Results: After 10.3±2.9 years of follow up, 924 males had 70 CHD (7.6%) events and 945 females had 44 CHD (4.7%) events. Muscle density was higher in males (44.5±4.9 HU) than females (40.1±5.2 HU), as was muscle area (116.7±23.9 vs. 80.4±23.9 cm 2 , respectively). Among males, and in mutually adjusted models, each incremental SD of muscle density was inversely associated with CHD (HR=0.67; 95%CI=0.49-0.92), while each SD of muscle area was associated with higher risk of CHD (HR=1.75; 95%CI=1.34-2.28; Figure). Overall patterns were similar but less strong among females for density (HR=0.79; 95%CI=0.50-1.22) and area (HR=1.17; 95%CI=0.79-1.73). Conclusions: Greater muscle density is associated with lower CHD risk, while greater muscle size is associated with increased CHD risk. These associations were independent of traditional CHD risk factors and measures of visceral and total body adiposity. Quantity and quality of skeletal muscle may represent distinct aspects of aging and physical functioning that are important in heart health.

Urinary metabolites and risk of coronary heart disease: A prospective investigation among urban Chinese adults

Background and aimsStudies have linked several metabolites to the risk of coronary heart disease (CHD) among Western populations, but prospective studies among Asian populations on the metabolite–CHD association remain limited. Methods and ResultsWe evaluated the association of urinary metabolites with CHD risk among Chinese adults in a nested case–control study of 275 incident cases and 275 matched controls (127 pairs of men and 148 pairs of women). Fifty metabolites were measured by a predefined metabolomics panel and adjusted using urinary creatinine. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs). After adjusting for traditional CHD risk factors, urinary tryptophan showed a positive association with incident CHD: OR (95% CI) for the highest vs. lowest quartiles was 2.02 (1.15–3.56) among all study participants (p-trend = 0.02). The tryptophan–CHD association was more evident among individuals with dyslipidemia than among those without the condition (OR [95% CI] for the highest vs. lowest quartiles = 3.90 [1.86–8.19] and 0.74 [0.26–2.06], respectively; p-interaction<0.01). Other metabolites did not show significant associations with CHD risk among all study participants. However, a positive association of methionine with CHD risk was observed only among women (OR [95% CI] for the highest vs. lowest quartiles = 2.77 [1.17–6.58]; p-interaction = 0.03), and an inverse association of inosine with CHD risk was observed only among men (OR [95% CI] for the highest vs. lowest quartiles = 0.29 [0.11–0.81]; p-interaction = 0.04). ConclusionElevated urinary tryptophan may be related to CHD risk among Chinese adults, especially for those with dyslipidemia.

Accelerated coronary atherosclerosis not explained by traditional risk factors in 13% of young individuals

Most individuals who die of sudden cardiac death (SCD) display very advanced lesions of atherosclerosis in their coronary arteries. Thus, we sought to identify and characterize a putative subpopulation of young individuals exhibiting accelerated coronary artery atherosclerosis. Our analysis of the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study-which examined 2651 individuals, obtaining quantitative measurements of traditional risk factors for coronary heart disease (CHD)-aimed to identify individuals with advanced coronary artery lesions, and to determine whether risk factors could account for such rapid disease progression, or not. Using the cross-sectional PDAY study data, an exploratory de facto analysis stratified the population by age and observed number of coronary raised lesions and examined these groups via Poisson regression modeling. A separate de novo approach utilized Poisson mixture modeling to generate low- and high-growth groups based on measurements of traditional risk factors, and identified factors contributing to disease progression. Participants, n = 2651 individuals aged 15-34, who had died of non-cardiac death, were recruited post mortem. Tissues and other samples were harvested for analysis (details in previously published PDAY studies). Main Outcome(s) and Measure(s). Using quantitative measurements of raised coronary lesions and traditional risk factors of CHD, we sought to identify which risk factors account for disease progression. A group of ~13% of the PDAY population exhibits accelerated coronary atherosclerosis despite their young age. Several traditional risk factors were associated with increased odds of inclusion in this subgroup, reflecting current understanding of these markers of disease. However, only age was a significant contributing factor to the observed coronary lesion burden. While a range of traditional risk factors contribute to an individual's inclusion to the identified subgroup with accelerated atherosclerosis, these factors, with the exceptions of age, are not able to predict an individual's lesion burden. Moreover, unattributed variances in observations indicate the need to study novel risk factors. Hypothesis The extent of coronary atherosclerotic disease is limited and homogeneous within youth, and its progression can be accounted for by traditional risk factors in this population. A subpopulation (~13%) of the Pathobiological Determinants of Atherosclerosis in Youth cohort exhibited accelerated coronary artery atherosclerosis. While several traditional risk factors contribute to an individual's inclusion in this subgroup, these factors, with the exceptions of age, do not predict accurately an individual's lesions burden. Critically, unattributed variances in observations indicate the need for the identification of novel risk factors. Screening of the general population at a young age for high-risk group membership could provide opportunity for disease prevention and avoidance of the worse complications such as myocardial infarction and sudden cardiac death later in life.

Usefulness of Higher Levels of Cardiac Troponin T in Patients With Stable Angina Pectoris to Predict Risk of Acute Myocardial Infarction

In patients with stable angina, the association between high-sensitivity cardiac troponin T (hs-cTnT) and incident acute myocardial infarction (AMI), as well as pathophysiologic mechanisms accounting for an adverse prognosis, remain to be determined. We explored the association between hs-cTnT and future AMI among 3,882 patients evaluated for suspected stable angina pectoris and investigated to which extent hs-cTnT attenuated the relations between traditional coronary heart disease (CHD) risk factors and AMI. Associations between increasing hs-cTnT categories (≤3, 4 to 9, 10 to 19, and 20 to 30 ng/L) and risk of AMI were studied by Cox regression. We investigated whether the associations between traditional CHD risk factors and future AMI were influenced by adjusting for hs-cTnT. Median age was 62 years. During median (25th to 75th percentile) 8 (6.4 to 8.7) years of follow-up, 460 (11.8%) experienced an AMI. There was a strong association between hs-cTnT categories and risk of AMI. The relation was somewhat attenuated, but still present, when adjusting for potential confounders, traditional CHD risk factors, previous peripheral vascular disease, and percutaneous coronary intervention or coronary bypass surgery. Moreover, hs-cTnT slightly attenuated the risk relations between traditional CHD risk factors and incident AMI, but each risk factor remained significantly associated with AMI. In conclusion, among patients with suspected stable angina, hs-cTnT was positively related to incident AMI.

Plasma cystathionine and risk of acute myocardial infarction among patients with coronary heart disease: Results from two independent cohorts

BackgroundCystathionine is a thio-ether and a metabolite formed from homocysteine during transsulfuration. Elevated plasma cystathionine levels are reported in patients with cardiovascular disease; however prospective relationships with acute myocardial infarction (AMI) are unknown. We investigated associations between plasma cystathionine and AMI among patients with suspected and/or verified coronary heart disease (CHD). MethodsSubjects from two independent cohort studies, the Western Norway Coronary Angiography Cohort (WECAC) (3033 patients with stable angina pectoris; 263 events within 4.8 years of median follow-up) and the Norwegian Vitamin Trial (NORVIT) (3670 patients with AMI; 683 events within 3.2 years of median follow-up) were included. ResultsIn both cohorts, plasma cystathionine was associated with several traditional CHD risk factors (P < 0.001). Comparing the cystathionine quartile 4 to 1, age and gender adjusted hazard ratios (95% confidence intervals) for AMI were 2.08 (1.43–3.03) and 1.41 (1.12–1.76) in WECAC and NORVIT, respectively. Additional adjustment for traditional risk factors slightly attenuated the risk estimates, which were generally stronger in both cohorts among non-smokers, patients with higher age, and lower BMI or PLP status (P-interaction ≤ 0.04). Risk associations also tended to be stronger in patients not treated with B-vitamins. Additionally, in a subset of 80 WECAC patients, plasma cystathionine associated strongly negatively with glutathione, an important antioxidant and positively with lanthionine, a marker of H2S production (P < 0.001). ConclusionsPlasma cystathionine is associated with increased risk of AMI among patients with either suspected or verified coronary heart disease, and is possibly related to altered redox homeostasis.

PROSPECTIVE OUTPATIENT REGISTRY OF MYOCARDIAL INFARCTION PATIENTS (PROFILE-MI): STUDY DESIGN AND FIRST RESULTS

Aim. To characterize patients included to the registry PROFILE-MI; to present data reflecting the condition of patients before the onset of acute myocardial infarction (MI). Material and methods. Totally, 160 patients included: 106 males, 54 females — 66,2%/33,8%, respectively, consequently visited cardiologist in the City Polyclinics №9 of Moscow or one of two its branches, after hospitalization for MI. Results. Mean age of patients 70,4±10,8 (39-87) y.o., males were in average 10 years younger than women. About 40% were >60 y.o., about a half were retired, and of those most were women, ~1/3 of patients were already disabled; in ~3/4 there was arterial hypertension. For smoking and lipid disorders, in most patients there was no data: only for 29,4 and 46,9%, respectively; diabetes was found in 28,1%. Anamnesis of coronary heart disease (CHD) had been registered in anamnesis of 47 (29.4%), and most of those already experienced myocardial infarction (MI). Half of the included patients had had visited medical institutions during 2 year period before the MI event, most of them — local outpatient institutions (polyclinics), but 1/3 of patients did not request for medical help during last ≥2 years. Conclusion. Patients included to PROFILE-MI registry, had in general similar demographic and clinical parameters with other registries of MI in Russia. Most post MI patients already had cardiovascular diseases of atherosclerotic origin, or a combination of traditional CHD risk factors, so MI onset was quite predictable. Most of them were not under the coverage of primary and secondary CHD preventions before MI event.

The strength of the multivariable associations of major risk factors predicting coronary heart disease mortality is homogeneous across different areas of the Seven Countries Study during 50-year follow-up

Objectives: To compare the magnitude of multivariable coefficients and hazard ratios of four cardiovascular risk factors across five worldwide regions of the Seven Countries Study in predicting 50-year coronary deaths.Material and methods: A total of 13 cohorts of middle-aged men at entry (40–59 years old) were enrolled in the mid-1900s from five relatively homogeneous groups of cohorts (areas): USA, Finland and Zutphen – the Netherlands, Italy and Greece, Serbia, Japan for a total of 10,368 middle-aged men. The major risk factors measured at baseline were age, number of cigarettes smoked, systolic blood pressure and serum cholesterol. Cox proportional hazards models were solved for 50-year (45 years for Serbia) deaths from coronary heart disease (CHD), and the multivariable coefficients were compared for heterogeneity.Results: The highest levels of risk factors and CHD death rates were found in Finland and Zutphen – the Netherlands and the lowest in Japan. All four risk factors were predictive for long-term CHD mortality in all regions, except serum cholesterol in Japan where the mean levels and CHD events were lowest. Tests of heterogeneity of coefficients for single risk factors in predicting CHD mortality were non-significant across the five areas. The same analyses for the first 25 years of follow-up produced similar findings.Conclusions: The strength of the multivariable associations of four major traditional CHD risk factors with long-term CHD mortality appears to be relatively homogeneous across areas, pending needed further evidence.

Red blood cell folate concentrations and coronary heart disease prevalence: A cross-sectional study based on 1999–2012 National Health and Nutrition Examination Survey

Background and aimFolate is involved in a number of metabolic pathways. Red blood cell (RBC) folate is a well-established indicator of folate intake. However, studies focused on the association between RBC folate and coronary heart disease (CHD) are limited. The aim of the current study was to investigate the effect of RBC folate concentrations on the presence of CHD in a nationally representative sample of American adults. Methods and resultsIn the 1999–2012 National Health and Nutrition Examination Survey (NHANES), 22,499 subjects aged 30–74 years with RBC folate concentrations, CHD status and responses to co-variates questions were included; 822 (3.65%) participants were identified as having CHD. Bio-Rad Quanta Phase II radioassay and microbiological assay were used to measure RBC folate concentrations. Firstly, we treated RBC folate as a categorical variable, based on RBC folate tertiles, and used logistic regression analysis to display the RBC folate and CHD relationship. Secondly, we explored associations using a combination of restricted cubic spline and logistic regression models, stratified by sex. After adjusting for several well-established traditional CHD risk factors, RBC folate was positively related to CHD presence in the total population and the association was more pronounced among males than females. A J-shaped pattern was observed in RBC folate concentrations for females. ConclusionElevated RBC folate concentrations were associated with higher CHD risk. Further investigation is needed to test the association in large-scale follow-up studies.

3-year risk prediction of Coronary Heart Disease in hypertension patients: A preliminary study.

Hypertension is associated with increased morbidity and mortality in Coronary Heart Disease (CHD). However, the risk factors that cause hypertension patients develop into CHD remain unclear. This paper aims to study traditional and nontraditional risk factors of CHD in hypertension population. Data were extracted from the regional medical big data system of Shenzhen, a big city of China. In this study, we included 3395 hypertension patients aged from 30 to 79 years old. Among them, 1153 CHD events occurred within 3 years after they were first followed-up. A logistic regression model was used to evaluate the risk factors quantitatively and predict 3-year risk of CHD events. The results showed that traditional general-population-based CHD risk factors such as age, body mass index, diabetes, hyperlipemia, and chronic kidney disease still remained predictive in hypertension patients. In addition, the odds ratio (95% confidence interval) of CHD was 1.54 (1.19 to 2.01) for emotional or mental disorders, and 1.69 (1.21 to 2.34) for sleep disorders. And the model showed a good discriminative performance with an AUC of 0.839. It offered a new insight for hypertension patients that keeping psychological health and maintaining a good sleep quality could be helpful in preventing CHD. Given the high risk for CHD in patients with hypertension, control of these risk factors may have a substantial preventive effect on CHD.

Combination of susceptibility gene and traditional risk factors might enhance the performance of coronary heart disease screening strategy.

Coronary heart disease (CHD) associated risk factors and susceptibility genes were studied in parallel for decades, however, the combination of the classic CHD risk factors and genetic risk factors has been rarely studied. Previously; we reported that a single nucleotide polymorphism (SNP) in the stromal cell-derived factor 1 (SDF-1) gene was associated with CHD risk; in addition, we also established a CHD screening strategy using traditional CHD risk factors as independent variables. To explore how to combine genetic factors and traditional risk factors in CHD screening strategy, the CHD probabilities were tested in 218 males and 121 females according to their stromal cell-derived factor 1 (SDF-1) genotypes using CHD screening equations we reported previously. The genotypes had not altered the distribution characteristics of age, high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), lipoprotein(a) (LP(a)), homocysteine (HCY) and total bilirubin (TBil) in males and age, HDL-C, HCY and γ-glutamyl transpeptidase (GGT) in females among genotypes. However, the mean CHD probability of subjects with G/G genotype was significantly higher than that of subjects with A/A genotype (0.51 ± 0.35 vs. 0.31 ± 0.31, P = 0.035). The mean CHD probability of subjects with G homozygous and G heterozygote was 0.48 ± 0.34 which displayed a difference trend to that of subjects with A homozygous (0.31 ± 0.31, P = 0.059). Our data suggested that genetic risk factors might be used as a classification standard to improve current CHD screening strategies.

Association of Sickle Cell Trait with Risk of Coronary Heart Disease in African Americans

BackgroundThe incidence of and mortality from coronary heart disease (CHD) is significantly higher among African Americans (AAs) compared to Whites, even after adjusting for traditional CHD risk factors. Studies suggests that the unexplained excess risk might be the result of genetic modifiers associated with African ancestry conferring a higher risk of CHD. One such gene variant is the sickle cell mutation. The heterozygous state, or sickle cell trait (SCT), with a prevalence of 8 - 12% among AAs, was previously deemed clinically benign; however, recent evidence indicates that SCT is associated with increased risk of chronic kidney disease venous thromboembolism and sudden death following exertion. Individuals with SCT have higher circulating levels of C-reactive protein, fibrinogen, prothrombin fragment 1.2 and D-dimer. We hypothesized that AAs with SCT have a higher risk for myocardial infarction (MI) and coronary heart disease (CHD) than AAs who are homozygous for wild-type hemoglobin.MethodsWe obtained genotype and phenotype data from the Women's Health Initiative (WHI) REasonsfor Geographic and Racial Differences in Stroke (REGARDS), Multi-Ethnic Study of Atherosclerosis (MESA), Jackson Heart Study (JHS) and Atherosclerosis Risk In Communities (ARIC) cohorts. The outcomes were incident MI or CHD. Incident MI was defined as adjudicated non-fatal or fatal MI, while incident CHD was defined as 1) adjudicated non-fatal MI, 2) fatal MI, 3) documented coronary revascularization procedures or 4) non-MI CHD death. SCT status was determined by either direct genotyping or imputation for rs334 using the 1000Genome reference panel. Homozygous individuals and those with a prior history of CHD were excluded. Individuals with incident “micro MI”, only defined in REGARDS, were also excluded from the analysis. Analysis was performed separately in each cohort using a Cox proportional hazard models to estimate the hazard ratio (HR) for incident MI or CHD comparing SCT carriers to non-carriers. Models in each cohort were adjusted for age, sex, study site or region of residence, hypertension or systolic blood pressure, diabetes, serum LDL or HDL or total cholesterol, and population stratification (using principal components of global ancestry). The results from each cohorts were then meta-analyzed using a random effect model due to significant heterogeneity between studies (I2 = 39.1%, p = 0.02 for MI meta-analysis and I2 = 56%, p = 0.01 for CHD meta-analysis).ResultsA total of 20,053 African American men and women were included in the combined sample; 1503 with SCT (7.5% prevalence). Average ages in years at baseline were: 65.0±6.0 in WHI (N = 2248), 62.0 ± 9.2 in REGARDS (N = 10573); 62.2±10.2 in MESA (N = 1556); 50.0 ± 11.9 in JHS (N = 2133); and 54.0 ± 6.0 in ARIC (N = 3543). There were no statistically significant differences in the distribution of traditional cardiovascular risk factors by SCT status within cohorts, except that atrial fibrillation was more prevalent among REGARDS participants with SCT compared to those without SCT (9.9% vs. 7.8%, p = 0.03). The crude incidence rate of MI per 1000 person years in those with SCT compared to those without SCT was: 4.0 vs. 5.2 in WHI; 5.7 vs. 5.0 in REGARDS; 5.8 vs 4.3 in MESA, 2.0 vs 2.1 in JHS; and 4.1 vs 5.9 in ARIC. For CHD, the crude incidence rate was: 5.8 vs. 7.2 in WHI, 8.9 vs. 7.4 in REGARDS; 15.4 vs. 6.4 in MESA; 3.4 vs. 3.4 in JHS; and 10.5 vs. 9.5 in ARIC.The HR (95% CI) for MI was: 0.96 (0.49 - 1.89) in WHI; 1.27 (0.8 - 2.0) in REGARDS; 1.84 (0.74 - 4.60) in MESA; 1.24 (0.28 - 5.44) in JHS; and 0.68 (0.42 - 1.10) in ARIC. And that for CHD was: 1.05 (0.63 - 1.74) in WHI; 1.49 (1.01 - 2.18) in REGARDS; 2.82 (1.48 - 5.38) in MESA; 1.45 (0.50 - 4.19) in JHS; and 1.10 (0.80 - 1.50) in ARIC. Meta-analysis showed that, while SCT status was not significantly associated with incident MI (1.10 [0.73 - 1.64]), it was significantly associated with incident CHD (1.42 [1.02 - 1.98] Figures 1a and 1b).ConclusionsThis study showed a significant association between SCT and incident CHD, but not MI. Our conclusion is limited by the significant heterogeneity that existed between studies. Since SCT status was not associated with MI, but was associated with CHD, further work is needed to confirm these findings, determine which CHD component(s) explain the observed association and elucidate the possible mechanism(s) involved. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Abstract P192: Metabolomic Profiles Associated with Coronary Heart Disease in Women

Background: Prior studies of metabolomic profiles and coronary heart disease (CHD) have been limited by relatively small case numbers and scant data in women. Methods: The discovery set examined 371 metabolites in 400 confirmed, incident CHD cases and 400 controls (frequency matched on age, race/ethnicity, hysterectomy status and time of enrollment) in the Women’s Health Initiative Observational Study (WHI-OS). All selected metabolites were validated in a separate set of 394 cases and 397 matched controls drawn from the placebo arms of the WHI Hormone Therapy trials and the WHI-OS. Discovery used 4 methods: false-discovery rate (FDR) adjusted logistic regression for individual metabolites, permutation corrected least absolute shrinkage and selection operator (LASSO) algorithms, sparse partial least squares discriminant analysis (PLS-DA) algorithms, and random forest algorithms. Each method was performed with matching factors only and with matching plus both medication use (aspirin, statins, anti-diabetics and anti-hypertensives) and traditional CHD risk factors (smoking, systolic blood pressure, diabetes, total and HDL cholesterol). Replication in the validation set was defined as a logistic regression coefficient of p&lt;0.05 for the metabolites selected by 3 or 4 methods (tier 1), or a FDR adjusted p&lt;0.05 for metabolites selected by only 1 or 2 methods (tier 2). Results: Sixty-seven metabolites were selected in the discovery data set (30 tier 1 and 37 tier 2). Twenty-six successfully replicated in the validation data set (21 tier 1 and 5 tier 2), with 25 significant with adjusting for matching factors only and 11 significant after additionally adjusting for medications and CHD risk factors. Validated metabolites included amino acids, sugars, nucleosides, eicosanoids, plasmologens, polyunsaturated phospholipids and highly saturated triglycerides. These include novel metabolites as well as metabolites such as glutamate/glutamine, which have been shown in other populations. Conclusions: Multiple metabolites in important physiological pathways with robust associations for risk of CHD in women were identified and replicated. These results may offer insights into biological mechanisms of CHD as well as identify potential markers of risk.

Ethnic Minorities and Coronary Heart Disease: an Update and Future Directions.

Heart disease remains the leading cause of death in the USA. Overall, heart disease accounts for about 1 in 4 deaths with coronary heart disease (CHD) being responsible for over 370,000 deaths per year. It has frequently and repeatedly been shown that some minority groups in the USA have higher rates of traditional CHD risk factors, different rates of treatment with revascularization procedures, and excess morbidity and mortality from CHD when compared to the non-Hispanic white population. Numerous investigations have been made into the causes of these disparities. This review aims to highlight the recent literature which examines CHD in ethnic minorities and future directions in research and care.

C-reactive protein and serum creatinine, but not haemoglobin A1c, are independent predictors of coronary heart disease risk in non-diabetic Chinese.

In western populations, high-sensitivity C-reactive protein (hsCRP), and to a lesser degree serum creatinine and haemoglobin A1c, predict risk of coronary heart disease (CHD). However, data on Asian populations that are increasingly affected by CHD are sparse and it is not clear whether these biomarkers can be used to improve CHD risk classification. We conducted a nested case-control study within the Singapore Chinese Health Study cohort, with incident 'hard' CHD (myocardial infarction or CHD death) as an outcome. We used data from 965 men (298 cases, 667 controls) and 528 women (143 cases, 385 controls) to examine the utility of hsCRP, serum creatinine and haemoglobin A1c in improving the prediction of CHD risk over and above traditional risk factors for CHD included in the ATP III model. For each sex, the performance of models with only traditional risk factors used in the ATP III model was compared with models with the biomarkers added using weighted Cox proportional hazards analysis. The impact of adding these biomarkers was assessed using the net reclassification improvement index. For men, loge hsCRP (hazard ratio 1.25, 95% confidence interval: 1.05; 1.49) and loge serum creatinine (hazard ratio 4.82, 95% confidence interval: 2.10; 11.04) showed statistically significantly associations with CHD risk when added to the ATP III model. We did not observe a significant association between loge haemoglobin A1c and CHD risk (hazard ratio 1.83, 95% confidence interval: 0.21; 16.06). Adding hsCRP and serum creatinine to the ATP III model improved risk classification in men with a net gain of 6.3% of cases (p-value = 0.001) being reclassified to a higher risk category, while it did not significantly reduce the accuracy of classification for non-cases. For women, squared hsCRP was borderline significantly (hazard ratio 1.01, 95% confidence interval: 1.00; 1.03) and squared serum creatinine was significantly (hazard ratio 1.81, 95% confidence interval: 1.49; 2.21) associated with CHD risk. However, the association between squared haemoglobin A1c and CHD risk was not significant (hazard ratio 1.05, 95% confidence interval: 0.99; 1.12). The addition of hsCRP and serum creatinine to the ATP III model resulted in 3.7% of future cases being reclassified to a higher risk category (p-value = 0.025), while it did not significantly reduce the accuracy of classification for non-cases. Adding hsCRP and serum creatinine, but not haemoglobin A1c, to traditional risk factors improved CHD risk prediction among non-diabetic Singaporean Chinese. The improved risk estimates will allow better identification of individuals at high risk of CHD than existing risk calculators such as the ATP III model.

Review of Cardiovascular Disease in HIV-Infected Women

Rates of coronary heart disease (CHD) are over twice as high in younger HIV-infected patients compared to uninfected patients, but most of these studies were conducted in men or in predominantly male cohorts. In the general population, the death rate from CHD has decreased among men, but continues to increase in women. It is unclear if the same increased rate of deaths due to CHD exist in HIV-infected women, and whether rates or risk of CHD differ between HIV-infected men and women, and between seropositive and seronegative women. We reviewed the literature on the rates of cardiovascular events and surrogate measures of atherosclerosis or CHD risk in HIV-infected women. We also reviewed rates of metabolic disease and other markers of inflammation and immune activation that could contribute to increased cardiovascular risk. We found that HIV-infected women have increased rates of acute myocardial infarctions and ischemic strokes compared to HIV-uninfected women and likely HIV-infected men despite women being projected to have lower CHD risk based on Framingham risk scores. Studies assessing CHD risk by measuring anatomical or physiological measures of subclinical atherosclerosis have reported mixed results, and there are no well-validated risk assessment tools or surrogate measures of subclinical CHD among HIV-infected patients to help identify high-risk women for targeting intensive preventive measures. Potential explanations for the increased rates of CHD and subclinical atherosclerosis may be partly explained by increased levels of inflammation and immune activation in HIV-infected women despite virological suppression on antiretroviral therapy. It appears unlikely that disproportionate representation of traditional CHD risk factors and metabolic indices among HIV-infected women can explain well the observed increased rates of CHD. Future studies that include large numbers of HIV-infected women with extended follow-up periods using surrogate measure of CVD and investigating pathogenic mechanisms underlying these observations are urgently needed.