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Background and Aims: Our study examined the trends of cardiovascular health metrics in individuals with coronary heart disease (CHD) and their associations with all-cause and cardiovascular disease mortality in the US., Methods and Results: The cohort study was conducted based on the National Health and Nutrition Examination Survey 1999-2018 and their linked mortality files (through 2019). Baseline CHD was defined as a composite of self-reported doctor-diagnosed coronary heart disease, myocardial infarction, and angina pectoris. Cardiovascular health metrics were assessed according to the American Heart Association recommendations. Long-term all-cause and cardiovascular disease mortality were the primary outcomes. Survey-adjusted Cox regression models were used to estimate hazard ratios and corresponding 95% confidence intervals for the associations between cardiovascular health metrics and all-cause and cardiovascular disease mortality. The prevalence of one or fewer ideal cardiovascular health metrics increased from 14.15% to 22.79% (P < 0.001) in CHD, while the prevalence of more than four ideal cardiovascular health metrics decreased from 21.65% to 15.70 % (P < 0.001) from 1999 to 2018, respectively. Compared with CHD participants with one or fewer ideal cardiovascular health metrics, those with four or more ideal cardiovascular health metrics had a 35% lower risk (hazard ratio, 0.65; 95% confidence interval: 0.51, 0.82) and a 44% lower risk (0.56; 0.38, 0.84) in all-cause and cardiovascular disease mortality, respectively., Conclusion: Substantial declines were noted in ideal cardiovascular health metrics in US adults with CHD. A higher number of cardiovascular health metrics was associated with lower all-cause and cardiovascular disease mortality in them., Competing Interests: Conflict of interest None declared., (Copyright © 2024 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Background: Social determinants of health (SDoH) are associated with cardiovascular risk factors and outcomes; however, they are absent from risk prediction models. We aimed to assess if the addition of SDoH improves the predictive ability of the MESA (Multi-Ethnic Study of Atherosclerosis) Risk Score., Methods and Results: This was a community-based prospective population cohort study that enrolled 6286 men and women, ages 45-84 years, who were free of clinical coronary heart disease (CHD) at baseline. Data from 10-year follow-up were examined for CHD events, defined as myocardial infarction, fatal CHD, resuscitated cardiac arrest, and revascularization in cases of anginal symptoms. Participants included 53% women with average age of 62 years. When adjusting for traditional cardiovascular risk factors, SDoH, and coronary artery calcium, economic strain, specifically low family income, was associated with a greater risk of CHD events (hazard ratio [HR], 1.42 [95% CI, 1.17-1.71], P value<0.001). Area under the curve of risk prediction with SDoH was 0.822, compared with 0.816 without SDoH. The calibration slope was 0.860 with SDoH and 0.878 in the original model., Conclusions: Significant associations were found between economic/financial SDoH and CHD risk factors and outcomes. Incorporation of SDoH into the MESA Risk Score did not improve predictive ability of the model. Our findings do not support the incorporation of SDoH into current risk prediction algorithms.

Background: Comprehensive blood lipoprotein profiles and their association with incident coronary heart disease (CHD) among racially and geographically diverse populations remain understudied., Methods and Results: We conducted nested case-control studies of CHD among 3438 individuals (1719 pairs), including 1084 White Americans (542 pairs), 1244 Black Americans (622 pairs), and 1110 Chinese adults (555 pairs). We examined 36 plasma lipids, lipoproteins, and apolipoproteins, measured by nuclear magnetic resonance spectroscopy, with incident CHD among all participants and subgroups by demographics, lifestyle, and metabolic health status using conditional or unconditional logistic regression adjusted for potential confounders. Conventionally measured blood lipids, that is, total cholesterol, triglycerides, low-density lipoprotein-cholesterol, and high-density lipoprotein-cholesterol, were each associated with incident CHD, with odds ratios (ORs) being 1.33, 1.32, 1.24, and 0.79 per 1-SD increase among all participants. Seventeen lipoprotein biomarkers showed numerically stronger associations than conventional lipids, with ORs per 1-SD among all participants ranging from 1.35 to 1.57 and a negative OR of 0.78 (all false discovery rate <0.05), including apolipoprotein B100 to apolipoprotein A1 ratio (OR, 1.57 [95% CI, 1.45-1.7]), low-density lipoprotein-triglycerides (OR, 1.55 [95% CI, 1.43-1.69]), and apolipoprotein B (OR, 1.49 [95% CI, 1.37-1.62]). All these associations were significant and consistent across racial groups and other subgroups defined by age, sex, smoking, obesity, and metabolic health status, including individuals with normal levels of conventionally measured lipids., Conclusions: Our study highlighted several lipoprotein biomarkers, including apolipoprotein B/ apolipoprotein A1 ratio, apolipoprotein B, and low-density lipoprotein-triglycerides, strongly and consistently associated with incident CHD. Our results suggest that comprehensive lipoprotein measures may complement the standard lipid panel to inform CHD risk among diverse populations.

Background: The 2023 Multisociety Guideline for the Management of Chronic Coronary Disease (CCD) updates recommendations for CCD, formerly known as "stable ischemic heart disease." This condition encompasses a spectrum of coronary vascular pathologies from subclinical to clinical ischemic heart disease., Hypothesis: The new "ABC" mnemonic offers clinicians a streamlined framework for applying Class One Recommendations (COR1) and integrating recent updates into CCD management., Methods: A critical analysis of the 2023 CCD guidelines was conducted, with this review highlighting key elements., Results: The review outlines crucial changes, including novel recommendations supported by current clinical evidence. The focus is on these developments, clarifying their importance for day-to-day clinical practice., Conclusions: The review encourages a synergistic approach between primary healthcare providers and cardiologists to develop comprehensive strategies for lifestyle modification and medication therapy in CCD care. Furthermore, it suggests that utilizing comprehensive risk assessment tools can refine medical decision-making, ultimately enhancing patient care and clinical outcomes., (© 2024 The Author(s). Clinical Cardiology published by Wiley Periodicals LLC.)

Background: Dyslipidemia is an independent risk factor for coronary heart disease (CHD). Standard lipid panel cannot capture the complexity of the blood lipidome (ie, all molecular lipids in the blood). To date, very few large-scale epidemiological studies have assessed the full spectrum of the blood lipidome on risk of CHD, especially in a longitudinal setting., Methods and Results: Using an untargeted liquid chromatography-mass spectrometry, we repeatedly measured 1542 lipid species from 1835 unique American Indian participants who attended 2 clinical visits (≈5.5 years apart) and followed up to 17.8 years in the Strong Heart Family Study (SHFS). We first identified baseline lipid species associated with risk of CHD, followed by replication in a European population. The model adjusted for age, sex, body mass index, smoking, hypertension, diabetes, low-density lipoprotein cholesterol, estimated glomerular filtration rate, education, and physical activity at baseline. We then examined the longitudinal association between changes in lipid species and changes in cardiovascular risk factors during follow-up. Multiple testing was controlled by the false discovery rate. We found that baseline levels of multiple lipid species (eg, phosphatidylcholines, phosphatidylethanolamines, and ceramides) were associated with the risk of CHD and improved the prediction accuracy over conventional risk factors in American Indian people. Some identified lipids in American Indian people were replicated in European people. Longitudinal changes in multiple lipid species (eg, acylcarnitines, phosphatidylcholines, and triacylglycerols) were associated with changes in cardiovascular risk factors., Conclusions: Baseline plasma lipids and their longitudinal changes over time are associated with risk of CHD. These findings provide novel insights into the role of dyslipidemia in CHD.

Background: Screening for cardiovascular disease is currently recommended before kidney transplantation. The present study aimed to validate the proposed algorithm by the American Heart Association (AHA-2022) considering cardiovascular findings and outcomes in kidney transplant candidates, and to compare AHA-2022 with the previous recommendation (AHA-2012)., Methods and Results: We applied the 2 screening algorithms to an observational cohort of kidney transplant candidates (n=529) who were already extensively screened for coronary heart disease by referral to cardiac computed tomography between 2014 and 2019. The cohort was divided into 3 groups as per the AHA-2022 algorithm, or into 2 groups as per AHA-2012. Outcomes were degree of coronary heart disease, revascularization rate following screening, major adverse cardiovascular events, and all-cause death. Using the AHA-2022 algorithm, 69 (13%) patients were recommended for cardiology referral, 315 (60%) for cardiac screening, and 145 (27%) no further screening. More patients were recommended cardiology referral or screening compared with the AHA-2012 (73% versus 53%; P <0.0001). Patients recommended cardiology referral or cardiac screening had a higher risk of major adverse cardiovascular events (hazard ratio [HR], 5.5 [95% CI, 2.8-10.8]; and HR, 2.1 [95% CI, 1.2-3.9]) and all-cause death (HR, 12.0 [95% [CI, 4.6-31.4]; and HR, 5.3 [95% CI, 2.1-13.3]) compared with patients recommended no further screening, and were more often revascularized following initial screening (20% versus 7% versus 0.7%; P <0.001)., Conclusions: The AHA-2022 algorithm allocates more patients for cardiac referral and screening compared with AHA-2012. Furthermore, the AHA-2022 algorithm effectively discriminates between kidney transplant candidates at high, intermediate, and low risk with respect to major adverse cardiovascular events and all-cause death.

Introduction: Although a recent joint society scientific statement (the American Association of Cardiovascular Pulmonary Rehabilitation, the American Heart Association, and the American College of Cardiology) suggests home-based cardiac rehab (CR) is appropriate for low- and moderate-risk patients, there are no paradigms to define such individuals with coronary heart disease., Methods: We reviewed a decade of data from all patients with coronary heart disease enrolled in a single CR center (University of Michigan) to identify the prevalence of low-risk factors, which may inform on consideration for participation in alternative models of CR. Low-risk factors included not having any of the following: metabolic syndrome, presence of implantable cardioverter defibrillator or permanent pacemaker, active smoking, prior stroke, congestive heart failure, obesity, advanced renal disease, poor exercise capacity, peripheral arterial disease, angina, or clinical depression (MI'S SCOREPAD). We report on the proportion of participants with these risk factors and the proportion with all of these low-risk factors., Results: The mean age of CR participants ( n = 1984) was 63 years; 25% were women, and 82% were non-Hispanic White. The mean number of low-risk factors was 8.5, which was similar in the 2011-2012 and 2018-2019 cohorts (8.5 vs. 8.3, respectively, P = 0.08). Additionally, 9.3% of the 2011-2012 cohort and 7.6% of the 2018-2019 cohort had all 11 of the low-risk factors., Conclusion: In this observational study, we provide a first paradigm of identifying factors among coronary heart disease patients that may be considered low-risk and likely high-gain for participation in alternative models of CR. Further work is needed to track clinical outcomes in patients with these factors to determine thresholds for enrolling participants in alternative forms of CR., Competing Interests: Brandt reports research funding from the National Institutes of Health and the Blue Cross Blue Shield of Michigan Foundation. He has received consulting fees from New Amsterdam Pharmaceuticals., (Copyright © 2023 Eric J. Brandt et al.)

Importance: Testing for coronary heart disease (CHD) in asymptomatic kidney transplant candidates before transplant is widespread and endorsed by various professional societies, but its association with perioperative outcomes is unclear., Objective: To estimate the association of pretransplant CHD testing with rates of death and myocardial infarction (MI)., Design, Setting, and Participants: This retrospective cohort study included all adult, first-time kidney transplant recipients from January 2000 through December 2014 in the US Renal Data System with at least 1 year of Medicare enrollment before and after transplant. An instrumental variable (IV) analysis was used, with the program-level CHD testing rate in the year of the transplant as the IV. Analyses were stratified by study period, as the rate of CHD testing varied over time. A combination of US Renal Data System variables and Medicare claims was used to ascertain exposure, IV, covariates, and outcomes., Exposures: Receipt of nonurgent invasive or noninvasive CHD testing during the 12 months preceding kidney transplant., Main Outcomes and Measures: The primary outcome was a composite of death or acute MI within 30 days of after kidney transplant., Results: The cohort comprised 79 334 adult, first-time kidney transplant recipients (30 147 women [38%]; 25 387 [21%] Black and 48 394 [61%] White individuals; mean [SD] age of 56 [14] years during 2012 to 2014). The primary outcome occurred in 4604 patients (244 [5.3%]; 120 [2.6%] death, 134 [2.9%] acute MI). During the most recent study period (2012-2014), the CHD testing rate was 56% in patients in the most test-intensive transplant programs (fifth IV quintile) and 24% in patients at the least test-intensive transplant program (first IV quintile, P < .001); this pattern was similar across other study periods. In the main IV analysis, compared with no testing, CHD testing was not associated with a change in the rate of primary outcome (rate difference, 1.9%; 95% CI, 0%-3.5%). The results were similar across study periods, except for 2000 to 2003, during which CHD testing was associated with a higher event rate (rate difference, 6.8%; 95% CI, 1.8%-12.0%)., Conclusions and Relevance: The results of this cohort study suggest that pretransplant CHD testing was not associated with a reduction in early posttransplant death or acute MI. The study findings potentially challenge the ubiquity of CHD testing before kidney transplant and should be confirmed in interventional studies.

Background: Racial differences in metabolomic profiles may reflect underlying differences in social determinants of health by self-reported race and may be related to racial disparities in coronary heart disease (CHD) among women in the United States. However, the magnitude of differences in metabolomic profiles between Black and White women in the United States has not been well-described. It also remains unknown whether such differences are related to differences in CHD risk., Methods: Plasma metabolomic profiles were analyzed using liquid chromatography-tandem mass spectrometry in the WHI-OS (Women's Health Initiative-Observational Study; 138 Black and 696 White women), WHI-HT trials (WHI-Hormone Therapy; 156 Black and 1138 White women), MESA (Multi-Ethnic Study of Atherosclerosis; 114 Black and 219 White women), JHS (Jackson Heart Study; 1465 Black women with 107 incident CHD cases), and NHS (Nurses' Health Study; 2506 White women with 136 incident CHD cases). First, linear regression models were used to estimate associations between self-reported race and 472 metabolites in WHI-OS (discovery); findings were replicated in WHI-HT and validated in MESA. Second, we used elastic net regression to construct a racial difference metabolomic pattern (RDMP) representing differences in the metabolomic patterns between Black and White women in the WHI-OS; the RDMP was validated in the WHI-HT and MESA. Third, using conditional logistic regressions in the WHI (717 CHD cases and 719 matched controls), we examined associations of metabolites with large differences in levels by race and the RDMP with risk of CHD, and the results were replicated in Black women from the JHS and White women from the NHS., Results: Of the 472 tested metabolites, levels of 259 (54.9%) metabolites, mostly lipid metabolites and amino acids, significantly differed between Black and White women in both WHI-OS and WHI-HT after adjusting for baseline characteristics, socioeconomic status, lifestyle factors, baseline health conditions, and medication use (false discovery rate <0.05); similar trends were observed in MESA. The RDMP, composed of 152 metabolites, was identified in the WHI-OS and showed significantly different distributions between Black and White women in the WHI-HT and MESA. Higher RDMP quartiles were associated with an increased risk of incident CHD (odds ratio=1.51 [0.97-2.37] for the highest quartile comparing to the lowest; P trend =0.02), independent of self-reported race and known CHD risk factors. In race-stratified analyses, the RDMP-CHD associations were more pronounced in White women. Similar patterns were observed in Black women from the JHS and White women from the NHS., Conclusions: Metabolomic profiles significantly and substantially differ between Black and White women and may be associated with CHD risk and racial disparities in US women.

Background: Understanding the effect of lifestyle and genetic risk on the lifetime risk of coronary heart disease (CHD) is important to improving public health initiatives. Our objective was to quantify remaining lifetime risk and years free of CHD according to polygenic risk and the American Heart Association's Life's Simple 7 (LS7) guidelines in a population-based cohort study., Methods: Our analysis included data from participants of the ARIC (Atherosclerosis Risk in Communities) study: 8372 White and 2314 Black participants; 45 years of age and older; and free of CHD at baseline examination. A polygenic risk score (PRS) comprised more than 6 million genetic variants was categorized into low (<20th percentile), intermediate, and high (>80th percentile). An overall LS7 score was calculated at baseline and categorized into "poor," "intermediate," and "ideal" cardiovascular health. Lifetime risk and CHD-free years were computed according to polygenic risk and LS7 categories., Results: The overall remaining lifetime risk was 27%, ranging from 16.6% in individuals with an ideal LS7 score to 43.1% for individuals with a poor LS7 score. The association of PRS with lifetime risk differed according to ancestry. In White participants, remaining lifetime risk ranged from 19.8% to 39.3% according to increasing PRS categories. Individuals with a high PRS and poor LS7 had a remaining lifetime risk of 67.1% and 15.9 fewer CHD-free years than did those with intermediate polygenic risk and LS7 scores. In the high-PRS group, ideal LS7 was associated with 20.2 more CHD-free years compared with poor LS7. In Black participants, remaining lifetime risk ranged from 19.1% to 28.6% according to increasing PRS category. Similar lifetime risk estimates were observed for individuals of poor LS7 regardless of PRS category. In the high-PRS group, an ideal LS7 score was associated with only 4.5 more CHD-free years compared with a poor LS7 score., Conclusions: Ideal adherence to LS7 recommendations was associated with lower lifetime risk of CHD for all individuals, especially in those with high genetic susceptibility. In Black participants, adherence to LS7 guidelines contributed to lifetime risk of CHD more so than current PRSs. Improved PRSs are needed to properly evaluate genetic susceptibility for CHD in diverse populations.

Background: We examined the relationship between ratios of select biomarkers of kidney and liver function on all-cause and coronary heart disease (CHD) mortality, both in isolation, and in combination with metabolic syndrome (MetS), among adults (20 + years, n = 10,604)., Methods: Data was derived from the U.S. National Health and Nutrition Examination Survey (1999-2016) including public-use linked mortality follow-up files through December 31, 2015., Results: Select biomarker ratios of kidney (UACR or albuminuria and BUN-CR) and liver (AST-ALT and GGT-ALP) function in isolation and in combination with MetS were associated with all-cause and CHD mortality. Compared to individuals with neither elevated biomarker ratios nor MetS (HR = 1.00, referent), increased risk of all-cause mortality was observed in the following groups: MetS with elevated UACR (HR, 95% CI = 2.57, 1.99-3.33), MetS with elevated AST-ALT (HR = 2.22, 1.61-3.07), elevated UACR without MetS (HR = 2.12, 1.65-2.72), and elevated AST-ALT without MetS (HR = 1.71, 1.35-2.18); no other biomarker ratios were associated with all-cause mortality. For cause-specific deaths, elevated risk of CHD mortality was associated with MetS with elevated UACR (HR = 1.67, 1.05-2.67), MetS with elevated AST-ALT (HR = 2.80, 1.62-4.86), and elevated BUN-CR without MetS (HR = 2.12, 1.12-4.04); no other biomarker ratios were associated with CHD mortality., Conclusion: Future longitudinal studies are necessary to examine the utility of these biomarker ratios in risk stratification for chronic disease management., (© 2021. The Author(s).)

Background: Highly fragmented ambulatory care (i.e., care spread across many providers without a dominant provider) has been associated with excess tests, procedures, emergency department visits, and hospitalizations. Whether fragmented care is associated with worse health outcomes, or whether any association varies with health status, is unclear., Objective: To determine whether fragmented care is associated with the risk of incident coronary heart disease (CHD) events, overall and stratified by self-rated general health., Design and Participants: We conducted a secondary analysis of the nationwide prospective Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort study (2003-2016). We included participants who were ≥ 65 years old, had linked Medicare fee-for-service claims, and had no history of CHD (N = 10,556)., Main Measures: We measured fragmentation with the reversed Bice-Boxerman Index. We used Cox proportional hazards models to determine the association between fragmentation as a time-varying exposure and adjudicated incident CHD events in the 3 months following each exposure period., Key Results: The mean age was 70 years; 57% were women, and 34% were African-American. Over 11.8 years of follow-up, 569 participants had CHD events. Overall, the adjusted hazard ratio (HR) for the association between high fragmentation and incident CHD events was 1.14 (95% confidence interval (CI) 0.92, 1.39). Among those with very good or good self-rated health, high fragmentation was associated with an increased hazard of CHD events (adjusted HR 1.35; 95% CI 1.06, 1.73; p = 0.01). Among those with fair or poor self-rated health, high fragmentation was associated with a trend toward a decreased hazard of CHD events (adjusted HR 0.54; 95% CI 0.29, 1.01; p = 0.052). There was no association among those with excellent self-rated health., Conclusion: High fragmentation was associated with an increased independent risk of incident CHD events among those with very good or good self-rated health.

Objective: HDL (high-density lipoprotein) contains functional proteins that define single subspecies, each comprising 1% to 12% of the total HDL. We studied the differential association with coronary heart disease (CHD) of 15 such subspecies. Approach and Results: We measured plasma apoA1 (apolipoprotein A1) concentrations of 15 protein-defined HDL subspecies in 4 US-based prospective studies. Among participants without CVD at baseline, 932 developed CHD during 10 to 25 years. They were matched 1:1 to controls who did not experience CHD. In each cohort, hazard ratios for each subspecies were computed by conditional logistic regression and combined by meta-analysis. Higher levels of HDL subspecies containing alpha-2 macroglobulin, CoC3 (complement C3), HP (haptoglobin), or PLMG (plasminogen) were associated with higher relative risk compared with the HDL counterpart lacking the defining protein (hazard ratio range, 0.96-1.11 per 1 SD increase versus 0.73-0.81, respectively; P for heterogeneity <0.05). In contrast, HDL containing apoC1 or apoE were associated with lower relative risk compared with the counterpart (hazard ratio, 0.74; P =0.002 and 0.77, P =0.001, respectively)., Conclusions: Several subspecies of HDL defined by single proteins that are involved in thrombosis, inflammation, immunity, and lipid metabolism are found in small fractions of total HDL and are associated with higher relative risk of CHD compared with HDL that lacks the defining protein. In contrast, HDL containing apoC1 or apoE are robustly associated with lower risk. The balance between beneficial and harmful subspecies in a person's HDL sample may determine the risk of CHD pertaining to HDL and paths to treatment.

Background: Elevated lipoprotein(a) (Lp[a]) and family history (FHx) of coronary heart disease (CHD) are individually associated with cardiovascular risk, and Lp(a) is commonly measured in those with FHx., Objectives: The aim of this study was to determine independent and joint associations of Lp(a) and FHx with atherosclerotic cardiovascular disease (ASCVD) and CHD among asymptomatic subjects., Methods: Plasma Lp(a) was measured and FHx was ascertained in 2 cohorts. Elevated Lp(a) was defined as the highest race-specific quintile. Independent and joint associations of Lp(a) and FHx with cardiovascular risk were determined using Cox regression models adjusted for cardiovascular risk factors., Results: Among 12,149 ARIC (Atherosclerosis Risk In Communities) participants (54 years, 56% women, 23% black, 44% with FHx), 3,114 ASCVD events were observed during 21 years of follow-up. FHx and elevated Lp(a) were independently associated with ASCVD (hazard ratio [HR]: 1.17; 95% confidence interval [CI]: 1.09 to 1.26, and HR: 1.25; 95% CI: 1.12 to 1.40, respectively), and no Lp(a)-by-FHx interaction was noted (p = 0.75). Compared with subjects without FHx and nonelevated Lp(a), those with either elevated Lp(a) or FHx were at a higher ASCVD risk, while those with both had the highest risk (HR: 1.43; 95% CI: 1.27 to 1.62). Similar findings were observed for CHD risk in ARIC, in analyses stratified by premature FHx, and in an independent cohort, the DHS (Dallas Heart Study). Presence of both elevated Lp(a) and FHx resulted in greater improvement in ASCVD and CHD risk reclassification and discrimination indexes than either marker alone., Conclusions: Elevated plasma Lp(a) and FHx have independent and additive joint associations with cardiovascular risk and may be useful concurrently for guiding primary prevention therapy decisions., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objective: Various organizations have highlighted the need to examine whether abdominal obesity cut points are appropriate for identification of cardiovascular risk among ethnic minority adults, particularly Hispanic/Latino adults living in Western societies. This study aimed 1 ) to establish optimal definitions for abdominal obesity among Hispanics/Latinos and 2 ) to determine the level of agreement between the presence of metabolic syndrome diagnosed by the current Joint Interim Statement (JIS) definition and an updated definition with optimal abdominal obesity cut points., Research Design and Methods: The sample included 16,289 adults who self-identified as Hispanic/Latino ages 18-74 years enrolled in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). Receiver operating characteristic curves were used to derive sensitivity and specificity values. The largest sum of sensitivity plus specificity was used to determine appropriate cut points., Results: Among U.S. Hispanic/Latino adults, waist circumference cut points of >102 cm in men (in line with current JIS criteria) and >97 cm (9 points higher than JIS criteria) in women provide optimal discrimination for cardiovascular risk as judged by the presence of coronary heart disease. When using these cut points to create an updated metabolic syndrome definition among women, we found disagreement between our updated definition and the current JIS criteria. The prevalence of the metabolic syndrome was overestimated by ∼5 percentage points among women based on JIS criteria in comparison with our definition., Conclusions: Our results suggest that the current recommendations for waist circumference cut points may not be appropriate for U.S. Hispanic/Latino women., (© 2020 by the American Diabetes Association.)

Background: Coronary artery calcium (CAC) predicts atherosclerotic cardiovascular disease (ASCVD) events, inclusive of coronary heart disease (CHD) and stroke, and is a decision-making aid for primary prevention. The predictive value of CAC categories for CHD and stroke separately and across sex and race groups of an asymptomatic population is unclear., Methods: White, Black, and Hispanic participants of MESA (Multi-Ethnic Study of Atherosclerosis) and DHS (Dallas Heart Study) underwent CAC measurement at enrollment and were followed for incident ASCVD events. Ten-year CHD-to-stroke incidence ratios across CAC score categories 0, 1 to 99, and ≥100 were assessed. Associations of CAC with incident CHD and stroke events were evaluated using multivariable-adjusted Cox models and multiplicative interactions of CAC with sex/race were tested., Results: Among 7042 participants (mean age, 57 years, 54% women, 36% Black, 23% Hispanic, 49% CAC=0, 19% CAC ≥100), 574 incident ASCVD events (333 CHD and 241 stroke) were observed over 12.3-year follow-up. Ten-year CHD-to-stroke incidence ratio increased significantly across CAC categories in men, women, Whites, Blacks, and Hispanics (all P <0.001). High CAC burden (score ≥100) was independently associated with ASCVD and CHD risk in all groups and with stroke risk in the overall cohort and Blacks. No sex- or race-based CAC interactions for ASCVD, CHD, and stroke events were observed. Adding CAC to a traditional risk factor model improved risk discrimination and reclassification for CHD but not for stroke events., Conclusions: In 2 population-based cohorts of asymptomatic individuals, 10-year CHD-to-stroke incidence ratio was higher with increasing CAC score categories across sex and race groups, and CAC was consistently a better predictor of CHD than stroke. High CAC burden comparably associated with ASCVD risk across sex and race groups.

There are paucity of data on gender-based differences in the effect of thrombocytopenia and coronary heart disease (CHD) towards development of acute coronary syndrome (ACS). We used National Inpatient Sample (NIS) database of the United States to assess the gender-based differences in the association of thrombocytopenia with CHD and the impact of thrombocytopenia on mortality, length of stay and hospitalization costs on ACS subgroup of CHD. Our analysis found that thrombocytopenia was associated with increased odds of CHD on univariate (odds ratio [OR] 1.31 (95% CI 1.30-1.32) p < 0.001) and multivariate (OR 1.36 (95% CI 1.34-1.38) p < 0.001) analyses. Thrombocytopenic CHD patients had increased odds of developing ACS only in women (OR 1.15, 95% CI 1.12-1.17, p < 0.001). Thrombocytopenia was found to be associated with poor short-term outcome in ACS subgroup of CHD with higher in-hospital mortality (OR 1.64, CI 1.58 to 1.71, p < 0.001), length of stay (3.4 days, CI 3.30-3.52, p < 0.001), and cost of hospitalization ($55,652, CI 53,717-57,587, p < 0.001). Thrombocytopenic women with ACS have greater odds of mortality compared to men. Our study suggests that thrombocytopenia among women with CHD is associated with increased odds of developing ACS. Women with ACS have greater mortality compared to men. Thrombocytopenic ACS patients have worse in-hospital outcome compared to patients with normal platelet count. We demonstrated association only and is not possible to establish causality with our study.

Background and Aim: The association of serum cholesterol levels with the occurrence of coronary heart disease (CHD) mortality during a follow-up of 50 years was rarely investigated previously. Thus, we took advantage of results at hand in 10 pooled cohorts of men aged 40-59 years from the Seven Countries Study (9063 individuals and 2057 CHD fatal events) and we assessed this., Methods and Results: Cox proportional hazards models were run with CHD fatal events (as dependent variable) and cholesterol levels (as independent variables) at years 0, 10, and 25 (in 5 cohorts). Cumulative events during subsequent decades (cumulative approach: CA) and separately in each subsequent decade (partitioned approach: PA) were analyzed. The ecological correlation of average baseline serum cholesterol levels with CHD mortality was very high (R = 0.97). Serum cholesterol and CHD mortality for 50 years were associated at the individual level, and the association estimated by the Cox's coefficients (and related hazards ratios) was initially strong in both CA and PA, but slightly declined during later decades. Hazards ratios (for a difference of 40 mg/dl) ranged from 1.39 to 1.20 for CA and from 1.39 to 0.80 for PA. Coefficients were larger for CA than for PA and the decline was more evident for the latter. Partitioned coefficient became negative and significant in the last decade (from year 40-50). Coefficients derived from cholesterol levels measured at year 10 of follow-up showed similar trends but their magnitude was smaller., Conclusion: Thus, the relationship of serum cholesterol levels with CHD mortality remained relatively stable during at least 40 years after a single cholesterol measurement at baseline in middle-aged men., (Copyright © 2020 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Background Relatively little is known about the long-term consequences of venous thromboembolism (VTE) on physical functioning. We compared long-term frailty status, physical function, and quality of life among survivors of VTE with survivors of coronary heart disease (CHD) and stroke, and with those without these diseases. Methods and Results Cases of VTE, CHD, and stroke were continuously identified since ARIC (Atherosclerosis Risk in Communities Study) recruitment during 1987 to 1989. Functional measures were objectively captured at ARIC clinic visits 5 (2011-2013) and 6 (2016-2017); quality of life was self-reported. The 6161 participants at visit 5 were, on average, 75.7 (range, 66-90) years of age. By visit 5, 3.2% had had a VTE, 6.9% CHD, and 3.4% stroke. Compared with those without any of these conditions, VTE survivors were more likely to be frail (odds ratio [OR], 3.11; 95% CI, 1.80-5.36) and have low (<10) versus good scores on the Short Physical Performance Battery (OR, 3.59; 95% CI, 2.36-5.47). They also had slower gait speed, less endurance, and lower physical quality of life. VTE survivors were similar to coronary heart disease and stroke survivors on categorical frailty and outcomes on Short Physical Performance Battery assessment. When score on the Short Physical Performance Battery instrument was modeled continuously, VTE survivors performed better than stroke survivors but worse than CHD survivors. Conclusions VTE survivors had triple the odds of frailty and poorer physical function than those without the vascular diseases considered. Their function was somewhat worse than that of CHD survivors, but better than stroke survivors. These findings suggest that VTE patients may benefit from additional efforts to improve postevent physical functioning.

Background and Aims: Despite the proven evidence of high glycemic index (GI) and glycemic load (GL) diets to increase cardiometabolic risks, knowledge about the meta-evidence for carbohydrate quality within world geographic regions is limited. We conducted a meta-analysis to synthesize the evidence of GI/GL studies and carbohydrate quality, gathering additional exposures for carbohydrate, high glycemic carbohydrate, total dietary fiber, and cereal fiber and risks for type 2 diabetes (T2DM), coronary heart disease (CHD), stroke, and mortality, grouped into the US, Europe, and Asia. Secondary aims examined cardiometabolic risks in overweight/obese individuals, by sex, and dose-response dietary variable trends., Methods and Results: 40-prospective observational studies from 4-Medline bibliographical databases (Ovid, PubMed, EBSCOhost, CINAHL) were search up to November 2019. Random-effects hazard ratios (HR) and 95% confidence intervals (CI) for highest vs. lowest categories and continuous form combined were reported. Heterogeneity (I 2 >50%) was frequent in US GI/GL studies due to differing study characteristics. Increased risks ((HR GI,T2DM,US =1.14;CI:1.06,1.21), HR GL,T2DM,US =1.02 (1.01, 1.03)), HR GI,T2DM,Asia =1.25;1.02,1.53), and HR GL,T2DM,Asia =1.37 (1.17, 1.60)) were associated with cardiometabolic diseases. GI/GL in overweight/obese females had the strongest magnitude of risks in US-and Asian studies. Total dietary fiber (HR T2DM,US  = 0.92;0.88,0.96) and cereal fiber (HR T2DM,US  = 0.83;0.77,0.90) decreased risk of developing T2DM. Among females, we found protective dose-response risks for total dietary fiber (HR 5g-total-dietary-fiber,T2DM,US  = 0.94;0.92,0.97) , but cereal fiber showed better ability to lower T2DM risk (HR 5g-cereal-fiber , T2DM,US  = 0.67;0.60,0.74). Total dietary-and cereal fibers' dose-response effects were nullified by GL, but not so for cereal fiber with GI., Conclusions: Overweight/obese females could shift their carbohydrate intake for higher cereal fiber to decrease T2DM risk, but higher GL may cancel-out this effect., Competing Interests: Declaration of Competing Interest All authors declare no competing conflicts of interests., (Copyright © 2020 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Background and Aims: Cell-mediated immunity is implicated in atherosclerosis. We evaluated whether innate and adaptive immune cell subsets in peripheral blood are risk factors for coronary heart disease., Methods: A nested case-cohort study (n = 2155) was performed within the Multi-Ethnic Study of Atherosclerosis (MESA) and the Cardiovascular Health Study (CHS). Cases of incident myocardial infarction (MI) and incident angina (n = 880 total cases) were compared with a cohort random sample (n = 1275). Immune cell phenotypes (n = 34, including CD14 + monocytes, natural killer cells, γδ T cells, CD4 + , CD8 + and CD19 + lymphocyte subsets) were measured from cryopreserved cells by flow cytometry. Cox proportional hazards models with adjustment for cardiovascular disease risk factors were used to evaluate associations of cell phenotypes with incident MI and a composite phenotype of incident MI or incident angina (MI-angina) over a median 9.3 years of follow-up. Th1, Th2, Th17, T regulatory (CD4 + CD25 + CD127 - ), naive (CD4 + CD45RA + ), memory (CD4 + CD45RO + ), and CD4 + CD28 - cells were specified as primary hypotheses. In secondary analyses, 27 additional cell phenotypes were investigated., Results: After correction for multiple testing, there were no statistically significant associations of CD4 + naive, memory, CD28 - , or T helper cell subsets with MI or MI-angina in MESA, CHS, or combined-cohort meta analyses. Null associations were also observed for monocyte subsets, natural killer cells, γδ T cells, CD19 + B cell and differentiated CD4 + and CD8 + cell subsets., Conclusions: The proportions of peripheral blood monocyte and lymphocyte subsets are not strongly related to the future occurrence of MI or angina in adults free of autoimmune disease., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background Soluble CD14 (sCD14), a circulating pattern recognition receptor, has been suggested as a cardiovascular disease risk factor. Prospective studies evaluating sCD14 with incident cardiovascular disease events are limited, particularly among racially diverse populations. Methods and Results Between 2003 and 2007, the REGARDS (Reasons for Geographic and Racial Differences in Stroke) study recruited 30 239 black and white participants across the United States. In a nested case-cohort study, sCD14 was measured in baseline serum from 548 cases of incident ischemic stroke, 612 cases of incident coronary heart disease (CHD), and a cohort random sample (n=1039). Cox models estimated hazards ratios (HR) of incident ischemic stroke or CHD per 1 SD higher sCD14, adjusting for cardiovascular disease risk factors. There was a differential association of sCD14 with ischemic stroke and CHD risk by race. Among blacks, the adjusted HR of stroke per SD increment of sCD14 was 1.42 (95% CI: 1.12, 1.80), with no association among whites (HR 1.02 [95% CI: 0.82, 1.27]). Higher sCD14 was associated with increased CHD risk in blacks but not whites, and relationships between sCD14 and CHD were stronger at younger ages. Adjusted for risk factors, the HR of CHD per SD higher sCD14 among blacks at age 45 years was 2.30 (95% CI: 1.45, 3.65) compared with 1.56 (95% CI: 0.94, 2.57) among whites. At age 65 years, the CHD HR was 1.51 (95% CI: 1.20, 1.91) among blacks and 1.02 (95% CI: 0.80, 1.31) among whites. Conclusions sCD14 may be a race-specific stroke and CHD risk marker.

Background: Data are lacking with concern to the prevalence and management of aspirin (ASA) hypersensitivity. Objective: To study the prevalence, different types of reactions, and implications for clinical management of ASA hypersensitivity in a cardiology practice. Methods: We conducted an electronic medical record review of 11,375 individuals, 5052 (44%) in the ambulatory setting, and 6323 (56%) admitted for percutaneous coronary intervention (PCI), from January 2012 to December 2013. Results: The prevalence of ASA hypersensitivity was 1.88% (n = 214). Skin reactions were the most common (40 [19%]), followed by angioedema (10 [4.6%]), respiratory (9 [4.2%]), and anaphylaxis (6 [2.8%]). No records were found for 74 patients (34.5%), and 69 patients (32.2%) were mistakenly labeled as allergic for having gastrointestinal symptoms. Of the 214 patients who had documented ASA hypersensitivity, 108 individuals (50.46%) had coronary artery disease. The medications at discharge were the following: ASA (30 [14%]), thienopyridine (48 [22%]), a combination of ASA and thienopyridine (13 [6%]), anticoagulation only (26 [12%]), and no antiplatelet (97 [43%]). Conclusion: ASA hypersensitivity is often not documented correctly or is often misdiagnosed or not appropriately managed. There is a need for improved management of ASA hypersensitivity, including appropriate referral for ASA desensitization and combating unnecessary avoidance in patients with intolerance due to adverse effects.

Objective: To deepen understanding of the relationship between food insecurity, acculturation, and diagnosis of CHD and related health outcomes among immigrant adults., Design: Using cross-sectional, nationally representative data from the National Health Interview Survey 2011 to 2015, we address two research questions. First, what is the relationship of household food insecurity and acculturation with: CHD, angina pectoris, heart attack, self-rated poor health and obesity? Second, what is the association of food insecurity with these health outcomes over years of living in the USA? We estimate multivariate logistic regressions without (question 1) and with (question 2) an interaction term between food insecurity and acculturation for CHD and related health outcomes., Setting: USA., Participants: Low-income immigrant adults., Results: Food insecurity and acculturation are both associated with diagnosis of CHD and related health outcomes among immigrant adults. Food insecurity and acculturation are associated with the health of female immigrants more than males. Also, the differences by food security status in the probability of having several poor health outcomes (self-rated heath, obesity, women's angina pectoris) are largest for those in the USA for less than 5 years, decrease for those who have lived in the USA for 5-14 years, and are larger again for those in the USA for 15 or more years., Conclusions: Recent and long-term food-insecure immigrants are more vulnerable to CHD and related health outcomes than those in the USA for 5-14 years. Further research is needed to understand why.

Background Cyclic guanosine monophosphate (cGMP) is a second messenger regulated through natriuretic peptide and nitric oxide pathways. Stimulation of cGMP signaling is a potential therapeutic strategy for heart failure with preserved ejection fraction (HFpEF) and atherosclerotic cardiovascular disease (ASCVD). We hypothesized that plasma cGMP levels would be associated with lower risk for incident HFpEF, any HF, ASCVD, and coronary heart disease (CHD). Methods and Results We conducted a case-cohort analysis nested in the ARIC (Atherosclerosis Risk in Communities) study. Plasma cGMP was measured in 875 participants at visit 4 (1996-1998), with oversampling of incident HFpEF cases. We used Cox proportional hazard models to assess associations of cGMP with incident HFpEF, HF, ASCVD (CHD+stroke), and CHD. The mean (SD) age was 62.4 (5.6) years and median (interquartile interval) cGMP was 3.4 pmol/mL (2.4-4.6). During a median follow-up of 9.9 years, there were 283 incident cases of HFpEF, 329 any HF, 151 ASCVD, and 125 CHD. In models adjusted for CVD risk factors, the hazard ratios (95% CI) associated with the highest cGMP tertile compared with lowest for HFpEF, HF, ASCVD, and CHD were 1.88 (1.17-3.02), 2.18 (1.18-4.06), 2.84 (1.44-5.60), and 2.43 (1.19-5.00), respectively. In models further adjusted for N-terminal-proB-type natriuretic peptide, associations were attenuated for HFpEF and HF but remained statistically significant for ASCVD (2.56 [1.26-5.20]) and CHD (2.25 [1.07-4.71]). Conclusions Contrary to our hypothesis, higher cGMP levels were associated with incident CVD in a community-based cohort. The associations of cGMP with HF or HFpEF may be explained by N-terminal-proB-type natriuretic peptide, but not for ASCVD and CHD.

Background and Aims: Many traditional assessments of risk for coronary heart disease (CHD) and diabetes require laboratory studies performed after an 8-h fast. We assessed whether metabolic-syndrome (MetS) severity would remain linked to future CHD and diabetes even when assessed from non-fasting samples., Methods and Results: Participants in the Atherosclerosis Risk in Communities study were assessed at 4 visits and followed for 20-years of adjudicated CHD outcomes. We used Cox proportional-hazard models (for 20-year CHD outcomes) and logistic regression (for 9-year diabetes outcomes) to compare incident disease risk associated with a race/ethnicity-specific MetS-severity Z-score (MetS-Z) calculated in participants who were fasting (≥8 h) or non-fasting. All analyses were adjusted for sex, race, education, income and smoking. MetS Z-scores were overall similar between participants who were always fasting vs. those non-fasting at Visits 1-3 (all values -0.1 to 0.4), while MetS-Z for participants who were non-fasting at Visit-4 were higher at each visit. Baseline MetS-Z was linked to future CHD when calculated from both fasting and non-fasting measurements, with hazard ratio (HR) for fasting MetS-Z 1.53 (95% confidence interval [CI] 1.42, 1.66) and for non-fasting 1.28 (CI 1.08, 1.51). MetS-Z at Visit-1 also remained linked to future diabetes when measured from non-fasting samples, with odds ratio for fasting MetS-Z 3.10 (CI 2.88, 3.35) and for non-fasting 1.92 (CI 1.05, 3.51)., Conclusions: MetS-Z remained linked to future CHD and diabetes when assessed from non-fasting samples. A score such as this may allow for identification of at-risk individuals and serve as a motivation toward interventions to reduce risk., (Copyright © 2019 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Background: DNA methylation is implicated in coronary heart disease (CHD), but current evidence is based on small, cross-sectional studies. We examined blood DNA methylation in relation to incident CHD across multiple prospective cohorts., Methods: Nine population-based cohorts from the United States and Europe profiled epigenome-wide blood leukocyte DNA methylation using the Illumina Infinium 450k microarray, and prospectively ascertained CHD events including coronary insufficiency/unstable angina, recognized myocardial infarction, coronary revascularization, and coronary death. Cohorts conducted race-specific analyses adjusted for age, sex, smoking, education, body mass index, blood cell type proportions, and technical variables. We conducted fixed-effect meta-analyses across cohorts., Results: Among 11 461 individuals (mean age 64 years, 67% women, 35% African American) free of CHD at baseline, 1895 developed CHD during a mean follow-up of 11.2 years. Methylation levels at 52 CpG (cytosine-phosphate-guanine) sites were associated with incident CHD or myocardial infarction (false discovery rate<0.05). These CpGs map to genes with key roles in calcium regulation (ATP2B2, CASR, GUCA1B, HPCAL1), and genes identified in genome- and epigenome-wide studies of serum calcium (CASR), serum calcium-related risk of CHD (CASR), coronary artery calcified plaque (PTPRN2), and kidney function (CDH23, HPCAL1), among others. Mendelian randomization analyses supported a causal effect of DNA methylation on incident CHD; these CpGs map to active regulatory regions proximal to long non-coding RNA transcripts., Conclusion: Methylation of blood-derived DNA is associated with risk of future CHD across diverse populations and may serve as an informative tool for gaining further insight on the development of CHD.

Background: We assessed whether plasma troponin I measured by a high-sensitivity assay (hs-TnI) is associated with incident cardiovascular disease (CVD) and mortality in a community-based sample without prior CVD., Methods: ARIC study (Atherosclerosis Risk in Communities) participants aged 54 to 74 years without baseline CVD were included in this study (n=8121). Cox proportional hazards models were constructed to determine associations between hs-TnI and incident coronary heart disease (CHD; myocardial infarction and fatal CHD), ischemic stroke, atherosclerotic CVD (CHD and stroke), heart failure hospitalization, global CVD (atherosclerotic CVD and heart failure), and all-cause mortality. The comparative association of hs-TnI and high-sensitivity troponin T with incident CVD events was also evaluated. Risk prediction models were constructed to assess prediction improvement when hs-TnI was added to traditional risk factors used in the Pooled Cohort Equation., Results: The median follow-up period was ≈15 years. Detectable hs-TnI levels were observed in 85% of the study population. In adjusted models, in comparison to low hs-TnI (lowest quintile, hs-TnI ≤1.3 ng/L), elevated hs-TnI (highest quintile, hs-TnI ≥3.8 ng/L) was associated with greater incident CHD (hazard ratio [HR], 2.20; 95% CI, 1.64-2.95), ischemic stroke (HR, 2.99; 95% CI, 2.01-4.46), atherosclerotic CVD (HR, 2.36; 95% CI, 1.86-3.00), heart failure hospitalization (HR, 4.20; 95% CI, 3.28-5.37), global CVD (HR, 3.01; 95% CI, 2.50-3.63), and all-cause mortality (HR, 1.83; 95% CI, 1.56-2.14). hs-TnI was observed to have a stronger association with incident global CVD events in white than in black individuals and a stronger association with incident CHD in women than in men. hs-TnI and high-sensitivity troponin T were only modestly correlated ( r=0.47) and were complementary in prediction of incident CVD events, with elevation of both troponins conferring the highest risk in comparison with elevation in either one alone. The addition of hs-TnI to the Pooled Cohort Equation model improved risk prediction for atherosclerotic CVD, heart failure, and global CVD., Conclusions: Elevated hs-TnI is strongly associated with increased global CVD incidence in the general population independent of traditional risk factors. hs-TnI and high-sensitivity troponin T provide complementary rather than redundant information.

Background and Aims: Constipation is one of the most frequent symptoms encountered in daily clinical practice and is implicated in the development of atherosclerosis, potentially through altered gut microbiota. However, little is known about its association with incident cardiovascular events., Methods: In a nationally representative cohort of 3,359,653 US veterans with an estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m 2 between October 1, 2004 and September 30, 2006 (baseline period), with follow-up through 2013, we examined the association of constipation status (absence or presence; defined using diagnostic codes and laxative use) and laxative use (none, one, or ≥2 types of laxatives) with all-cause mortality, incident coronary heart disease (CHD), and incident ischemic stroke., Results: Among 3,359,653 patients, 237,855 (7.1%) were identified as having constipation. After multivariable adjustments for demographics, prevalent comorbidities, medications, and socioeconomic status, patients with (versus without) constipation had 12% higher all-cause mortality (hazard ratio [HR], 1.12; 95% CI, 1.11-1.13), 11% higher incidence of CHD (HR, 1.11; 95% CI, 1.08-1.14), and 19% higher incidence of ischemic stroke (HR, 1.19; 95% CI, 1.15-1.22). Patients with one and ≥2 (versus none) types of laxatives experienced a similarly higher risk of all-cause mortality (HRs [95% CI], 1.15 [1.13-1.16] and 1.14 [1.12-1.15], respectively), incident CHD (HRs [95% CI], 1.11 [1.07-1.15] and 1.10 [1.05-1.15], respectively) and incident ischemic stroke (HRs [95% CI], 1.19 [1.14-1.23] and 1.21 [1.16-1.26], respectively)., Conclusions: Constipation status and laxative use are independently associated with higher risk of all-cause mortality and incident CHD and ischemic stroke., (Published by Elsevier B.V.)

Aims: Relatively little is known about the health outcomes associated with very low plasma concentrations of high-density lipoprotein cholesterol (HDL-C) mainly because of the small numbers of individuals with such extreme values included in clinical trials. We, therefore, investigated the association between low and very low HDL-C concentration at baseline and incident all-cause-mortality, death from malignant disease (i.e. cancer), and with fatal or non-fatal incident coronary heart disease (CHD) in individuals from the Reasons for Geographical And Racial Differences in Stroke (REGARDS) study., Methods and Results: Analysis was based on 21 751 participants from the REGARDS study who were free of CHD, other cardiovascular disease, and cancer at baseline and were categorized by baseline HDL-C into <30 mg/dL (very low), 30-<40 mg/dL (low), and ≥40 mg/dL (reference). A series of incremental Cox proportional hazards models were employed to assess the association between the HDL-C categories and outcomes. Statistical analysis was performed using both complete case methods and multiple imputations with chained equations. After adjustment for age, race, and sex, the hazard ratios (HRs) comparing the lowest and highest HDL-C categories were 1.48 [95% confidence interval (CI) 1.28-1.73] for all-cause mortality, 1.35 (95% CI 1.03-1.77) for cancer-specific mortality and 1.39 (95% CI 0.99-1.96) for incident CHD. These associations became non-significant in models adjusting for demographics, cardiovascular risk factors, and treatment for dyslipidaemia. We found evidence for an HDL paradox, whereby low HDL (30-<40 mg/dL) was associated with reduced risk of incident CHD in black participants in a fully adjusted complete case model (HR 0.63; 95% CI 0.46-0.88) and after multiple imputation analyses (HR 0.76; 95% CI 0.58-0.98). HDL-C (<30 mg/dL) was significantly associated with poorer outcomes in women for all outcomes, especially with respect to cancer mortality (HR 2.31; 95% CI 1.28-4.16) in a fully adjusted complete case model, replicated using multiple imputation (HR 1.81; 95% CI 1.03-3.20)., Conclusion: Low HDL-C was associated with reduced risk of incident CHD in black participants suggesting a potential HDL paradox for incident CHD. Very low HDL-C in women was significantly associated with cancer mortality in a fully adjusted complete case model.

Background In the large-scale ADAPT-DES study (Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents), drug-eluting stent implantation with intravascular ultrasound (IVUS) guidance was associated with a reduction in 1-year rates of stent thrombosis, myocardial infarction (MI), and major adverse cardiac events (cardiac death, MI, or stent thrombosis) compared with angiography guidance alone. We assessed whether the benefits of IVUS guidance were maintained, reduced, or increased at 2 years. Methods and Results ADAPT-DES was a prospective, multicenter, nonrandomized all-comers study of 8582 consecutive patients at 11 US and German sites designed to determine the frequency, timing, and correlates of adverse events after drug-eluting stents. Propensity-adjusted multivariable analysis was performed to examine the impact of IVUS guidance on 2-year outcomes. IVUS guidance (n=3361; 39%) compared with angiography guidance (n=5221; 61%) was associated with reduced 2-year adjudicated rates of (1) major adverse cardiac events (cardiac death, MI, or stent thrombosis; 4.9% versus 7.5%; adjusted hazard ratio, 0.72; 95% CI, 0.59-0.89; P=0.003), (2) definite/probable stent thrombosis (0.55% versus 1.16%; adjusted hazard ratio, 0.40; 95% CI, 0.22-0.73; P=0.003), and (3) MI (3.5% versus 5.6%; adjusted hazard ratio, 0.65; 95% CI, 0.51-0.83; P=0.0006). By landmark analysis, IVUS guidance compared with angiography guidance was also associated with significantly reduced rates of major adverse cardiac events, MI, stent thrombosis, and clinically driven target lesion revascularization between 1 and 2 years after drug-eluting stent implantation. The number needed to treat with IVUS guidance to prevent 1 major adverse cardiac event was reduced from 64 (42-137) at 1 year to 41 (29-69) at 2 years. Conclusions In ADAPT-DES, the early improvement in event-free survival after drug-eluting stent implantation with IVUS guidance compared with angiography guidance was further increased with longer term follow-up to 2 years. Clinical Trial Registration URL: https://www.clinicaltrials.gov . Unique identifier: NCT00638794.

Background and Aims: It is not known if ultrasound carotid plaque features are associated with cardiovascular disease (CVD) risk factors or if they predict future CVD events., Methods: We measured total carotid plaque area (TPA) and grayscale plaque features (grayscale median, black areas, and discrete white areas) by B-mode carotid ultrasound among 2205 participants who participated in the first (baseline) visit of the Multi-Ethnic Study of Atherosclerosis. Multivariable linear regression was used to examine relationships between ultrasound plaque features and CVD risk factors at baseline. Cox proportional hazards models were used to assess if TPA, grayscale features, and carotid plaque score (number of arterial segments with a plaque) could predict incident coronary heart disease and cerebrovascular disease events over a mean follow-up of 13.3 years., Results: Participants were mean (standard deviation [SD]) 65.4 (9.6) years, 49% male, 39% White, 11% Chinese, 28% Black, and 22% Hispanic. Mean TPA 27.7 (24.7) mm 2 , but no grayscale plaque features, was associated with CVD risk factors. In fully adjusted models, TPA but no grayscale features predicted incident coronary heart disease (CHD) events (HR 1.23; 95%CI 1.11-1.36; p<0.001), however, C-statistics for CHD were similar to carotid plaque score but less than for coronary artery calcium (CAC) scoring. Neither TPA nor grayscale features independently predicted cerebrovascular events., Conclusions: In middle-aged adults free of known cardiovascular disease, TPA but not grayscale plaque features was associated with CVD risk factors and predicted incident CHD events. For CHD, prediction indices for TPA were similar to carotid plaque score but less than for CAC., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objective: This study sought to characterise the main dyslipidaemic phenotypes present in chronic kidney disease (CKD) and their association with coronary heart disease (CHD) risk., Methods: Analyses included 6612 individuals in the multiethnic study of atherosclerosis free of CHD at baseline. CKD was defined as an estimated glomerular filtration rate (eGFR) of 15 to <60 mL/min/1.73 m 2 (stages 3-4). Principal component analyses were used to characterise the main dyslipidaemic phenotypes of CKD accounting for the correlation among different lipoproteins and lipoprotein particles. CHD was defined as incident myocardial infarction, angina followed by revascularisation, resuscitated cardiac arrest or CHD death., Results: CHD developed in 303 individuals (5%) with eGFR ≥60 and in 72 individuals (12%) with CKD (p for difference <0.001). A dyslipidaemic phenotype (principal component 1 (PC1)) consisting of elevations in triglycerides, triglyceride-rich lipoproteins (VLDL particles), small LDL particles and reductions in HDL particles, was more common in those with CKD, compared with those without CKD (p for difference <0.001). This phenotype was also more strongly associated with CHD in those with CKD: adjusted HRs (95% CIs) per SD increase in PC1 1.13 (95% CI 1.00 to 1.27; P=0.05) and 1.51 (95% CI 1.17 to 1.94; P<0.001) in eGFR ≥60 and CKD, respectively (P for interaction=0.05)., Conclusion: In individuals with mainly stage 3 CKD, a dominant lipid phenotype consisting of triglyceride-rich lipoproteins and other closely correlated lipoproteins is strongly associated with CHD risk. Future studies should investigate whether modification of the components of this phenotype leads to a reduction in the CHD burden in individuals with CKD., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background:  Haemostatic balance represented by low protein C (PC) and elevated factor VIII (FVIII) has been inconsistently associated with stroke and coronary heart disease (CHD) risk., Objective:  This article assesses whether an elevated FVIII and a low PC would increase cardiovascular risk more than either individually., Patients and Methods:  REGARDS recruited 30,239 black and white U.S. participants aged ≥ 45 years between 2003 and 2007. FVIII and PC were measured in a case-cohort sample of 646 stroke, 654 CHD, and a 1,104-person random sample with follow-up for approximately 4.5 years. Hazard ratios (HRs) were estimated using Cox models adjusted for demographic and cardiovascular risk factors., Results:  Elevated FVIII (per standard deviation [SD] increase) was associated with increased risk of both stroke (HR, 1.26; 95% confidence interval [CI], 1.08, 1.46) and CHD (HR, 1.52; 95% CI, 1.29, 1.79), while there was no association of PC per SD decrease. For PC, there was a trend towards increased cardiovascular disease risk in the lowest values (bottom 5%). For stroke, there was no interaction between FVIII and low PC ( p interaction  = 0.55). For CHD, the adjusted HR of FVIII per SD increase was significantly greater with PC in the bottom 5% (HR, 3.59; 95% CI, 1.39, 8.29) than PC in the upper 95% (HR, 1.45; 95% CI, 1.23, 1.71; p interaction  = 0.07)., Conclusion:  Higher FVIII was associated with both CHD and stroke risk and the risk potentiated by low PC for CHD. Findings demonstrate that risks for cardiovascular diseases conferred by adverse levels of haemostasis biomarkers may be augmented by levels of other biomarkers., Competing Interests: None., (Georg Thieme Verlag KG Stuttgart · New York.)

Background: The proportion of foreign-born US adults has almost tripled since 1970. However, less is known about the cardiovascular morbidity by birthplace among adults residing in the United States. This study's objective was to compare the prevalence of coronary heart disease (CHD) and stroke among US adults by birthplace., Methods and Results: We used data from the 2006 to 2014 National Health Interview Survey. Birthplace was categorized as United States or foreign born. Foreign born was then grouped into 6 birthplace regions. We defined CHD and stroke as ever being told by a physician that she or he had CHD or stroke. We adjusted for select demographic and health characteristics in the analysis. Of US adults, 16% were classified as foreign born. Age-standardized prevalence of both CHD and stroke were higher among US- than foreign-born adults (CHD: 8.2% versus 5.5% for men and 4.8% versus 4.1% for women; stroke: 2.7% versus 2.1% for men and 2.7% versus 1.9% for women; all P <0.05). Comparing individual regions with those of US- born adults, CHD prevalence was lower among foreign-born adults from Asia and Mexico, Central America, or the Caribbean. For stroke, although men from South America or Africa had the lowest prevalence, women from Europe had the lowest prevalence. Years of living in the United States was not related to risk of CHD or stroke after adjustment with demographic and health characteristics., Conclusions: Overall, foreign-born adults residing in the United States had a lower prevalence of CHD and stroke than US-born adults. However, considerable heterogeneity of CHD and stroke risk was found by region of birth., (© 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Chronic exposure to fine particulate matter (PM 2.5 ) is accepted as a causal risk factor for coronary heart disease (CHD). However, most of the evidence for this hypothesis is based upon cohort studies in whites, comprised of either only males or females who live in urban areas. It is possible that many estimates of the effect of chronic exposure to PM 2.5 on risk for CHD do not generalize to more diverse samples., Methods: Therefore, we estimated the relationship between chronic exposure to PM 2.5 and risk for CHD in among participants in the REasons for Geographic And Racial Differences in Stroke (REGARDS) cohort who were free from CHD at baseline (n=17,126). REGARDS is a sample of whites and blacks of both genders living across the continental United States. We fit Cox proportional hazards models for time to CHD to estimate the hazard ratio for baseline 1-year mean PM 2.5 exposure, adjusting for environmental variables, demographics, and other risk factors for CHD including the Framingham Risk Score., Results: The hazard ratio (95% CI) for a 2.7-μg/m 3 increase (interquartile range) 1-year mean concentration of PM 2.5 was 0.94 (0.83-1.06) for combined CHD death and nonfatal MI, 1.13 (0.92-1.40) for CHD death, and 0.85 (0.73-0.99) for nonfatal MI. We also did not find evidence that these associations depended upon overall CHD risk factor burden., Conclusions: Our results do not provide strong evidence for an association between PM 2.5 and incident CHD in a heterogeneous cohort, and we conclude that the effects of chronic exposure to fine particulate matter on CHD require further evaluation., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: The severity of the metabolic syndrome (MetS) is significantly associated with future coronary heart disease (CHD) among individuals without baseline Type 2 diabetes. However, the validity of assessing MetS severity among individuals with diabetes is unknown., Objective: To assess for differences in MetS severity by timing of Type 2 diabetes diagnosis and to assess for associations between MetS severity and future CHD among individuals with diabetes., Methods: We analyzed data from participants of the Atherosclerosis Risk in Communities study, including 1419 with- and 7241 without diabetes, followed during 4 visits and adjudicated CHD diagnoses over a 20-year period. We used Cox-regression techniques to assess hazard ratios (HR) of CHD based on a sex- and race/ethnicity-specific MetS-severity Z-score (standard MetS score) and a similar MetS-severity score formulated without incorporating glucose as a component of MetS (no-glucose MetS score)., Results: For both the standard- and no-glucose MetS-severity scores, scores were highest in the baseline-diabetes group, lowest in the never-diabetes group and intermediate in the incident-diabetes groups. Among participants with diabetes, increasing MetS-severity score at baseline was associated with incident CHD, using both the standard MetS score (HR 1.29, 95% confidence interval [CI] 1.21, 1.39) and the no-glucose score (HR 1.42, CI 1.24, 1.62) (both p < 0.001). For the baseline-diabetes group, this relationship remained significant when Visit 2 Hemoglobin-A 1c was included in the model, both for the standard MetS score (HR 1.21, CI 1.09, 1.34; p < 0.001) and the no-glucose score (HR 1.25, CI 1.04, 1.51; p = 0.02)., Conclusions: MetS severity appears to provide an estimate of metabolic disarray in the setting of diabetes and is predictive of future CHD events beyond HbA1c. Identifying MetS severity among individuals with diabetes may help in identifying those at higher risk, who could then receive further preventative treatment.

Background: The National Death Index (NDI) is widely used to detect coronary heart disease (CHD) and cardiovascular disease (CVD) deaths, but its reliability has not been examined recently., Methods and Results: We compared CHD and CVD deaths detected by NDI with expert adjudication of 4010 deaths that occurred between 2003 and 2013 among participants in the REGARDS (REasons for Geographic And Racial Differences in Stroke) cohort of black and white adults in the United States. NDI derived CHD mortality had sensitivity 53.6%, specificity 90.3%, positive predictive value 54.2%, and negative predictive value 90.1%. NDI-derived CVD mortality had sensitivity 73.4%, specificity 84.5%, positive predictive value 70.6%, and negative predictive value 86.2%. Among NDI-derived CHD and CVD deaths, older age (odds ratios, 1.06 and 1.04 per 1-year increase) was associated with a higher probability of disagreement with the adjudicated cause of death, whereas among REGARDS adjudicated CHD and CVD deaths a history of CHD or CVD was associated with a lower probability of disagreement with the NDI-derived causes of death (odds ratios, 0.59 and 0.67, respectively)., Conclusions: The modest accuracy and differential performance of NDI-derived cause of death may impact CHD and CVD mortality statistics., (© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Background: The Physician Consortium for Performance Improvement recently proposed percutaneous coronary intervention (PCI)-specific process measures. However, information about hospital performance on these measures and the association of PCI process and outcomes measures are not available., Methods and Results: We linked the National Cardiovascular Data Registry (NCDR) CathPCI Registry with Medicare claims data to assess hospital performance on established PCI process measures (aspirin, thienopyridines, and statins on discharge; door-to-balloon time; and referral to cardiac rehabilitation), newly proposed PCI process measures (documentation of contrast dose, glomerular filtration rate, and PCI indication; appropriate indication for elective PCI; and use of embolic protection device), and a composite of all process measures. We calculated weighted pair-wise correlations between each set of process metrics and performed weighted correlation analyses to assess the association between composite measure performance with corresponding 30-day risk-standardized mortality and readmission rates. We reported the variance in risk-standardized 30-day outcome rates explained by process measures. We analyzed 1 268 860 PCIs from 1331 hospitals. For many process measures, median hospital performance exceeded 90%. We found strong correlations between medication-specific process measures ( P <0.01) and weak correlations between hospital performance on the newly proposed and established process measures. The composite process measure explained only 1.3% and 2.0% of the observed variation in mortality and readmission rates, respectively., Conclusions: Hospital performance on many PCI-specific process measures demonstrated little opportunity for improvement and explained only a small percentage of hospital variation in 30-day outcomes. Efforts to measure and improve hospital quality for PCI patients should focus on both process and outcome measures., (© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

D-dimer, a biomarker of coagulation, is higher in blacks than in whites and has been associated with stroke and coronary heart disease (CHD). It was our objective to assess the association of higher D-dimer with stroke and CHD in blacks and whites. REGARDS recruited 30,239 black and white participants across the contiguous US and measured baseline D-dimer in stroke (n=646) and CHD (n=654) cases and a cohort random sample (n=1,104). Cox models adjusting for cardiovascular risk factors determined the hazard ratio (HR) for increasing D-dimer for cardiovascular disease with bootstrapping to assess the difference in HR for CHD versus stroke by race. D-dimer was higher with increasing age, female sex, diabetes, hypertension, pre-baseline cardiovascular disease and higher C-reactive protein (CRP). Accounting for cardiovascular risk factors, each doubling of D-dimer was associated with increased stroke (hazard ratio [HR] 1.15; 95 % confidence interval [CI] 1.01, 1.31) and CHD (HR 1.27; 95 % CI 1.11, 1.45) risk. The difference in the HR between CHD and stroke was 0.20 (95 % CI >0.00, 0.58) for blacks and 0.02 (95 % CI -0.30, 0.27) for whites. CRP mediated 22 % (95 % CI 5 %, 41 %) of the association between D-dimer and CHD and none of the association with stroke. Higher D-dimer increased the risk of stroke and CHD independent of cardiovascular risk factors and CRP, with perhaps a stronger association for CHD versus stroke in blacks than whites. These findings highlight potential different pathophysiology of vascular disease by disease site and race suggesting potential further studies targeting haemostasis in primary prevention of vascular disease.

Objectives: We sought to compare 2 contrast-induced nephropathy (CIN) risk prediction models in a validation cohort using a consensus definition., Background: Contrast-induced nephropathy (CIN) is independently associated with mortality following percutaneous coronary intervention (PCI). Multiple prediction models for the development of CIN have been published using heterogeneous outcome definitions., Methods: We analyzed 5,540 patients who underwent PCI from January 2005 to June 2012 at a single academic medical center. The primary outcome was development of CIN, defined as an increase in serum creatinine of ≥0.5 mg/dl or a relative increase of ≥25% from baseline. Receiver operator characteristic (ROC) curves were used to evaluate the discriminatory power of Mehran and WBH prediction models., Results: The mean age of our cohort was 68 ± 12 years. The mean baseline creatinine was 1.2 ± 0.53 mg/dl (eGFR 73 ± 27 ml/min). The mean contrast volume used was 212 ± 92 ml. CIN occurred in 436 patients (7.9%). The Mehran risk score demonstrated better discrimination than the William Beaumont Hospital (WBH) risk score to predict the occurrence of CIN (c statistic: 0.82 vs. 0.73, respectively). Mortality at 30 days was approximately 8 times higher among patients with CIN as compared to those without (14.7% vs. 1.8% P < 0.01)., Conclusions: In an independent validation cohort, the Mehran risk model demonstrates greater discriminatory power than the WBH model in predicting the incidence of CIN. Mortality was significantly higher in patients who developed CIN after PCI., (© 2016, Wiley Periodicals, Inc.)

Background: The arachidonate 5-lipoxygenase enzyme plays a crucial role in mediating inflammation to maintain homeostasis, yet certain allelic variants of the 5-lipoxygenase gene, ALOX5, may increase risk of atherosclerosis and coronary heart disease (CHD). Further, relations between ALOX5 and disease outcomes may be enhanced or attenuated depending on the bioavailability of 5-lipoxygenase enzyme substrates. By using a candidate gene approach in 6153 Multi-Ethnic Study of Atherosclerosis (MESA) participants, associations were determined among 1348 ALOX5 single nucleotide polymorphisms (SNPs) and carotid intima-media thickness (cIMT) as well as incident CHD, and interactions with plasma concentrations of arachidonic acid, eicosapentaenoic acid, or docosahexaenoic acid were tested., Methods and Results: Multivariable linear regression was used to test for associations between cIMT and ALOX5 SNPs, and Cox regression was used for incident CHD. Bonferroni correction was used for multiple hypothesis testing. No significant associations between ALOX5 SNPs and cIMT or CHD events were observed. Levels of arachidonic acid, eicosapentaenoic acid, or docosahexaenoic acid concentrations did not modify the relations of ALOX5 with either outcome., Conclusions: ALOX5 gene variants do not appear to be related to clinical CHD events or subclinical atherosclerosis regardless of bioavailable enzyme substrate levels in this multiethnic cohort. Further studies that directly examine protein expression or enzyme activity may better define the arachidonate 5-lipoxygenase pathway in disease development and progression., (© 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Background: US blood pressure reduction policies are largely restricted to hypertensive populations and associated benefits are often estimated based on unrealistic interventions., Methods and Results: We used multivariable linear regression to estimate incidence rate differences contrasting the impact of 2 pragmatic hypothetical interventions to reduce coronary heart disease, stroke, and heart failure (HF) incidence: (1) a population-wide intervention that reduced systolic blood pressure by 1 mm Hg and (2) targeted interventions that reduced the prevalence of unaware, untreated, or uncontrolled blood pressure above goal (per Eighth Joint National Committee treatment thresholds) by 10%. In the Atherosclerosis Risk in Communities Study (n=15 744; 45 to 64 years at baseline, 1987-1989), incident coronary heart disease and stroke were adjudicated by physician panels. Incident HF was defined as the first hospitalization with discharge diagnosis code of "428." A 10% proportional reduction in unaware, untreated, or uncontrolled blood pressure above goal resulted in ≈4.61, 3.55, and 11.01 fewer HF events per 100,000 person-years in African Americans, and 3.77, 1.63, and 4.44 fewer HF events per 100 000 person-years, respectively, in whites. In contrast, a 1 mm Hg population-wide systolic blood pressure reduction was associated with 20.3 and 13.3 fewer HF events per 100 000 person-years in African Americans and whites, respectively. Estimated event reductions for coronary heart disease and stroke were smaller than for HF, but followed a similar pattern for both population-wide and targeted interventions., Conclusions: Modest population-wide shifts in systolic blood pressure could have a substantial impact on cardiovascular disease incidence and should be developed in parallel with interventions targeting populations with blood pressure above goal., (© 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Background: High-density lipoprotein (HDL) particles have properties beyond reverse cholesterol transport. We hypothesized that their protection extends to inflammation-related disease. The predictive value of HDL particle subclasses and inflammatory markers was studied for noncardiovascular, noncancer chronic inflammation-related death and hospitalization, and for incident cardiovascular disease (CVD)., Methods and Results: A multiethnic, multicenter, prospective observational study was conducted in 6475 men and women (aged 45 to 84 years) free of known CVD at baseline with median follow-up of 10.1 years. Fasting venous samples were analyzed for baseline lipid profile and lipoprotein particles. We focused on the HDL family of variables (small-, medium-, and large-diameter HDL particles and HDL cholesterol). Analyses identified the sum of small- plus medium-diameter HDL particles as important. Small- plus medium-diameter HDL particles were inversely associated with diagnostic code-based noncardiovascular, noncancer chronic inflammation-related death and hospitalization (n=1054) independent of covariates: relative risk per SD 0.85 (95% CI: 0.79 to 0.91, P<0.0001). Small- plus medium-diameter HDL particles were also associated with adjudicated fatal and nonfatal coronary heart disease events (n=423): relative risk per SD 0.88 (95% CI 0.77 to 0.98, P=0.02)., Conclusions: Small- plus medium-diameter HDL particles are an independent predictor for noncardiovascular, noncancer chronic inflammation-related death and hospitalization and for coronary heart disease events in subjects initially free of overt CVD. These findings support the hypothesis that smaller HDL particles of diameter <9.4 nm have anti-inflammatory properties in the general population., (© 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Background: Cardiovascular calcification outside of the coronary tree, known as extracoronary calcification (ECC), is highly prevalent, often occurs concurrently in multiple sites, and yet its prognostic value is unclear., Objective: To determine whether multisite ECC is associated with coronary heart disease (CHD) events, CHD mortality, and all-cause mortality., Methods: We evaluated 5903 participants from the Multi-Ethnic Study of Atherosclerosis without diabetes who underwent CT imaging for calcification of the aortic valve, aortic root, mitral valve, and thoracic aorta. Participants were followed for 10.3 years. Multivariable adjusted hazard ratios estimated risk of outcomes for increasing numbers of ECC sites (0, 1, 2, 3, and 4), and receiver operator characteristic analysis assessed model discrimination., Results: Prevalence of any ECC was 45%; median age was 62 years. Compared with those without ECC, those with ECC in 4 sites had increased hazards of 4.5, 7.1 and 2.3 for CHD events, CHD mortality, and all-cause mortality, respectively, independent of traditional risk factors (TRF; all P ≤ .05), and had ≥2-fold increased hazards for outcomes independent of coronary artery calcification (CAC). Each additional site of ECC was positively associated with each outcome in a graded fashion. When added to TRF, ECC significantly increased the area under the receiver operator characteristic curve for all outcomes and modestly increased the area under the curve for mortality beyond TRF + CAC (0.799 to 0.802; P = .03)., Conclusion: Increasing multisite ECC has a graded association with higher CHD and mortality risk, contributing information beyond TRF. Multisite ECC incidentally identified on imaging can be used to improve individualized risk prediction., (Copyright © 2015 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

Background: Patients with stable coronary heart disease (CHD) have widely varying prognoses and treatment options. Validated models for risk stratification of patients with CHD are needed. We sought to evaluate traditional and novel risk factors as predictors of secondary cardiovascular (CV) events, and to develop a prediction model that could be used to risk stratify patients with stable CHD., Methods and Results: We used independent derivation (912 participants in the Heart and Soul Study) and validation (2876 participants in the PEACE trial) cohorts of patients with stable CHD to develop a risk prediction model using Cox proportional hazards models. The outcome was CV events, defined as myocardial infarction, stroke, or CV death. The annual rate of CV events was 3.4% in the derivation cohort and 2.2% in the validation cohort. With the exception of smoking, traditional risk factors (including age, sex, body mass index, hypertension, dyslipidemia, and diabetes) did not emerge as the top predictors of secondary CV events. The top 4 predictors of secondary events were the following: N-terminal pro-type brain natriuretic peptide, high-sensitivity cardiac troponin T, urinary albumin:creatinine ratio, and current smoking. The 5-year C-index for this 4-predictor model was 0.73 in the derivation cohort and 0.65 in the validation cohort. As compared with variables in the Framingham secondary events model, the Heart and Soul risk model resulted in net reclassification improvement of 0.47 (95% CI 0.25 to 0.73) in the derivation cohort and 0.18 (95% CI 0.01 to 0.40) in the validation cohort., Conclusions: Novel risk factors are superior to traditional risk factors for predicting 5-year risk of secondary events in patients with stable CHD., (© 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)