Hard Atherosclerotic Cardiovascular Disease Research Articles

One-size-fits-all versus risk-category-based screening interval strategies for cardiovascular disease prevention in Chinese adults: a prospective cohort study

In non-high-risk individuals, risk-category-based atherosclerotic cardiovascular disease (ASCVD) screening strategies may be more cost-effective than one-size-fits-all approaches. However, current decisions are constrained by a lack of research evidence. We aimed to explore appropriate risk-category-based screening interval strategies for non-high-risk individuals in ASCVD primary prevention in the Chinese population. We used data from 28,624 participants in the China Kadoorie Biobank (CKB) who had completed at least two field surveys. The risk assessment tools were the 10-year ASCVD risk prediction models developed based on the CKB cohort. We constructed multistate Markov models to model disease progression and estimate transition probabilities between different risk categories. The total person-years spent unidentified in the high-risk state over a 10-year period were calculated for each screening interval protocol. We also estimated the number of ASCVD events prevented, quality-adjusted life years (QALYs) gained, and costs saved when compared to the 3-yearly screening protocol. When compared to the uniform 3-yearly protocol, most risk-category-based screening interval protocols would identify more high-risk individuals timely, thus preventing more ASCVD events and gaining QALYs. A few of them would reduce total health-care costs. The protocol, which used 6-year, 3-year, and 2-year screening intervals for low-risk, intermediate-low-risk, and intermediate-high risk individuals, was optimal, and would reduce the person-years spent unidentified in the high-risk category by 17.9% (95% CI: 13.1%-21.9%), thus preventing an estimated 113 thousand (95% CI: 83-138) hard ASCVD events for Chinese adults aged 30-79 over a 10-year period. When using a lower cost of statin therapy, more screening protocols would gain QALYs while saving costs. For the primary prevention of ASCVD, risk-category-based screening protocols outperformed the one-size-fits-all approach in the Chinese population. This work was supported by National Natural Science Foundation of China (82192904, 82388102, 82192900) and grants (2023YFC2509400) from the National Key R&D Program of China. The CKB baseline survey and the first re-survey were supported by a grant from the Kadoorie Charitable Foundation in Hong Kong. The long-term follow-up is supported by grants from the UK Wellcome Trust (212946/Z/18/Z, 202922/Z/16/Z, 104085/Z/14/Z, 088158/Z/09/Z), grants (2016YFC0900500) from the National Key R&D Program of China, National Natural Science Foundation of China (81390540, 91846303, 81941018), and Chinese Ministry of Science and Technology (2011BAI09B01).

Association between dietary magnesium and 10-year risk of a first hard atherosclerotic cardiovascular disease event

BackgroundTo test whether dietary magnesium is associated with 10-year risk of a first hard atherosclerotic cardiovascular disease event. MethodsIn this cross-sectional study, a total of 2980 participants, aged 40 to 79 years, from the National Health and Nutrition Examination Survey 1999–2018 were analyzed. The association between dietary magnesium and 10-year risk of a first hard atherosclerotic cardiovascular disease (ASCVD) event was assessed following adjustment for clinical risk factors, including sex, age, race, educational level, body mass index (BMI), alcohol drinking, smoking, systolic blood pressure (SBP), diastolic blood pressure (DBP), hypertension treated or not, diabetes and low density lipoprotein cholesterol (LDL-C), total energy and dietary fiber. We performed multivariate linear regression models and smooth curve fittings to evaluate the associations between dietary magnesium and 10-year risk of a first hard atherosclerotic cardiovascular disease event. ResultsWe observed a significant inverse association between dietary magnesium and predicted 10-year risk of a first hard atherosclerotic cardiovascular disease event (β=-0.01, [95% CI: -0.01, -0.00], P = 0.0256). We divided the 10-year risk into two categories, with a statistically significant reduction of ASCVD risk when the 10-year risk ≥7.5% (β=-0.01, [95% CI: -0.01, -0.00], P = 0.0440). ConclusionsDietary magnesium intake was inversely associated with the predicted 10-year risk of a first hard atherosclerotic cardiovascular disease event.

Trimethylamine-N-Oxide and Related Metabolites: Assessing Cardiovascular Risk in the Dallas Heart Study

ObjectiveTo evaluate the association between trimethylamine N-oxide (TMAO) and related metabolites with adverse cardiovascular events in a multiethnic urban primary prevention population. MethodsWe performed a case-control study of 361 participants of the Dallas Heart Study, including 88 participants with an incident atherosclerotic cardiovascular disease (ASCVD) event and 273 controls matched for age, sex, and body mass index without an ASCVD event during 12 years of follow-up (January 1, 2000, through December 31, 2015). Plasma levels of TMAO, choline, carnitine, betaine, and butyrobetaine were measured by mass spectrometry. The differential odds for incident ASCVD by metabolite levels between cases and controls were compared by a conditional logistic regression model adjusted for cardiovascular risk factors. ResultsParticipants with incident ASCVD had higher levels of TMAO and related metabolites compared with those without ASCVD (P<.05 for all). Those with plasma TMAO concentrations in quartile 4 had a more than 2-fold higher odds of ASCVD compared with those in quartile 1 (odds ratio, 2.77 [95% CI, 1.05 to 7.7; P=.04] for hard ASCVD and 2.41 [95% CI, 1.049 to 5.709; P=.04]). Similar trends were seen with the related metabolites choline, betaine, carnitine, and butyrobetaine. ConclusionOur results suggest that TMAO and related metabolites are independently associated with ASCVD events. Although further studies are needed, measurement of TMAO and related metabolites may have a role in ASCVD risk stratification for primary prevention.

Circulating MicroRNA-19 and cardiovascular risk reduction in response to weight-loss diets

MicroRNA-19 (miR-19) plays a critical role in cardiac development and cardiovascular disease (CVD). We examined whether change in circulating miR-19 was associated with change in CVD risk during weight loss. This study included 509 participants with overweight or obesity from the 24-month weight-loss diet intervention study (the POUNDS Lost trial) and with available data on circulating miR-19a-3p and miR-19b-3p at baseline and 6 months. The primary outcome for this analysis was the change in atherosclerotic CVD (ASCVD) risk at 6 and 24 months, which estimates the 10-year probability of hard ASCVD events. Secondary outcomes were the changes in ASCVD risk score components. Circulating miR-19a-3p and miR-19b-3p levels significantly decreased during the initial 6-month dietary intervention period (P=0.008, 0.0004, respectively). We found that a greater decrease in miR-19a-3p or miR-19b-3p was related to a greater reduction in ASCVD risk (β[SE]=0.33 [0.13], P=0.01 for miR-19a-3p; β[SE]=0.3 [0.12], P=0.017 for miR-19b-3p) over 6 months, independent of concurrent weight loss. Moreover, we found significant interactions between change in miR-19 and sleep disturbance on change in ASCVD risk over 24 months of intervention (P interaction=0.01 and 0.008 for miR-19a-3p and miR-19b-3p, respectively). Participants with a greater decrease in miR-19 without sleep disturbance had a greater reduction of ASCVD risk than those with slight/moderate/great amounts of sleep disturbance. In addition, change in physical activity significantly modified the associations between change in miR-19 and change in ASCVD risk over 24 months (P interaction=0.006 and 0.004 for miR-19a-3p and miR-19b-3p, respectively). A greater decrease in miR-19 was significantly associated with a greater reduction in ASCVD risk among participants with an increase in physical activity, while non-significant inverse associations were observed among those without an increase in physical activity. In conclusion, decreased circulating miR-19 levels during dietary weight-loss interventions were related to a significant reduction in ASCVD risk, and these associations were more evident in people with no sleep disturbance or increase in physical activity. ClinicalTrials.gov NCT00072995.

Abstract 14359: Life’s Essential 8 and Cardiovascular Health of Veterans: The Million Veteran Program

Background and Hypothesis: The American Heart Association (AHA) recently proposed the Life’s Essential 8 (LE8) score as an enhanced measurement tool for cardiovascular health. No studies to date have estimated its association with the risk for atherosclerotic cardiovascular disease (ASCVD) incidence and prognosis. Methods: A prospective cohort study of 384,518 Veterans enrolled in the VA Million Veteran Program (MVP) (2011-2021). LE8 score was developed using AHA guidelines. Primary outcome was total ASCVD. Secondary outcome was hard ASCVD which included non-fatal myocardial infarction, non-fatal stroke, and fatal CVD. Results: Based on 1.16 million person-years of follow-up among Veterans with no ASCVD at baseline, 46,295 Veterans had ASCVD events during follow-up. LE8 score was associated with ASCVD and its subtypes in a linear dose-response manner (Figure 1A). The overall population-attributable fractions for all non-ideal LE8 scores was 59% (95%CI: 51%-66%) for ASCVD, where non-ideal blood pressure was most influential (Figure 1B). Based on 0.6 million person-years of follow-up among patients with ASCVD at baseline, the hazard ratio for incident or recurrent hard ASCVD was 0.52 (95%CI: 0.48-0.56) comparing veterans with ≥650 to those with LE8 score &lt;350, with a dose-response linear association pattern. Conclusions: Based on 1.76 million person years of follow-up among Veterans, a high LE8 score was associated with a significantly lower ASCVD risk and a lower likelihood of developing adverse cardiovascular events regardless of ASCVD status at baseline. Theoretically, an ideal LE8 could potentially prevent almost 59% of ASCVD in this study. Our results support the importance of AHA’s promotion of LE8.

Abstract P338: Circulating microRNA-19 and Cardiovascular Risk Reduction in Response to Weight-Loss Diets: The Preventing Overweight Using Novel Dietary Strategies (Pounds Lost) Trial

Introduction: MicroRNA-19 (MiR-19) plays a critical role in cardiac development and cardiovascular disease (CVD). Hypothesis: We assessed the hypothesis that change in circulating miR-19 would be associated with changes in 10-year atherosclerotic CVD (ASCVD) risk and individual cardiovascular risk factors in a dietary weight-loss intervention. Methods: This study included 509 participants with overweight or obesity from the 2-year weight-loss diet intervention study (the POUNDS LOST trial) and with available data on circulating miR-19a/b-3p at baseline and 6 months. The primary outcome was the 6-month change in the ASCVD risk score, which estimates the 10-year probability of hard ASCVD events. Secondary outcomes were the change in each ASCVD component including blood pressure, lipid profiles, insulin resistance, glucose metabolism, and adiposity measures. Change in habitual physical activity and sleep disturbance were assessed from baseline to 6 months. Results: Circulating miR-19a/b-3p levels significantly decreased during the initial 6-month dietary intervention period (P=0.008, 0.0004, respectively). We found that greater decreases in log-transformed miR-19a/b-3p were related to a greater reduction in ASCVD risk (β[SE]=0.35 [0.13], P=0.01 for miR-19a-3p; β[SE]=0.33 [0.13], P=0.01 for miR-19b-3p) over 6 months. Similar positive associations were observed for changes in diastolic blood pressure with miR-19a/b-3p. Moreover, we found that sleep disturbance was significantly associated with reductions in miR-19a/b-3p from baseline to 6 months (P trend &lt;0.05). There were significant interactions between changes in miR-19a/b-3p and sleep disturbance for changes in ASCVD risk (P interaction&lt;0.005). Participants with greater decreases in miR-19a/b-3p with no/slight amount of sleep disturbance had a greater reduction of ASCVD risk from baseline to 6 months than those with moderate/great amount of sleep disturbance. In addition, changes in physical activity modified the associations between changes in miR-19a-3p and ASCVD risk. A greater decrease in miR-19a-3p was significantly associated with a greater reduction in ASCVD among participants with an increase in physical activity from baseline to 6 months. These positive associations were reversed and not significant among participants with no change/decrease in physical activity and moderate/great amount of sleep disturbance. Conclusions: In conclusion, decreased circulating miR-19 levels induced by dietary weight-loss interventions were related to a significant reduction in ASCVD risk, and such associations were more evident in people with no/slight amount of sleep disturbance and an increase in physical activity.

Triglyceride-glucose index and estimated 10-year risk of a first hard cardiovascular event.

Whether Triglyceride-glucose (TyG) index is associated with 10-year risk of a first hard atherosclerotic cardiovascular disease (ASCVD) event in the United States remains unclear. In this cross-sectional study, the participants, ranged from 40 to 79 years old, were from the National Health and Nutrition Examination Survey (NHANES) between 1999 and 2018. TyG index was the independent variable and 10-year risk of a first hard ASCVD was the dependent variable. The other variables, such as age, gender, race, body mass index (BMI), hypertension treatment states, smoking states and low-density lipoprotein cholesterol (LDL-C) et al. were considered as the potential confounding factors. Multivariate linear regression models and smooth curve fittings were used to evaluate the association between TyG index and 10-year risk of a first hard ASCVD event. A total of 2,142 participants were included in the analysis. The results showed that TyG index was associated with an increased 10-year risk of a first hard ASCVD event [β = 2.208, 95% (1.716, 2.700), P < 0.00001]. The association had statistical significance in both men [β = 3.862 95% CI (3.274, 4.450), P < 0.00001] and women [β = 1.067, 95% CI (0.286, 1.849), P = 0.00756)] according to subgroup analysis. Smooth curve fittings revealed that TyG index was linearly associated with 10-year risk of ASCVD in both male and female. Triglyceride-glucose index was associated with an increased 10-year risk of a first hard ASCVD event in the United States, suggesting it is necessary to monitor and control an appropriate range of TyG index.

The Association Between Remnant Cholesterol and the Estimated 10-Year Risk of a First Hard Cardiovascular Event.

BackgroundRemnant cholesterol (Remnant-C), rather than TG, is believed to increase the risk of atherosclerotic cardiovascular disease. We evaluated whether Remnant-C is associated with an estimated 10-year risk of a first hard atherosclerotic cardiovascular disease event.MethodsThis cross-sectional study was performed on 2,048 participants (1,130 men and 918 women), aged 40 to 79 years, from the National Health and Nutrition Examination Survey (NHANES) between 1999 and 2018. The independent variable was Remnant-C; the dependent variable was the 10-year risk of a first hard atherosclerotic cardiovascular disease event (defined as non-fatal myocardial infarction, coronary heart disease death, or stroke, over a 10-year period among people free from atherosclerotic cardiovascular disease at the beginning of the period). The other variables, such as smoking behavior, hypertension, diabetes etc., were considered as the potential effect modifiers. Multivariate linear regression models and smooth curve fittings were used to evaluate the association between Remnant-C and the 10-year risk of a first hard atherosclerotic cardiovascular disease event. Subgroup analyses stratified by gender and race were also performed.ResultsA positive association between Remnant-C and the 10-year risk of a first hard atherosclerotic cardiovascular disease event was demonstrated in the fully adjusted model (β = 0.078, [95%CI: 0.061–0.094], P < 0.001). The 10-year risk was increased by 0.078% for each 1 mg/dl increase in Remnant-C. In the subgroup analysis for gender, this association remained in both men (β = 0.128, [95%CI: 0.108–0.148], P < 0.001) and women (β = 0.043, [95%CI: 0.016–0.070], P = 0.00179). However, in the subgroup analysis for race, the association between Remnant-C and the 10-year risk reached an inflection point at remnant-C 38 mg/dL, where a positive association was not as obvious for the non-Hispanic Black population as for other racial groups.ConclusionsRemnant-C positively correlates with a 10-year risk of a first hard atherosclerotic cardiovascular disease event.

Breast Arterial Calcification: a Novel Cardiovascular Risk Enhancer Among Postmenopausal Women.

Breast arterial calcification (BAC), a common incidental finding in mammography, has been shown to be associated with angiographic coronary artery disease and cardiovascular disease (CVD) outcomes. We aimed to (1) examine the association of BAC presence and quantity with hard atherosclerotic CVD (ASCVD) and global CVD; (2) ascertain model calibration, discrimination and reclassification of ASCVD risk; (3) assess the joint effect of BAC presence and 10-year pooled cohorts equations risk on ASCVD. A cohort study of 5059 women aged 60-79 years recruited after attending mammography screening between October 2012 and February 2015 was conducted in a large health plan in Northern California, United States. BAC status (presence versus absence) and quantity (calcium mass mg) was determined using digital mammograms. Prespecified end points were incident hard ASCVD and a composite of global CVD. Twenty-six percent of women had BAC >0 mg. After a mean (SD) follow-up of 6.5 (1.6) years, we ascertained 155 (3.0%) ASCVD events and 427 (8.4%) global CVD events. In Cox regression adjusted for traditional CVD risk factors, BAC presence was associated with a 1.51 (95% CI, 1.08-2.11; P=0.02) increased hazard of ASCVD and a 1.23 (95% CI, 1.002-1.52; P=0.04) increased hazard of global CVD. While there was no evidence of dose-response association with ASCVD, a threshold effect was found for global CVD at very high BAC burden (95th percentile when BAC present). BAC status provided additional risk stratification of the pooled cohorts equations risk. We noted improvements in model calibration and reclassification of ASCVD: the overall net reclassification improvement was 0.12 (95% CI, 0.03-0.14; P=0.01) and the bias-corrected clinical-net reclassification improvement was 0.11 (95% CI, 0.01-0.22; P=0.04) after adding BAC status. Our results indicate that BAC has potential utility for primary CVD prevention and, therefore, support the notion that BAC ought to be considered a risk-enhancing factor for ASCVD among postmenopausal women.

Abstract 12521: Atherosclerotic Cardiovascular Disease Risk and Small Dense Low-Density Lipoprotein Cholesterol in Men, Women, African Americans and Non-African Americans

Introduction: Increased small dense low-density lipoprotein cholesterol (sdLDL-C) has been reported to be a significant atherosclerotic cardiovascular disease (ASCVD) risk factor Hypothesis: SdLDL-C is an independent ASCVD risk factor in men, women, African Americans, and non-African Americans. Methods: A total of 15,933 participants (median age 62 years, 56.7% female, 19.7% African-American, free of inclusive ASCVD at baseline) pooled from three studies (Atherosclerosis Risk in Communities Study, Framingham Offspring Study, and Multi-Ethnic Study of Atherosclerosis) were followed for 10 years for incident hard ASCVD and inclusive ASCVD (includes angioplasty and/or coronary artery bypass). These endpoints occurred in 6.1% and 9.7% of subjects, respectively. Information on all standard risk factors was obtained, and serum sdLDL-C levels were measured at baseline using automated analysis. The utility of traditional cardiovascular risk factors and sdLDL-C in 10-year hard and inclusive ASCVD risk was assessed-using univariate and multivariable regression analyses. Results: All standard risk factors were significant for hard and inclusive ASCVD in men, women, African-Americans and non-African-Americans on univariate statistical analysis. SdLDL-C was a significant risk factor when added to the pooled cohort equation for hard and inclusive ASCVD in all subjects, and for inclusive ASCVD in all subgroups, and significantly improved the C-Statistic and affected the net reclassification index for all subjects (p&lt;0.0001). When subjects with elevated sdLDL-C levels of &gt; 50 mg/dL were compared to those with optimal levels of &lt;25 mg/dL after adjustment for all standard risk factors, the hazard ratios (HR) and confidence intervals (CI) for incident inclusive ASCVD were all significant at p&lt;0.01: all subjects (HR 1.54, CI 1.30-1.83), men (HR 1.59, CI 1.27-1.99), women (HR 1.51, CI 1.05-1.27), non-African-Americans (HR 1.49, CI 1.24-1.80[CLA3] ), and African-Americans (HR 1.88, CI 1.23-2.89). Conclusions: An elevated sdLDL-C value &gt; 50 mg/dL was independently associated with a 50% increased 10-year inclusive ASCVD risk in all subjects regardless of sex or race[MD1] , and therefore is an important ASCVD risk enhancer.

Breast Arterial Calcification and Cardiovascular Risk Among Postmenopausal Women

Background: Breast arterial calcification (BAC) is commonly seen in mammograms but considered an incidental finding. Prior studies have shown correlation of BAC with angiographic coronary artery disease and cardiovascular disease (CVD) outcomes. To shed light on the utility of BAC for primary prevention, we aimed to: 1) Examine the association of BAC presence and quantity with hard atherosclerotic CVD (ASCVD) and global CVD; 2) Ascertain improvement in model calibration, discrimination and reclassification of ASCVD risk; 3) Assess the joint effect of BAC presence and 10-year Pooled Cohorts Equation (PCE) risk on ASCVD. Methods: Cohort study of 5,059 women aged 60-79 years when they attended mammography screening (10/2012 - 2/2015) followed up for 6.5 years (SD=1.6 years). BAC status (presence vs. absence) and quantity (mg of calcium mass) were determined using digital mammograms. Findings: Twenty-six percent of women had BAC > 0 mg. BAC presence was associated with age, ethnicity, education level, diabetes, hypertension and parity. In adjusted Cox regression, BAC presence was associated with a 1.51 (95% CI, 1.08-2.11; p=0.02) increased hazard of ASCVD and a 1.23 (95% CI, 1.002-1.52; p=0.04) increased hazard of global CVD. There was evidence of dose-response associations and of additional risk stratification of the PCE risk by BAC status. We noted improvements in model calibration, discrimination and reclassification (22 to 28%) after adding BAC information. Interpretation: Our results add to the body of evidence that presence and quantity of BAC assessed with contemporary digital mammography has potential utility for primary CVD prevention among post-menopausal women. Funding: MINERVA is an investigator-initiated cohort study funded by the National Heart, Lung, and Blood Institute (RO1HL106-043; multiple PIs Iribarren and Molloi). Declaration of Interest: None to declare. Ethical Approval: The study was approved by the Institutional Review Boards of the participating institutions and all participants signed an informed consent.

Abstract 15793: Joint Prediction of Hard Ascvd by Pooled Cohorts Equations Risk and Presence of Breast Arterial Calcification: The Minerva Study

Introduction: Prior studies have documented independent associations of breast arterial calcification (BAC) detected on mammographic screening with coronary artery disease or prospective cardiovascular disease outcomes. This study aims to ascertain the additional predictive ability for hard atherosclerotic cardiovascular disease (ASCVD) imparted by presence of BAC on top of the 10-year AHA/ACC Pooled Cohort Equations (PCE) Risk estimator. Hypothesis: BAC presence on mammograms will help further risk stratify women for risk of ASCVD. Methods: We used data from MINERVA, a multiethnic cohort of women aged 60 to 79 years at baseline (2012-15), free of symptomatic CVD, and recruited after mammography screening at Kaiser Permanente of Northern California. The sample available for analyses with complete data on BAC and PCE was 5,046. A BAC continuous mass score (mg) was obtained from digital mammograms using a validated densitometry method. BAC presence was BAC score &gt; 0 mg. Follow-up for hospitalization and death was through 5/31/20 (mean, 6.2 years). We defined hard ASCVD as acute myocardial infarction or stroke or CVD death (n=122 events). Results: The mean (SD) age at baseline was 66 (4) years; 47 percent were non-white. Overall, 26.4 percent had a BAC score &gt; 0 mg, 33 percent had low (&lt; 5%), 36 percent intermediate (between 5 and 10%) and 31 percent high (&gt; 10%) PCE risk. Using Cox models, there was a graded association by level of PCE risk and, within each level of PCE risk, women with BAC presence were at higher risk for ASCVD than women without BAC. In models adjusting for age, race/ethnicity, education level, BMI, statin use, menopausal hormone therapy, breast feeding and parity, being in the intermediate PCE risk group (relative to being at low PCE risk and having no BAC) was associated with 3.1 (95% CI, 1.5 - 6.5) increased hazard of ASCVD when no BAC was present and with 3.8 (95% CI, 1.7 - 8.7) increased hazard of ASCVD when BAC was present. Corresponding hazard ratios for women in the high PCE risks were 4.3 (95% CI, 1.9-9.6) and 7.5 (95% CI, 3.1-17.8), respectively. Conclusions: Our findings support additional predictive utility of BAC for ASCVD. In women at intermediate or high risk for ASCVD, BAC presence may help guide primary prevention.

Predicting Risk of Atherosclerotic Cardiovascular Disease Using Pooled Cohort Equations in Older Adults With Frailty, Multimorbidity, and Competing Risks.

BackgroundAssessment of atherosclerotic cardiovascular disease (ASCVD) risk is crucial for prevention and management, but the performance of the pooled cohort equations in older adults with frailty and multimorbidity is unknown. We evaluated the pooled cohort equations in these subgroups and the impact of competing risks.Methods and ResultsIn 4249 community‐dwelling adults, aged ≥65 years, from the CHS (Cardiovascular Health Study), we calculated 10‐year risk of hard ASCVD. Frailty was determined using the Fried phenotype. Latent class analysis was used to identify individuals with multimorbidity patterns using chronic conditions. We assessed discrimination using the C‐statistic and calibration by comparing predicted ASCVD risks with estimated risk using cause‐specific and cumulative incidence models, by multimorbidity patterns and frailty status. A total of 917 (21.6%) participants had an ASCVD event, and 706 (16.6%) had a competing event of death. C‐statistic was 0.68 in men and 0.69 in women; calibration was good when compared with cause‐specific and cumulative incidence estimated risks (males, −0.1% and 3.3%; females, 0.6% and 1.4%). Latent class analysis identified 4 patterns: minimal disease, cardiometabolic, low cognition, musculoskeletal‐lung depression. In the cardiometabolic pattern, ASCVD risk was overpredicted compared with cumulative incidence risk in men (7.4%) and women (6.8%). Risk was underpredicted in men (−10.7%) and women (−8.2%) with frailty compared with cause‐specific risk. Miscalibration occurred mostly at high predicted risk ranges.ConclusionsASCVD prediction was good in this cohort of adults aged ≥65 years. Although calibration varied by multimorbidity patterns, frailty, and competing risks, miscalibration was mostly present at high predicted risk ranges and thus less likely to alter decision making for primary prevention therapy.

Risk of Atherosclerotic Cardiovascular Disease Among US Adults: Use of 1999-2014 NHANES Data.

One in four deaths in the US is caused by cardiovascular disease (CVD), and early detection may be a key aspect of prevention. We assessed the probability of a first hard atherosclerotic cardiovascular disease (ASCVD) event within 10years in US Non-Hispanic White and African American population aged 40-79years. With data from 16years of the National Health and Nutrition Examination Survey (NHANES), we utilized the 2013 Pooled Cohort Equations developed by the American College of Cardiology and the American Heart Association to calculate risk scores for a representative sample. NHANES is a repeated, cross-sectional survey aimed at assessing the health and nutritional status of the country. Out of 17,087 eligible participants, a sample of 1876 (11%) remained for the analysis after excluding participants missing data required to compute the scores. Our results showed that 25.2% of the sample had a greater than 10% risk of contracting ASCVD within 10years, and we also found sex-, race-, and age-based disparities. The ASCVD risk scores can thus be used to evaluate the general cardiac health of the population. Results showed that a quarter of the US adult population was at risk to contract ASCVD in the next 10years, indicating the need for targeted preventative measures. With the aging population and rise in obesity rates, these results may also indicate trend continuation of high CVD-related morbidity and mortality.

Estimating the performance of three cardiovascular disease risk scores: the Estonian Biobank cohort study

BackgroundWe aim to investigate the predictive ability of PCE (Pooled Cohort Equations), QRISK2 and SCORE (Systematic COronary Risk Estimation) scoring systems for atherosclerotic cardiovascular disease (ASCVD) risk prediction in Estonia,...

The prognostic value of interleukin 6 in multiple chronic diseases and all-cause death: The Multi-Ethnic Study of Atherosclerosis (MESA)

Background and aimsWe aimed to evaluate the associations and prognostic value of interleukin-6 (IL6) for the prediction of atherosclerotic cardiovascular disease (ASCVD) events, heart failure (HF), and other chronic diseases in a large, multi-ethnic, contemporary population. MethodsWe included 6617 participants from the Multi-Ethnic Study of Atherosclerosis (5640 non-users, 977 users of statins at baseline). Main outcomes were hard ASCVD events and HF; secondary outcomes included all-cause death, atrial fibrillation, venous thromboembolism and cancer. ResultsMedian follow-up was 13.2 years. Strong associations were observed in Cox regression analyses between higher IL6 levels and ASCVD events, HF, and mortality, particularly among statins users. In the latter, associations remained strong after adjusting for traditional risk factors and other inflammation biomarkers (e.g., risk factor, hsCRP-adjusted hazard ratio for incident HF comparing 3rd vs. 1st IL6 tertiles: 3.55, 95% CI 1.23–10.27). Although IL6 did not improve CHD prediction beyond traditional risk factors, among statin users it improved the prediction of stroke (improvement in the C statistic +0.018), incident HF (+0.028, the largest C statistic increase across all study outcomes), and all-cause death (+0.017). ConclusionsIL6 is strongly and independently associated with ASCVD events, HF, and all-cause mortality, particularly among statin users. Although the prognostic value of IL6 is limited for the prediction of CHD events, it may have a role for the prediction of stroke, HF and all-cause death in asymptomatic statin users. Larger studies are needed to replicate these findings.

Cardiovascular disease risk prediction equations in 400 000 primary care patients in New Zealand: a derivation and validation study

Most cardiovascular disease risk prediction equations in use today were derived from cohorts established last century and with participants at higher risk but less socioeconomically and ethnically diverse than patients they are now applied to. We recruited a nationally representative cohort in New Zealand to develop equations relevant to patients in contemporary primary care and compared the performance of these new equations to equations that are recommended in the USA. The PREDICT study automatically recruits participants in routine primary care when general practitioners in New Zealand use PREDICT software to assess their patients' risk profiles for cardiovascular disease, which are prospectively linked to national ICD-coded hospitalisation and mortality databases. The study population included male and female patients in primary care who had no prior cardiovascular disease, renal disease, or congestive heart failure. New equations predicting total cardiovascular disease risk were developed using Cox regression models, which included clinical predictors plus an area-based deprivation index and self-identified ethnicity. Calibration and discrimination performance of the equations were assessed and compared with 2013 American College of Cardiology/American Heart Association Pooled Cohort Equations (PCEs). The additional predictors included in new PREDICT equations were also appended to the PCEs to determine whether they were independent predictors in the equations from the USA. Outcome events were derived for 401 752 people aged 30-74 years at the time of their first PREDICT risk assessment between Aug 27, 2002, and Oct 12, 2015, representing about 90% of the eligible population. The mean follow-up was 4·2 years, and a third of participants were followed for 5 years or more. 15 386 (4%) people had cardiovascular disease events (1507 [10%] were fatal, and 8549 [56%] met the PCEs definition of hard atherosclerotic cardiovascular disease) during 1 685 521 person-years follow-up. The median 5-year risk of total cardiovascular disease events predicted by the new equations was 2·3% in women and 3·2% in men. Multivariable adjusted risk increased by about 10% per quintile of socioeconomic deprivation. Māori, Pacific, and Indian patients were at 13-48% higher risk of cardiovascular disease than Europeans, and Chinese or other Asians were at 25-33% lower risk of cardiovascular disease than Europeans. The PCEs overestimated of hard atherosclerotic cardiovascular disease by about 40% in men and by 60% in women, and the additional predictors in the new equations were also independent predictors in the PCEs. The new equations were significantly better than PCEs on all performance metrics. We constructed a large prospective cohort study representing typical patients in primary care in New Zealand who were recommended for cardiovascular disease risk assessment. Most patients are now at low risk of cardiovascular disease, which explains why the PCEs based mainly on old cohorts substantially overestimate risk. Although the PCEs and many other equations will need to be recalibrated to mitigate overtreatment of the healthy majority, they also need new predictors that include measures of socioeconomic deprivation and multiple ethnicities to identify vulnerable high-risk subpopulations that might otherwise be undertreated. Health Research Council of New Zealand, Heart Foundation of New Zealand, and Healthier Lives National Science Challenge.

Ten-year association of coronary artery calcium with atherosclerotic cardiovascular disease (ASCVD) events: the multi-ethnic study of atherosclerosis (MESA).

While coronary artery calcium (CAC) has been extensively validated for predicting clinical events, most outcome studies of CAC have evaluated coronary heart disease (CHD) rather than atherosclerotic cardiovascular disease (ASCVD) events (including stroke). Also, virtually all CAC studies are of short- or intermediate-term follow-up, so studies across multi-ethnic cohorts with long-term follow-up are warranted prior to widespread clinical use. We sought to evaluate the contribution of CAC using the population-based MESA cohort with over 10 years of follow-up for ASCVD events, and whether the association of CAC with events varied by sex, race/ethnicity, or age category. We utilized MESA, a prospective multi-ethnic cohort study of 6814 participants (51% women), aged 45-84 years, free of clinical CVD at baseline. We evaluated the relationship between CAC and incident ASCVD using Cox regression models adjusted for age, race/ethnicity, sex, education, income, cigarette smoking status, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, diabetes, lipid-lowering medication, systolic blood pressure, antihypertensive medication, intentional physical exercise, and body mass index. Only the first event for each individual was used in the analysis. Overall, 500 incident ASCVD (7.4%) events were observed in the total study population over a median of 11.1 years. Hard ASCVD included 217 myocardial infarction, 188 strokes (not transient ischaemic attack), 13 resuscitated cardiac arrest, and 82 CHD deaths. Event rates in those with CAC = 0 Agatston units ranged from 1.3% to 5.6%, while for those with CAC > 300, the 10-year event rates ranged from 13.1% to 25.6% across different age, gender, and racial subgroups. At 10 years of follow-up, all participants with CAC > 100 were estimated to have >7.5% risk regardless of demographic subset. Ten-year ASCVD event rates increased steadily across CAC categories regardless of age, sex, or race/ethnicity. For each doubling of CAC, we estimated a 14% relative increment in ASCVD risk, holding all other risk factors constant. This association was not significantly modified by age, sex, race/ethnicity, or baseline lipid-lowering use. Coronary artery calcium is associated strongly and in a graded fashion with 10-year risk of incident ASCVD as it is for CHD, independent of standard risk factors, and similarly by age, gender, and ethnicity. While 10-year event rates in those with CAC = 0 were almost exclusively below 5%, those with CAC ≥ 100 were consistently above 7.5%, making these potentially valuable cutpoints for the consideration of preventive therapies. Coronary artery calcium strongly predicts risk with the same magnitude of effect in all races, age groups, and both sexes, which makes it among the most useful markers for predicting ASCVD risk.

Impact of National Health Checkup Service on Hard Atherosclerotic Cardiovascular Disease Events and All-Cause Mortality in the General Population

Whether health checkups favorably impact the occurrence of atherosclerotic cardiovascular disease (ASCVD) and all-cause mortality in the general population remains in debate. We investigated further the impact of health checkups on hard ASCVD events and all-cause mortality. We compared the occurrence of hard ASCVD events and all-cause deaths for 4 years starting in 2010 between participants who used the National Health Checkup Service (NHCS) more than twice and nonparticipants who never used the NHCS from 2006 to 2009. From the 342,594 survivors aged 40 to 69 years old in 2006 listed in the National Health Insurance Service-National Sample Cohort, a total of 55,275 pairs were selected by propensity matching. Hard ASCVD events were defined as the composite of myocardial infarction and stroke. In the 55,275 matched pairs, we found a significant association between the use of the NHCS and the reduction in hard ASCVD events (adjusted hazard ratio = 0.84, 95% confidence interval 0.76 to 0.92, p <0.001) and all-cause deaths (adjusted hazard ratio = 0.50, 95% confidence interval 0.45 to 0.55, p <0.001). The participants had more medical care, including outpatient care and hospitalizations, and took more hypertension and dyslipidemia medications, whereas hospitalizations for more than 60 days were significantly more frequent in the nonparticipants. In the subgroup analysis, the reduction in hard ASCVD events for NHCS participants was significantly greater in patients without a previous history of dyslipidemia or who did not have outpatient care. In conclusion, the use of the NHCS was significantly associated with reduced hard ASCVD events and all-cause mortality in the general population.

Pericardial, But Not Hepatic, Fat by CT Is Associated With CV Outcomes and Structure: The Multi-Ethnic Study of Atherosclerosis

ObjectivesThe study sought to determine the associations between local (pericardial) fat and incident cardiovascular disease (CVD) events and cardiac remodeling independent of markers of overall adiposity. BackgroundThe impact of pericardial fat—a local fat depot encasing the heart—on myocardial function and long-term CV prognosis independent of systemic consequences of adiposity or hepatic fat is an area of active debate. MethodsWe studied 4,234 participants enrolled in the MESA (Multi-Ethnic Study of Atherosclerosis) study with concomitant cardiac magnetic resonance imaging and computed tomography (CT) measurements for pericardial fat volume and hepatic attenuation (a measure of liver fat). Poisson and Cox regression were used to estimate the annualized risk of incident hard atherosclerotic CVD (ASCVD), all-cause death, heart failure, all-cause CVD, hard coronary heart disease, and stroke as a function of pericardial and hepatic fat. Generalized additive models were used to assess the association between cardiac magnetic resonance indices of left ventricular (LV) structure and function and pericardial fat. Models were adjusted for relevant clinical, demographic, and cardiometabolic covariates. ResultsMESA study participants with higher pericardial and hepatic fat were more likely to be older, were more frequently men, and had a higher prevalence of cardiometabolic risk factors (including dysglycemia, dyslipidemia, hypertension), as well as adiposity-associated inflammation. Over a median 12.2-year follow-up (interquartile range: 11.6 to 12.8 years), pericardial fat was associated with a higher rate of incident hard ASCVD (standardized hazard ratio: 1.22; 95% confidence interval: 1.10 to 1.35; p = 0.0001). Hepatic fat by CT was not significantly associated with hard ASCVD (standardized hazard ratio: 0.96; 95% confidence interval: 0.86 to 1.08; p = 0.52). Higher pericardial fat was associated with greater indexed LV mass (37.8 g/m2.7 vs. 33.9 g/m2.7, highest quartile vs. lowest quartile; p < 0.01), LV mass-to-volume ratio (1.2 vs. 1.1, highest quartile vs. lowest quartile; p < 0.01). In adjusted models, a higher pericardial fat volume was associated with greater LV mass (p < 0.0001) and concentricity (p < 0.0001). ConclusionsPericardial fat is associated with poorer CVD prognosis and LV remodeling, independent of insulin resistance, inflammation, and CT measures of hepatic fat.