Atherosclerotic Cardiovascular Disease Events Research Articles

#1164 Smoking cessation and atherosclerotic cardiovascular events and mortality in chronic kidney disease

Abstract Background and Aims Smoking cessation is recommended to reduce excess atherosclerotic cardiovascular disease (ASCVD) and mortality in patients with chronic kidney disease (CKD). However, this recommendation is largely based on observational studies on the general population, involving participants with preserved kidney function. Therefore, we aimed to evaluate the association of smoking dose and smoking cessation duration with ASCVD and mortality in patients with CKD. Method We compiled a comprehensive pooled dataset comprising 66,245 participants with CKD from the KNOW-CKD and the UK Biobank cohort. Participants were categorized according to smoking dose and duration of smoking cessation base on a questionnaire. The primary outcome encompassed a composite of ASCVD or all-cause mortality. An ASCVD event was defined according to the ICD-10 codes in the claim and death register records. Results Over a median follow-up period of 13.2 years, 14,671 (22.1%) participants reached the primary outcome. Compared to never smokers, former and current smokers exhibited a 1.30- and 2.14-fold higher risk of the primary outcome, respectively. Among former smokers, the hazard ratios (HRs) (95% confidence intervals [CIs]) for smoking loads <20 and ≥20 pack-years were 1.05 (1.00–1.10) and 2.14 (2.05–2.25), respectively. The increased risk of the primary outcome was attenuated by longer smoking cessation. The HRs (95% CIs) for smoking cessation of <10 years, 10–20 years, and >20 years were 1.75 (1.65–1.86), 1.43 (1.34–1.52), and 1.11 (1.06-1.16), respectively, compared with never smokers. Conclusion Among former smokers with CKD, the risk of ASCVD or mortality was substantially attenuated with less smoking load and a longer duration of smoking cessation. Our findings support the preexisting recommendations for smoking cessation to improve clinical outcomes in patients with CKD.

Prognostic Value of Cardiovascular Biomarkers in the Population

Identification of individuals at high risk for atherosclerotic cardiovascular disease within the population is important to inform primary prevention strategies. To evaluate the prognostic value of routinely available cardiovascular biomarkers when added to established risk factors. Individual-level analysis including data on cardiovascular biomarkers from 28 general population-based cohorts from 12 countries and 4 continents with assessments by participant age. The median follow-up was 11.8 years. Measurement of high-sensitivity cardiac troponin I, high-sensitivity cardiac troponin T, N-terminal pro-B-type natriuretic peptide, B-type natriuretic peptide, or high-sensitivity C-reactive protein. The primary outcome was incident atherosclerotic cardiovascular disease, which included all fatal and nonfatal events. The secondary outcomes were all-cause mortality, heart failure, ischemic stroke, and myocardial infarction. Subdistribution hazard ratios (HRs) for the association of biomarkers and outcomes were calculated after adjustment for established risk factors. The additional predictive value of the biomarkers was assessed using the C statistic and reclassification analyses. The analyses included 164 054 individuals (median age, 53.1 years [IQR, 42.7-62.9 years] and 52.4% were women). There were 17 211 incident atherosclerotic cardiovascular disease events. All biomarkers were significantly associated with incident atherosclerotic cardiovascular disease (subdistribution HR per 1-SD change, 1.13 [95% CI, 1.11-1.16] for high-sensitivity cardiac troponin I; 1.18 [95% CI, 1.12-1.23] for high-sensitivity cardiac troponin T; 1.21 [95% CI, 1.18-1.24] for N-terminal pro-B-type natriuretic peptide; 1.14 [95% CI, 1.08-1.22] for B-type natriuretic peptide; and 1.14 [95% CI, 1.12-1.16] for high-sensitivity C-reactive protein) and all secondary outcomes. The addition of each single biomarker to a model that included established risk factors improved the C statistic. For 10-year incident atherosclerotic cardiovascular disease in younger people (aged <65 years), the combination of high-sensitivity cardiac troponin I, N-terminal pro-B-type natriuretic peptide, and high-sensitivity C-reactive protein resulted in a C statistic improvement from 0.812 (95% CI, 0.8021-0.8208) to 0.8194 (95% CI, 0.8089-0.8277). The combination of these biomarkers also improved reclassification compared with the conventional model. Improvements in risk prediction were most pronounced for the secondary outcomes of heart failure and all-cause mortality. The incremental value of biomarkers was greater in people aged 65 years or older vs younger people. Cardiovascular biomarkers were strongly associated with fatal and nonfatal cardiovascular events and mortality. The addition of biomarkers to established risk factors led to only a small improvement in risk prediction metrics for atherosclerotic cardiovascular disease, but was more favorable for heart failure and mortality.

Independent Relationship of Lipoprotein(a) and Carotid Atherosclerosis With Long-Term Risk of Cardiovascular Disease.

Lipoprotein(a) (Lp(a)) is considered to be a causal risk factor of atherosclerotic cardiovascular disease (ASCVD), but whether there is an independent or joint association of Lp(a) and atherosclerotic plaque with ASCVD risk remains uncertain. This study aims to assess ASCVD risk independently or jointly conferred by Lp(a) and carotid atherosclerotic plaque. A total of 5471 participants with no history of cardiovascular disease at baseline were recruited and followed up for ASCVD events (all fatal and nonfatal acute coronary and ischemic stroke events) over a median of 11.5 years. Independent association of Lp(a), or the joint association of Lp(a) and carotid plaque with ASCVD risk, was explored using Cox proportional hazards models. Overall, 7.6% of the participants (60.0±7.9 years of age; 2649 [48.4%] men) had Lp(a) ≥50 mg/dL, and 539 (8.4/1000 person-years) incident ASCVD events occurred. Lp(a) concentrations were independently associated with long-term risk of total ASCVD events, as well as coronary events and ischemic stroke events. Participants with Lp(a) ≥50 mg/dL had a 62% higher risk of ASCVD incidence (95% CI, 1.19-2.21) than those with Lp(a) <10 mg/dL, and they exhibited a 10-year ASCVD incidence of 11.7%. This association exists even after adjusting for prevalent plaque. Moreover, participants with Lp(a) ≥30 mg/dL and prevalent plaque had a significant 4.18 times higher ASCVD risk than those with Lp(a) <30 mg/dL and no plaque. Higher Lp(a) concentrations are independently associated with long-term ASCVD risk and may exaggerate cardiovascular risk when concomitant with atherosclerotic plaque.

European and US Guideline-Based Statin Eligibility, Genetically Predicted Coronary Artery Disease, and the Risk of Major Coronary Events.

A study was designed to investigate whether the coronary artery disease polygenic risk score (CAD-PRS) may guide lipid-lowering treatment initiation as well as deferral in primary prevention beyond established clinical risk scores. Participants were 311 799 individuals from the UK Biobank free of atherosclerotic cardiovascular disease, diabetes, chronic kidney disease, and lipid-lowering treatment at baseline. Participants were categorized as statin indicated, statin indication unclear, or statin not indicated as defined by the European and US guidelines on statin use. For a median of 11.9 (11.2-12.6) years, 8196 major coronary events developed. CAD-PRS added to European-Systematic Coronary Risk Evaluation 2 (European-SCORE2) and US-Pooled Cohort Equation (US-PCE) identified 18% and 12% of statin-indication-unclear individuals whose risk of major coronary events were the same as or higher than the average risk of statin-indicated individuals and 16% and 12% of statin-indicated individuals whose major coronary event risks were the same as or lower than the average risk of statin-indication-unclear individuals. For major coronary and atherosclerotic cardiovascular disease events, CAD-PRS improved C-statistics greater among statin-indicated or statin-indication-unclear than statin-not-indicated individuals. For atherosclerotic cardiovascular disease events, CAD-PRS added to the European evaluation and US equation resulted in a net reclassification improvement of 13.6% (95% CI, 11.8-15.5) and 14.7% (95% CI, 13.1-16.3) among statin-indicated, 10.8% (95% CI, 9.6-12.0) and 15.3% (95% CI, 13.2-17.5) among statin-indication-unclear, and 0.9% (95% CI, 0.6-1.3) and 3.6% (95% CI, 3.0-4.2) among statin-not-indicated individuals. CAD-PRS may guide statin initiation as well as deferral among statin-indication-unclear or statin-indicated individuals as defined by the European and US guidelines. CAD-PRS had little clinical utility among statin-not-indicated individuals.

Discordance among apoB, non-high-density lipoprotein cholesterol, and triglycerides: implications for cardiovascular prevention.

Despite growing evidence that apolipoprotein B (apoB) is the most accurate marker of atherosclerotic cardiovascular disease (ASCVD) risk, its adoption in clinical practice has been low. This investigation sought to determine whether low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (HDL-C), and triglycerides are sufficient for routine cardiovascular care. A sample of 293 876 UK Biobank adults (age: 40-73 years, 42% men), free of cardiovascular disease, with a median follow-up for new-onset ASCVD of 11 years was included. Distribution of apoB at pre-specified levels of LDL-C, non-HDL-C, and triglycerides was examined graphically, and 10-year ASCVD event rates were compared for high vs. low apoB. Residuals of apoB were constructed after regressing apoB on LDL-C, non-HDL-C, and log-transformed triglycerides and used as predictors in a proportional hazards regression model for new-onset ASCVD adjusted for standard risk factors, including HDL-C. ApoB was highly correlated with LDL-C and non-HDL-C (Pearson's r = .96, P < .001 for both) but less so with log triglycerides (r = .42, P < .001). However, apoB ranges necessary to capture 95% of all observations at pre-specified levels of LDL-C, non-HDL-C, or triglycerides were wide, spanning 85.8-108.8 md/dL when LDL-C 130 mg/dL, 88.3-112.4 mg/dL when non-HDL-C 160 mg/dL, and 67.8-147.4 md/dL when triglycerides 115 mg/dL. At these levels (±10 mg/dL), 10-year ASCVD rates for apoB above mean + 1 SD vs. below mean - 1 SD were 7.3 vs. 4.0 for LDL-C, 6.4 vs. 4.6 for non-HDL-C, and 7.0 vs. 4.6 for triglycerides (all P < .001). With 19 982 new-onset ASCVD events on follow-up, in the adjusted model, residual apoB remained statistically significant after accounting for LDL-C and HDL-C (hazard ratio 1.06, 95% confidence interval 1.0-1.07), after accounting for non-HDL-C and HDL-C (hazard ratio 1.04, 95% confidence interval 1.03-1.06), and after accounting for triglycerides and HDL-C (hazard ratio 1.13, 95% confidence interval 1.12-1.15). None of the residuals of LDL-C, non-HDL-C, or of log triglycerides remained significant when apoB was included in the model. High variability of apoB at individual levels of LDL-C, non-HDL-C, and triglycerides coupled with meaningful differences in 10-year ASCVD rates and significant residual information contained in apoB for prediction of new-onset ASCVD events demonstrate that LDL-C, non-HDL-C, and triglycerides are not adequate proxies for apoB in clinical care.

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. MethodIn 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. ResultWe 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). ConclusionDietary magnesium intake was inversely associated with the predicted 10-year risk of a first hard atherosclerotic cardiovascular disease event.

Association of the triglyceride-glucose index with early-onset atherosclerotic cardiovascular disease events and all-cause mortality: a prospective cohort study

BackgroundThe association between the triglyceride glucose (TyG) index and the risk of early-onset atherosclerotic cardiovascular disease (ASCVD) events or all-cause mortality in young and middle-aged people is not fully elucidated.MethodsThe present study included 64,489 young and middle-aged people who participated in the 2006 Kailuan Study physical examination. Multivariate Cox proportional hazards models and restricted cubic spline curves were used to assess the association of TyG index with early-onset ASCVD events and all-cause mortality.ResultsDuring a median of 11-year follow-up, 1984 (3.08%) participants experienced at least one ASCVD event and 1,392 (2.16%) participants experienced all-cause death. A higher TyG index was significantly associated with a higher risk of early-onset ASCVD events (HR: 1.61, 95% CI 1.38–1.89) and all-cause mortality (HR: 1.39, 95% CI 1.17–1.65), respectively. For each unit increase in TyG index, the risk of early-onset ASCVD events increased by 20%. In addition, there was a non-linear association between the TyG index and early-onset ASCVD events (P for non-linear < 0.01), and a linear association between TyG index and all-cause mortality (P for non-linear = 0.476).ConclusionsA higher TyG index is significantly associated with an increased incidence of early-onset ASCVD events and all-cause mortality in a young and middle-aged population from North China.

Cardiovascular Risk Associated With Social Determinants of Health at Individual and Area Levels

The benefit of adding social determinants of health (SDOH) when estimating atherosclerotic cardiovascular disease (ASCVD) risk is unclear. To examine the association of SDOH at both individual and area levels with ASCVD risks, and to assess if adding individual- and area-level SDOH to the pooled cohort equations (PCEs) or the Predicting Risk of CVD Events (PREVENT) equations improves the accuracy of risk estimates. This cohort study included participants data from 4 large US cohort studies. Eligible participants were aged 40 to 79 years without a history of ASCVD. Baseline data were collected from 1995 to 2007; median (IQR) follow-up was 13.0 (9.3-15.0) years. Data were analyzed from September 2023 to February 2024. Individual- and area-level education, income, and employment status. ASCVD was defined as the composite outcome of nonfatal myocardial infarction, death from coronary heart disease, and fatal or nonfatal stroke. A total of 26 316 participants were included (mean [SD] age, 61.0 [9.1] years; 15 494 women [58.9%]; 11 365 Black [43.2%], 703 Chinese American [2.7%], 1278 Hispanic [4.9%], and 12 970 White [49.3%]); 11 764 individuals (44.7%) had at least 1 adverse individual-level SDOH and 10 908 (41.5%) had at least 1 adverse area-level SDOH. A total of 2673 ASCVD events occurred during follow-up. SDOH were associated with increased risk of ASCVD at both the individual and area levels, including for low education (individual: hazard ratio [HR], 1.39 [95% CI, 1.25-1.55]; area: HR, 1.31 [95% CI, 1.20-1.42]), low income (individual: 1.35 [95% CI, 1.25-1.47]; area: HR, 1.28 [95% CI, 1.17-1.40]), and unemployment (individual: HR, 1.61 [95% CI, 1.24-2.10]; area: HR, 1.25 [95% CI, 1.14-1.37]). Adding area-level SDOH alone to the PCEs did not change model discrimination but modestly improved calibration. Furthermore, adding both individual- and area-level SDOH to the PCEs led to a modest improvement in both discrimination and calibration in non-Hispanic Black individuals (change in C index, 0.0051 [95% CI, 0.0011 to 0.0126]; change in scaled integrated Brier score [IBS], 0.396% [95% CI, 0.221% to 0.802%]), and improvement in calibration in White individuals (change in scaled IBS, 0.274% [95% CI, 0.095% to 0.665%]). Adding individual-level SDOH to the PREVENT plus area-level social deprivation index (SDI) equations did not improve discrimination but modestly improved calibration in White participants (change in scaled IBS, 0.182% [95% CI, 0.040% to 0.496%]), Black participants (0.187% [95% CI, 0.039% to 0.501%]), and women (0.289% [95% CI, 0.115% to 0.574%]). In this cohort study, both individual- and area-level SDOH were associated with ASCVD risk; adding both individual- and area-level SDOH to the PCEs modestly improved discrimination and calibration for estimating ASCVD risk for Black individuals, and adding individual-level SDOH to PREVENT plus SDI also modestly improved calibration. These findings suggest that both individual- and area-level SDOH may be considered in future development of ASCVD risk assessment tools, particularly among Black individuals.

Thoracic versus coronary calcification for atherosclerotic cardiovascular disease events prediction

This study compared the prognostic value of quantified thoracic artery calcium (TAC) including aortic arch on chest CT and coronary artery calcium (CAC) score on ECG-gated cardiac CT.MethodsA total of...

Discordance Between Very Low-Density Lipoprotein Cholesterol and Low-Density Lipoprotein Cholesterol Increases Cardiovascular Disease Risk in a Geographically Defined Cohort.

Clinical risk scores are used to identify those at high risk of atherosclerotic cardiovascular disease (ASCVD). Despite preventative efforts, residual risk remains for many individuals. Very low-density lipoprotein cholesterol (VLDL-C) and lipid discordance could be contributors to the residual risk of ASCVD. Cardiovascular disease-free residents, aged ≥40 years, living in Olmsted County, Minnesota, were identified through the Rochester Epidemiology Project. Low-density lipoprotein cholesterol (LDL-C) and VLDL-C were estimated from clinically ordered lipid panels using the Sampson equation. Participants were categorized into concordant and discordant lipid pairings based on clinical cut points. Rates of incident ASCVD, including percutaneous coronary intervention, coronary artery bypass grafting, stroke, or myocardial infarction, were calculated during follow-up. The association of LDL-C and VLDL-C with ASCVD was assessed using Cox proportional hazards regression. Interaction between LDL-C and VLDL-C was assessed. The study population (n=39 098) was primarily White race (94%) and female sex (57%), with a mean age of 54 years. VLDL-C (per 10-mg/dL increase) was significantly associated with an increased risk of incident ASCVD (hazard ratio, 1.07 [95% CI, 1.05-1.09]; P<0.001]) after adjustment for traditional risk factors. The interaction between LDL-C and VLDL-C was not statistically significant (P=0.11). Discordant individuals with high VLDL-C and low LDL-C experienced the highest rate of incident ASCVD events, 16.9 per 1000 person-years, during follow-up. VLDL-C and lipid discordance are associated with a greater risk of ASCVD and can be estimated from clinically ordered lipid panels to improve ASCVD risk assessment.

Public Health Relevance of US EPA Air Quality Index Activity Recommendations

Reducing exposure to fine particulate matter (<2.5 μm [PM2.5]) air pollution improves cardiopulmonary morbidity and mortality. However, the public health relevance of air quality index (AQI) activity guidelines under present-day environmental conditions in the US has not been critically assessed. To evaluate the public health relevance of following PM2.5 AQI activity guidance in preventing serious atherosclerotic cardiovascular disease (ASCVD) and pulmonary events among adults in the US. This cross-sectional modeling study involved the general adult population and sensitive individuals as designated by the US Environmental Protection Agency (EPA), including adults with preexisting ASCVD or lung disease (asthma or chronic obstructive pulmonary disease). The study was conducted between August 1, 2023, and January 31, 2024. Daily AQI strata for PM2.5 and the corresponding activity recommendations. The main outcome was the number needed to treat (NNT) per day by following activity guidance across daily AQI strata to prevent 1 serious ASCVD or pulmonary event among relevant populations. To calculate PM2.5-induced excess disease event rates per day, estimated baseline disease-specific daily event rates for each group were multiplied by the increase in risks due to PM2.5 levels at each AQI stratum. The number of events prevented per day was calculated by multiplying each excess disease event rate by the percentage in exposure reduction plausibly incurred by following population-specific activity guidance at each AQI level. The NNT is the reciprocal of the number of events prevented. The NNT to prevent ASCVD events was high for the general population and for patients with ASCVD across all AQI strata. The range of values was comparatively lower to prevent pulmonary events among adults with lung disease. During most days (96%) when activity recommendations were promulgated due to elevated PM2.5 (AQI, 101-200), the NNT to prevent a serious disease event remained very high for the general population (>18 million), patients with ASCVD (approximately 1.6-5 million), and adults with lung disease (approximately 66 000-202 000). These findings suggest that existing PM2.5 AQI activity recommendations are of questionable public health relevance in present-day conditions and merit consideration for updating to improve their potential effectiveness.

Glucagon-like Peptide-1 analogues and delipidation of coronary atheroma in statin-treated type 2 diabetic patients with coronary artery disease: The prespecified sub-analysis of the OPTIMAL randomized clinical trial

Background and aimsRandomized clinical trials have demonstrated the ability of glucagon-like peptide-1 analogues (GLP-1RAs) to reduce atherosclerotic cardiovascular disease events in patients with type 2 diabetes (T2D). How GLP-1RAs modulate diabetic atherosclerosis remains to be determined yet. MethodsThe OPTIMAL study was a prospective randomized controlled study to compare the efficacy of 48-week continuous glucose monitoring- and HbA1c-guided glycemic control on near infrared spectroscopty (NIRS)/intravascular ultrasound (IVUS)-derived plaque measures in 94 statin-treated patients with T2D (jRCT1052180152, UMIN000036721). Of these, 78 patients with evaluable serial NIRS/IVUS images were analyzed to compare plaque measures between those treated with (n = 16) and without GLP-1RAs (n = 72). ResultsAll patients received a statin, and on-treatment LDL-C levels were similar between the groups (66.9 ± 11.6 vs. 68.1 ± 23.2 mg/dL, p = 0.84). Patients receiving GLP-1RAs demonstrated a greater reduction of HbA1c [-1.0 (-1.4 to −0.5) vs. −0.4 (-0.6 to −0.2)%, p = 0.02] and were less likely to demonstrate a glucose level >180 mg/dL [-7.5 (-14.9 to −0.1) vs. 1.1 (-2.0 - 4.2)%, p = 0.04], accompanied by a significant decrease in remnant cholesterol levels [-3.8 (-6.3 to −1.3) vs. −0.1 (-0.8 - 1.1)mg/dL, p = 0.008]. On NIRS/IVUS imaging analysis, the change in percent atheroma volume did not differ between the groups (−0.9 ± 0.25 vs. −0.2 ± 0.2%, p = 0.23). However, GLP-1RA treated patients demonstrated a greater frequency of maxLCBI4mm regression (85.6 ± 0.1 vs. 42.0 ± 0.6%, p = 0.01). Multivariate analysis demonstrated that the GLP-1RA use was independently associated with maxLCBI4mm regression (odds ratio = 4.41, 95%CI = 1.19–16.30, p = 0.02). ConclusionsIn statin-treated patients with T2D and CAD, GLP-1RAs produced favourable changes in lipidic plaque materials, consistent with its stabilization.

Sex differences in incident atherosclerotic cardiovascular disease events among women and men with HIV: Erratum.

Sex differences in incident atherosclerotic cardiovascular disease events among women and men with HIV: Erratum.

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.

Statin utilization and cardiovascular outcomes in a real-world primary prevention cohort of older adults

BackgroundStatins are a cost-effective therapy for prevention of atherosclerotic cardiovascular disease (ASCVD). Guidelines on statins for primary prevention are unclear for older adults (>75 years). ObjectiveInvestigate statin utility in older adults without ASCVD events, by risk stratifying in a large healthcare network. MethodsWe included 8,114 older adults, without CAD, PVD or ischemic stroke. Statin utilization based on ACC/AHA 10-year ASCVD risk calculation, was evaluated in intermediate (7.5%-19.9%) and high-risk patients (≥ 20%); and categorized using low and ‘moderate or high’ intensity statins with a follow up period of ∼7 years. Cox regression models were used to calculate hazard ratios for incident ASCVD and mortality across risk categories stratified by statin utilization. Data was adjusted for competing risk using Elixhauser Comorbidity Index. ResultsCompared with those on moderate or high intensity statins, high-risk older patients not on any statin had a significantly increased risk of MI [HR 1.51 (1.17–1.95); p<0.01], stroke [HR 1.47 (1.14–1.90); p<0.01] and all-cause mortality [HR 1.37 (1.19–1.58); p<0.001] in models adjusted for Elixhauser Comorbidity Index. When comparing the no statin group versus the moderate or high intensity statin group in the intermediate risk cohort, although a trend for increased risk was seen, it did not meet statistical significance thresholds for MI, stroke or all-cause mortality. ConclusionLack of statin use was associated with increased cardiovascular events and mortality in high-risk older adults. Given the benefits appreciated, statin use may need to be strongly considered for primary ASCVD prevention among high-risk older adults. Future studies will assess the risk-benefit ratio of statin intervention in older adults.

Association of cardiac biomarkers with long-term cardiovascular events in a community cohort

Introduction: We hypothesized that combining biomarkers of atherosclerotic cardiovascular disease (ASCVD) would improve prediction of ASCVD events in a primary prevention cohort. Materials and methods The study assessed major adverse cardiac events (MACE) (myocardial infarction, coronary artery bypass graft, percutaneous intervention, stroke, and death. Cox proportional hazards models assessed apolipoprotein AI (ApoA1), apolipoprotein B (ApoB), ceramide score, cystatin C, galectin-3 (Gal3), LDL-C, Non-HDL-C, total cholesterol (TC), N-terminal B-type natriuretic peptide (NT proBNP), high-sensitivity cardiac troponin (HscTnI) and soluble interleukin 1 receptor-like 1. In adjusted models, Ceramide score was defined by from N-palmitoyl-sphingosine [Cer(16:0)], N-stearoyl-sphingosine [Cer(18:0)], N-nervonoyl-sphingosine [Cer(24:1)] and N-lignoceroyl-sphingosine [Cer(24:0)]. Multi-biomarker models were compared with C-statistics and Integrated Discrimination Index (IDI). Results A total of 1131 patients were included. Adjusted NT proBNP per 1 SD resulted in a 31% increased risk of MACE/death (HR = 1.31) and a 31% increased risk for stroke/MI (HR = 1.31). Adjusted Ceramide per 1 SD showed a 13% increased risk of MACE/death (HR = 1.13) and a 29% increased risk for stroke/MI (HR = 1.29). These markers added to clinical factors for both MACE/death (p = 0.003) and stroke/MI (p = 0.034). HscTnI was not a predictor of outcomes when added to the models. Discussion Ceramide score and NT proBNP improve the prediction of MACE and stroke/MI in a community primary prevention cohort.

Fixed-dose combination therapy for the prevention of atherosclerotic cardiovascular disease.

Fixed-dose combination (FDC) therapy, also known as polypill therapy, targets risk factors for atherosclerotic cardiovascular disease (ASCVD) and has been proposed as a strategy to reduce global ASCVD burden. Here we conducted a systematic search for relevant studies from 2016-2022 to assess the effects of FDC therapy for prevention of ASCVD. The studies selected include randomized trials evaluating FDC therapy with at least one blood pressure-lowering drug and one lipid-lowering drug. The study data were independently extracted, the quality of evidence was appraised by multiple reviewers and effect estimates were pooled using a fixed-effect meta-analysis when statistical heterogeneity was low to moderate. The main outcomes of the analysis were all-cause mortality, fatal and nonfatal ASCVD events, adverse events, systolic blood pressure, low-density lipoprotein cholesterol and adherence. Among 26 trials (n = 27,317 participants, 43.2% female and mean age range 52.9-76.0), FDC therapy was associated with lower low-density lipoprotein cholesterol and systolic blood pressure, with higher rates of adherence and adverse events in both primary and mixed secondary prevention populations. For studies with a mostly primary prevention population, FDC therapy was associated with lower risk of all-cause mortality by 11% (5.6% versus 6.3%; relative risk (risk ratio) of 0.89; 95% confidence interval 0.78 to 1.00; I2 = 0%; four trials and 16,278 participants) and risk of fatal and nonfatal ASCVD events by 29% (6.1% versus 8.4%; relative risk (risk ratio) of 0.71; 95% confidence interval 0.63 to 0.79; I2 = 0%; five trials and 15,503 participants). One adequately powered trial in an exclusively secondary prevention population showed that FDC therapy reduced the risk of major adverse cardiovascular events by 24%. These findings support adoption and implementation of polypills to lower risk for all-cause mortality and ASCVD.

Abstract P530: Thoracic Aorta and Coronary Artery Calcification and Atherosclerotic Cardiovascular Disease Risk in South Asian Americans

Background: South Asian populations have a high risk of atherosclerotic cardiovascular disease (ASCVD). Subclinical atherosclerosis measures, including thoracic aortic calcification (TAC) and coronary artery calcification (CAC), are associated with ASCVD events, and TAC is a stronger predictor in women than men. However, no prior studies have investigated TAC in South Asians. Methods: We examined data from the Mediators of Atherosclerosis in South Asians Living in America (MASALA) study from 2015-2018. TAC and CAC were measured from computerized tomography scans using the Agatston method, and scores were categorized as 0, 1-99, and 100 or greater. Ten-year ASCVD risk was calculated using the 2013 pooled cohort equations, categorized as low, intermediate, or high risk. We determined associations of traditional risk factors with TAC and CAC and used multivariable ordinal logistic regression to examine associations between TAC and CAC with ASCVD risk in stepwise models. Results: Of 958 participants, 30% had TAC scores between 1-99 and 24% had TAC ≥100. TAC and CAC were modestly correlated (r = 0.30). There was a graded prevalence of TAC and CAC scores with levels of ASCVD risk (Figure). Both TAC and CAC were associated with several traditional risk factors; however, only CAC was associated with current smoking, HDL-cholesterol, triglycerides, and diastolic blood pressure. After adjusting for age, gender, and these four additional risk factors, only TAC ≥100 remained associated with ASCVD risk (OR 3.29, 95% CI 1.86 - 2.23), while CAC and TAC &lt;100 were not. The association between TAC and ASCVD risk was stronger for women than men (p-for-interaction &lt;0.001). Conclusion: Though TAC and CAC are associated with traditional risk factors, high TAC levels were independently associated with ASCVD risk, especially among women. Further study is needed to determine whether high TAC scores may be predictive of ASCVD events in South Asian populations.

Abstract P282: Pooled Cohort Equation Performance at Quantile Thresholds of African and European Ancestry Among Hispanic/Latino: Findings From Multi-Ethnic Study of Atherosclerosis (MESA)

Background: Current recommendations include using the non-Hispanic White (NHW) pooled cohort equation (PCE) for 10-year atherosclerotic cardiovascular disease (ASCVD) risk estimation among Hispanic individuals and the non-Hispanic Black (NHB) PCE when African ancestry is present. We studied PCE performance at thresholds of African and European ancestry among US Hispanics. Methods: Hispanic participants from the Multi-Ethnic Study of Atherosclerosis (MESA), ages 44-75 years without diabetes mellitus or prior cardiovascular disease were included. ADMIXTURE software was used to estimate quantile thresholds of continental genetic ancestry (African and European). We compared 10-year survival Kaplan-Meier estimates among Mexican Hispanics, Caribbean Hispanics and Other Hispanics using a log-rank analysis. We calculated the predicted-to-observed (P/O) ASCVD event ratios using the NHW and NHB PCE across quantile threshold of African and European ancestry. Results: 966 MESA Hispanics were stratified into: Mexican (n=504), Caribbean (n=284) or Other Hispanic (n=178). At 10-years, there were 179 ASCVD events [Mexicans (n=107), Caribbean (n=49), Other Hispanic (n=23)]. We observed overestimation using the NHW and NHB PCE as evidenced by P/O ratios &gt;1. Both PCEs performed better (P/O ratios converge toward 1) with increasing quantiles of European Ancestry and performed worse (P/O ratios diverge from 1) with increasing quantiles of African Ancestry. At a greater than 0.7 quantile of African ancestry, a sharp increase in overestimation was recorded for both PCEs. (Fig1A). Though Mexican Hispanics had the lowest ASCVD-free survival probability at 10 years’ time mark, results were not statistically significant. (Fig 1B) Conclusion: We observed overestimation in the 10-year ASCVD risk estimation using the NHW and NHB PCE among Hispanics as evidenced by P/O ratios &gt;1. Both PCEs performed better with increasing quantiles of European ancestry and performed poorly with increasing quantiles of African ancestry.

Abstract P283: Hispanic/Latino Ethnic Background and Genetic Ancestry in Relation to Atherosclerotic Cardiovascular Disease Risk Estimation: Insights From the Multi-Ethnic Study of Atherosclerosis (MESA)

Background: Hispanics are a highly admixed population. Pooled Cohort Equation (PCE) excluded them in its derivation. We analyzed Hispanic background and genetic ancestry in relation to atherosclerotic cardiovascular disease (ASCVD) risk. Methods: We included 966 Hispanics from Multi-Ethnic Study of Atherosclerosis (MESA), aged 44-75 years and free of diabetes/prior CVD. Statin users and those with LDL-C&gt;190 mg/dL were excluded. Continental genetic ancestry (West African [AA], European [EA]) was estimated by ADMIXTURE software. Predicted ASCVD events (myocardial infarction, stroke, coronary heart disease death) based on non-Hispanic White (NHW) and non-Hispanic Black (NHB) PCE versions, were compared with observed events based on 10-years Kaplan-Meier Estimates and presented as predicted-to-observed (P/O) ratios across Hispanic backgrounds and &gt;median genetic ancestry. Risk discrimination was assessed by Harrell’s C-statistic based on Cox models. Results: MESA Hispanics included 504 Mexicans [ME], 284 Caribbean [CA] and 178 Other Hispanics [OH]. At 10-years, there were 179 ASCVD events: 107 ME; 49 CA; 23 OH. PCE overestimates ASCVD risk (reflected by P/O ratio &gt;1.0). Using the NHW PCE, all Hispanics had a similar P/O ratio compared to NHW in the low-risk category, and lower P/O ratio compared to NHW in the high-risk category. The extent of overestimation varied across disaggregated Hispanic background (least in ME intermediate risk; most in CA high risk category). Higher P/O ratios were observed among Hispanics of &gt;median AA ancestry and lowest in Hispanics of &gt;median EA ancestry (Figure 1). Harrell’s C-statistic showed no statistically significant difference within groups. Conclusion: Disaggregating Hispanics by background and ancestry led to variability in PCE performance with greater overestimation of ASCVD risk for those of CA background or with &gt;median AA compared to those of ME background or &gt;median EA. The relationship between ethnicity, ancestry, and ASCVD risk in Hispanics should be further explored.