Incident Atherosclerotic Cardiovascular Disease Research Articles

Genome-wide polygenic risk scores for hypertensive disease during pregnancy can also predict the risk for long-term cardiovascular disease

Hypertensive disorders during pregnancy are associated with the risk of long-term cardiovascular disease after pregnancy, but it has not yet been determined whether genetic predisposition for hypertensive disorders during pregnancy can predict the risk for long-term cardiovascular disease. This study aimed to evaluate the risk for long-term atherosclerotic cardiovascular disease according to polygenic risk scores for hypertensive disorders during pregnancy. Among UK Biobank participants, we included European-descent women (n=164,575) with at least 1 live birth. Participants were divided according to genetic risk categorized by polygenic risk scores for hypertensive disorders during pregnancy (low risk, score ≤25th percentile; medium risk, score 25th∼75th percentile; high risk, score >75th percentile), and were evaluated for incident atherosclerotic cardiovascular disease, defined as the new occurrence of one of the following: coronary artery disease, myocardial infarction, ischemic stroke, or peripheral artery disease. Among the study population, 2427 (1.5%) had a history of hypertensive disorders during pregnancy, and 8942 (5.6%) developed incident atherosclerotic cardiovascular disease after enrollment. Women with high genetic risk for hypertensive disorders during pregnancy had a higher prevalence of hypertension at enrollment. After enrollment, women with high genetic risk for hypertensive disorders during pregnancy had an increased risk for incident atherosclerotic cardiovascular disease, including coronary artery disease, myocardial infarction, and peripheral artery disease, compared with those with low genetic risk, even after adjustment for history of hypertensive disorders during pregnancy. High genetic risk for hypertensive disorders during pregnancy was associated with increased risk for atherosclerotic cardiovascular disease. This study provides evidence on the informative value of polygenic risk scores for hypertensive disorders during pregnancy in prediction of long-term cardiovascular outcomes later in life.

Role of the Gut Microbiome in the Development of Atherosclerotic Cardiovascular Disease

Atherosclerotic cardiovascular disease (ASCVD) is the primary cause of death globally, with nine million deaths directly attributable to ischemic heart diseases in 2020. Since the last few decades, great effort has been put toward primary and secondary prevention strategies through identification and treatment of major cardiovascular risk factors, including hypertension, diabetes, dyslipidemia, smoking, and a sedentary lifestyle. Once labelled "the forgotten organ", the gut microbiota has recently been rediscovered and has been found to play key functions in the incidence of ASCVD both directly by contributing to the development of atherosclerosis and indirectly by playing a part in the occurrence of fundamental cardiovascular risk factors. Essential gut metabolites, such as trimethylamine N-oxide (TMAO), secondary bile acids, lipopolysaccharides (LPS), and short-chain fatty acids (SCFAs), have been associated with the extent of ischemic heart diseases. This paper reviews the latest data on the impact of the gut microbiome in the incidence of ASCVD.

Abstract P453: Apolipoprotein B, Low-Density Lipoprotein Particle Number, Non-High-Denisity Lipoprotein Cholesterol, Low-Density Lipoprotein Cholesterol, and Total Cholesterol for Atherosclerotic Cardiovascular Disease Risk Prediction in Young Adults

Introduction: Measures of atherogenic particle number (apoB and LDL particle number [LDL-P]) are stronger predictors of atherosclerotic cardiovascular disease (ASCVD) risk than measures of cholesterol concentration (LDL-C, non-HDL-C, total cholesterol [TC]) in middle-aged adults. It is unclear if this is true for younger adults. Methods: Among CARDIA participants (ppts), NMR was used to measure apoB and LDL-P. Non-HDL-C and TC were measured using standard assays; LDL-C was calculated using the Friedewald equation. We stratified the ppts into two age windows: age 20-30y (n=1645) and age 30-40y (n=2922). We used adjusted Cox proportional hazards models to assess the associations of 1SD higher apoB, LDL-P, non-HDL-C, LDL-C, or TC with incident ASCVD events. We substituted each measure of atherogenic lipid burden for TC in a modified Pooled Cohort Equation (PCE) model (with and without HDL-C); and model performance (discrimination and reclassification) was evaluated. Results: There were 81 and 163 ASCVD events over (median [IQR]) 31.8y (31.1-32.0y) for the age 20-30 age window and over 26.8y (19.1-27.1y) for the 30-40y age window, respectively. In ppts age 20-30y, a 1SD higher apoB, LDL-P, non-HDL-C, and LDL-C were significantly associated with incident ASCVD in demographic adjusted models. The strengths of associations with ASCVD were not significantly different across these measures. For the 30-40y age window, all measures of atherogenic lipoproteins were significantly associated with ASCVD; the strengths of association were not significantly different across atherogenic lipid measures in all models. There were no significant differences in the C-statistic and no improvement in reclassification when each measure was used to replace TC in the PCE model. Conclusions: ApoB, LDL-P, LDL-C or non-HDL-C may be slightly better markers of long-term ASCVD risk than TC in adults < 30y. However, in adults between 30-40y all measures of atherogenic lipid burden appeared to be equivalent predictors of long-term risk.

Abstract P451: Coronary Artery Calcium and the Association Between Dietary Fish Intake and Atherosclerotic Cardiovascular Disease Risk

Introduction: Current guidelines recommend ≥2 servings of fish/week for the prevention of atherosclerotic cardiovascular disease (ASCVD). However, a recent large meta-analysis suggested that the benefit may exist only for persons with a prior ASCVD event. Whether coronary artery calcium (CAC) can help to identify individuals who are likely to benefit from habitual fish consumption is unknown. Hypothesis: CAC will stratify persons who may and may not benefit from habitual fish consumption. Methods: There were 4977 participants in the Multi-Ethnic Study of Atherosclerosis who reported their frequency of fish intake and underwent CAC scanning at Visit 1. Adjusted Cox proportional hazards regression models stratified by the presence/absence of CAC assessed the association between fish intake and incident ASCVD over a median follow-up of 15.7 years. Results: The mean age was 61 years old, 53% were women, 26% were Black, and 49% of participants had prevalent CAC. A similar proportion of individuals reported consuming ≥2 servings of fish/week for those with CAC=0 and CAC >0 (35% versus 33%, p=0.12). The absolute ASCVD event rate for those with <2 or ≥2 servings of fish/week was 5.5 vs. 4.2 per 1,000 person-years for CAC=0 and 18.2 vs. 19.0 person-years for CAC >0 (Figure 1). Each additional serving of fish/week was associated with a 9% lower risk of ASCVD for participants with CAC=0 (HR=0.91, 95% CI: 0.83-0.99) whereas there was no significant association for persons with CAC >0 (HR=1.03, 95% CI: 0.99-1.07). Conclusions: A higher amount of fish consumption was associated with a lower risk of incident ASCVD for participants with CAC=0, but not those with CAC >0, although the absolute ASCVD event rate was low for persons with CAC=0 regardless of fish consumption frequency.

Abstract 42: Artificial Intelligence Electrocardiogram to Detect Coronary Calcification and to Predict Atherosclerotic Cardiovascular Events in the Community

Background: We developed a deep learning algorithm that detects coronary artery calcium (CAC) score using 12-lead electrocardiograms (CAC- ECG). We tested the hypothesis that the output from the CAC-ECG algorithm would be associated with incident atherosclerotic cardiovascular disease (ASCVD) events and that the CAC- ECG would refine the AHA/ACC Pooled Cohort Equation’s (PCE) predictive capabilities. Methods: A community-based cohort of consecutive patients seeking primary care in Olmsted County, MN, between 1998-2000 with passive follow-up via record linkage. Inclusion was identical to the PCE. The original CAC-ECG was developed in 43,210 subjects yielding an AUC of 0.83. Herein, we used the CAC-ECG output to predict a high CAC (≥ 300). Primary outcome was ASCVD defined as fatal and non-fatal myocardial infarction and ischemic stroke, secondary outcome was Major Adverse Cardiovascular Events (MACE) further including PCI, CABG, and mortality. Events were validated in duplicate. Cox proportional hazard models adjusted for variables included in the PCE and were stratified to evaluate the effect of the CAC-ECG on PCE-predicted risk. Follow-up was truncated at 10 years for PCE analyses. Results: We included 24,793 subjects, mean ± SD age 53.9 ± 12.1, 52% women, 95% white. After 16.7±3.7 yrs follow-up, 2,366 (9.5%) had ASCVD and 3,401 (13.7%) had MACE. Risk of ASCVD and MACE increased with CAC-ECG probability quintiles, independent of risk factors, p for trend <0.001 ( Fig. A-B ). The CAC-ECG enhanced the predicted capabilities of the PCE across all ASCVD risk groups ( Fig. C ). Net reclassification improved 13.7% with comparable C-statistic from 0.77 vs. 0.78 for PCE and CAC-ECG. Conclusions: CAC-ECG was associated with ASCVD and MACE and improved PCE predicted risk. The CAC-ECG algorithm could identify individuals at risk in primary prevention; Unlike the PCE, the CAC-ECG can be applied without chart review or performing a computer tomography and may be reliably used retrospectively in cohorts with digitally stored ECGs.

Abstract P200: Cumulative Circulating Branched Chain Amino Acid Exposure in Young Adulthood and Incident Atherosclerotic Cardiovascular Disease (ASCVD) in Later Life: The CARDIA Study

Introduction: Circulating branched chain amino acid (BCAA) levels are associated with the development of diabetes mellitus (DM) and downstream ASCVD in middle-aged women. It is unknown if BCAAs in young adult men and women are associated with ASCVD events. BCAA levels may be dynamic in middle-aged adults prior to the development of DM or ASCVD events, thus cumulative BCAA measures in early life may better quantify exposure risk than a single measure at mid-life. Methods: We measured plasma BCAA levels in 3110 Coronary Artery Risk Development in Young Adults study participants using nuclear magnetic resonance (NMR) at Years (y) 2, 7, 15, and 20. To minimize missingness bias, BCAA levels were imputed for the residual 1835 participants without NMR measures. Cumulative BCAA exposure from 19-40y of age was calculated as the area under the curve using a spline-based mixed-effects model to estimate subject-specific BCAA trajectories from 19-40y. Sex-specific associations between cumulative BCAA exposure and incident ASCVD events after 40y of age were assessed by multivariable (Table) Cox proportional hazards regression models including BCAA levels and fasting blood glucose (FBG) at age 40y and further stratified by DM status. Results: Among 4945 participants (55.3% female), there were 255 ASCVD events and 675 DM cases over a median of 18.8 years of follow-up after age 40y. In adjusted models, cumulative BCAA exposure from 19-40y was associated with ASCVD events after 40y of age in women, but not men (Table). The associations in women were robust to adjustment for BCAAs and FBG at age 40y. There was no significant difference in the cumulative BCAA-ASCVD association among men or women who developed DM before ASCVD versus those who did not. Conclusions: Cumulative BCAA exposure in early adulthood is associated with ASCVD in women independent of mid-life BCAA levels. Elevated BCAA levels in women during early adulthood may reflect behaviors and/or metabolic pathways that increase risks for ASCVD independent of the development of hyperglycemia.

Incidence of Atherosclerotic Cardiovascular Disease in Young Adults at Low Short-Term But High Long-Term Risk

BackgroundYoung adults may have high long-term atherosclerotic cardiovascular disease (ASCVD) risk despite low short-term risk. ObjectivesIn this study, we sought to compare the performance of short-term and long-term ASCVD risk prediction tools in young adults and evaluate ASCVD incidence associated with predicted short-term and long-term risk. MethodsWe included adults aged 18 to 39 years, from 2008 to 2009 in a U.S. integrated health care system, and followed them through 2019. We calculated 10-year and 30-year ASCVD predicted risk and assessed ASCVD incidence. ResultsAmong 414,260 young adults, 813 had an incident ASCVD event during a median of 4 years (maximum 11 years). Compared with 10-year predicted risk, 30-year predicted risk improved reclassification (net reclassification index: 16%) despite having similar discrimination (Harrell’s C: 0.749 vs 0.726). Overall, 1.0% and 2.2% of young adults were categorized as having elevated 10-year (≥7.5%) and elevated 30-year (≥20%) predicted risk, respectively, and 1.6% as having low 10-year (<7.5%) but elevated 30-year predicted risk. The ASCVD incidence rate per 1,000 person-years was 2.60 (95% CI: 1.92-3.52) for those with elevated 10-year predicted risk, 1.87 (95% CI: 1.42-2.46) for those with low 10-year but elevated 30-year predicted risk, and 0.32 (95% CI: 0.30-0.35) for those with low 10-year and 30-year predicted risk. The age- and sex-adjusted incidence rate ratio was 3.04 (95% CI: 2.25-4.10) comparing those with low 10-year but elevated 30-year predicted risk and those with low 10-year and 30-year predicted risk. ConclusionsLong-term ASCVD risk prediction tools further discriminate a subgroup of young adults with elevated observed risk despite low estimated short-term risk.

The Association of Serum Immunoglobulins with Risk of Cardiovascular Disease and Mortality: the Rotterdam Study

PurposeInflammation is implicated in cardiovascular disease (CVD), but the association of total serum immunoglobulin (Ig) A, G, and M with CVD across the whole spectrum of atherosclerosis in community-dwelling elderly is unknown.MethodsThis study was embedded in the Rotterdam Study, an ongoing population-based cohort study. We performed Cox regression for the associations of Igs with incident atherosclerotic CVD (ACVD; composite of myocardial infarction, revascularization, and stroke), cardiovascular mortality, and all-cause mortality, and multinomial logistic regression for the association between Igs and coronary artery calcification (CAC) scores. We adjusted for age, sex, lifestyle, and cardiovascular risk factors and presented results per standard deviation increase.ResultsWe included 8767 participants (median age 62.2 years, 57% women). Higher IgG was associated with an increased ACVD risk (hazard ratio [HR]: 1.08; 95% confidence interval [95% CI]: 1.01–1.15). Higher IgA and IgG were associated with an increased cardiovascular mortality risk, mainly within Ig reference ranges, and with an increased all-cause mortality risk, although less marked. Higher IgA was associated with severe atherosclerosis, i.e., CAC score > 400 (odds ratio: 1.29; 95% CI: 1.03–1.62), while for higher IgG a trend was seen with severe atherosclerosis.ConclusionIn middle-aged and older individuals from the general population, higher serum IgA and IgG, but not IgM, are associated with CVD, cardiovascular mortality, and severe atherosclerosis, particularly within Ig reference ranges and independent of serum C-reactive protein. Future studies are needed to elucidate potential causality of the reported associations.

P141 Risk Factors of Atherosclerotic Cardiovascular Disease (Ischemic Heart Disease and Cerebrovascular Accident) in Patients With Inflammatory Bowel Disease: a hospital-based cohort

Abstract Background Immune-mediated inflammatory diseases (IMIDs) involve an increased risk of developing atherosclerotic cardiovascular disease (ASCVD). However, the association between inflammatory bowel disease (IBD) and ASCVD is not well established. Our aims were to evaluate the frequency of ASCVD [ischemic heart disease (IHD) and cerebrovascular accident (CVA)] after IBD diagnosis and to identify the risk factors associated with its development. Methods Observational, single-centre study which included all patients seen at the IBD Unit of the Hospital Universitario Central de Asturias (Spain) between May 2010 and April 2022. Cardiovascular risk factors and the development of ASCVD were prospectively assessed; in addition, this information was sought selectively prior to IBD diagnosis and patients’ first visit to the unit. Regarding classical risk factors, we analysed hypertension, dyslipidaemia and diabetes mellitus. As possible risk factors related to IBD, we analysed the presence of complex IBD which, in the case of Crohn’s disease (CD), we defined as the presence of stricturing or penetrating behaviour or the need for bowel resection surgery, and, in the case of ulcerative colitis (UC), as an E3 extension or the need for colectomy. Finally, we analysed the coexistence of other IMIDs as a risk factor. Results A total of 2,153 patients were included (52% CD, 45% UC and 3% IBD-unclassified). Forty-nine percent were women and mean age at IBD diagnosis was 39 years. Twenty-four percent had hypertension, 14% dyslipidaemia and 8.6% diabetes; 59% were current or former smokers; 37% had an associated IMID (12% cutaneous and 7.9% joint). Prior to IBD diagnosis, 62 patients had presented with ASCVD (41 IHD and 21 CVA). After IBD diagnosis, 95 patients had at least one ASCVD (49 IHD and 46 CVA); after 31,516 patient-years of follow-up, the incidence of a first ASCVD was 0.31 per 100 patient-years (0.16 IHD and 0.15 CVA). The incidence of ASCVD was stable over time after IBD diagnosis. In the multivariate analysis (Table 1), age at IBD diagnosis &amp;gt;50 years (p&amp;lt;0.001), hypertension (p=0.006), dyslipidaemia (p=0.032), male sex (p=0.004) and a history of ASCVD prior to IBD diagnosis (p=0.011) were associated with an increased risk of ASCVD. With these variables, a Cox regression survival analysis was performed (Figure 1 and 2). Neither the type of IBD, the existence of complex IBD nor the coexistence of other IMIDs was associated with an increased risk of ASCVD. Table 1. Figure 1. Figure 2. Conclusion The development of ASCVD in patients with IBD is associated with classical risk factors (hypertension and dyslipidaemia), as well as older age at diagnosis and male sex. The coexistence of other IMIDs does not increase the risk of ASCVD in these patients.

Differential Associations of Cystatin C Versus Creatinine-Based Kidney Function With Risks of Cardiovascular Event and Mortality Among South Asian Individuals in the UK Biobank.

Background South Asian individuals have increased cardiovascular disease and mortality risks. Reliance on creatinine- rather than cystatin C-based estimated glomerular filtration rate (eGFRcys) may underestimate the cardiovascular disease risk associated with chronic kidney disease. Methods and Results Among 7738 South Asian UK BioBank participants without prevalent heart failure (HF) or atherosclerotic cardiovascular disease, we investigated associations of 4 eGFRcys and creatinine-based estimated glomerular filtration rate categories (<45, 45-59, 60-89, and ≥90 mL/min per 1.73 m2) with risks of all-cause mortality, incident HF, and incident atherosclerotic cardiovascular disease. The mean age was 53±8 years; 4085 (53%) were women. Compared with creatinine, cystatin C identified triple the number of participants with estimated glomerular filtration <45 (n=35 versus n=113) and 6 times the number with estimated glomerular filtration 45 to 59 (n=80 versus n=481). After multivariable adjustment, the eGFRcys 45 to 59 category was associated with higher risks of mortality (hazard ratio [HR], 2.38 [95% CI, 1.55-3.65]) and incident HF (sub-HR [sHR], 1.87 [95% CI, 1.09-3.22]) versus the eGFRcys ≥90 category; the creatinine-based estimated glomerular filtration rate 45 to 59 category had no significant associations with outcomes. Of the 7623 participants with creatinine-based estimated glomerular filtration rate ≥60, 498 (6.5%) were reclassified into eGFRcys <60 categories. Participants who were reclassified as having eGFRcys <45 had higher risks of mortality (HR, 4.88 [95% CI, 2.56-9.31]), incident HF (sHR, 4.96 [95% CI, 2.21-11.16]), and incident atherosclerotic cardiovascular disease (sHR, 2.29 [95% CI, 1.14-4.61]) versus those with eGFRcys ≥90; those reclassified as having eGFRcys 45 to 59 had double the mortality risk (HR, 2.25 [95% CI, 1.45-3.51]). Conclusions Among South Asian individuals, cystatin C identified a high-risk chronic kidney disease population that was not detected by creatinine and enhanced estimated glomerular filtration rate-based risk stratification for mortality, incident HF, and incident atherosclerotic cardiovascular disease.

Atherosclerotic cardiovascular disease risk and small dense low-density lipoprotein cholesterol in men, women, African Americans and non-African Americans: The pooling project

Background and aimsElevated small dense low-density lipoprotein-cholesterol (sdLDL-C) has been reported to be associated with increased atherosclerotic cardiovascular disease (ASCVD) risk. Our aims were to determine whether direct and calculated sdLDL-C were significant independent ASCVD risk factors in sex and race subgroups. MethodsIn a total of 15,933 participants free of ASCVD at baseline (median age 62 years, 56.7% female, 19.7% African American) fasting plasma lipids and sdLDL-C were measured by standardized automated methods. All subjects were followed for 10 years for incident ASCVD, which developed in 9.7% of subjects. SdLDL-C values were also calculated. Univariate and multivariate analyses were carried out to assess for independent associations with incident ASCVD after adjustment for all standard risk factors. ResultsAll standard risk factors were significantly associated with incident ASCVD on univariate analysis, as were direct and calculated sdLDL-C. These latter parameters were also significant when added to the pooled cohort risk equation. However, associations were significantly stronger for direct sdLDL-C and were not significant for calculated values once direct values were in the model. In contrast to calculated values, top quartile direct sdLDL-C was significantly independently associated with incident ASCVD versus bottom quartile values in all subjects and subgroups, except African Americans (hazard ratios ≥1.50, p < 0.01). Subjects with direct values ≥ 50 mg/dL versus <25 mg/dL had significantly higher independent ASCVD risk in all groups (hazard ratios >1.49, all p < 0.01). ConclusionsHaving a direct small dense low-density lipoprotein cholesterol value ≥ 50 mg/dL is a significant independent ASCVD risk-enhancer.

Combining European and U.S. risk prediction models with polygenic risk scores to refine cardiovascular prevention: the CoLaus|PsyCoLaus Study.

A polygenic risk score (PRS) has the potential to improve individual atherosclerotic cardiovascular disease (ASCVD) risk assessment. To determine whether a PRS combined with two clinical risk scores, the Systematic COronary Risk Evaluation 2 (SCORE2) and the Pooled Cohort Equation (PCE) improves the prediction of ASCVD. Using a population-based European prospective cohort, with 6733 participants at the baseline (2003-2006), the PRS presenting the best predictive accuracy was combined with SCORE2 and PCE to assess their joint performances for predicting ASCVD Discrimination, calibration, Cox proportional hazard regression, and net reclassification index were assessed. : 4218 subjects (53% women; median age, 53.4 years), with 363 prevalent and incident ASCVD, were used to compare four PRSs. The metaGRS_CAD PRS presented the best predictive capacity (AUROC = 0.77) and was used in the following analyses. 3383 subjects (median follow-up of 14.4 years), with 190 first-incident ASCVD, were employed to test ASCVD risk prediction. The changes in C statistic between SCORE2 and PCE models and those combining metaGRS_CAD with SCORE2 and PCE were 0.008 (95% CI, -0.00008-0.02, P = 0.05) and 0.007 (95% CI, 0.005-0.01, P = 0.03), respectively. Reclassification was improved for people at clinically determined intermediate-risk for both clinical scores [NRI of 9.6% (95% CI, 0.3-18.8) and 12.0% (95% CI, 1.5-22.6) for SCORE2 and PCE, respectively]. Combining a PRS with clinical risk scores significantly improved the reclassification of risk for incident ASCVD for subjects in the clinically determined intermediate-risk category. Introducing PRSs in clinical practice may refine cardiovascular prevention for subgroups of patients in whom prevention strategies are uncertain.

Blood lipids after COVID-19 infection

Blood lipids after COVID-19 infection

Life satisfaction and the risk of atherosclerotic cardiovascular disease in the general Japanese population: the Suita Study.

Atherosclerotic cardiovascular disease (ASCVD) is a major cause of morbidity and mortality. Life satisfaction is a measure of mental health with a potential cardioprotective role. This study aimed to investigate the association between life satisfaction and ASCVD risk in the general Japanese population. We used data from 6,877 people (30-84 years) registered in the Suita Study, a Japanese population-based prospective cohort study. All participants were free from stroke and coronary heart disease (CHD) at baseline. Then, participants were followed up for incident ASCVD, including cerebral infarction and CHD. Cox proportional hazards models were used to calculate the hazard ratio (HR) and 95% confidence interval (95% CI) of incident ASCVD according to life satisfaction. Within 102,545 person-years (median follow-up = 16.6 years), 482 incident ASCVD events were identified. In the age- and sex-adjusted model, being very satisfied, rather satisfied, or not sure, compared to being dissatisfied with life, showed a lower risk of ASCVD: HR (95% CI) = 0.55 (0.41, 0.74), 0.67 (0.50, 0.89), and 0.57 (0.36, 0.88), respectively (p-trend < 0.001). The associations remained consistent after adjusting for stress and unfortunate events: HR (95% CI) = 0.57 (0.42, 0.77), 0.68 (0.50, 0.91), and 0.54 (0.35, 0.84), respectively (p-trend < 0.001). The results did not vary between cerebral infarction and CHD: HR (95% CI) for being very satisfied with life = 0.58 (0.37, 0.91) and 0.55 (0.36, 0.84), respectively. Life satisfaction was inversely associated with the risk of ASCVD in the investigated general Japanese population.

Stair climbing and the incidence of atherosclerotic cardiovascular disease: a population-based prospective cohort study.

Stair climbing is a readily available form of physical activity with potential cardioprotective merits. Herein, we investigated the association between stair climbing and atherosclerotic cardiovascular disease (ASCVD) incidence among Japanese people. This prospective cohort study used data from 7,282 participants, aged 30-84 years, registered in the Suita Study and free from stroke and ischemic heart disease (IHD). Standard approaches were used to detect incident ASCVD events, including cerebral infarction and IHD, during follow-up. Stair climbing was assessed using a baseline questionnaire. We applied the Cox regression to calculate the hazard ratios (HRs) and 95% confidence intervals (95% CIs) of incident ASCVD for climbing stairs in 20-39%, 40-59%, and ≥60% compared to <20% of the time. We adjusted the regression models for age, sex, body mass index, smoking, alcohol consumption, physical activity, hypertension, diabetes, atrial fibrillation, lipid profile, chronic kidney disease, and history of cardiac murmur or valvular diseases. A total of 536 new ASCVD events were detected within a median follow-up period of 16.6 years. In the age- and sex-adjusted model, stair climbing 20-39%, 40-59%, and ≥60% of the time was associated with lower ASCVD incidence: HRs (95% CIs) = 0.72 (0.56, 0.92), 0.86 (0.68, 1.08), and 0.78 (0.61, 0.99), respectively (p-trend = 0.020). The corresponding associations were attenuated after adjusting for lifestyle and clinical factors: HRs (95% CIs) = 0.74 (0.58, 0.95), 0.90 (0.71, 1.13), and 0.89 (0.69, 1.13), respectively (p-trend = 0.152). Frequent stair climbing was associated with lower ASCVD incidence; however, this association was partly explained by lifestyle and clinical factors of participants.

Development of new scores for atherosclerotic cardiovascular disease using specific medical examination items: the Suita Study.

We previously developed risk models predicting stroke, coronary heart disease (CHD), and cardiovascular disease (CVD) among Japanese people from the Suita Study. Yet, applying these models at the national level was challenging because some of the included risk factors differed from those collected in the Japanese governmental health check-ups, such as Tokutei-Kenshin. We, therefore, conducted this study to develop new risk models for stroke, CHD, and atherosclerotic CVD (ASCVD), based on data from the Suita Study. The new models used traditional cardiovascular risk factors similar to those in the Japanese governmental health check-ups. We included 7,413 participants, aged 30-84 years, initially free from stroke and CHD. All participants received baseline health examinations, including a questionnaire assessing their lifestyle and medical history, medical examination, and blood and urine analysis. The risk factors of stroke, CHD, and ASCVD (cerebral infarction or CHD) were determined using the multivariable-adjusted Cox regression. The models' performance was assessed using the C-statistics for discrimination and the Hosmer-Lemeshow for calibration. We also developed three simple scores (zero to 100) that could predict the 10-year incidence of stroke, CHD, and ASCVD. Within 110,428 person-years (median follow-up = 16.6 years), 410 stroke events, 288 CHD events, and 527 ASCVD events were diagnosed. Age, smoking, hypertension, and diabetes were associated with stroke, CHD, and ASCVD risk. Men and those with decreased high-density lipoproteins or increased low-density lipoproteins showed a higher risk of CHD and ASCVD. Urinary proteins were associated with an increased risk of stroke and ASCVD. The C-statistic values of the risk models were >0.750 and the p-values of goodness-of-fit were >0.30. The 10-year incidence of stroke, CVD, and ASCVD events was 3.8%, 3.5%, and 5.7% for scores 45-54, 10.3%, 11.8%, and 19.6% for scores 65-74, and 27.7%, 23.5%, and 60.5% for scores ≥85, respectively. We developed new Suita risk models for stroke, CHD, and ASCVD using variables similar to those in the Japanese governmental health check-ups. We also developed new risk scores to predict incident stroke, CHD, and ASCVD within 10 years.

Deficits and Disparities in Early Uptake of Glucagon-Like Peptide 1 Receptor Agonists and SGLT2i Among Medicare-Insured Adults Following a New Diagnosis of Cardiovascular Disease or Heart Failure.

To examine the association of race/ethnicity and socioeconomic deprivation with initiation of guideline-recommended diabetes medications with cardiovascular benefit (glucagon-like peptide 1 receptor agonists [GLP1-RA] and sodium-glucose cotransporter 2 inhibitors [SGLT2i]) among older adults with type 2 diabetes (T2D) and either incident atherosclerotic cardiovascular disease (ASCVD) or congestive heart failure (CHF). Using Medicare data (2016-2019), we identified 4,057,725 individuals age >65 years with T2D and either incident ASCVD or CHF. We estimated incidence rates and hazard ratios (HR) of GLP1-RA or SGLT2i initiation within 180 days by race/ethnicity and zip code-level Social Deprivation Index (SDI) using adjusted Cox proportional hazards models. Incidence rates of GLP1-RA or SGLT2i initiation increased over time but remained low (<0.6 initiations per 100 person-months) in all years studied. Medication initiation was less common among those of Black or other race/ethnicity (HR 0.81 [95% CI 0.79-0.84] and HR 0.84 [95% CI 0.75-0.95], respectively) and decreased with increasing SDI (HR 0.96 [95% CI 0.96-0.97]). Initiation was higher in ASCVD than CHF (0.35 vs. 0.135 initiations per 100 person-months). Moderate (e.g., nephropathy, nonalcoholic fatty liver disease) but not severe (e.g., advanced chronic kidney disease, cirrhosis) comorbidities were associated with higher probability of medication initiation. Among older adults with T2D and either ASCVD or CHF, initiation of GLP1-RA or SGLT2i was low, suggesting a substantial deficit in delivery of guideline-recommended care or treatment barriers. Individuals of Black and other race/ethnicity and those with higher area-level socioeconomic deprivation were less likely to initiate these medications.

Sleep Duration and Risks of Incident Cardiovascular Disease and Mortality Among People With Type 2 Diabetes.

People with type 2 diabetes may have insufficient or prolonged sleep that could accelerate cardiovascular disease (CVD) onset, but existing evidence from prospective studies has been limited. We examined the association of sleep duration with CVD incidence and mortality in this high-risk population. This prospective study included 18,876 participants with type 2 diabetes in the UK Biobank who were free of CVD and cancer at baseline. Habitual sleep duration was obtained using a baseline questionnaire. Cox proportional hazards regression models were used to examine the association between sleep duration and CVD events. During an average follow-up of 11.0-12.0 years, we documented 2,570 incident cases of atherosclerotic cardiovascular disease (ASCVD) and 598 CVD deaths. Compared with sleeping for 7 h/day, the multivariable-adjusted hazard ratios of ≤5 and ≥10 h/day were 1.26 (95% CI 1.08, 1.48) and 1.41 (1.16, 1.70) for incident ASCVD, 1.22 (0.99, 1.50) and 1.16 (0.88, 1.52) for coronary artery disease, 1.70 (1.23, 2.35) and 2.08 (1.44, 3.01) for ischemic stroke, 1.02 (0.72, 1.44) and 1.45 (1.01, 2.10) for peripheral artery disease, and 1.42 (1.02, 1.97) and 1.85 (1.30, 2.64) for CVD mortality. Similar results were observed in most sensitivity analyses that aimed to address potential reverse causation and in the joint analyses of sleep duration and metabolic control or diabetes severity status. Short and long sleep durations were independently associated with increased risks of CVD onset and death among people with type 2 diabetes.

Abstract 12445: Association of Remnant Cholesterol With Incident Cardiovascular Disease Among Koreans: A National Population-Based Study

Aims: We sought to investigate the association of remnant cholesterol (remnant-C) and low-density lipoprotein cholesterol (LDL-C) levels with incident atherosclerotic cardiovascular disease (ASCVD) in various subgroups among Koreans. Methods: National Health Information Database, collated by Korean National Health Insurance System, was used for analysis. Among the individuals between 40 and 70 years of age and without history of cerebro-cardiovascular disease, those who had twice or more health screenings between 2009 and 2011 were selected. All subjects were divided into 4 groups by LDL-C level of 3.4 mmol/L (130mg/dL) and remnant-C level of 0.8mmol/L (30mg/dL). The primary outcome was defined as the incidence of ASCVD. Results: 3,686,034 individuals (45.6% women) fulfilled the study requirements. By the end of 2017, 144,004 ASCVD events occurred. High remnant-C and low LDL-C group was 19% of total. Compared with low remnant-C and low LDL-C group, the high remnant-C and high LDL-C group had highest ASCVD risk (HR 1.266, CI 1.243-1.289) and the high remnant-C alone group (HR 1.102, CI 1.087-1.118) had similar ASCVD risk to the high LDL-C alone group (HR 1.098, CI 1.083-1.113). The association of high remnant-C (≥0.8 mmol/L) with an increased ASCVD risk was consistent across various strata. Remnant-C levels remained significantly to associate with ASCVD after adjustment for several confounders, including LDL-C levels. Conclusions: Elevated remnant-C values, apart from LDL-C levels, were independently associated with a risk of incident ASCVD. Combination of high LDL-C and high remnant-C levels better predicted ASCVD incidence than each one alone. Therefore, we might take into account remnant-C measurement in risk stratification for primary prevention of ASCVD.

Abstract 13954: Cardiovascular Imaging Markers and Atherosclerotic Cardiovascular Disease in Lung Cancer Survivors

Introduction: Lung cancer survivors have heightened risk of atherosclerotic cardiovascular disease (ASCVD) due to shared risk factors. Chest computed tomography (CT) is routinely performed for cancer staging and radiotherapy (RT) planning. However, the extent of coronary artery calcium (CAC) and thoracic aortic calcium (TAC) is not routinely evaluated for ASCVD risk assessment. Methods: We evaluated the extent of CAC and TAC from chest CTs obtained for routine care prior to RT in a cohort of lung cancer survivors from 2007 to 2021 at a single academic health system that serves a large multiracial community. The demographics, baseline cardiovascular risk factors and baseline ASCVD (the composite of myocardial infarction, cerebrovascular disease, or peripheral arterial disease) were compared between survivors with and without CAC or TAC. The primary end point was incident ASCVD. Results: The cohort studied 603 subjects, including 19% non-Hispanic Whites, 33% non-Hispanic Blacks and 32% Hispanics. Mean age was 65±11 years, with 45% women. CAC was present in 72% of subjects and TAC in 85%. Individuals with CAC had higher prevalence of hypertension (75% vs 57%, p&lt;0.001), diabetes (41% vs 20%, p&lt;0.001) and hyperlipidemia (49% vs 26%, p&lt;0.001). Survivors with CAC had a higher prevalence of baseline ASCVD (33% vs 18%, p=0.001). Survivors with TAC yielded similar findings. In individuals without prior ASCVD, 10-year ASCVD risk score was higher in survivors with CAC (20%±21% vs 12%±13%, p=0.009) or with TAC (19%±20% vs 8%±8%, p=0.007). In a median follow-up time of 15 months, the new development of ASCVD appeared higher in survivors with CAC (23% vs 14%, p=0.04, Figure A) and with TAC (22% vs 8%, p=0.01, Figure B). Conclusions: In a large cohort of multiracial lung cancer survivors, presence of CAC or TAC based on routine chest CT at baseline is associated with a higher burden of ASCVD risk and predicts a higher risk of the new development of ASCVD during follow- up.