Incident Atherosclerotic Cardiovascular Disease Research Articles

Risk Prediction and Management of Chronic Kidney Disease in People Living with Type 2 Diabetes Mellitus.

People with type 2 diabetes mellitus have increased risk of chronic kidney disease and atherosclerotic cardiovascular disease. Improved care delivery and implementation of guideline-directed medical therapy have contributed to the declining incidence of atherosclerotic cardiovascular disease in high-income countries. By contrast, the global incidence of chronic kidney disease and associated mortality is either plateaued or increased, leading to escalating direct and indirect medical costs. Given limited resources, better risk stratification approaches to identify people at risk of rapid progression to end-stage kidney disease can reduce therapeutic inertia, facilitate timely interventions and identify the need for early nephrologist referral. Among people with chronic kidney disease G3a and beyond, the kidney failure risk equations (KFRE) have been externally validated and outperformed other risk prediction models. The KFRE can also guide the timing of preparation for kidney replacement therapy with improved healthcare resources planning and may prevent multiple complications and premature mortality among people with chronic kidney disease with and without type 2 diabetes mellitus. The present review summarizes the evidence of KFRE to date and call for future research to validate and evaluate its impact on cardiovascular and mortality outcomes, as well as healthcare resource utilization in multiethnic populations and different healthcare settings.

Assessment of the application of atherosclerotic disease risk scores in the workplace

In occupational health activities in Japan, evaluating workers' fitness for work following health checkups is a primary task. Health checkups are used to identify workers at high risk of cerebrovascular and cardiovascular diseases and conduct fit-for-work evaluations. However, identifying high-risk individuals based on a single risk factor may overlook those with multiple risk factors who have a high risk of developing cerebrovascular and cardiovascular diseases. Presently, we aimed to investigate the atherosclerotic cardiovascular disease (ASCVD) risk score from a previous study by Hisayama (Hisayama study) and examine its use in the workplace. Baseline data from health checkups conducted in 2010 of 41,815 employees (men; 34,024, women; 7,791) aged 19-64 years without previous cerebrovascular or cardiovascular disease were analyzed. The relationship between baseline ASCVD risk scores and the incidence of ASCVD > 10 years (2011-2020) was examined using Cox regression analysis with hazard ratios (HR). Receiver operating curve (ROC) analysis was conducted to evaluate the model's performance and determine optimal cut-off values for the identification of high-risk individuals in the workplace. The 10-year incidence of ASCVD was 2.6% (men; 3.0%, women; 0.8%). In men, each 1% increase in ASCVD risk score was associated with a 1.5-fold increase in ASCVD incidence (HR; 1.46, 95% confidence interval [CI]; 1.42-1.51, p < .001), which was observed from age 30 and even after multivariate adjustment. In women, univariate analysis showed an association between increased ASCVD risk score and incidence (HR; 3.19, 95% CI; 2.10-4.85, p < .001); however, this was not significant after adjustment. ROC analysis identified 1.62% as the optimal cut-off (sensitivity; 58.6%, specificity; 71.9%, positive predictive value [PPV]; 5.2%). The ASCVD risk score is a useful tool for risk management and prevention in the workplace, particularly for men. In women, this association disappeared after age adjustment, possibly due to reduced estrogen effects with aging. Based on the ROC analysis, stratifying at ≥ 1.5% for intervention, ≥ 2.0% (top 20%) for "high risk," and ≥ 3.5% (PPV > 10%) for "extremely high risk" is advised. However, this study may have underestimated the risk levels; therefore, companies should adapt the use of ASCVD risk scores flexibly according to their circumstances.

Elevated lipoprotein(a) increases risk of subsequent major adverse cardiovascular events (MACE) and coronary revascularisation in incident ASCVD patients: A cohort study from the UK Biobank

Background and aimsElevated lipoprotein(a) [Lp(a)] is a genetic driver for atherosclerotic cardiovascular disease (ASCVD). We aimed to provide novel insights into the associated risk of elevated versus normal Lp(a) levels on major adverse cardiovascular events (MACE) in an incident ASCVD cohort. MethodsThis was an observational cohort study of incident ASCVD patients. MACE counts and incidence rates (IRs) per 100-person-years were reported for patients with normal (<65 nmol/L) and elevated (>150 nmol/L) Lp(a) within the first year after incident ASCVD diagnosis and overall follow-up. Cox proportional hazard models quantified the risk of MACE associated with a 100 nmol/L increase in Lp(a). ResultsThe study cohort included 32,537 incident ASCVD patients; 5204 with elevated and 22,257 with normal Lp(a). Of those with elevated Lp(a), 41.2% had a subsequent MACE, versus 35.61% with normal Lp(a). Within the first year of follow-up, the IRs of composite MACE and coronary revascularisation were significantly higher (p < 0.001) in patients with elevated versus normal Lp(a) (IR difference 6.79 and 4.66). This trend was also observed in the overall follow-up (median 4.7 years). Using time to first subsequent MACE, a 100 nmol/L increase in Lp(a) was associated with an 8.0% increased risk of composite MACE, and 18.6% increased risk of coronary revascularisation during the overall follow-up period. ConclusionsThe association of elevated Lp(a) with increased risk of subsequent MACE and coronary revascularisation highlights a population who may benefit from earlier and more targeted intervention for cardiovascular risk including Lp(a), particularly within the first year after ASCVD diagnosis. Proactive Lp(a) testing as part of routine clinical practice can help identify and better manage these higher-risk individuals.

Risk Prediction for Atherosclerotic Cardiovascular Disease With and Without Race Stratification

Use of race-specific risk prediction in clinical medicine is being questioned. Yet, the most commonly used prediction tool for atherosclerotic cardiovascular disease (ASCVD)-pooled cohort risk equations (PCEs)-uses race stratification. To quantify the incremental value of race-specific PCEs and determine whether adding social determinants of health (SDOH) instead of race improves model performance. Included in this analysis were participants from the biracial Reasons for Geographic and Racial Differences in Stroke (REGARDS) prospective cohort study. Participants were aged 45 to 79 years, without ASCVD, and with low-density lipoprotein cholesterol level of 70 to 189 mg/dL or non-high-density lipoprotein cholesterol level of 100 to 219 mg/dL at baseline during the period of 2003 to 2007. Participants were followed up to 10 years for incident ASCVD, including myocardial infarction, coronary heart disease death, and fatal and nonfatal stroke. Study data were analyzed from July 2022 to February 2023. Discrimination (C statistic, Net Reclassification Index [NRI]), and calibration (plots, Nam D'Agostino test statistic comparing observed to predicted events) were assessed for the original PCE, then for a set of best-fit, race-stratified equations including the same variables as in the PCE (model C), best-fit equations without race stratification (model D), and best-fit equations without race stratification but including SDOH as covariates (model E). This study included 11 638 participants (mean [SD] age, 61.8 [8.3] years; 6764 female [58.1%]) from the REGARDS cohort. Across all strata (Black female, Black male, White female, and White male participants), C statistics did not change substantively compared with model C (Black female, 0.71; 95% CI, 0.68-0.75; Black male, 0.68; 95% CI, 0.64-0.73; White female, 0.77; 95% CI, 0.74-0.81; White male, 0.68; 95% CI, 0.64-0.71), in model D (Black female, 0.71; 95% CI, 0.67-0.75; Black male, 0.68; 95% CI, 0.63-0.72; White female, 0.76; 95% CI, 0.73-0.80; White male, 0.68; 95% CI, 0.65-0.71), or in model E (Black female, 0.72; 95% CI, 0.68-0.76; Black male, 0.68; 95% CI, 0.64-0.72; White female, 0.77; 95% CI, 0.74-0.80; White male, 0.68; 95% CI, 0.65-0.71). Comparing model D with E using the NRI showed a net percentage decline in the correct assignment to higher risk for male but not female individuals. The Nam D'Agostino test was not significant for all race-sex strata in each model series, indicating good calibration in all groups. Results of this cohort study suggest that PCE performed well overall but had poorer performance in both BM and WM participants compared with female participants regardless of race in the REGARDS cohort. Removal of race or the addition of SDOH did not improve model performance in any subgroup.

Atherosclerotic cardiovascular disease events among adults with high predicted risk without established risk factors

ObjectiveAge is the strongest contributor to 10-year predicted atherosclerotic cardiovascular disease (ASCVD) risk. Some older adults have a predicted ASCVD risk ≥7.5 %, without established risk factors. We sought to compare ASCVD incidence among adults with predicted ASCVD risk ≥7.5 %, with and without established ASCVD risk factors, to adults with predicted risk <7.5 %. MethodsWe analyzed data from REasons for Geographic and Racial Differences in Stroke study participants, 45–79 years old, without ASCVD or diabetes, not taking statins and with low-density lipoprotein cholesterol 70–189 mg/dL. Participants were categorized into 3 groups based on their 10-year predicted ASCVD risk and presence of established risk factors: <7.5 %, ≥7.5 % with established risk factors and ≥7.5 % without established risk factors. Established risk factors included smoking, systolic blood pressure ≥130 mmHg or antihypertensive medication use, total cholesterol ≥200 mg/dL, or high-density lipoprotein cholesterol <50 mg/dL for women (<40 mg/dL for men). Participants were followed for ASCVD events. ResultsAmong 11,115 participants, 911 incident ASCVD events occurred over a median of 11.1 years. ASCVD incidence rates were 3.6, 12.8, and 9.8 per 1,000 person-years for participants with predicted risk <7.5 %, predicted risk ≥7.5 % with established risk factors and predicted risk ≥7.5 % without established risk factors, respectively. Compared to adults with predicted risk <7.5 %, hazard ratios for incident ASCVD in participants with risk ≥7.5 % with and without established risk factors were 3.58 (95 %CI 3.03 – 4.21) and 2.72 (95 %CI 1.91–3.88), respectively. ConclusionsAdults with a 10-year predicted ASCVD risk ≥7.5 % but without established risk factors had a high ASCVD incidence.

Associations of pedometer-measured ambulatory activity with incidence of atherosclerotic cardiovascular diseases: Strong heart family study

ObjectiveCoronary heart disease has several risk factors that require a multifactorial community intervention approach in prevention efforts. Prevalence of coronary heart disease and its risk factors have been disproportionately high among American Indians. The objective of this study is to evaluate the impact of ambulatory activity levels on the development of coronary heart disease in this population. MethodsUsing pedometer data and other lifestyle and clinical factors from 2492 participants in the Strong Heart Family Study, we examined the associations of average daily step counts with incident coronary heart disease during an 18 to 20 year follow-up. ResultsAfter adjusting for potential confounders, participants with daily step counts in the 4th quartile (>7282 steps per day) had significantly lower odds of developing coronary heart disease compared to those in the 1st quartile (<3010 steps per day) (p = 0.035). ConclusionsHigher daily step count (over 7282 steps per day) is significantly associated with lower incidence of coronary heart disease among American Indian participants of the Strong Heart Family Study in a 20-year follow-up period.

Low-density lipoprotein cholesterol reduction and short-term incidence of ASCVD in the population-based cohort study LATINO

Abstract Background/Introduction In Portugal, 25,000 people die from atherosclerotic cardiovascular diseases (ASCVD) every year, accounting for more than 20% of all deaths in 2019. Reducing low-density lipoprotein cholesterol (LDL-C) is an effective intervention to lower the risk of CV events, including ischemic stroke (IS), coronary heart disease (CHD) and Peripheral Artery Disease (PAD). Purpose This study aims to assess the extent of ASCVD risk prevention associated with different levels of LDL-C lowering in an unselected population in Portugal. Methods We used electronic health records to conduct a population-level retrospective cohort study of individuals aged 40–80 years who were followed in 1 hospital and 14 primary care facilities in Portugal from 1/1/2012 to 31/12/2020. Patients started being followed when they fulfilled criteria to be exclusively characterised as high CV risk at the index date (defined according to the ESC/EAS 2019 guidelines). This analysis focused on the 24-month risk of developing ASCVD, by percentual LDL-C reduction between 360 and 540 days from the maximum LDL-C. The primary endpoint of ASCVD included the risk of IS, CHD or PAD, as defined by the corresponding ICD-9-CM/ICD-10-CM codes. IS, CHD and PAD were also analysed separately as secondary endpoints. LDL-C values were obtained from laboratory results and CV and diabetes medications’ use from prescription data registered according to the Anatomical Therapeutic Chemical Classification System recorded. A Cox regression model adjusted for sex, age, all relevant CV risk variables, risk-enhancing factors, and CV and diabetes medications was developed. Results The total cohort at 24 months of follow-up consisted of 21,101 observations corresponding to 16,055 distinct patients. Higher LDL-C percentual reduction was associated with a lower risk of ASCVD, with adjusted hazard ratios (aHR) (95% confidence intervals (CI)) of 0.82 (0.66-1.02), 0.86 (0.66-1.11) and 0.44 (0.24-0.79) per reduction of ]0,30%], ]30,50%] and ]50,90%] of LDL-C respectively, versus having no reduction or increase. IS was the secondary endpoint that contributed the most to the reduction of risk of ASCVD with an aHR (95% CI) of 0.89 (0.69-1.15), 0.67 (0.47-0.96) and 0.41 (0.19-0.86) for the same corresponding LDL-C reduction categories. However, these results were not statistically significant for PAD or CHD when assessed isolated. Conclusion This real-world evidence study shows that, independently of age, sex, and other CV risks and medications, reductions of &amp;gt;50% in LDL-C significantly reduced by 56% the risk of ASCVD at 24 months in high CV risk patients. This reduction was more striking for ischemic stroke. Therefore, LDL-C reductions &amp;gt;50% should be a paramount objective in public health policies worldwide.

Surviving critical COVID-19 requiring mechanical ventilation is associated with a high risk of cardiovascular events post discharge

Abstract Background The long-term risk for cardiovascular adverse events after severe COVID-19 requiring intensive care are largely unknown. Purpose The primary aim of this study was to investigate the composite risk of incident atherosclerotic cardiovascular disease (ASCVD) during six months after discharge from an intensive care unit (ICU) for severe COVID-19 requiring mechanical ventilation. Secondary aims were to assess the risk for individual cardiovascular and thrombotic events. Methods We performed a nationwide case-control study on all patients with severe COVID-19 treated with mechanical ventilation and discharged alive from an intensive care unit in Sweden between March 2020 and June 2021. Each case was matched (age, sex, district of residence) with up to 10 population-based controls. The study database was merged with multiple national registries. Patients with pre-existing diagnosis for MI longer than one month ago, CVL or Heart failure were excluded. Also COVID-19 patients receiving the same diagnosis during their ICU-stay as in the follow up period were excluded, making sure all post-covid events were new. The primary outcome was a composite of ASCVD defined as a fatal or non-fatal myocardial infarction, unstable angina pectoris requiring urgent revascularization, fatal and non-fatal ischemic stroke and cardiovascular death. Secondary outcomes were pre-specified as, fatal or nonfatal MI, fatal or nonfatal stroke, myocarditis, pericarditis, PE and DVT. To compare groups, Hazard ratios (HR) with (95% CI) were calculated with adjustments for age, sex, comorbidities (hypertension, hyperlipedemia, diabetes 1&amp;2, obesity, chronic kidney failure, atrial fibrillation, COPD, asthma, malignancy), level of education, marital status, and income quintile. Results In total, included 3 023 patients with severe Covid-19 that were treated with mechanical ventilation at a Swedish ICU and were subsequently discharged alive and compared with 28,463 control subjects. All results in Table 1. The incidence rate for ASCVD was 22.2 (14.9-33.2) per 1,000 person years in patients discharged after severe COVID-19 compared to 2.9 (2.3-3.8) in control subjects. When adjusted for confounders, the risk for ASCVD during the follow-up period was increased compared to control subjects (HR 4.0, 95% CI 2.4-6.7). The incidence rate for pulmonary embolism was 97.4 (80.6-120.0) per 1,000 person years after severe COVID-19 compared to 1.0 (0.6-1.7) in control subjects with a markedly increased risk HR 89.8 (95% CI 48.6-166.1) in patients discharged after severe Covid-19 compared to controls. Conclusions Among patients treated at the intensive care due to severe Covid-19, we found a significant and substantial increased risks for ASCVD and thrombotic events within 6 months from discharge. This finding implies that these patients should be closely monitored after discharge with a low threshold to initiate preventive treatment for ASCVD and thrombotic events during this period.

Abstract 15536: Impact of Social Determinants of Health on Atherosclerotic Cardiovascular Diseases Incidence

INTRODUCTION: Individuals with an unfavorable socioeconomic status have a higher risk of developing chronic diseases such as atherosclerotic cardiovascular disease (ASCVD). However, the shared contribution of socioeconomic status, psychosocial factors and living environment on ASCVD risk remains unknown. We investigated the contribution of these social determinants of health on the incidence of ASCVD. METHODS: We developed a polysocial risk score (PsRS) using latent class analysis based on socioeconomic factors (household income, level/quality of education and employment status), psychosocial factors (living alone, social support, social activities, social isolation, emotional distress, and diagnosis of psychiatric disorders), and living environment (social deprivation score, crime rate, housing quality, housing stability, proximity to green/blue spaces and proximity to nature). The study sample included 319 842 participants of the UK Biobank, free of ASCVD recruited between 2006 and 2010. As of August 2021, 23 840 of them had incident ASCVD (fatal or nonfatal myocardial infarction, ischemic stroke, or cardiac revascularization procedures). Participants were divided into three groups based on latent class analysis adjusted for age. The impact of the PsRS on incident ASCVD was assessed using Cox proportional hazards for all participants, women and men adjusted for age, sex, and ethnicity. RESULTS: Compared to participants with a low PsRS, those with an intermediate score had a slightly higher risk of ASCVD (hazard ratio [HR]=1.05 [95% CI, 1.01-1.09], p=0.024) while those with a high PsRS had a higher risk of ASCVD (HR=1.46 [95% CI, 1.40-1.52], p&lt;0.001). The effect of the PsRS on ASCVD incidence appeared to be more pronounced in women (HR=1,59 [95% CI, 1.48-1.71], p&lt;0.001 and HR=1.39 [95% IC, 1.32-1.46], p&lt;0.001, respectively, for women and men with a high PsRS compared to individuals with a low PsRS within the same sex). CONCLUSION: A PsRS based on the living environment as well as socioeconomic and psychosocial factors was associated with incident ASCVD in participants of the UK Biobank. Multifactor approaches targeting both social determinants of health and traditional risk factors could reduce the burden of ASCVD in the general population.

Abstract 12346: Atherosclerotic Cardiovascular Disease Risk Associated With Social Determinants of Health at Individual and Area Levels

Introduction: Adverse social determinants of health (SDOH) are associated with an increased risk for atherosclerotic cardiovascular disease (ASCVD). However, it is unclear if the ASCVD risks associated with area-level SDOH are similar to those with individual-level measures. Further, SDOH are not included in the Pooled Cohort Equations (PCEs) when estimating 10-year ASCVD risk. Studies have shown that PCEs systematically underestimate risk for socially deprived individuals. Aims To examine the association of individual- and area-level SDOH including education, income, and employment with incident ASCVD. Also, we assessed if adding SDOH to the PCEs improves risk prediction accuracy. Methods: We pooled data from four cohorts: Jackson Heart Study, Multi-Ethnic Study of Atherosclerosis, Framingham Heart Study Offspring Cohort, and Reasons for Geographic and Racial Differences in Stroke Study. We excluded participants with a history of ASCVD. Individual-level SDOH were based on participants’ self-report and area-level SDOH were derived by linking participants’ addresses to US Census tract data. We used Cox proportional hazards models to assess the associations between SDOH and ASCVD. We also assessed the changes in discrimination (Harrell’s C-index) and calibration (Integrated Brier Score) after adding SDOH to risk prediction models. Results: We analyzed data from 27,603 participants (mean age 61.4 years, 59% women, and 49% White). During a median follow-up of 13 years, 2,839 incident ASCVD events occurred. Both individual- and area-level SDOH were associated with ASCVD ( Figure, Panel A ). Adding both individual- and area-level SDOH to risk prediction modestly improved model discrimination and calibration in Black men and women ( Figure, Panels B &amp; C ), and also improved calibration in non-Black women. Conclusions: The findings suggest that SDOH may be considered in the development of future ASCVD risk assessment tools, particularly among Black individuals.

Abstract 17498: Association Between 5-Year Change in Cardiovascular Risk and Atherosclerotic Cardiovascular Disease Incidence: A Multicohort Study

Introduction: Early measurement of atherosclerotic cardiovascular disease (ASCVD) risk factors contains valuable information about an individual's risk history. Hypothesis: Individuals with different historical cardiovascular risk statuses have varied risks of future ASCVD incidence. Methods: We analyzed pooled data from 7 community-based prospective cohort studies with up to 20-year follow-ups ( panel A ). White or Black participants aged 40-75 years without prevalent ASCVD were included. Cardiovascular risk was assessed using the pooled cohort equation and was categorized into non-high (&lt;20%) or high risk (≥20%). Changes in CVD risk over a 5-year interval were considered. The main outcome is incident ASCVD. Results: Among 11026 participants (mean [SD] age,60.0 [8.1] years). 4272 (38.7%) were female and 3127 (28.4%) were Black. During a median follow-up of 9.9 years, 2560 (23.2%) ASCVD events occurred. Compared to individuals with consistently high risk, participants with non-high to high risk (HR 0.67; 95%CI 0.59-0.77), high to non-high risk (HR 0.57; 95%CI 0.41-0.80), and consistently non-high risk (HR 0.33; 95%CI 0.29-0.37) had a lower risk of incident ASCVD. Compared to individuals with consistently non-high risk, participants with high to non-high risk (HR 1.74; 95%CI 1.26-2.41), non-high to high risk (HR 2.04; 95%CI 1.84-2.27), and consistently high risk (HR 3.03; 95%CI 2.69-3.42) had an increased risk of incident ASCVD ( panel B ). Conclusions: Changes in the CVD risk status over time inform dissimilar ASCVD risk than a single risk assessment. Dynamic risk evaluation might enable more accurate cardiovascular risk stratification and decision on preventive interventions should take historical risk status into account.

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 14460: Impact of Carotid Artery Plaque Detection on Cardiovascular Disease Risk and the Importance of Age in the Multi-Ethnic Study of Atherosclerosis

Background Carotid artery plaque (CAP) predicts future atherosclerotic cardiovascular disease (ASCVD) events; however, its prevalence increases with age and differs by sex and race/ethnicity, so how its presence influences ASCVD risk in clinical settings is uncertain. Hypothesis: We hypothesized that the impact of CAP detection on relative ASCVD risk declines with age. Methods: CAP was detected and quantified by ultrasound in adults free of clinical ASCVD at Exam 1 of the Multi-Ethnic Study of Atherosclerosis who were followed longitudinally for coronary death, myocardial infarction, angina, stroke, and ASCVD death. Cox proportional hazards models investigated associations of CAP and incident ASCVD events in subsets defined by age categories. These models were adjusted for confounders and an age*CAP interaction. Results: The 5198 participants were a mean (standard deviation) 61.8 (10.1) years old (53% female, 27% Black, 22% Hispanic, 12% Chinese) and experienced 880 ASCVD events over 14.3 (5.7) years. Prevalence of CAP and the age at which 50% of participants had detectable CAP differed by age, sex, and race/ethnicity, ranging from 13% in Chinese women &lt;50 years old to 97% in Non-Hispanic White men 80-84 years old (Figure). CAP presence independently predicted ASCVD events (hazard ratio, 1.35, [95% confidence interval 1.17-1.57], p&lt;0.001), however the strength of this association declined with increasing age (p interaction =0.029, Figure). CAP detection in younger individuals conferred higher relative ASCVD risk than in older participants who had higher absolute risk, regardless of CAP. Conclusions: Prevalence of CAP varies by sex and race/ethnicity. CAP becomes very common with increasing age and its relative association with future ASCVD events declines. These data can assist in guiding ASCVD risk assessment in younger adults and provide perspective for incidentally detected CAP on clinical imaging studies in older adults who have higher absolute ASCVD risk.

Abstract 15781: Associations Between Hysterectomy and Incident Metabolic Syndrome: The Multi-Ethnic Study of Atherosclerosis (MESA)

Background: Metabolic syndrome is linked to increased risk of incident atherosclerotic cardiovascular disease (CVD), heart failure, and all-cause mortality. Notable associations exist between hysterectomy with bilateral salpingo-oophorectomy and metabolic syndrome. However, there is emerging evidence that even with ovarian conservation, hysterectomy independently increases long-term risk for CVD. Despite these associations, extant literature on the independent link between ovary-sparing hysterectomy and metabolic syndrome is scarce. We, therefore, examined the associations between hysterectomy with ovarian preservation and metabolic syndrome risk in a multi-ethnic cohort. Methods: We studied 1,355 female MESA participants who had data on self-reported history of hysterectomy, oophorectomy, and hystero-oophorectomy and were free of metabolic syndrome and CVD at exam 1 (2000-2002). Metabolic syndrome was defined by the NCEP Adult Treatment Panel III criteria. We used multivariable Cox regression models to evaluate the associations between hysterectomy/oophorectomy subgroups and incident metabolic syndrome from exams 2 (2002-2004) to 6 (2016-2018). Results: The mean ± SD age was 59.0 ± 9.5 years, with 42% White, 27% Black, 19% Hispanic, and 13% Chinese-American participants. 29% and 22% had a history of hysterectomy and oophorectomy, respectively. Over a median follow-up of 10.5 (3.01-17.62) years, there were 750 metabolic syndrome events. Hysterectomy [HR 1.32; 95% CI (1.01-1.73)] and hystero-oophorectomy [1.40 (1.13-1.74)] were strongly associated with metabolic syndrome (Table) . Conclusion: Hysterectomy with ovarian preservation is independently associated with a higher risk of metabolic syndrome. If our findings are confirmed by other studies, screening and preventive strategies focused on females with ovary-sparing hysterectomy and the pathways driving these associations should be explored.

Genome-Wide Association Study of Cardiovascular Resilience Identifies Protective Variation in the CETP Gene.

Background The risk of atherosclerotic cardiovascular disease (ASCVD) increases sharply with age. Some older individuals, however, remain unaffected despite high predicted risk. These individuals may carry cardioprotective genetic variants that contribute to resilience. Our aim was to assess whether asymptomatic older individuals without prevalent ASCVD carry cardioprotective genetic variants that contribute to ASCVD resilience. Methods and Results We performed a genome-wide association study using a 10-year predicted ASCVD risk score as a quantitative trait, calculated only in asymptomatic older individuals aged ≥70 years without prevalent ASCVD. Our discovery genome-wide association study of N=12 031 ASCVD event-free individuals from the ASPREE (Aspirin in Reducing Events in the Elderly) trial identified 2 independent variants, rs9939224 (P<5×10-8) and rs56156922 (P<10-6), in the CETP (cholesteryl ester transfer protein) gene. The CETP gene is a regulator of plasma high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and lipoprotein(a) levels, and it is a therapeutic drug target. The associations were replicated in the UK Biobank (subpopulation of N=13 888 individuals aged ≥69 years without prevalent ASCVD). Carriers of the identified CETP variants (versus noncarriers) had higher plasma high-density lipoprotein cholesterol levels, lower plasma low-density lipoprotein cholesterol levels, and reduced risk of incident ASCVD events during follow-up. Expression quantitative trait loci analysis predicted the identified CETP variants reduce CETP gene expression across various tissues. Previously reported associations between genetic CETP inhibition and increased risk of age-related macular degeneration were not observed among the 3917 ASPREE trial participants with retinal imaging and genetic data available. Conclusions Common genetic variants in the CETP gene region are associated with cardiovascular resilience during aging. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01038583.

Social disadvantage, coronary artery calcium, and their interplay in the prediction of atherosclerotic cardiovascular disease events

Background and aimsSocial determinants of health (SDOH) are key for the identification of populations at increased risk of atherosclerotic cardiovascular disease (ASCVD). However, whether at the individual level SDOH improve current ASCVD risk prediction paradigms beyond traditional risk factors and the coronary artery calcium (CAC) score, is unknown. We evaluated the interplay between CAC and SDOH in ASCVD risk prediction. MethodsMESA is a prospective study of US adults free of clinical ASCVD at baseline. We used an SDOH index inclusive of 14 determinants from 5 domains. The index ranged 0–1 and was divided into quartiles, with higher ones representing worse SDOH. Cox regression was used to evaluate the adjusted associations between CAC, SDOH, their interplay, and ASCVD events. The C-statistic was computed to assess improvement in risk discrimination for prediction of ASCVD events. ResultsWe included 6479 MESA participants (50% with CAC = 0, 24% CAC>100). ASCVD incidence increased with increasing CAC scores across SDOH quartiles. The lowest incidence was noted in those with CAC = 0 and favourable SDOH (2/1000 person-years) and highest in those with CAC>100 and most unfavourable SDOH (20.6/1000 person-years). While CAC was strongly associated with ASCVD across SDOH quartiles, SDOH was weakly associated with ASCVD across CAC strata. CAC improved the discriminatory ability of all prediction models beyond traditional risk factors, the improvement in C-statistic ranging +0.02 - +0.05. Improvements with SDOH were smaller, and were none on top of CAC. ConclusionsCAC improves ASCVD risk stratification across the spectrum of social vulnerability, while SDOH fail to improve risk prediction beyond traditional RFs and CAC.

Modification of Association of Cystatin C With Kidney and Cardiovascular Outcomes by Obesity

Cystatin C-based estimated glomerular filtration rate (eGFRcys) has stronger associations with adverse clinical outcomes than creatinine-based eGFR (eGFRcr). Obesity may be associated with higher cystatin C levels, independent of kidney function, but it is unknown whether obesity modifies associations of eGFRcys with kidney and cardiovascular outcomes. Cohort study. 27,249 US adults in the Reasons for Geographic and Racial Differences in Stroke Study. eGFRcys, eGFRcr, waist circumference, and body mass index (BMI). All-cause mortality, kidney failure, incident atherosclerotic cardiovascular disease (ASCVD), and incident heart failure (HF). Multivariable Cox and Fine-Gray models with multiplicative interaction terms were constructed to investigate whether waist circumference quartiles or BMI categories modified associations of eGFRcys with risks of 4 clinical outcomes. Participants had a mean age of 65 years; 54% were women, 41% were Black, and 21% had an eGFRcys<60mL/min/1.73m2. The baseline prevalence of abdominal obesity (waist circumference≥88cm for women or≥102cm for men) was 48% and obesity was 38%. In multivariable adjusted analyses, each 15mL/min/1.73m2 lower eGFRcys was associated with higher HR and 95% CI of mortality in each waist circumference quartile (first quartile, 1.19 [1.15-1.24]; second quartile, 1.22 [1.18-1.26]; third quartile, 1.20 [1.16-1.24]; fourth quartile, 1.19 [1.15-1.23]) as well as within each BMI category (BMI<24.9: 1.21 [1.17-1.25]; BMI 25.0-29.9: 1.21 [1.18-1.25]; BMI 30.0-34.9: 1.20 [1.16-1.25]; BMI≥35: 1.17, [1.12-1.22]). Neither waist circumference nor BMI modified the association of eGFRcys with mortality, kidney failure, incident ASCVD, or incident HF (all Pinteraction>0.05). Included only Black and White persons in the United States. Obesity did not modify the association of eGFRcys with all-cause mortality, kidney failure, incident ASCVD, or incident HF. Among individuals with obesity, cystatin C may be used to provide eGFR-based risk prognostication for adverse outcomes. Cystatin C is increasingly used in clinical practice to estimate kidney function, and cystatin C-based eGFR (eGFRcys) may be used to determine risk for adverse clinical outcomes. Adiposity may increase serum levels of cystatin C, independent of kidney function. This cohort study investigated whether associations of eGFRcys with adverse kidney and cardiovascular outcomes are modified by measures of obesity, waist circumference, and body mass index. We found that obesity does not modify associations of eGFRcys with 4 clinical outcomes and conclude that among individuals with obesity, cystatin C may be used to provide eGFR-based risk prognostication for adverse outcomes.

Impact of Guideline-Directed Statin Intervention for Primary Prevention in Patients With Diabetes.

We examined guideline-directed statin intensity (GDSI) use and atherosclerotic cardiovascular disease (ASCVD) outcomes in patients with diabetes across a contemporary health care system. Patients without preexisting ASCVD were categorized by diabetes status and 10-year ASCVD risk (borderline [5-7.4%], intermediate [7.5-19.9%], high [≥20%]). Mean ±SD time to start of or change to GDSI was calculated. Incident ASCVD and all-cause mortality association, stratified by ASCVD risk, was calculated using Cox regression. Among 282,298 patients, 28,807 (10.2%) had diabetes and 253,491 (89.8%) did not. Only two-thirds of intermediate- and high-risk patients with diabetes were receiving GDSI therapy at 5-year follow-up. In fully adjusted models, patients with diabetes not taking a statin (vs. GDSI) had a significantly higher risk of stroke and mortality in the intermediate- and high-risk groups (hazard ratio for mortality 1.81 [95% CI 1.58-2.07] vs. 1.41 [1.26-1.57]; P for interaction < 0.01). Significant gaps remain in GDSI use for high-risk patients with diabetes, conferring an increased risk of ASCVD outcomes and all-cause mortality.

Association between remnant cholesterol and incident atherosclerotic cardiovascular disease, heart failure, and atrial fibrillation

It remains unclear if remnant cholesterol is associated with atherosclerotic cardiovascular disease (ASCVD) (myocardial infarction, angina pectoris and stroke), heart failure (HF), and atrial fibrillation (AF) under primary prevention settings. We aimed to clarify this issue among a general population without a history of ASCVD, HF or AF. Analyses were conducted with a nationwide health claims database collected in the JMDC Claims Database between 2005 and 2022 (n = 1,313,722; median age, 42 years; 54.6% men). We assessed the associations between remnant cholesterol calculated as total cholesterol minus HDL cholesterol minus LDL cholesterol and composite CVD outcomes, including, ASCVD, HF, and AF using Cox proportional hazard model, dividing the individuals into tertiles of remnant cholesterol (T1-T3). The mean follow-up duration was 3.0 years. In total, 43,755 events were recorded. Remnant cholesterol was significantly associated with composite CVD outcomes after adjustments (T3 vs T1: hazard ratio [HR]; 1.07, 95% confidence interval [CI]: 1.04-1.10, p-trend<0.001). Remnant cholesterol was associated with myocardial infarction (T3 vs T1:HR: 1.20, 95% CI: 1.06-1.34, p-trend=0.002), angina pectoris (T3 vs T1:HR: 1.09, 95% CI: 1.05-1.14, p-trend<0.001), stroke (T3 vs T1:HR: 1.08, 95% CI: 1.02-1.14, p-trend=0.007), and HF (T3 vs T1:HR: 1.08, 95% CI: 1.04-1.12, p-trend<0.001), while we found a marginal inverse association between remnant cholesterol and AF (T3 vs T1:HR: 0.92, 95% CI: 0.86-1.00, p-trend=0.054). Remnant cholesterol was positively associated with ASCVD and HF, while we found a marginal inverse association between remnant cholesterol and AF.

FRI117 Major Adverse Cardiovascular Events In Severe Insulin Resistance Syndromes: Lipodystrophy Compared To Pathogenic Variants Of The Insulin Receptor

Abstract Disclosure: M. Lightbourne: None. R.J. Brown: None. Patients with insulin resistance (IR) associated with obesity and/or type 2 diabetes have increased atherosclerotic cardiovascular disease (ASCVD) risk. Rare, syndromic forms of severe IR (SIR) exist, in which ASCVD risk is not established. SIR can be classified into post-receptor IR, where insulin signaling is increased in some signaling pathways, and decreased in others (i.e. lipodystrophy) or receptor IR, where all insulin signaling is blocked at the insulin receptor (i.e. insulin receptor pathogenic variants, INSR). These differences in insulin signaling associate with differences in ASCVD risk factors, i.e. dyslipidemia and uric acid (high in lipodystrophy, low in INSR), but the incidence of ASCVD in these population is unknown. We hypothesized that patients with post-receptor IR due to lipodystrophy would have more major adverse cardiovascular events (MACE) vs those with receptor IR due to INSR. This is a retrospective chart review of patients with lipodystrophy and INSR aged ≥18 years. Our primary outcome was incidence of MACE (composite of cardiovascular death, non-fatal myocardial infarction, ischemic stroke and hospitalization for unstable angina, heart failure or revascularization). Patients with INSR (n=24) were younger than those with lipodystrophy (n=241) (32 ± 12 vs 40 ± 15 years, p=0.02) at first MACE or last follow-up. 62% of patients with INSR were female vs 82% with lipodystrophy (p=0.02); 50% with INSR were white vs 75% with lipodystrophy (p=0.0098). Of patients with lipodystrophy, 153 had partial, 79 had generalized, and 9 had progeroid forms of lipodystrophy. Nine patients with INSR had homozygous or compound heterozygous variants and 15 had heterozygous variants. MACE occurred in 33 patients with lipodystrophy (5 generalized, 24 partial, 4 progeroid; age 42.6 ± 12.7 years) and in 0 patients with INSR with a Hazard Ratio of 2.9 (95% CI 0.6-14.5, P=0.2). In patients with lipodystrophy, 9 patients had cardiovascular deaths (mean age 32.4 ± 15.4 years, 3 with progeroid syndromes); 11 had non-fatal myocardial infarcts with 2 patients having recurrent events; 8 were hospitalized for strokes or transient ischemic attacks; 12 were hospitalized for coronary revascularization with 7 patients having recurrent events; 5 were hospitalized due to heart failure. In addition to MACE, 4 patients with lipodystrophy had peripheral revascularization or amputation vs 0 with INSR. MACE events did not occur in patients with INSR and were highly prevalent at a young age in patients with lipodystrophy, suggesting higher risk of MACE in lipodystrophy. There was no statistical difference for MACE events between the 2 groups; however, statistical power was limited by the small sample size and young age of patients INSR. These data suggest that contributions from both increased and decreased insulin signal transduction in patients with post-receptor IR may lead to increased ASCVD risk. Presentation: Friday, June 16, 2023