Dual-pathway Inhibition with Low-dose Aspirin and Rivaroxaban versus Aspirin Monotherapy in Patients with Coronary Artery Disease and Peripheral Artery Disease: Systematic Literature Review and Meta-analysis.

Background: Low-dose aspirin lowers cardiovascular event risk; dual-pathway inhibition (DPI) using low-dose aspirin with low-dose rivaroxaban may reduce this risk further. A systematic literature review and meta-analysis compared the efficacy, safety and net clinical benefit (NCB) of DPI with aspirin. Methods: PubMed and Embase were searched for randomised controlled trials reporting clinical efficacy, safety and NCB of DPI compared with aspirin alone in patients with coronary artery disease (CAD) and/or peripheral artery disease. Six articles representing four trials were included. Results: DPI versus aspirin alone significantly reduced major adverse cardiovascular events (HR 0.77; 95% CI [0.69-0.87]; p<0.01), increased International Society on Thrombosis and Haemostasis major bleeding events (HR 1.67; 95% CI [1.37-2.02]; p<0.01) and resulted in a significant NCB (HR 0.79; 95% CI [0.70-0.90]; p<0.01). Conclusion: These results underscore the potential benefit of DPI in patients with CAD, including those in the immediate post-acute coronary syndrome stage and with established CAD, as well as patients with peripheral artery disease.

The utility of coronary artery calcium scoring to enhance cardiovascular risk assessment for South Asian adults.

South Asian individuals represent a highly diverse population and are one of the fastest growing ethnic groups in the United States. This population has a high prevalence of traditional and non-traditional cardiovascular disease (CVD) risk factors and a disproportionately high prevalence of coronary heart disease. To reflect this, current national society guidelines have designated South Asian ancestry as a "risk enhancing factor" which may be used to guide initiation or intensification of statin therapy. However, current methods of assessing cardiovascular risk in South Asian adults may not adequately capture the true risk in this diverse population. Coronary artery calcium (CAC) scoring provides a reliable, reproducible, and highly personalized method to provide CVD risk assessment and inform subsequent pharmacotherapy recommendations, if indicated. This review describes the utility of CAC scoring for South Asian individuals.

The association of body mass index variability with cardiovascular disease and mortality: a mediation analysis of pooled cohorts.

Aim: We aimed to investigate the effect of BMI variability on CVD and mortality and to explore the mediation effects of the main cardiovascular risk factors contributing to this association. Method: Participants aged 40-65 years were pooled from three cohort studies(ARIC [Atherosclerosis Risk in Communities], MESA [Multi-ethnic Study of Atherosclerosis], and TLGS [Tehran Lipid and Glucose Study]. We employed root mean squared error of the fractional mixed model to calculate BMI variability in the measurement period. In the event assessment period, the hazard ratios for CVD and mortality were estimated using Cox proportional hazard regression models. In the next step, the mediation and interaction effects of fasting plasma glucose, total cholesterol, and systolic blood pressure were determined. Results: A total of 19073 participants were included in this pooled analysis. During a median of 20.7 years of follow-up, 3900 (20.44%) CVD and 6480 (33.97%) all-cause mortality events were recorded. After adjusting for potential confounders, BMI variability was linked to the 1.3 (1.2-1.4) and 1.7 (1.6-1.8) increased risk of CVD and mortality, respectively. Fasting plasma glucose mediated approximately 24% and 8% of the effect of BMI variability on CVD and mortality, respectively. However, systolic blood pressure and total cholesterol did not have mediation effects in this association. Conclusion: High BMI variability is independently associated with the development of CVD and mortality. This association is partly mediated through fasting plasma glucose. Modern cardiometabolic therapies that lower fasting glucose may reduce the risk of future CVD and mortality in individuals with high BMI variability.

The impact of chronic electronic cigarette use on endothelial dysfunction measured by flow-mediated vasodilation: A systematic review and meta-analysis.

INTRODUCTION: Despite electronic cigarettes (e-cigarettes) being marketed as a safer alternative to combustible cigarettes, the effects of chronic e-cigarette use on vascular health remain uncertain. Our meta-analysis aimed to assess the health implications of chronic exclusive e-cigarette use on endothelial dysfunction, as measured by flow-mediated vasodilation (FMD). METHODS: PubMed, Embase and Scopus were searched for studies from 1 January 2004 to 31 March 2024. Four cross-sectional studies (n=769) were pooled using a random-effects model. The mean differences (MD) of FMD were reported by comparing exclusive e-cigarette use versus non-use; exclusive e-cigarette use versus combustible cigarette use; and combustible cigarette use versus non-use. RESULTS: A non-significant reduction in FMD in exclusive e-cigarette use compared to non-use was reported (MD of FMD: -1.47%; 95% CI: -3.96 - 1.02; I2= 84%). Similar MD of FMD in exclusive e-cigarette use and exclusive combustible cigarette use (vs non-use) suggested that both of these products might have comparable adverse influences on endothelial health. CONCLUSIONS: The limited availability of studies assessing the chronic impact of e-cigarette use restricted our ability to provide definitive findings. We emphasize the importance of additional research that explores the long-term impact of e-cigarette use on endothelial dysfunction, and identify key areas and give suggestions for further study.

The ABCs of the 2023 AHA/ACC/ACCP/ASPC/NLA/PCNA guideline for the management of patients with chronic coronary disease.

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

Coronary artery calcium in 2023: Guidelines for LDL-C goals, non-statin therapies, and aspirin use.

Personalizing risk assessment and treatment decisions for the primary prevention of atherosclerotic cardiovascular disease (ASCVD) rely on pooled cohort equations and increasingly coronary artery calcium (CAC) score. A growing body of evidence supports that elevated CAC scores correspond to progressively elevated ASCVD risk, and that scores of ≥100, ≥300, and ≥1000 denote risk that is equivalent to certain secondary prevention populations. This has led consensus guidelines to incorporate CAC score thresholds for guiding escalation of preventive therapy for lowering low-density lipoprotein cholesterol goals, initiation of non-statin lipid lowering medications, and use of low-dose daily aspirin. As data on CAC continues to grow, more decision pathways will incorporate CAC score cutoffs to guide management of blood pressure and cardiometabolic medications. CAC score is also being used to enrich clinical trial study populations for elevated ASCVD risk, and to screen for subclinical coronary atherosclerosis in patients who received chest imaging for other diagnostic purposes.

Aspirin use for primary prevention among US adults with and without elevated Lipoprotein(a).

Objective: Lipoprotein(a) [Lp(a)] is an atherogenic and prothrombotic lipoprotein associated with atherosclerotic cardiovascular disease (ASCVD). We assessed the association between regular aspirin use and ASCVD mortality among individuals with versus without elevated Lp(a) in a nationally representative US cohort. Methods: Eligible participants were aged 40-70 years without clinical ASCVD, reported on aspirin use, and had Lp(a) measurements from the Third National Health and Nutrition Examination Survey (NHANES III, 1988-1994), the only cycle of this nationally representative US cohort to measure Lp(a). Regular aspirin use was defined as taking aspirin ≥30 times in the previous month. Using NHANES III linked mortality records and weighted Cox proportional hazards regression, the association between regular aspirin use and ASCVD mortality was observed in those with and without elevated Lp(a) (≥50 versus <50 mg/dL) over a median 26-year follow-up. Results: Among 2,990 persons meeting inclusion criteria (∼73 million US adults), the mean age was 50 years, 86% were non-Hispanic White, 9% were non-Hispanic Black, 53% were female, and 7% reported regular aspirin use. The median Lp(a) was 14 mg/dL and the proportion with elevated Lp(a) was similar among those with versus without regular aspirin use (15.1% versus 21.9%, p = 0.16). Among individuals with elevated Lp(a), the incidence of ASCVD mortality per 1,000 person-years was lower for those with versus without regular aspirin use (1.2, 95% CI: 0.1-2.3 versus 3.9, 95% CI: 2.8-4.9). In multivariable modeling, regular aspirin use was associated with a 52% lower risk of ASCVD mortality among individuals with elevated Lp(a) (HR=0.48, 95% CI: 0.28-0.83), but not for those without elevated Lp(a) (HR=1.01, 95% CI: 0.81-1.25; p-interaction=0.001). Conclusion: Regular aspirin use was associated with significantly lower ASCVD mortality in adults without clinical ASCVD who had elevated Lp(a). These findings may have clinical and public health implications for aspirin utilization in primary prevention.

Association of High-Density Lipoprotein Parameters and Risk of Heart Failure: A Multicohort Analysis.

BACKGROUND: High-density lipoprotein (HDL) is commonly characterized by its cholesterol concentration (HDL-C) and inverse association with atherosclerotic cardiovascular disease. OBJECTIVES: The authors sought to evaluate the association of HDL particle concentration (HDL-P), HDL particle size (HDL-size), HDL-C, and cholesterol content per particle (HDL-C/HDL-P) with risk of overall heart failure (HF) and subtypes. METHODS: Participants from the Atherosclerosis Risk In Communities Study, Dallas Heart Study, Multi-Ethnic Study of Atherosclerosis, and Prevention of Renal and Vascular End-stage Disease studies without HF history were included. Associations of HDL-P, HDL-size, HDL-C, and HDL-C/HDL-P with risk of overall HF, HF with reduced and preserved ejection fraction were assessed using adjusted Cox models. RESULTS: Among 16,925 participants (53.5% women; 21.8% Black), there were 612 incident HF events (3.6%) (HF with reduced ejection fraction, 309 [50.5%]; HF preserved ejection fraction, 303 [49.5%]) over median follow-up of 11.4 years. In adjusted models, higher HDL-P was significantly associated with lower HF risk (HR of highest vs lowest tertile of HDL-P: 0.76 [95% CI: 0.62-0.93]). Larger HDL-size was significantly associated with higher overall HF risk (HR of largest vs smallest tertile of HDL-size: 1.27 [95% CI: 1.03-1.58]). HF risk associated with HDL-P and HDL-size was similar for HF subtypes. In adjusted analyses, there was no significant association between HDL-C and HF risk. Higher HDL-C/HDL-P was significantly associated with higher overall HF risk (HR of highest vs lowest tertile of HDL-C/HDL-P: 1.29 [95% CI: 1.04-1.60]). CONCLUSIONS: Higher HDL-P was associated with a lower risk of HF. In contrast, larger HDL-size was associated with higher risk of HF and there was no significant association observed between HDL-C and HF risk after accounting for cardiovascular risk factors.

Cardiovascular Risk Profile Among Reproductive-Aged Women in the U.S.: The Behavioral Risk Factor Surveillance System, 2015-2020.

Introduction: Suboptimal cardiovascular health is associated with adverse pregnancy outcomes and long-term cardiovascular risk. The authors examined trends in cardiovascular risk factors and correlates of suboptimal cardiovascular risk profiles among reproductive-aged U.S. women. Methods: With data from 335,959 women in the Behavioral Risk Factor Surveillance System (2015-2020), the authors conducted serial cross-sectional analysis among nonpregnant reproductive-aged women (18-44 years) without cardiovascular disease who self-reported information on 8 cardiovascular risk factors selected on the basis of Life's Essential 8 metrics. The authors estimated the prevalence of each risk factor and suboptimal cardiovascular risk profile (≥2 risk factors) and examined trends overall and by age and race/ethnicity. Using multivariable Poisson regression, the authors assessed the sociodemographic correlates of suboptimal cardiovascular risk profile. Results: The weighted prevalence of women aged <35 years was approximately 64% in each survey year. The prevalence of suboptimal cardiovascular risk profile increased modestly from 72.4% (71.6%-73.3%) in 2015 to 75.9% (75.0%-76.7%) in 2019 (p<0.001). This increase was mainly driven by increases in overweight/obesity (53.1%-58.4%; p<0.001). Between 2015 and 2019, significant increases in suboptimal cardiovascular risk profile were observed among non-Hispanic White (69.8%-72.6%; p<0.001) and Hispanic (75.1%-80.3%; p<0.001) women but not among non-Hispanic Black (82.7%-83.7%; p=0.48) or Asian (68.1%-73.2%; p=0.09) women. Older age, rural residence, and non-Hispanic Black and Hispanic race and ethnicity were associated with a higher prevalence of suboptimal cardiovascular risk profile. Conclusions: There has been a modest but significant increase in suboptimal cardiovascular risk profile among U.S. women of reproductive age. Urgent preventive efforts are needed to reverse this trend and improve cardiovascular health, particularly among subgroups at increased risk, to mitigate its implications.

Subclinical Atherosclerosis to Guide Treatment in Dyslipidemia and Diabetes Mellitus.

PURPOSE OF REVIEW: Dyslipidemia and type 2 diabetes mellitus are two common conditions that are associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD). In this review, we aimed to provide an in-depth and contemporary review of non-invasive approaches to assess subclinical atherosclerotic burden, predict cardiovascular risk, and guide appropriate treatment strategies. We focused this paper on two main imaging modalities: coronary artery calcium (CAC) score and computed tomography coronary angiography. RECENT FINDINGS: Recent longitudinal studies have provided stronger evidence on the relationship between increased CAC, thoracic aorta calcification, and risk of cardiovascular events among those with primary hypercholesterolemia, highlighting the beneficial role of statin therapy. Interestingly, resilient profiles of individuals not exhibiting atherosclerosis despite dyslipidemia have been described. Non-conventional markers of dyslipidemia have also been associated with increased subclinical atherosclerosis presence and burden, highlighting the contribution of apolipoprotein B-100 (apoB)-rich lipoprotein particles, such as remnant cholesterol and lipoprotein(a), to the residual risk of individuals on-target for low-density lipoprotein cholesterol (LDL-C) goals. Regarding type 2 diabetes mellitus, variability in atherosclerotic burden has also been found, and CAC testing has shown significant predictive value in stratifying cardiovascular risk. Non-invasive assessment of subclinical atherosclerosis can help reveal the continuum of ASCVD risk in those with dyslipidemia and diabetes mellitus and can inform personalized strategies for cardiovascular disease prevention in the primary prevention setting.

Interaction Between Risk Factors, Coronary Calcium, and CCTA Plaque Characteristics in Patients Age 18-45.

AIMS: The atherosclerotic profile and advanced plaque subtype burden in symptomatic patients ≤45 years old have not been established. This study aimed to assess the prevalence and predictors of coronary artery calcium (CAC), plaque subtypes, and plaque burden by coronary computed tomography angiography (CCTA) in symptomatic young patients. METHODS AND RESULTS: We included 907 symptomatic young patients (18-45 years) from Montefiore undergoing CCTA for chest pain evaluation. Prevalence and predictors of CAC, plaque subtypes, and burden were evaluated using semi-automated software. In the overall population (55% female and 44% Hispanic), 89% had CAC = 0. The likelihood of CAC or any plaque by CCTA increased with >3 risk factors (RF, OR 7.13 [2.14-23.7] and OR 10.26 [3.36-31.2], respectively). Any plaque by CCTA was present in 137 (15%); the strongest independent predictors were age ≥35 years (OR 3.62 [2.05-6.41]) and family history of premature CAD (FHx) (OR 2.76 [1.67-4.58]). Stenosis ≥50% was rare (1.8%), with 31% of those having CAC = 0. Significant non-calcified (NCP, 37.2%) and low-attenuation (LAP, 4.24%) plaque burdens were seen, even in those with non-obstructive stenosis. Among patients with CAC = 0, 5% had plaque, and the only predictor of exclusively non-calcified plaque was FHx (OR 2.29 [1.08-4.86]). CONCLUSIONS: In symptomatic young patients undergoing CCTA, the prevalence of CAC or any coronary atherosclerosis was not negligible, and the likelihood increased with RF burden. The presence of coronary stenosis ≥50% was rare and most often accompanied by CAC > 0 but there was a significant burden of NCP and LAP even within the non-obstructive group.

Left Main Coronary Artery Calcium and Diabetes Confer Very-High-Risk Equivalence in Coronary Artery Calcium >1,000.

BACKGROUND: Although a coronary artery calcium (CAC) of ≥1,000 is a subclinical atherosclerosis threshold to consider combination lipid-lowering therapy, differentiating very high from high atherosclerotic cardiovascular disease (ASCVD) risk in this patient population is not well-defined. OBJECTIVES: Among persons with a CAC of ≥1,000, the authors sought to identify risk factors equating with very high-risk ASCVD mortality rates. METHODS: The authors studied 2,246 asymptomatic patients with a CAC of ≥1,000 from the CAC Consortium without a prior ASCVD event. Cox proportional hazards regression modelling was performed for ASCVD mortality during a median follow-up of 11.3 years. Crude ASCVD mortality rates were compared with those reported for secondary prevention trial patients classified as very high risk, defined by ≥2 major ASCVD events or 1 major event and ≥2 high-risk conditions (1.4 per 100 person-years). RESULTS: The mean age was 66.6 years, 14% were female, and 10% were non-White. The median CAC score was 1,592 and 6% had severe left main (LM) CAC (vessel-specific CAC ≥300). Diabetes (HR: 2.04 [95% CI: 1.47-2.83]) and severe LM CAC (HR: 2.32 [95% CI: 1.51-3.55]) were associated with ASCVD mortality. The ASCVD mortality per 100 person-years for all patients was 0.8 (95% CI: 0.7-0.9), although higher rates were observed for diabetes (1.4 [95% CI: 0.8-1.9]), severe LM CAC (1.3 [95% CI: 0.6-2.0]), and both diabetes and severe LM CAC (7.1 [95% CI: 3.4-10.8]). CONCLUSIONS: Among asymptomatic patients with a CAC of ≥1,000 without a prior index event, diabetes, and severe LM CAC define very high risk ASCVD, identifying individuals who may benefit from more intensive prevention therapies across several domains, including low-density lipoprotein-cholesterol lowering.

Association of cardiometabolic and vascular atherosclerosis phenotypes on non-contrast chest CT with incident heart failure in patients with severe hypercholesterolemia.

BACKGROUND: Coronary artery calcium (CAC), thoracic aorta calcification (TAC), non-alcoholic fatty liver disease (NAFLD), and epicardial adipose tissue (EAT) are associated with atherosclerotic cardiovascular disease (ASCVD) and heart failure (HF). OBJECTIVES: We aimed to determine whether these cardiometabolic and atherosclerotic risk factors identified by non-contrast chest computed tomography (CT) are associated with HF hospitalizations in patients with LDL-C≥ 190 mg/dL. METHODS: We conducted a retrospective cohort analysis of patients with LDL-C ≥190 mg/dL, aged ≥40 years without established ASCVD or HF, who had a non-contrast chest CT within 3 years of LDL-C measurement. Ordinal CAC, ordinal TAC, EAT, and NAFLD were measured. Kaplan-Meier curves and multivariable Cox regression models were built to ascertain the association with HF hospitalization. RESULTS: We included 762 patients with median age 60 (53-68) years, 68% (n=520) female, and median LDL-C level of 203 (194-216) mg/dL. Patients were followed for 4.7 (IQR 2.75-6.16) years, and 107 (14%) had a HF hospitalization. Overall, 355 (47%) patients had CAC=0, 210 (28%) had TAC=0, 116 (15%) had NAFLD, and median EAT was 79 mL (49-114). Moderate-Severe CAC (log-rank p<0.001) and TAC (log-rank p=0.006) groups were associated with increased HF hospitalizations. This association persisted when considering myocardial infarction (MI) as a competing risk. NAFLD and EAT volume were not associated with HF. CONCLUSIONS: In patients without established ASCVD and LDL-C≥190 mg/dL, CAC was independently associated with increased HF hospitalizations while TAC, NAFLD and EAT were not.

Coronary artery calcium as a marker of healthy and unhealthy aging in adults aged 75 and older: The Atherosclerosis Risk in Communities (ARIC) study.

BACKGROUND AND AIMS: Coronary artery calcium (CAC) is validated for risk prediction among middle-aged adults, but there is limited research exploring implications of CAC among older adults. We used data from the Atherosclerosis Risk in Communities (ARIC) study to evaluate the association of CAC with domains of healthy and unhealthy aging in adults aged ≥75 years. METHODS: We included 2,290 participants aged ≥75 years free of known coronary heart disease who underwent CAC scoring at study visit 7. We examined the cross-sectional association of CAC = 0, 1-999 (reference), and ≥1000 with seven domains of aging: cognitive function, hearing, ankle-brachial index (ABI), pulse-wave velocity (PWV), forced vital capacity (FVC), physical functioning, and grip strength. RESULTS: The mean age was 80.5 ± 4.3 years, 38.6% male, and 77.7% White. 10.3% had CAC = 0 and 19.2% had CAC≥1000. Individuals with CAC = 0 had the lowest while those with CAC≥1000 had the highest proportion with dementia (2% vs 8%), hearing impairment (46% vs 67%), low ABI (3% vs 18%), high PWV (27% vs 41%), reduced FVC (34% vs 42%), impaired grip strength (66% vs 74%), and mean composite abnormal aging score (2.6 vs 3.7). Participants with CAC = 0 were less likely to have abnormal ABI (aOR:0.15, 95%CI:0.07-0.34), high PWV (aOR:0.57, 95%CI:0.41-0.80), and reduced FVC (aOR:0.69, 95%CI:0.50-0.96). Conversely, participants with CAC≥1000 were more likely to have low ABI (aOR:1.74, 95%CI:1.27-2.39), high PWV (aOR:1.52, 95%CI:1.15-2.00), impaired physical functioning (aOR:1.35, 95%CI:1.05-1.73), and impaired grip strength (aOR:1.46, 95%CI:1.08-1.99). CONCLUSIONS: Our findings highlight CAC as a simple measure broadly associated with biological aging, with clinical and research implications for estimating the physical and physiological aging trajectory of older individuals.

Closing the Last Mile Gap in Access to Multimodality Imaging in Rural Settings: Design of the Imaging Core of the Risk Underlying Rural Areas Longitudinal Study.

Achieving optimal cardiovascular health in rural populations can be challenging for several reasons including decreased access to care with limited availability of imaging modalities, specialist physicians, and other important health care team members. Therefore, innovative solutions are needed to optimize health care and address cardiovascular health disparities in rural areas. Mobile examination units can bring imaging technology to underserved or remote communities with limited access to health care services. Mobile examination units can be equipped with a wide array of assessment tools and multiple imaging modalities such as computed tomography scanning and echocardiography. The detailed structural assessment of cardiovascular and lung pathology, as well as the detection of extracardiac pathology afforded by computed tomography imaging combined with the functional and hemodynamic assessments acquired by echocardiography, yield deep phenotyping of heart and lung disease for populations historically underrepresented in epidemiological studies. Moreover, by bringing the mobile examination unit to local communities, innovative approaches are now possible including engagement with local professionals to perform these imaging assessments, thereby augmenting local expertise and experience. However, several challenges exist before mobile examination unit-based examinations can be effectively integrated into the rural health care setting including standardizing acquisition protocols, maintaining consistent image quality, and addressing ethical and privacy considerations. Herein, we discuss the potential importance of cardiac multimodality imaging to improve cardiovascular health in rural regions, outline the emerging experience in this field, highlight important current challenges, and offer solutions based on our experience in the RURAL (Risk Underlying Rural Areas Longitudinal) cohort study.

Epidemiology and Prognostic Implications of Coronary Artery Calcium in Asymptomatic Individuals With Prediabetes: A Multicohort Study.

OBJECTIVE: To describe the epidemiology and prognostic value of coronary artery calcium (CAC) in individuals with prediabetes. RESEARCH DESIGN AND METHODS: We pooled participants free of clinical atherosclerotic cardiovascular disease (ASCVD) from four prospective cohorts: the Multi-Ethnic Study of Atherosclerosis, Heinz Nixdorf Recall Study, Framingham Heart Study, and Jackson Heart Study. Two definitions were used for prediabetes: inclusive (fasting plasma glucose [FPG] ≥100 to <126 mg/dL and hemoglobin A1c [HbA1c] ≥5.7% to <6.5%, if available, and no glucose-lowering medications) and restrictive (FPG ≥110 to <126 mg/dL and HbA1c ≥5.7% to <6.5%, if available, among participants not taking glucose-lowering medications). RESULTS: The study included 13,376 participants (mean age 58 years; 54% women; 57% White; 27% Black). The proportions with CAC ≥100 were 17%, 22%, and 37% in those with euglycemia, prediabetes, and diabetes, respectively. Over a median (25th-75th percentile) follow-up time of 14.6 (interquartile range 7.8-16.4) years, individuals with prediabetes and CAC ≥100 had a higher unadjusted 10-year incidence of ASCVD (13.4%) than the overall group of those with diabetes (10.6%). In adjusted analyses, using the inclusive definition of prediabetes, compared with euglycemia, the hazard ratios (HRs) for ASCVD were 0.79 (95% CI 0.62, 1.01) for prediabetes and CAC 0, 0.70 (0.54, 0.89) for prediabetes and CAC 1-99, 1.54 (1.27, 1.88) for prediabetes and CAC ≥100, and 1.64 (1.39, 1.93) for diabetes. Using the restrictive definition, the HR for ASCVD was 1.63 (1.29, 2.06) for prediabetes and CAC ≥100. CONCLUSIONS: CAC ≥100 is frequent among individuals with prediabetes and identifies a high ASCVD risk subgroup in which the adjusted ASCVD risk is similar to that in individuals with diabetes.

Lipoprotein(a) and Major Adverse Cardiovascular Events in Patients With or Without Baseline Atherosclerotic Cardiovascular Disease.

BACKGROUND: Lipoprotein(a) [Lp(a)] is associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD). However, whether the optimal Lp(a) threshold for risk assessment should differ based on baseline ASCVD status is unknown. OBJECTIVES: The purpose of this study was to assess the association between Lp(a) and major adverse cardiovascular events (MACE) among patients with and without baseline ASCVD. METHODS: We studied a retrospective cohort of patients with Lp(a) measured at 2 medical centers in Boston, Massachusetts, from 2000 to 2019. To assess the association of Lp(a) with incident MACE (nonfatal myocardial infarction [MI], nonfatal stroke, coronary revascularization, or cardiovascular mortality), Lp(a) percentile groups were generated with the reference group set at the first to 50th Lp(a) percentiles. Cox proportional hazards modeling was used to assess the association of Lp(a) percentile group with MACE. RESULTS: Overall, 16,419 individuals were analyzed with a median follow-up of 11.9 years. Among the 10,181 (62%) patients with baseline ASCVD, individuals in the 71st to 90th percentile group had a 21% increased hazard of MACE (adjusted HR: 1.21; P < 0.001), which was similar to that of individuals in the 91st to 100th group (adjusted HR: 1.26; P < 0.001). Among the 6,238 individuals without established ASCVD, there was a continuously higher hazard of MACE with increasing Lp(a), and individuals in the 91st to 100th Lp(a) percentile group had the highest relative risk with an adjusted HR of 1.93 (P < 0.001). CONCLUSIONS: In a large, contemporary U.S. cohort, elevated Lp(a) is independently associated with long-term MACE among individuals with and without baseline ASCVD. Our results suggest that the threshold for risk assessment may be different in primary vs secondary prevention cohorts.