Abohashem, Shady

Importance Elevated low-density lipoprotein cholesterol (LDL-C) is a modifiable risk factor for cardiovascular disease, the leading cause of premature death worldwide. Assessing the LDL-C–related burden is critical for guiding prevention and treatment strategies. Objectives To estimate the global, regional, and national burden of ischemic heart disease and ischemic stroke attributable to elevated LDL-C (relative to 35-54 mg/dL) from 1990 to 2023 and to quantify the contributions of population growth, aging, risk-deleted burden, and exposure changes to burden trends. Design, Setting, and Population This comparative risk assessment, part of the Global Burden of Disease Study 2023, estimated population-level LDL-C exposure and associated health loss in 204 countries and territories. Mean LDL-C levels were estimated using spatiotemporal gaussian process regression based on 806 studies across 161 countries. Relative risks were derived from meta-analyses of 38 randomized clinical trials. Population-attributable fractions for deaths and disability-adjusted life-years (DALYs) were estimated by age and sex for adults aged 25 years or older from 1990 to 2023, with 95% uncertainty intervals. Exposure Population-level LDL-C concentrations. Main Outcomes and Measures Population-attributable fractions, counts, and rates (all ages and age standardized per 100 000) of LDL-C–attributable deaths and DALYs from ischemic heart disease and ischemic stroke, with uncertainty intervals. Results In 2023, elevated LDL-C accounted for 3.6 million deaths (95% uncertainty interval, 2.2-5.4 million; 6.0% of global mortality) and 90.7 million DALYs (95% uncertainty interval, 58.9-123.3 million; 3.2% of DALYs). Although global all-ages rates remained stable, age-standardized death and DALY rates decreased by 45.6% and 39.5%, respectively, since 1990. In 2023, age-standardized LDL-C–attributable DALY rates were highest in Eastern Europe and lowest in high-income Asia-Pacific. One-third of the global LDL-C burden occurred in India and China. Population growth and aging drove the increasing burden, with notable regional disparities in LDL-C exposure and risk-deleted DALY rates shifting toward middle-sociodemographic settings. Conclusions and Relevance Despite declining age-standardized rates, the absolute LDL-C burden has increased since 1990 due to demographic changes and has shifted toward middle-sociodemographic countries. Measurement and surveillance gaps persist. Strengthened prevention, diagnosis, and treatment access strategies are essential to mitigate the health burden of LDL-C.

Importance Ischemic heart disease (IHD), the leading cause of death in the US, is predominantly due to modifiable risk factors. Estimates of IHD mortality attributable to risk factors provide evidence for health policy decision-making. Objective To estimate the burden of IHD death attributable to risk factors in the US from 1990-2023. Design, Setting, and Participants The Global Burden of Disease Study 2023 (GBD 2023) used vital records and a broad set of epidemiologic data to estimate IHD death rates, risk factor exposure, and relative risk curves for risk-outcome pairs for 1990-2023 for the general population. Data analysis was performed from October 2024 to December 2025. Exposure Twelve metabolic, behavioral, and environmental risk factors. Main Outcomes and Measures The primary outcomes were IHD death rates per 100 000 persons, counts, and attributable risks from 1990-2023 by age, sex, and US state. Estimates include 95% uncertainty intervals (UI). IHD death rates were estimated using ensemble modeling methods. Risk exposures were estimated using bayesian meta-regression methods. Relative risks were estimated following the Burden of Proof framework. Results In 2023, there were 473 000 IHD deaths (95% UI, 414 000-510 000) in the US, a decrease of 58.7% (95% UI, 56.8%-61.0%) in age-standardized rate since 1990. Between 2010 and 2023, there was a 19.0% decrease (95% UI, 15.0%-22.9%) for males and a 24.5% decrease (95% UI, 20.3%-29.7%) for females in IHD death rates. High systolic blood pressure (SBP), dietary risks, and high low-density lipoprotein cholesterol (LDL-C) were the leading risk factors for IHD deaths in 2023, accounting for 47.2% (95% UI, 36.4%-57.0%), 38.6% (95% UI, 17.2%-56.8%), and 28.5% (95% UI, 19.3%-39.6%) of IHD deaths, respectively. Increased exposure to several risk factors substantially increased their attributable burden for IHD deaths in 2023, with high fasting plasma glucose (FPG) increasing 38.8% (95% UI, 11.5%-81.1%) and high body mass index (BMI) increasing 54.5% (95% UI, 41.8%-66.3%) since 1990. Smoking and particulate matter pollution had the greatest decrease in attributable IHD mortality since 1990, at 33.3% (95% UI, 23.6%-41.7%) and 74.9% (95% UI, 46.7%-88.8%), respectively. Conclusion and Relevance Per the results of this systematic analysis of GBD 2023, a total of 88.7% (95% UI, 83.4%-92.5%) of IHD deaths were attributable to modifiable risk factors in the US in 2023, with high SBP, dietary risks, and high LDL-C being the greatest contributors. High BMI and high FPG showed the largest attribution increases, while exposure to other risks did not increase significantly for the population.

Abstract Background Climate-related stressors such as heat, wildfires, and extreme weather are increasingly recognized as determinants of cardiovascular and oncologic health. However, their joint impact on overlapping cancer–cardiovascular disease (CVD) burdens remains unknown. We developed a Cardio-Oncology Burden Index (COBI) to quantify the co-prevalence of cancer and CVD at the community level and examined its association with climate vulnerability across U.S. census tracts. Methods We conducted a cross-sectional ecological analysis of 82,679 census tracts (328,683,841 residents) using the CDC PLACES database. COBI was derived using principal component analysis of age-adjusted prevalence of cancer, coronary artery disease, and stroke. The Climate Burden Index (CBI, 0–1 percentile) integrates multiple climate-related exposures, including extreme temperature, wildfire frequency, and severe weather events. Population-weighted mixed-effects regression models with county-level random effects estimated associations between CBI and COBI, adjusting for region, rurality, and environmental justice indicators. β coefficients represent percentage-point differences in COBI per unit (or category) increase in climate burden. Exposure–response relationships were examined using restricted cubic splines (RCS). Robustness was assessed via geographically matched (<50 km) and fully matched (region, rural–urban commuting area, and environmental justice) analyses. Results Marked spatial heterogeneity was observed in both CBI and COBI across the U.S. (Fig. A–B). Higher climate burden was consistently associated with greater cardio-oncology burden (Fig. C), demonstrating a dose–response relationship: second vs lowest quartile β=0.92 (95% CI, 0.61–1.24); third vs lowest quartile β=1.61 (95% CI, 1.30–1.92); highest vs lowest quartile β=3.44 (95% CI, 3.11–3.76). The RCS model revealed a significant non-linear association (p_non-linear<0.001), with a plateau at moderate exposures and a steep rise at the highest CBI levels (Fig. D). Results remained robust in sensitivity analyses (β=4.17 [95% CI, 3.62–4.71] for geographically matched; β=4.39 [95% CI, 4.10–4.69] for fully matched tracts; Table). Conclusions Greater climate burden is independently associated with higher cardio-oncology burden across U.S. communities, with disproportionate effects in the most climate-vulnerable areas. This novel, population-level linkage between climate stress and onco-cardiovascular disease burden, highlights an emerging syndemic at the intersection of environment, cancer, and CVD. Targeted mitigation and prevention strategies integrating environmental resilience into chronic disease prevention are urgently needed.For image description, please refer to the figure legend and surrounding text.

Abstract Background Obesity is a major public health concern and a leading contributor to premature mortality worldwide. While body mass index (BMI) has long been the standard measure for assessing obesity-related health risks, it fails to distinguish between fat and lean mass or capture the distribution of adiposity—key determinants of metabolic and cardiovascular (CV) health. The Body Roundness Index (BRI), a novel anthropometric measure incorporating waist circumference and height, offers a more precise assessment of body fat distribution and its associated health risks. Although prior studies have linked BRI to all-cause and CV mortality in general populations, its predictive value for premature mortality and potential disparities remain unexplored. Purpose To investigate the association between BRI and premature all-cause (primary outcome) and cardiovascular-specific mortality (secondary outcome) in U.S. adults younger than 65 years. Additionally, we examine whether these associations vary across sociodemographic subgroups. Methods We conducted a nationally representative cohort study using the National Health and Nutrition Examination Survey (NHANES) data (1999–2018) linked to mortality records through December 31, 2019. Adults younger than 65 years were included, excluding those with CV disease or missing covariates. BRI, derived from waist circumference and height, was categorized into quintiles (Q3 as reference). Premature mortality was defined as deaths before age 65. Multivariable Cox proportional hazards models, accounting for NHANES’ complex survey design, were used to assess associations and ensure nationally representative estimates. Nonlinear relationships were examined using restricted cubic splines. Results Among 29,016 (weighted N=1,349,437,788) adults (mean age 42 years; 50% female), 751 premature deaths occurred over a median follow-up of 10 yrs, including 163 attributed to CV causes. In fully adjusted models*, participants in the highest BRI quintile (Q5 vs. Q3) had a 47% higher risk of premature all-cause mortality (HR 1.47; 95% CI, 1.12–1.93; p=0.006) and a 96% higher risk of premature cardiovascular mortality (HR 1.96; 95% CI, 1.12–3.41; p=0.02; Fig.1). Subgroup analyses indicated that the association between high BRI and premature mortality was most pronounced among middle-aged adults (45-64 years: HR 1.80; p-interaction=0.004), males (HR 1.66; p=0.006), and Hispanics (HR 2.17; p=0.007). Similar patterns were observed for premature cardiovascular mortality (Fig.2). Conclusions High BRI is independently associated with increased risks of premature all-cause and cardiovascular mortality, with the strongest effects observed in middle-aged adults. These findings highlight the potential of BRI in risk stratification and underscore the need for targeted interventions to address disparities in premature mortality. Integrating BRI into preventive cardiology and public health strategies may help reduce early mortality.Figure 1 Figure 2

Abstract Aims Obesity, particularly visceral adiposity, is a key driver of cardiovascular mortality (CVM), yet conventional measures such as body mass index (BMI) inadequately capture fat distribution. The Body Roundness Index (BRI) is a novel anthropometric measure integrating waist circumference and height to better reflect body shape and visceral fat. This study examined the association between BRI and CVM in U.S. adults and across sociodemographic subgroups. Methods and results We analysed data from 31 351 adults (median age 43 yrs, 50% females) aged ≥20 years in NHANES 1999–2018, excluding those with prior cardiovascular disease or cancer. BRI was computed using a validated equation and categorized into quintiles (Q3 as reference). The primary outcome was CVM; secondary outcomes included all-cause, heart disease, and cerebrovascular mortality. Weighted Cox proportional hazards and restricted cubic spline (RCS) models evaluated associations after adjustment for demographic, behavioural, and clinical factors. Subgroup and sensitivity analyses tested consistency and effect modification. During a median follow-up of 10.1 years (IQR: 5.3–14.9 years), 883 cardiovascular deaths occurred. In fully adjusted models, participants in the highest BRI quintile had a 54% higher risk of CVM (HR, 1.54; 95% CI, 1.13–2.08; P = 0.006) vs. Q3. This risk remained high even among those with normal BMI. RCS analysis indicated a modest U-shaped association. Stronger effects were observed among middle-aged adults (45–64 years) and those with higher educational attainment. Conclusion Higher BRI is independently associated with increased cardiovascular mortality, particularly among middle aged adults and those with normal BMI, underscoring its potential as a practical, noninvasive tool for cardiovascular risk stratification. Incorporating BRI into clinical and public health assessment may improve identification of individuals at elevated risk.