Cardiovascular Disease Mortality Research Articles

Association between homocysteine levels and mortality in CVD: a cohort study based on NHANES database.

Cardiovascular disease (CVD) is a major global health concern with increasing incident cases and deaths. Homocysteine (Hcy) has been investigated for its potential association with CVD, researchers have debated the extent to which Hcy should be considered a risk factor for cardiovascular diseases, as only 50% of CVD can be explained by classical risk factors. We conducted a prospective cohort study using NHANES 1999-2006 data, analyzing 1,739 US patients aged at least 30 with CVD. Cox proportional hazards regression and restricted cubic splines were used to examine the relationship between Hcy levels and mortality, adjusting for covariates. A total of 1,739 participants with cardiovascular disease (CVD) were enrolled, with a median follow-up period of 126 months. Among them, 1,194 participants died, including 501 deaths due to cardiovascular causes. After adjusting for covariates, the hazard ratios (HR) and 95% confidence intervals (CI) for CVD mortality at different levels of homocysteine (Hcy) (T1 (< 9.3), T2 (9.3-12.5), T3 (> 12.5)) were 1.26 (0.92, 1.73) (T2), and 1.69 (1.14, 2.51) (T3) (P for trend = 0.0086). The HR and 95% CI for all-cause mortality at different levels of Hcy were 1.22 (1.05, 1.42) (T2) and 1.64 (1.29, 2.09) (T3) (P for trend < 0.0001). Elevated Hcy levels were associated with increased risks of all-cause mortality and CVD deaths, even at levels below the conventional threshold. The nonlinear relationship was observed, with inflection points at 14.5 µmol/L for all-cause mortality and 14.6 µmol/L for CVD mortality. Subgroup analyses revealed interactions with age, serum vitamin B12, and smoking. Our study supports the notion that elevated Hcy levels are associated with higher all-cause and CVD mortality risks in CVD participants. The impact of Hcy on health outcomes can be observed at lower concentrations than previously thought.

Effectiveness of treat-to-target cholesterol-lowering interventions on cardiovascular disease and all-cause mortality risk in the community-dwelling population: a target trial emulation.

Little is known about the long-term effectiveness of risk-based treat-to-target cholesterol-lowering interventions on cardiovascular risk. Here, we show the emulated effectiveness of guideline-recommended low-density and non-high-density lipoprotein cholesterol-lowering interventions using the absolute risk reduction (ARR) and the restricted mean event-free time-based number needed to treat (NNT). With 5,375 participants, the 29-year risks for cardiovascular disease (CVD), all-cause mortality, and atherosclerotic CVD were 18.6%, 25.6%, and 17.7%, respectively. Long-term treat-to-target interventions showed significant reductions in CVD (ARR -2.3%, 95%CI -3.4% to -0.8%; NNT 115), all-cause mortality (-3.0%, -4.3% to -1.8%; 95), and atherosclerotic CVD (-2.6%, -3.5% to -1.2%; 104). Such effects appear more pronounced in women, smokers, and those with body mass index < 24 kg/m² or higher adherence rates.

Use of bisphosphonates in chronic kidney disease is associated with cardiovascular death.

Chronic kidney disease (CKD) is associated with increased cardiovascular risk, which may be mediated by vascular calcification. Based on evidence that bisphosphonates inhibit vascular calcification, we hypothesized use of bisphosphonates in CKD would be associated with lower incident cardiovascular disease (CVD), CVD-related mortality, and all-cause mortality. This was a longitudinal observational study including 2,593 Framingham Offspring participants. We used propensity score-adjusted Cox regression models to determine the association between bisphosphonate use and outcomes: time to incident CVD, time to CVD-related mortality, and time to all-cause mortality. The data were stratified by presence or absence of CKD, defined as estimated glomerular filtration rate <60 mL/min/1.73m2. The propensity score included age, sex, hypertension, smoking status, diabetes, total cholesterol, high-density lipoprotein, and self-reported history of fracture. In unadjusted and propensity score-adjusted analyses, those with CKD using bisphosphonates had a trend toward increased incident CVD risk (adjusted hazard ratio (HR) 1.66 (95% CI, 93-2.97)) compared to those with CKD not using bisphosphonates. Those with CKD using bisphosphonates also had increased risk of cardiovascular mortality in the propensity score-adjusted model (adjusted HR 2.20 (95% CI, 1.12-4.32)). There was no significant association between bisphosphonate use and all-cause mortality in participants with CKD. Among individuals without CKD, bisphosphonate use was significantly associated with an increase in all-cause mortality in the propensity-score adjusted analysis (adjusted HR 1.59 (95% CI, 1.27-1.98)). However, there was no significant association between bisphosphonate use and incident CVD events (adjusted HR 0.85 95% CI, 0.63-1.16) or CVD-related death (adjusted HR 0.70 (95% CI 0.36-1.37) in those without CKD. Contrary to our hypothesis, bisphosphonate use was associated with a trend toward increased incident CVD and a two-fold higher risk of CVD mortality in CKD.

J-shaped association of serum uric acid with all-cause and cardiovascular mortality in patients with diabetic kidney disease.

The association of serum uric acid (SUA) with mortality remains unclear in patients with diabetic kidney disease (DKD). Thus, this prospective cohort study aimed to explore the association of SUA with all-cause and cardiovascular disease (CVD) mortality among patients with DKD in a large, nationally representative sample. This cohort study included data from the National Health and Nutrition Examination Survey (NHANES) 1999-2018 and the National Death Index mortality data until 31 December 2019. The restricted cubic spline and the Cox proportional hazards regression were conducted to describe the association of SUA with all-cause and CVD mortality and evaluate potential nonlinear associations. The analysis included 3470 patients with DKD from NHANES 1999-2018. During the follow-up time of 24,633 person-years, we recorded 1489 all-cause deaths, including 542 CVD deaths. We identified a J-shaped association of SUA with all-cause and CVD mortality. The corresponding inflection points were observed at 5.1 and 5.7mg/dL. When SUA were higher than inflection points, each 1mg/dL increase in SUA was linked to a 13% and 22% higher risk of all-cause (HR: 1.13; 95% CI: 1.07-1.20;P < 0.001) and CVD (HR: 1.22; 95% CI: 1.06-1.41;P = 0.006) mortality, respectively. This study indicated the J-shaped association of SUA with all-cause and CVD mortality in patients with DKD. The corresponding inflection points were 5.1 mg/dL for all causes and 5.7mg/dL for CVD, respectively. More clinical randomized trials are needed to confirm the optimal uric acid-lowering target.

Analysing premature cardiovascular disease mortality in the United States by obesity status and educational attainment.

In the United States (US), premature cardiovascular disease (CVD) mortality rates (35-74years) have exhibited increases in recent years, particularly in younger adults, and large differentials by educational attainment. This trend has occurred concurrently with high and increasing obesity prevalence, which also show significant differences by education. This study aims to jointly model premature CVD mortality trends in the US according to obesity status and educational attainment. We used multiple cause of death data from the National Center for Health Statistics, obesity prevalence data from the National Health and Nutrition Examination Survey (NHANES), and educational attainment data from the American Community Survey and NHANES. We applied Bayes' theorem to these data to calculate the conditional probability of premature CVD mortality given obesity status and educational attainment for 2003-2019. We then projected this conditional probability for 2020-2029 using the Lee-Carter model. The probability of premature CVD mortality was greatest for obesity and low education (not graduated high school) and was substantially higher (females 6.7 times higher, males 5.9) compared with non-obesity and high education (Bachelor's degree or higher) in 2019. There was a widening of the gap in premature CVD mortality from 2003 to 2019 between the obese and non-obese populations, which occurred at each education level and was projected to continue in 2020-2029, especially for males. The conditional probability of premature CVD death for obesity and middle education (finished high school but no Bachelor's degree) increased substantially and was projected to surpass the level for non-obesity and low education in coming years for males and in younger age groups. At high education, the conditional probability of premature CVD death for the obese population was projected to increase to 2029, while for non-obesity it was projected to remain steady for females and fall for males; this projected widening is greatest at older age groups. The findings demonstrate the public health challenge to reduce premature US CVD mortality posed by continued high obesity prevalence, especially for younger ages, lower education groups and males. The relative importance of obesity in influencing premature CVD mortality trends has risen partly due to the decline in CVD mortality attributable to other risk factors.

Association of unemployment and increased depressive symptoms with all-cause mortality: follow-up study of a cardiovascular prevention programme.

Unemployment has been associated with increased risk of cardiovascular disease (CVD) and all-cause mortality. However, factors behind this association remain unsettled. A primary care CVD prevention programme was conducted in two Finnish towns in 2005-07. Of the participants (n = 4450), a cohort of apparently healthy CVD risk subjects belonging to the labour force (n = 1487) was identified. Baseline depressive symptoms were assessed by Beck's Depression Inventory. Data on employment status and mortality were obtained from official statistics. The effect of employment status and depressive symptoms on all-cause mortality after a median follow-up of 15 years was estimated in models adjusted for age, sex, body mass index, non-high-density lipoprotein cholesterol, physical activity, alcohol use, current smoking, glucose metabolism, and hypertension. In comparison to employed non-depressive subjects, fully adjusted hazard ratio (HR) for all-cause mortality was 3.53 (1.90-6.57) in unemployed subjects with increased depressive symptoms, 1.26 (0.68-2.34) in unemployed non-depressive subjects, and 1.09 (0.63-1.90) in employed depressive subjects. Factors independently associated with mortality were unemployment with increased depressive symptoms [HR 3.56 (95% CI 1.92-6.61)], screen-detected diabetes [HR 2.71 (95% CI 1.59-4.63)], current smoking [HR 1.77 (95% CI 1.19-2.65)], and higher age [HR 1.10 (95% CI 1.05-1.15)]. Unemployment in itself was not associated with all-cause mortality. If unemployment was accompanied with increased depressive symptoms, risk of death was significantly elevated.

Cardiorespiratory fitness, body mass index and mortality: a systematic review and meta-analysis

ObjectiveThe purpose of this review was to assess the joint relationship of cardiorespiratory fitness (CRF) and Body Mass Index (BMI) on both cardiovascular disease (CVD) and all-cause mortality risk.DesignA systematic review and meta-analysis was conducted. Pooled HR and 95% CI were calculated using a three-level restricted maximum likelihood estimation random-effects model with robust variance estimation. The reference group was normal weight-fit and was compared with normal weight-unfit, overweight-unfit and fit, and obese-unfit and fit.Data sourcesElectronic databases (PubMed/MEDLINE, Web of Science and SportDiscus) were searched following registration on PROSPERO.Eligibility criteriaArticles meeting the following criteria were included: (1) published between January 1980 and February 2023, (2) prospective cohort study, (3) CRF assessed using a maximal or VO2peak exercise test, (4) BMI reported and directly measured, (5) joint impact of CRF and BMI on all-cause mortality or CVD mortality were analysed, and (6) the reference group was normal weight, fit individuals.Results20 articles were included in the analysis resulting in a total of 398 716 observations. Compared with the reference group, overweight-fit (CVD HR (95% CI): 1.50 (0.82–2.76), all-cause HR: 0.96 (0.61–1.50)) and obese-fit (CVD: 1.62 (0.87–3.01), all-cause: 1.11 (0.88–1.40)) did not have a statistically different risk of mortality. Normal weight-unfit (CVD: 2.04 (1.32–3.14), all-cause: 1.92 (1.43–2.57)), overweight-unfit (CVD: 2.58 (1.48–4.52), all-cause: 1.82 (1.47–2.24)) and obese-unfit (CVD: 3.35 (1.17–9.61), all-cause: 2.04 (1.54–2.71)) demonstrated 2–3-fold greater mortality risks.ConclusionsCRF is a strong predictor of CVD and all-cause mortality and attenuates risks associated with overweight and obesity. These data have implications for public health and risk mitigation strategies.

The Role of Primary Care in Achieving Life's Essential 8: A Scientific Statement From the American Heart Association.

To reduce morbidity and mortality rates of cardiovascular disease, an urgent need exists to improve cardiovascular health among US adults. In 2022, the American Heart Association issued Life's Essential 8, which identifies and defines 8 health behaviors and factors that, when optimized through a combination of primary prevention, risk factor management, and effective treatments, can promote ideal cardiovascular health. Because of its central role in patient care across the life span, primary care is in a strategic position to promote Life's Essential 8 and improve cardiovascular health in the United States. High-quality primary care is person-centered, team-based, community-aligned, and designed to provide affordable optimized health care. The purpose of this scientific statement from the American Heart Association is to provide evidence-based guidance on how primary care, as a field and practice, can support patients in implementing Life's Essential 8. The scientific statement aims to describe the role and functions of primary care, provide evidence for how primary care can be leveraged to promote Life's Essential 8, examine the role of primary care in providing access to care and mitigating disparities in cardiovascular health, review challenges in primary care, and propose solutions to address challenges in achieving Life's Essential 8.

Impact of serum carotenoids on cardiovascular mortality risk in middle-aged and elderly adults with metabolic syndrome

BackgroundMetabolic syndrome (MetS), characterized by abdominal adiposity, hypertension, hyperglycemia, and dyslipidemia, is associated with dysregulated immune function, elevated oxidative stress, and chronic low-grade inflammation. Aging exacerbates insulin resistance and the prevalence of MetS. Dietary antioxidants, such as carotenoids, may play a role in preventing cardiovascular disease (CVD) mortality, but evidence remains mixed, particularly among middle-aged and elderly individuals with MetS.MethodsWe analyzed data from 6,601 participants aged 40 years and above with MetS from the National Health and Nutrition Examination Survey (NHANES) III (1988–1994) and NHANES 2001–2006 cycles. Serum concentrations of α-carotene, β-carotene, lycopene, β-cryptoxanthin, and combined lutein/zeaxanthin were quantified. Participants were followed for a median of 16.8 years. Cox proportional-hazards models were used to assess the association between serum carotenoid concentrations and CVD mortality risk, with adjustment for potential confounders.ResultsDuring the follow-up period, 1,237 CVD deaths were identified. Analysis revealed an inverse dose–response relationship between serum lycopene levels and cardiovascular mortality risk. Compared to the lowest quartile, the multivariable-adjusted hazard ratios (95% confidence intervals) for ascending quartiles of serum lycopene were 0.84 (0.71, 1.00), 0.87 (0.74, 1.03), and 0.77 (0.61, 0.97), with a significant trend (p = 0.039). No significant associations were observed for other carotenoids.ConclusionIn this prospective cohort study of 40-year-old and older individuals with MetS, we observed an inverse association between serum lycopene levels and CVD mortality risk.

Abstract 4137880: Access to exercise opportunities, physical inactivity and cardiovascular mortality: A nationwide study in the U.S.

Aims: Despite efforts to promote physical activity, the prevalence of physical inactivity continues to rise. Exercise access influences population activity levels, but county-level variation in physical activity and its link to cardiovascular disease (CVD) mortality is unclear. We explored the associations between access to exercise opportunities, levels of physical inactivity, and CVD mortality across U.S. counties Methods: The County Health Rankings and Roadmaps data and CDC WONDER mortality data were integrated. We compared age-adjusted CVD mortality across county-level quartiles of access to exercise opportunities and physical inactivity. Stratification was performed based on age, sex, race, and urbanization. The rate ratio (RR) for CVD mortality was calculated using generalized linear models. Results: CVD mortality decreased from high to low values of the county-level of physical activity across all demographic subgroups (P&lt;0.001) (Table 1&amp;Figure 1). Access to exercise opportunities was significantly associated with a reduced risk of CVD mortality (RR, 0.93 [0.91–0.95]), which was most pronounced in relation to acute myocardial infarction (AMI) mortality (RR, 0.80 [0.76–0.85]). The county-level physical inactivity was associated with an increased risk of CVD mortality (RR, 1.16 [1.14–1.17]), especially for ischemic heart disease (IHD) mortality (RR, 1.35 [1.31–1.38]) and AMI mortality (RR, 1.32 [1.25–1.38]) (Figure 2). All demographic subgroups demonstrated similar benefits by improving the county-level indicators of physical activity. Conclusion: Counties have the potential to make significant strides in preventing CVD and improving the cardiovascular health of their populations by enhancing access to exercise opportunities and reducing physical inactivity.

Abstract 4138301: Burden of Hyperlipidemia, Cardiovascular Mortality, and COVID-19: A Retrospective-Cohort Analysis of US Data

Background: Hyperlipidemia (HLD) is a major risk factor for cardiovascular disease (CVD). Little is known regarding temporal variation in CVD mortality related to HLD. The COVID-19 pandemic added complexity to factors influencing CVD mortality. Question: What are the yearly trends and impact of the COVID-19 pandemic on HLD-related CVD mortality in the United States? Methods: Mortality and demographic data for adults were obtained from CDC repository from 1999-2020, using ICD-10 codes HLD (E78.0-E78.5) and CVD (I00-I99). Age adjusted mortality rates (AAMR) per 1,000,000 population was standardized to the 2000 US population. Log-linear regression models evaluated mortality shifts. Average annual percentage change (AAPC) from 1999-2019 was used to calculate projected AAMR in 2020, subsequently compared to actual 2020 death rates to estimate pandemic-attributed excess deaths. Results: A total of 483,155 HLD-related CVD deaths were recorded between 1999-2020. Despite the CVD mortality decline in general population, HLD-related CVD AAMR rose from 36.33 [95% CI, 35.52-37.13] in 1999 to 99.77 [98.67-100.87] in 2019. Ischemic heart diseases (AAMR 49.39) were the most common causes of death while hypertension had the highest annual mortality increase (AAPC +10.23%) in populations with HLD. Higher HLD-related CVD mortality was observed in males (AAMR 104.87) than females (AAMR 61.93), in those ≥75 years (AAMR 646.45) than 35-75 years (AAMR 54.11), in non-Hispanic (NH) (AAMR 82.49) than Hispanic (AAMR 58.98) populations, and in rural (AAMR 89.98) than urban (AAMR 78.94) regions. NH Black populations (AAMR 84.35) and Western US regions (AAMR 96.88) had the highest HLD-related CVD. The first year of COVID-19 pandemic resulted in 10.55% excess HLD-related CVD death, with the most prominent increase in the 35-75 years age group (14.23%), Hispanic (17.96%), Black (14.82%), and urban (11.68%) populations. Conclusions: Our study revealed an increase in HLD-related CVD mortality which was exacerbated by the COVID-19 pandemic. Higher CVD mortality disproportionately affected males, Black, elderly (≥75 years), and rural populations with HLD. Further research is needed to validate our findings and identify contributing factors.

Abstract 4132159: Dietary Intake of Niacin and Risk of Cardiovascular Mortality in The Golestan Cohort Study

Introduction: Recent studies have linked niacin metabolism with vascular inflammation and cardiovascular disease (CVD); however, the association is still inconclusive regarding dietary intake, and the findings may not be generalizable to various populations. In this longitudinal study within a Middle Eastern population, we aimed to assess the relationship between dietary intake of B vitamins, including niacin, and the risk of CVD mortality. Methods: Our study utilized data from the Golestan Cohort Study, which has tracked 50,045 participants aged 40-75 years since 2004. We excluded subjects who reported extreme total energy intake or had a positive history of cancer, CVD, or diabetes at baseline. Vitamin B intake estimations including thiamin, riboflavin, niacin, pyridoxamine, folate, and cobalamin intake were derived from the baseline food frequency questionnaire, noting that supplement use was uncommon in this cohort. To adjust for calorie intakes, we employed the nutrient density method. Cox proportional hazard models were used to calculate hazard ratios (HR) and 95% confidence intervals (CI) for cardiovascular mortality, using the lowest quintile of intake as the reference group for vitamins and adjusting for potential confounders. Results: We analyzed 42,456 subjects with a mean age of 51.5 ± 8.7 years at baseline. During 579,339 person-years of follow-up (median: 14.1 years), 3,065 CVD deaths were recorded. The median dietary intake of niacin was 25.3 mg/d (Recommended Dietary Allowance = 14-16 mg/d). We observed significant associations between niacin intake (HR Q5 vs. Q1 = 1.13, 95% CI = 1.01-1.26, P trend &lt;0.05) and CVD mortality. When niacin was modeled as a continuous linear variable, it was associated with a greater risk of CVD mortality (HR = 1.05, 95% CI = 1.01-1.09) per 2 mg/1000Kcal/d increase. None of the other B vitamin intakes evaluated were associated with CVD mortality in this population. Conclusion: These findings suggest that among B vitamins, only dietary niacin intake was positively associated with CVD mortality. Further confirmation in larger studies is needed.

Abstract 4121454: Machine-extractable Markers in Chest Radiograph to Predict Cardiovascular Risk in Screening Population

Introduction: Recent research has shown that AI is able to assess biological aging and cardiovascular disease (CVD) risk using chest radiographs. However, the lack of explainability of such deep learning algorithms hinders clinical utility and adoption. This motivates the current study which searches for and tests the use of machine extractable quantitative features in chest radiographs to predict CVD risk in population screening. Method: Chest radiograph measurements characterizing cardiomediastinal geometry, aortic calcification and tortuosity were handpicked for development of a segmentation-based feature extraction algorithm. The algorithm was applied on the PLCO lung screening dataset for analysis. The association between measurement-based imaging features, clinical characteristics (age, sex, BMI, smoking status, hypertension, diabetes, liver disease) with CVD mortality and 10-year major adverse cardiovascular events (MACE) were analysed by using proportional hazard regression, with feature selection done by LASSO. Result: Of 29,453 eligible subjects, 5693 subjects from a single study centre were used for fitting of all models. The median follow-up time was 19 years. A total of 32 imaging features were extracted and analysed. For both 10-year MACE and CVD mortality, model using imaging features, age, and sex performed similarly to model using conventional risk factors, and a deep learning chest radiograph CVD risk model. Two imaging features, mediastinal width at valve-level [HR 1.36 (1.23-1.50)] and maximal lateral displacement of descending aorta [HR 1.29 (1.18-1.42)] were found to be prognostic. To the best of our knowledge, these features have not been reported previously. Conclusion: Quantitative imaging features can predict CVD risk in chest radiograph similar to deep learning models while providing feature interpretability and explainability. Two novel imaging features prognostic of CVD risk were found and shown to be complementary to conventional risk factors.

Abstract 4121359: Heart Disease and Heart Failure: Trends and Disparities in Mortality Rates in the United States from 2000 to 2020

Background: The remarkable decline in the overall prevalence and mortality rates of cardiovascular diseases (CVD) in the United States (US) over the past few decades has not been consistent across all age groups, sexes, races, and types of cardiovascular diseases. Heart disease (HD) and heart failure (HF) still pose a significant burden to the healthcare system. Objectives: This study sought to describe the age, sex and racial disparities in the trends in mortality rates for these two outcomes in the US over the past two decades. Methods: This was an ecological study with trend analysis of the mortality from heart disease and heart failure in the US between 2000 and 2020. Data on CVD was obtained from the National Centers for Disease Control and Prevention (CDC) surveillance databases and analyzed. Binomial regression models were used to evaluate trends in outcomes. Statistical significance was considered for p-values &lt; 0.05. Results: There was a significant decrease in the age-standardized mortality for HD over the past two decades (from 343.5 per 100,000 cases to 215.1 per 100,000 cases (p&lt;0.001)). Mortality rates were significantly higher in males (p&lt;0.001, R2 = 0.92), non-Hispanic blacks (p&lt;0.001) and non-Hispanic whites (p&lt;0.001) compared to Hispanics, (R2 = 0.94) and in adults aged 65+ (p&lt;0.001) and 75+ (p&lt;0.001) (R2 = 0.98). There was no significant decrease in the age-standardized mortality for HF (from 26.9 per 100,000 cases to 25.7 per 100,000 cases (p=0.706)) due to a reversal in the trend after 2011. Though the rates were significantly lower in males overall (p=0.001, R2 = 0.27), these rates became higher in males and in non-Hispanic Blacks compared to non-Hispanic Whites beyond 2016. Mortality rates due to HF were highest in the 65+ and 75+ age groups. Conclusions: This study on national trends in heart disease and heart failure across age groups, sexes and races over the past two decades confirmed a significant reduction in heart disease mortality rates over this period, but with persistent disparities between males and females, non-Hispanic Blacks and other races and the older age groups. This study also highlights important reversals of heart failure mortality rates trends in more recent years in males and females, and non-Hispanic Blacks and Whites, the reasons for which are amenable to further research.

Abstract 4124226: Long-term exposure to air pollutants and incidence of cardiovascular disease events and mortality in The Multi-Ethnic Study of Atherosclerosis and Air Pollution (MESA Air)

Introduction: Exposure to ambient air pollution may increase the risk of cardiovascular disease events and mortality, but prior publications have primarily included administrative cohorts with outcomes that have not been individually reviewed and with air pollution estimates created without cohort-specific exposure monitoring. Multi-Ethnic Study of Atherosclerosis (MESA) is a multi-site cohort study designed specifically to prospectively collect and adjudicate cardiovascular disease (CVD) events. MESA Air recruited additional participants into sub-cohorts for enhanced air pollution variation and sample size. Research Question: The aim of this analysis was to characterize the relationship between long-term exposure to nitrogen dioxide (NO 2 ) and fine particulate matter (PM 2.5 ) and all-cause mortality and CVD events. Methods: Air pollution exposure was assessed using address history with a purpose-built exposure model incorporating cohort-specific monitoring including measurement and validation at participant homes. We used Cox models to assess the risk of rolling 2-year average exposures on all cause-mortality and on a composite CVD endpoint (definite angina, probable angina with revascularization, myocardial infarction, atherosclerosis or other CVD death, resuscitated cardiac arrest, and stroke). Models were stratified for baseline hazard by age, sub-cohort, and recruitment year and were additionally adjusted for age, sex, race/ethnicity, field center, smoking/second-hand smoke, pack-years, physical activity, education, income, neighborhood socioeconomic status, and statin use. Results: MESA Air participants were aged 44-87 years at enrollment between 2000 and 2007; follow-up averaged 14 years. 6,915 participants had follow-up for events, NO 2 exposure, and covariate information. We observed 1,442 deaths and 985 CVD events. The interquartile range over all 2-year averages was 10.5-23.1 ppb for NO 2 and 10.1-14.9 µ/m 3 for PM 2.5 . The adjusted hazard ratio (aHR) for a 10 ppb increment in NO 2 was 1.38 (95% CI: 1.17, 1.64) for all-cause mortality and 1.16 (95% CI: 0.95, 1.42) for incident CVD events. The aHR for a 5 µg/m 3 increment in PM 2.5 was 1.20 (95% CI: 0.99, 1.46) for all-cause mortality and 1.15 (95% CI: 0.95, 1.39) for incident CVD events Conclusions: These results add to growing literature demonstrating an association between air pollution exposure, mortality, and CVD in a cohort with well-characterized clinical endpoints and cohort-specific exposure assessment.

Sitting less and moving more: the impact of physical activity on mortality in the population of Spain.

Sitting time (ST) constitutes a significant aspect of sedentary behavior, and its worldwide escalation raises concerns regarding public health. International guidelines recommend limiting sedentary time and replacing it with physical activity (PA) to reduce the risk of diseases and mortality. This study examines the impact of replacing ST with PA on all-cause, cardiovascular disease (CVD), and cancer mortality in a representative cohort of the population of Spain. We included 30 955 participants aged 15-69 years from two National Health Surveys performed in 2011 and 2017. Data were linked to mortality records as of December 2022. Data on ST, light PA (LPA), and moderate-vigorous PA (MVPA) were collected as part of the International Physical Activity Questionnaire at baseline. Isotemporal substitution analysis from Poisson regression models was used to estimate the relative risk ratio (RR) of replacing ST with LPA or MVPA. During a median follow-up of 5.7 years, 957 deaths were reported. The replacement of 1h per week of ST with 1h per week of MVPA was significantly associated with a lower risk of all-cause (3.3%), CVD (6.7%), and cancer mortality (3.1%). Similarly, replacing 1h per week of ST with 1h per week of LPA was significantly associated with a lower risk of all-cause (1.6%) and cancer mortality (2.1%). Finally, substituting 1h per week of LPA with 1h per week of MVPA was significantly associated with a 7.6% lower risk of CVD mortality. Substituting one hour per week of ST with an equivalent amount of PA was associated with a lower risk of all-cause, CVD, and cancer mortality.

Abstract 4137836: Association of AHA PREVENT Risk Score with Cardiovascular Mortality Across Social Determinants of Health: A Nationwide Retrospective Cohort Study

Introduction/Background: The AHA PREVENT risk calculator was recently developed to accurately predict the risk of cardiovascular disease (CVD) risk, including incident heart failure, stroke, and coronary heart disease. However, the risk prediction of this tool for CVD mortality overall and among groups with increasing social determinants of health (SDOH) burden in a multi-ethnic nationally representative cohort of American adults is unclear. Methods: This retrospective study included adult NHANES participants (age &gt; 30 years) from 1998-2018 cycles without known CVD. Individuals without data for risk estimation were excluded. AHA PREVENT risk was scored from 0 to 100. Multivariable-adjusted Cox regression models were used to estimate the risk of CVD mortality, accounting for 7 SDOH measures (employment, family income, food security, health access, health insurance, housing instability, and being married or living with partner). Population was stratified based on cumulative SDOH burden (1, 2, 3, 4, 5, &gt; 5 unfavorable SDOH markers). Model discrimination was assessed using C-statistics in these groups. Results: Among 19,887 participants (median age 53 years, 49% Female, 54% White, 19% Black), a 1% increase in AHA PREVENT Risk score calculation was associated with 13% higher risk of CVD mortality (HR adj 1.13, 95% CI: 1.12-1.14) with C-statistic of 0.91. While AHA PREVENT Risk score was predictive of CVD mortality across the SDOH burden strata, there was a decline in C-statistic from 0.91 among those without any unfavorable SDOH to 0.81 among those with &gt; 5 unfavorable SDOH measures. Conclusion: The AHA PREVENT Risk score is predictive of CVD mortality even when accounting for SDOH measures. However, the risk discrimination decreases among individuals with a higher SDOH burden. Further investigation is needed to identify means to improve CVD risk prediction among disadvantaged people with high unfavorable SDOH burden.

Abstract 4121568: The Influence of Cardiovascular Health on Atherosclerotic Cardiovascular Disease Progression and Life Expectancy Among Individuals with Type 2 Diabetes

Objective: This study aims to evaluate whether cardiovascular health (CVH) plays a similar role in the transition from a healthy state to atherosclerotic cardiovascular disease (ASCVD) and subsequent mortality rates in diabetic patients compared to those without diabetes. It also evaluates the effectiveness of CVH in reducing diabetes-related ASCVD risks and enhancing ASCVD-free life expectancy. Research design and methods: This cohort study included 176,669 adults from the UK Biobank, among whom 10,109 (22.3%) were diagnosed with type 2 diabetes mellitus (T2DM). CVH was assessed using the Life's Essential 8 score, encompassing diet, physical activity, smoking, sleep, BMI, blood lipids, blood glucose, and blood pressure. CVH scores were categorized into low, moderate, and high levels based on their distribution among diabetic patients. The main outcomes were the transitions from no ASCVD to the onset of ASCVD and then to mortality, as well as the ASCVD-free life expectancy. Results: In patients with T2DM, high CVH levels were associated with lower ASCVD risk (HR: 0.55, 95% CI: 0.45-0.68 for women; HR: 0.57, 95% CI: 0.50-0.65 for men) and reduced mortality in those with ASCVD (HR: 0.62, 95% CI: 0.39-0.98 for women; HR: 0.62, 95% CI: 0.48-0.79 for men), compared to the low CVH group. No significant difference in CVH's effect on ASCVD and mortality was observed between diabetic and non-diabetic groups. When compared with non-diabetic individuals, no excess risk was observed in incident ASCVD and post-ASCVD mortality among diabetic patients with high CVH. At the age of 40, women with low CVH were expected to live 38.5 years (38.0-39.1) free from ASCVD, which increased to 42.9 years (42.4-43.5) for those with high CVH, while non-diabetic women were predicted to have an ASCVD-free life expectancy of 44.1 years (43.5-44.6). For men at the age of 40, those with low CVH had an ASCVD-free life expectancy of 32.0 years (31.3-32.6), which rose to 37.9 years (37.4-38.6) with high CVH. Non-diabetic men were expected to live 38.3 years (37.7-39.0) free from ASCVD. Notably, life expectancy with ASCVD did not increase with higher CVH levels in both genders. Conclusions: Our findings suggest that the American Heart Association’s recommendations for promoting CVH, initially designed for the general population, are also beneficial for individuals with T2DM. Adopting these guidelines can help mitigate ASCVD progression and enhance life expectancy in diabetic patients.

Abstract 4137820: Extreme heat and cardiovascular disease in a changing climate: An urgent need for risk management and health research

Background: Extreme heat can trigger or exacerbate cardiovascular disease (CVD) through ischemia or thrombosis, and its deleterious impacts are inclined to worsen as increased heat exposure and heightened vulnerability from climate change interacted with natural and social environment. Research Questions: Previous studies have primarily focused on quantifying the increased risk of CVD due to heat exposure, while lacking a comprehensive understanding of the association, underlying mechanisms, and vulnerability in CVD patients. Consequently, there is a scarcity of clinical and public health interventions aimed at preventing the convergence of extreme heat exposure and the risk of CVD within the context of climate change. Methods: We conducted a systematic search in PubMed, Embase, and Web of Science from inception to December, 2023, and we retrieved articles which assessed the effects of extreme heat or climate change on CVD. Results: In this review, we outline the existing evidence on the epidemiology and pathophysiological mechanisms that elucidate how extreme heat affects the risk of CVD. Extreme heat is associated with increased risks for CVD morbidity and mortality, where older persons, low socioeconomic status, pre-existing medical conditions, and unfavorable living environments confer greater susceptibility to heat. The adverse effects of extreme heat on cardiovascular system involved a wide range of complex mechanisms between different organs and regulatory pathways (Figure 1). Additionally, we identify the factors that contribute to the vulnerability of CVD patients to heat exposure. The discrepancy in heat-related risk can be attributed to individual susceptibility, sociocultural factors, population temperature adaptations, and environmental factors. Future climate change is projected to exacerbate the burden of extreme heat, particularly due to the interaction of air pollution, population aging, and urbanization (Figure 2). Conclusions: Addressing extreme heat should be within the framework of the prevention of CVD. Health professionals and scientists are responsible for mitigating the cardiovascular effects mediated by extreme heat, with an emphasis on engaging in risk management tactics and health research to implement preventive strategies. As CVD is a climate sensitive disease, evidence-based interventions during heat extremes are urgently needed to cope with the cardiovascular risks associated with the inevitable trajectory of climate change.

Abstract 4131439: Routine Social Isolation Screening Among Adults with Cardiovascular Disease: A Survival Analysis

Background: Evidence linking social isolation to cardiovascular disease morbidity and mortality has grown in recent years. Still, information on how this may manifest in real world settings and its implications for screening practices is limited. In 2019, our large national integrated health care system implemented screening for social isolation as part of a broader universal social risk assessment. This repository of screening data was joined to administrative claims to test these associations in real world data and explore differences by demographic and medical factors. Methods: Social isolation responses recorded from 2019-2022 were included for a cohort of adult health plan members with documented atherosclerotic cardiovascular disease (ASCVD). We selected a single random assessment for each member and retained any other responses for sensitivity analyses. Cohort members had at least 10 months of enrollment surrounding assessment date for use as the baseline period and were followed for 365 days. We used cox proportional hazards regression with right censoring for coverage gaps to estimate the risk of all-cause mortality conferred by social isolation. We used Poisson regression to model the rate of inpatient stays. Results: There were 881 deaths among 7,484 members (18% of those with social isolation; 11% of those without). The isolated group skewed less male (54% vs. 65%, p &lt;0.001) and older (68.4 [SD 12.7] vs. 67.5 [SD 12.6] years, p &lt;0.05) than those not isolated. At baseline, the isolated group had higher rates of mean inpatient stays (2.3 [SD 1.9] vs. 1.9 [SD 1.6], p &lt;0.001), ED visits (1.2 [SD 1.9] vs. 0.9 [SD 1.6], p &lt; 0.001), and smoking (50% vs. 44%, p &lt; 0.05), and a higher mean Charlson Comorbidity Index (CCI) (3.6 [SD 2.6] vs. 3.0 [SD 2.4], p &lt; 0.001). Adjusted survival models suggested an independent 33% increase in all-cause mortality risk among those screening positive for social isolation (1.33 HR 95% CI 1.10, 1.62). Adjusted Poisson models found a similar increase in inpatient stays (1.36 IRR 95% CI 1.14, 1.62). Conclusions: Our findings corroborate the association between social isolation and morbidity and mortality among those with known ASCVD. The effect for social isolation was similar in magnitude to clinical comorbidities and smoking, suggesting that routine screening for social isolation may provide valuable information for assessing and managing the risk of death among patients with ASCVD.