Risk Of Incident Cardiovascular Disease Research Articles

Plasma Metabolome Predicts Aortic Stiffness and Future Risk of Coronary Artery Disease and Mortality After 23 Years of Follow-Up in the General Population.

Increased aortic stiffness (arteriosclerosis) is associated with early vascular aging independent of age and sex. The underlying mechanisms of early vascular aging remain largely unexplored in the general population. We aimed to investigate the plasma metabolomic profile in aortic stiffness (vascular aging) and associated risk of incident cardiovascular disease and mortality. We included 6865 individuals from 2 Swedish population-based cohorts. Untargeted plasma metabolomics was performed by liquid-chromatography mass spectrometry. Aortic stiffness was assessed directly by carotid-femoral pulse wave velocity (PWV) and indirectly by augmentation index (AIx@75). A least absolute shrinkage and selection operator (LASSO) regression model was created on plasma metabolites in order to predict aortic stiffness. Associations between metabolite-predicted aortic stiffness and risk of new-onset cardiovascular disease, cardiovascular mortality, and all-cause mortality were calculated. Metabolite-predicted aortic stiffness (PWV and AIx@75) was positively associated particularly with acylcarnitines, dimethylguanidino valeric acid, glutamate, and cystine. The plasma metabolome predicted aortic stiffness (PWV and AIx@75) with good accuracy (R2=0.27 and R2=0.39, respectively). Metabolite-predicted aortic stiffness (PWV and AIx@75) was significantly correlated with age, sex, systolic blood pressure, body mass index, and low-density lipoprotein. After 23 years of follow-up, metabolite-predicted aortic stiffness (PWV and AIx@75) was significantly associated with increased risk of new-onset coronary artery disease, cardiovascular mortality, and all-cause mortality. Aortic stiffness is associated particularly with altered metabolism of acylcarnitines, cystine, and dimethylguanidino valeric acid. These metabolic disturbances predict increased risk of new-onset coronary artery disease, cardiovascular mortality, and all-cause mortality after more than 23 years of follow-up in the general population.

Associations of Relative Intensity of Physical Activity with Incident Cardiovascular Events and All-Cause Mortality.

The relative intensity of a physical activity (PA) can be estimated as the percent of one's maximal effort required. We compared associations of relative and absolute intensity PA with incident major cardiovascular disease (CVD) and all-cause mortality in 5,633 women from the Objective Physical Activity and Cardiovascular Health Study (mean age 78.5±6.7). Absolute intensity was measured by accelerometry. Relative intensity was estimated by dividing accelerometer-estimated metabolic equivalents (METs) by maximal MET capacity. Both were aggregated into mean daily hours of light intensity PA (LPA) and moderate-to-vigorous PA (MVPA). Cox proportional hazards models estimated hazard ratios (HRs) for one-hour higher amounts of PA on outcomes. During follow-up (median=7.4 years), there were 748 incident CVD events and 1,312 deaths. Greater LPA and MVPA, on either scale, was associated with reduced risk of both outcomes. HRs for a one-hour increment of absolute LPA were 0.88 (95% CI:0.83-0.93) and 0.88 (95% CI:0.84-0.92) for incident CVD and mortality, respectively. HRs for a one-hour increment of absolute MPVA were 0.73 (95% CI:0.61-0.87) and 0.55 (95% CI:0.48-0.64) for the same outcomes. HRs for a one-hour increment of relative LPA were 0.70 (95% CI:0.59-0.84) and 0.78 (95% CI:0.68-0.89) for incident CVD and mortality, respectively. HRs for a one-hour increment of relative MPVA were 0.89 (95% CI:0.83-0.96) and 0.82 (95% CI:0.77-0.87) for the same outcomes. On the relative scale, LPA was more strongly, inversely associated with both outcomes than relative MVPA. Absolute MVPA was more strongly inversely associated with the outcomes than relative MVPA. Findings support the continued shift in the PA intensity paradigm towards recommendation of more movement, regardless of intensity. Relative LPA--a modifiable, more easily achieved behavioral target, particularly among ambulatory older adults--was associated with reduced risk of incident major CVD and death.

Abstract PO3-27-05: Racioethnic and Ancestral Differences in Risk of Cardiometabolic Conditions and Cardiovascular Disease in Women Treated for Breast Cancer: the Pathways Heart Study

Abstract Background: Despite the established literature of racioethnic disparities in cardiovascular disease (CVD) in the general population, few studies have examined such differences in women after BC treatment, who are at higher risk due to cardiotoxic cancer treatment. Moreover, few prior studies have considered genetic similarity among the participants in the analyses, which can be objectively inferred to delineate the ancestral background of an individual. Methods: The Pathways Heart Study was established to investigate the incidence of cardiometabolic risk factors and CVD events in women with a history of BC at Kaiser Permanente Northern California (KPNC). The main study endpoints for this analysis were cardiometabolic risk factors (hypertension, diabetes, and dyslipidemia) and CVD events, identified by ICD and CPT codes from EHR. Prevalent conditions were identified within 3 years prior to the date of BC diagnosis, and incident conditions were from the date of BC diagnosis to December 31, 2021. Ethnicity was self-reported and classified as non-Hispanic White (NHW), non-Hispanic Black (NHB), Asian, Hispanic, other, or unknown. Global genetic ancestry was estimated to capture the proportion of continental ancestries genetically similar to the reference populations in Africa, Americas, Asia, and Europe from the 1000 Genome Project and Human Genome Diversity Project (HGDP), which, with the current lack of universally accepted labeling, are herein referred to as African, Native American, Asian, and European ancestry, respectively. Multivariable logistic and Cox proportional hazards regression models with all-cause mortality considered as competing risk were used to analyze the associations of race and ethnicity and genetic similarity with prevalent and incident cardiometabolic risk factors and CVD events. Results: Of the 4,071 women with BC in this analysis, 2,713 (66.6%) self-reported as NHW, 305 (7.5%) as NHB, 512 (12.6) as Asian, 447 (11.0%) as Hispanic, and 94 (2.3%) as other or unknown. NHB, Asian, and Hispanic women were more like to have prevalent diabetes than NHW women, the pattern of which persisted after BC diagnosis. Adjusted OR (95% CI) of risk of incident diabetes was 1.74 (1.21-2.49) for NHB, 3.63 (2.59-5.08) for Asian, and 2.19 (1.58-3.04) for Hispanic women, as compared to NHW. Analysis of genetic similarity revealed results consistent with self-reported race and ethnicity (sHR [95% CI] per 25% increment of African ancestry 1.19 [1.07-1.34], Asian ancestry 1.57 [1.44-1.72], and Native American ancestry 1.60 [1.29-2.00]), in comparison to European ancestry. For CVD risk, NHB women were more like to develop any prevalent and incident CVD than NHW women, particularly for ischemic heart disease (incident risk sHR=1.80 [1.10-2.94]). Genetic similarity analyses also showed higher risk of ischemic heart disease associated with African ancestry (incident risk per 25% increment, sHR=1.23 [1.06-1.43]). In contrast, Hispanic women were at lower risk of any incident CVD, serious CVD, arrhythmia, heart failure or cardiomyopathy, and ischemic heart disease. Similarly, lower risk of these CVD conditions was associated with Native American ancestry. Conclusions: Compared with women who self-reported as NHW, those self-reported as NHB, Asian, and Hispanic were at higher risk of diabetes prior to BC diagnosis and the elevated risk persisted after BC diagnosis. Moreover, Black women had higher risk of prevalent and incident CVD, whereas Hispanic women had lower risk of CVD, the latter of which might be related to the admixture of Native American ancestry. To our knowledge, this is the largest multi-ethnic study of disparities in CVD health in women post BC treatment, demonstrating corroborating findings between self-reported race and ethnicity and genetic similarity. The results highlight disparities in cardiometabolic risk factors and CVD among BC survivors that may warrant more research and clinical attentions. Citation Format: Song Yao, Haiyang Sheng, Peter Fiorica, Richard Cheng, Lucas Mendicino, Angela Omilian, Qianqian Zhu, Janise Roh, Cecile Laurant, Valerie Lee, Isaac Ergas, Carlos Iribarren, Jamal Rana, Mai Nguyen-Huynh, Eileen Rillamas-Sun, Dawn Hershman, Christine Ambrosone, Lawrence Kushi, Heather Greenlee, Marilyn Kwan. Racioethnic and Ancestral Differences in Risk of Cardiometabolic Conditions and Cardiovascular Disease in Women Treated for Breast Cancer: the Pathways Heart Study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-27-05.

Premorbid physical activity and prognosis after incident myocardial infarction: the Atherosclerosis Risk in Communities Study

High to moderate levels of physical activity (PA) are associated with low risk of incident cardiovascular disease. However, it is unclear whether the benefits of PA in midlife extend to cardiovascular health following myocardial infarction (MI) in later life. Among 1,111 ARIC participants with incident MI during ARIC follow-up (mean age 73 [SD 9] years at MI, 54% men, 21% Black), PA on average 11.9 (SD 6.9) years prior to incident MI (premorbid PA) was evaluated as the average score of PA between visit 1 (1987-89) and visit 3 (1993-95) using a modified Baecke questionnaire. Total and domain-specific PA (sport, non-sport leisure, and work PA) was analyzed for associations with composite and individual outcomes of mortality, recurrent MI, and stroke after index MI using multivariable Cox models. During a median follow-up of 4.6 (IQI 1.0-10.5) years after incident MI, 823 participants (74%) developed a composite outcome. The 10-year cumulative incidence of the composite outcome was lower in the highest, as compared to the lowest tertile of premorbid total PA (56% vs. 70%, respectively). This association remained statistically significant even after adjusting for potential confounders (adjusted hazard ratio [aHR] 0.80 [0.67-0.96] for the highest vs. lowest tertile). For individual outcomes, high premorbid total PA was associated with a low risk of recurrent MI (corresponding aHR 0.64 [0.44, 0.93]). When domain-specific PA was analyzed, similar results were seen for sport and work PA. The association was strongest in the first year following MI (e.g., aHR of composite outcome 0.66 [95% CI 0.47, 0.91] for the highest vs. lowest tertile of total PA). Premorbid PA was associated positively with post-MI cardiovascular health. Our results demonstrate the additional prognostic advantages of PA beyond reducing the risk of incident MI.

Associations between Hysterectomy and Metabolic Syndrome: The Multi-Ethnic Study of Atherosclerosis

Metabolic syndrome is linked to an increased risk of incident cardiovascular disease (CVD) 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 may be independently associated with long-term CVD risk. To examine the associations between hysterectomy with ovarian preservation and metabolic syndrome risk in a multi-ethnic cohort. We studied 3,367 female participants in the Multi-Ethnic Study of Atherosclerosis who had data on self-reported history of hysterectomy, oophorectomy, hystero-oophorectomy and metabolic syndrome at baseline (2000-2002). We used adjusted logistic regression to assess the cross-sectional associations between hysterectomy/oophorectomy subgroups and prevalent metabolic syndrome at baseline. Furthermore, we investigated 1,355 participants free of baseline metabolic syndrome and used adjusted Cox regression models to evaluate incident metabolic syndrome from exams 2 (2002-2004) to 6 (2016-2018). 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 period 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 both strongly associated with incident metabolic syndrome compared to having neither hysterectomy or oophorectomy. Hysterectomy, even with ovarian preservation, may be independently associated with a higher risk of metabolic syndrome. If other studies confirm these findings, screening and preventive strategies focused on females with ovary-sparing hysterectomy and the mechanisms underpinning these associations may be explored.

Systolic blood pressure status modifies the associations between the triglyceride-glucose index and incident cardiovascular disease: a national cohort study in China

BackgroundThe triglyceride-glucose (TyG) index and blood pressure (BP) are correlated and serve as risk factors for cardiovascular disease (CVD). The potential impact of BP status on the association between the TyG index and CVD risk remains uncertain. This study aims to investigate the relationships between the TyG index and incident CVD in Chinese middle-aged and elderly adults, considering variations in BP status among participants.Methods6558 participants (mean age: 58.3 (± 8.7) years; 46.0% were men) without prevalent CVD were recruited from the China Health and Retirement Longitudinal Study. Participants were divided into three groups according to their systolic blood pressure (SBP) levels (< 120mmHg, 120 ∼ 129mmHg, ≥ 130mmHg). The TyG index was computed as ln[triglyceride (mg/dl) * fasting blood glucose (mg/dl)/2]. The primary outcome was CVD (heart disease and stroke), and the secondary outcomes were individual CVD components. Cox regression models and restricted cubic splines were performed to investigate the associations between continuous and categorical TyG with CVD.Results1599 cases of CVD were captured during 58,333 person-years of follow-up. Per 1-SD higher TyG index was associated with a 19% (HR: 1.19; 95% CI: 1.12, 1.27) higher risk for incident CVD, and the participants with the highest quartile of TyG index had a 54% (HR: 1.54; 95% CI: 1.29, 1.84) higher risk of CVD compared to those in the lowest quartile. SBP significantly modifies the association between the TyG index and CVD, with higher HRs for CVD observed in those with optimal and normal SBP. SBP partially mediated the associations between the TyG index with CVD. The results were generally consistent among participants with varying pulse pressure statuses rather than diastolic BP statuses.ConclusionsThe associations between the TyG index and CVD were modified by BP status, with greater HRs for CVD observed among those who had SBP < 130mmHg. SBP can partially mediate the association between the TyG index with CVD, highlighting the importance of early screening for the TyG index to identify at risk of hypertension and CVD.

Changes in Sleep Patterns, Genetic Susceptibility, and Incident Cardiovascular Disease in China

The associations of changes in sleep patterns with incident cardiovascular disease (CVD) are not fully elucidated, and whether these associations are modified by genetic susceptibility remains unknown. To investigate the associations of 5-year changes in sleep patterns with incident CVD and whether genetic susceptibility modifies these associations. This prospective cohort study of the Dongfeng-Tongji cohort was conducted from 2008 to 2018 in China. Eligible participants included those with complete sleep information at baseline survey (2008-2010) and the first follow-up survey (2013); participants who had no CVD or cancer in 2013 were prospectively assessed until 2018. Statistical analysis was performed in November 2023. Five-year changes in sleep patterns (determined by bedtime, sleep duration, sleep quality, and midday napping) between 2008 and 2013, and polygenic risk scores (PRS) for coronary heart disease (CHD) and stroke. Incident CVD, CHD, and stroke were identified from 2013 to 2018. Cox proportional hazards regression models were applied to estimate hazard ratios (HRs) and 95% CIs. Among 15 306 individuals (mean [SD] age, 65.8 [7.4] years; 8858 [57.9%] female and 6448 male [42.1%]), 5474 (35.78%) had persistent unfavorable sleep patterns and 3946 (25.8%) had persistent favorable sleep patterns. A total of 3669 incident CVD cases were documented, including 2986 CHD cases and 683 stroke cases, over a mean (SD) follow-up of 4.9 (1.5) years. Compared with those with persistent unfavorable sleep patterns, individuals with persistent favorable sleep patterns over 5 years had lower risks of incident CVD (HR, 0.80; 95% CI, 0.73-0.87), CHD (HR, 0.84; 95% CI, 0.76-0.92), and stroke (HR, 0.66; 95% CI, 0.54-0.82) in the subsequent 5-year period. No significant effect modification by PRS was observed for sleep pattern change and CHD or stroke risk. However, sleep pattern changes and PRS were jointly associated with the CHD and stroke risk in a dose-dependent manner, with the lowest risk being among those with persistent favorable sleep patterns combined with low PRS (HR for CHD, 0.65; 95% CI, 0.52-0.82 and HR for stroke, 0.48; 95% CI, 0.29-0.79). In this cohort study of middle-aged and older Chinese adults, individuals with persistent favorable sleep patterns had a lower CVD risk, even among those with higher genetic risk. These findings highlight the importance of maintaining favorable sleep patterns for CVD prevention.

Association between metabolic syndrome severity score and cardiovascular disease: results from a longitudinal cohort study on Chinese adults.

This study aimed to quantify the severity of metabolic syndrome(MetS) and investigate its association with cardiovascular disease(CVD) risk on Chinese adults. 13,500 participants from the Zhejiang Adult Chronic Disease Study were followed up between 2010 and 2021.A continuous MetS severity score derived from the five components of MetS was used to quantify MetS severity, and the association between MetS severity and the risk of incident CVD was assessed using Cox proportional hazard and restricted cubic spline regression. Both the presence and severity of MetS were strongly associated with CVD risk. MetS was related to an increased risk of CVD (hazard ratio(HR):1.700, 95% confidence interval(CI): 1.380-2.094). Compared with the hazard ratio for CVD in the lowest quartile of the MetS severity score, that in the second, third, and highest quartiles were 1.812 (1.329-2.470), 1.746 (1.265-2.410), and 2.817 (2.015-3.938), respectively. A linear and positive dose-response relationship was observed between the MetS severity and CVD risk (P for non-linearity = 0.437). Similar results were found in various sensitivity analyses. The MetS severity score was significantly associated with CVD risk. Assessing MetS severity and further ensuring intervention measures according to the different severities of MetS may be more useful in preventing CVD.

Long-term ambient ozone exposure and incident cardiovascular diseases: National cohort evidence in China

BackgroundLong-term ozone (O3) exposure has been associated with cardiovascular disease (CVD) mortality in mounting cohort evidence, yet its relationship with incident CVD was poorly understood, especially in low- and middle-income countries (LMICs) experiencing high ambient air pollution. MethodsWe carried out a nationwide perspective cohort study from 2010 through 2018 by dynamically enrolling 36948 participants across Chinese mainland. Warm-season (April–September) O3 concentrations were estimated using satellite-based machine-learning models with national coverage. Cox proportional hazards model with time-varying exposures was employed to evaluate the association of long-term O3 exposure with incident CVD (overall CVD, hypertension, stroke, and coronary heart disease [CHD]). Assuming causality, a counterfactual framework was employed to estimate O3-attributable CVD burden based on the exposure-response (E-R) relationship obtained from this study. Decomposition analysis was utilized to quantify the contributions of four key direct driving factors (O3 exposure, population size, age structure, and incidence rate) to the net change of O3-related CVD cases between 2010 and 2018. ResultsA total of 4428 CVD, 2600 hypertension, 1174 stroke, and 337 CHD events were reported during 9-year follow-up. Each 10-μg/m³ increase in warm-season O3 was associated with an incident risk of 1.078 (95% confidence interval [CI]: 1.050–1.106) for overall CVD, 1.098 (95% CI: 1.062–1.135) for hypertension, 1.073 (95% CI: 1.019–1.131) for stroke, and 1.150 (95% CI: 1.038–1.274) for CHD, respectively. We observed no departure from linear E-R relationships of O3 exposure with overall CVD (Pnonlinear= 0.22), hypertension (Pnonlinear= 0.19), stroke (Pnonlinear= 0.70), and CHD (Pnonlinear= 0.44) at a broad concentration range of 60–160 µg/m3. Compared with rural dwellers, those residing in urban areas were at significantly greater O3-associated incident risks of overall CVD, hypertension, and stroke. We estimated 1.22 million (10.6% of overall CVD in 2018) incident CVD cases could be attributable to ambient O3 pollution in 2018, representing an overall 40.9% growth (0.36 million) compared to 2010 (0.87 million, 9.7% of overall CVD in 2010). This remarkable rise in O3-attributable CVD cases was primary driven by population aging (+24.0%), followed by increase in O3 concentration (+10.5%) and population size (+6.7%). ConclusionsLong-term O3 exposure was associated with an elevated risk and burden of incident CVD in Chinese adults, especially among urban dwellers. Our findings underscored policy priorities of implementing joint control measures for fine particulate matter and O3 in the context of accelerated urbanization and population aging in China.

Heart Rate Variability Analysis in Obstructive Sleep Apnoea Patients with Daytime Sleepiness.

Recent studies suggest sleepy patients with OSA are at higher risk for incident cardiovascular disease. This study assessed cardiac autonomic function in sleepy versus non-sleepy patients with obstructive sleep apnoea (OSA) using heart rate variability (HRV) analysis. We hypothesised that HRV profiles of sleepy patients would indicate higher cardiovascular risk. Electrocardiograms (ECG) derived from polysomnograms (PSG) collected by the Sydney Sleep Biobank were used to study HRV in groups of sleepy (ESS≥10) and non-sleepy OSA patients (ESS<10). HRV parameters were averaged across available ECG signal during N2 sleep. A total of 421 patients were evaluated, with mean age of 54 (14) years, body mass index (BMI) of 33 (9) kg/m2, apnoea hypopnoea index (AHI) of 21 (28) events/h and, 66% male. The sleepy group consisted of 119 patients, and the non-sleepy group 302 patients. Sleepy patients exhibited lower HRV values for: root mean square successive difference (RMSSD, p= 0.028); total power (TP, p= 0.031); absolute low frequency (LF, p= 0.045); and high frequency (HF, p= 0.010) power compared to Non-Sleepy patients. Sleepy patients with moderate to severe OSA exhibited lower HRV values for: (RMSSD, p= 0.045; TP, p= 0.052) ; absolute LF (p= 0.051); and HF power (p= 0.025). There were no differences in other time and frequency domain HRV markers. This study shows a trend towards parasympathetic withdrawal in sleepy OSA patients, particularly in moderate to severe cases, lending mechanistic support to the link between the sleepy phenotype and CVD risk in OSA.

Abstract 2234: Cardiovascular disease risk among men with prostate cancer: Differences by prostate cancer aggressiveness

Abstract Background: Cardiovascular disease (CVD) is a major cause of morbidity and mortality among men diagnosed with prostate cancer. We evaluated the extent to which men with prostate cancer develop CVD accounting for potential factors that may contribute to the CVD burden in this population. Methods: We prospectively followed men diagnosed with prostate cancer and free from CVD (stroke and coronary heart disease, including myocardial infarction, coronary artery bypass graft, and percutaneous coronary intervention) before their cancer diagnosis in the Health Professionals Follow-up Study, between 1986 and 2016. Men were categorized by D’Amico prostate cancer risk groups as low-risk (stage T1-2a, Gleason score ≤6, and PSA at diagnosis ≤10 ng/mL), intermediate-risk (T2b and/or Gleason score 7 and/or PSA &amp;gt;10-20), or high-risk (≥T2c/N1/M1 or Gleason score 8-10 or PSA &amp;gt;20). Incident fatal and non-fatal CVD, defined as coronary heart disease and stroke after cancer diagnosis, were centrally adjudicated. CVD risk factors including smoking, hyperlipidemia, hypertension, diabetes mellitus, body mass index, were self-reported on biennial questionnaires. Deaths due to prostate cancer or other causes were treated as competing events when estimating cumulative incidence and cause-specific hazard ratios (HR). Results: Among 5,707 prostate cancer patients, 1,912 had low-risk, 2,261 had intermediate-risk, and 1,534 had high-risk cancer. 1,102 CVD events were documented over up to 30 years of follow-up after cancer diagnosis. The 10-year CVD risk was 8.1% for men with low-risk cancer, 8.8% for intermediate-risk, and 10.4% for high-risk cancer. The cause-specific HRs for CVD were 1.18 (95% CI 1.03, 1.36) in intermediate-risk and 1.59 (95% CI 1.36, 1.85) in high-risk prostate cancer, both compared to low-risk prostate cancer. Men with high-risk cancer tended to be older; after age adjustment, the HRs were 1.15 for intermediate-risk (95% CI 1.00, 1.33) and 1.35 for high-risk cancer (1.35, 95% CI 1.16, 1.58). Associations between cancer risk group and CVD were essentially unchanged after further adjustment for CVD risk factors present at cancer diagnosis, primary cancer treatment modality (surgery, radiation, androgen deprivation therapy, watchful waiting/active surveillance), and calendar year of diagnosis. Discussion: Despite the elevated risk of cancer mortality in men with intermediate-risk and high-risk prostate cancer compared to low-risk prostate cancer, CVD risk remains at least as common over time among these men as among men with low-risk prostate cancer. Incident CVD risk after cancer diagnosis among men with more aggressive cancers, which particularly occur in older men, is not primarily attributable to differences in pre-existing risk factor burden. These findings from a cohort with healthcare access and literacy indicate a need for continued clinical attention to CVD after cancer diagnosis. Citation Format: Caroline Himbert, Anna Plym, Jane B. Vaselkiv, Andreas Pettersson, Philip W. Kantoff, Lorelei A. Mucci, Kenneth J. Mukamal, Konrad H. Stosapck. Cardiovascular disease risk among men with prostate cancer: Differences by prostate cancer aggressiveness [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2234.

Joint Associations of Diet and Device-measured Physical Activity with Mortality and Incident CVD and Cancer: a prospective analysis of the UK Biobank Study.

We examined the joint associations of diet and device-measured intensity-specific PA with all-cause mortality (ACM), cardiovascular disease (CVD) and cancer incidence. We used data from 79,988 participants from the UK Biobank, a population-based prospective cohort study. Light PA (LPA), moderate-to-vigorous PA (MVPA), vigorous PA (VPA) and total PA (TPA) were measured using a wrist-worn accelerometer. Diet Quality Score (DQS) was based on 10 foods and ranged from 0 (unhealthiest) to 100 (healthiest) points. We derived joint PA and diet variables. Outcomes were all-cause mortality, CVD and cancer incidence including PA, diet and adiposity-related (PDAR) cancer. During a median follow-up of 8 years, 2,863 deaths occurred, 11,053 participants developed CVD, 7,005 developed cancer and 3,400 developed PDAR cancer. Compared with the least favourable referent group (bottom PA tertile/low DQS), participants with middle and high (total and intensity specific) PA, except for LPA, had lower all-cause mortality risk and incident CVD risk, regardless of DQS. For example, among middle and high VPA and high DQS groups, CVD HR were 0.79 (95%CI 0.74-0.86) and 0.75 (95%CI 0.69-0.82), respectively. The pattern of cancer results was less pronounced but in agreement with the ACM and CVD incidence findings (e.g. HR 0.90, 95%CI 0.81-0.99; 0.88,0.79-0.98 and 0.82,0.74-0.92 among high VPA for low, moderate and high DQS group, respectively). Device-measured PA reveals novel joint associations with diet on health outcomes. Our results emphasize the crucial role of PA in addition to a healthy diet for reducing chronic diseases and mortality risk.

Abstract P508: Comparisons of Cardiovascular Health in US Adults by Chronic Disease Status: National Health and Nutrition Examination Survey (NHANES), 2013-2018

Introduction: Cardiovascular health (CVH) assessment is typically applied to younger, healthy individuals in the setting of primordial prevention, but the concept may have important benefits for those with chronic diseases of aging (CDAs) at increased risk for incident cardiovascular disease (CVD). No studies have assessed CVH in adults with CDAs vs. healthy adults without CDAs using the new Life’s Essential 8 (LE8) metrics. Methods: We used NHANES data from 2013-2018 to identify presence of 15 CDAs by participant self-report of diagnosis. We included adults ages 20 to 79. CVH was defined by AHA’s LE8 metrics. Overall mean LE8 (range 0-100, higher = better CVH) and individual LE8 metric scores were calculated according to disease status for all participants and stratified by self-identified sex and race/ethnicity. Results: There were 12,296 adults, with mean age 46 years; 51% self-identified as female, 65% as White, 16% Hispanic, 11% Black, 5% Asian, 4% multiracial. Significantly, and often substantially, lower CVH scores were noted for adults with CDA (12 of 15 CDAs) vs. healthy adults, including all subtypes of CVD and lung diseases, liver disease, arthritis, cognitive decline, and depression. Greatest mean LE8 differences were detected for COPD, emphysema, and congestive heart failure. For example, mean overall LE8 score was 14.0 points lower in those with vs. without COPD (51.0 vs. 65.0, P&lt;0.0001) with smoking and physical activity having the largest absolute differences in individual metric scores (36.4 and 23.6, respectively). There were no significant differences in LE8 scores for participants with vs. without cancer, HIV, or osteoporosis. Males and Black adults consistently had lower LE8 scores. Conclusions: CVH is significantly poorer in adults with many of the CDAs compared to healthy adults. These data establish the utility of the LE8 CVH score to identify groups for targeted optimization of CVH to enhance primary and secondary prevention efforts for CVD and potentially for other concomitant CDAs.

Abstract P486: Dietary Acculturation is Associated With Altered Gut Microbiome, Circulating Metabolites, and Cardiovascular Disease Risk in US Hispanics/ Latinos: Results From the Hispanic Community Health Study/Study of Latinos

Introduction: Dietary acculturation, defined as diet adaptation after migration, is related to human health. However, the influence of dietary acculturation on cardiovascular disease (CVD) is largely unknown, nor is the potential mechanism clear. Hypothesis: Dietary acculturation (diet reflecting U.S. exposure - years in the U.S. and nativity [U.S. 50 states/DC vs. foreign-born]) is associated with altered gut microbiota and related metabolites, which may contribute to CVD risk. Methods: A dietary acculturation score was derived from 14172 participants with two 24-hr dietary recalls at baseline (2008-11) using LASSO regression (29 food groups as predictors of U.S. exposure). We evaluated associations of dietary score with incident CVD over 7 years follow-up (including coronary heart disease, stroke and heart failure, n=14172/211 total/cases) and gut microbiota (shotgun sequencing, n=2349, 2014-17). Further, we identified serum metabolites associated with diet-related microbiome (n=694, 2014-17) and examined associations of baseline metabolites with incident CVD (n=5256/108 total/cases). Results: We identified a dietary acculturation pattern (Fig1A) which increased with years in the U.S. and was highest in U.S.-born adults (Fig1B). Higher dietary acculturation was associated with risk of incident CVD (HR per SD, 1.33 [95%CI: 1.13-1.57]), adjusting for sociodemographic, lifestyle, and clinical factors. We identified 69 diet-related species (17 enriched and 52 depleted, mainly from Clostridium , Prevotella and Eubacterium , Fig1C), and 25 metabolites associated with both diet-related microbiome score and incident CVD (Fig1D). Proxy association analysis based on these metabolites suggested a positive relationship between diet-related microbiome and incident CVD (r=0.70, p&lt;0.001) (Fig1E). Conclusions: Among U.S. Hispanics/Latinos, greater dietary acculturation was associated with increased risk of CVD, possibly via diet-related alterations in gut microbiota and related serum metabolites.

Abstract 62: Association of Cardiovascular Health Trajectories Through Young Adulthood With Later-Life Incident Cardiovascular Disease and Mortality: The Coronary Artery Risk Development in Young Adults (CARDIA) Study

Introduction: Associations of mid-life cardiovascular health (CVH) and incident cardiovascular disease (CVD) are well-studied. Less is known about patterns of young adulthood (YA) CVH, including its changes, and associations with later-life CVD outcomes. Methods: CVH was defined by Life’s Essential 8 (LE8) score. First, we used latent class modeling (SAS Proc Traj) to determine trajectories of continuous CVH scores (0-100) for CARDIA participants with ≥3 CVH measurements in YA (from year [Y]0, mean age 25, to Y20, mean age 45). Second, we examined direction and magnitude of change in CVH status (low, moderate, or high) between 2 CVH measurements (at Y0 and Y20), comparing participants with increased, decreased, or stable CVH status. Outcomes included incident CVD (MI, heart failure, stroke, CVD death) after Y20. Cox proportional hazards regression was used to estimate HRs for associations of YA CVH patterns with incident CVD. Results: There were 4,257 participants in YA (44% female, 48% Black) included. In the trajectory analysis, we identified four distinct CVH trajectory groups ( Figure 1A ): compared to the Persistently-High CVH group, the Moderate-Low-Declining and Moderate-Declining CVH trajectory groups had substantially higher hazards for incident CVD ( Figure 1B ). In the CVH status change analysis (N=2,884; Figure 1B ), compared to Stable High CVH in YA, Stable Low CVH had a 19-fold higher risk for incident CVD, and both increasing and decreasing CVH status in YA had greater risk for incident CVD as well. Conclusions: Trajectories of declining moderate and low CVH in YA had substantially higher risk for later-life incident CVD events. Those with decreasing CVH and those who started with lower CVH and improved it through YA, were also at higher risk. These data suggest that early life CVH and maintaining high CVH through YA are both important for prevention of later-life CVD.

Abstract P235: Subjective Well-Being as Compared With Traditional Risk Factors in Relation to Incident Cardiovascular Diseases

Introduction: Emerging evidence suggests a role of subjective well-being (SWB) in modifying the risk of developing cardiovascular disease (CVD), while supportive data from prospective studies are scarce. Hypothesis: Low SWB is independently associated with higher incidence of CVD, comparable in magnitude to several established traditional risk factors. Methods: The study included a total of 154,217 women and men from the UK Biobank study, free of CVD at baseline and with measurements of SWB based on general happiness, personal health, family relationships, friendships, and financial situation, followed up until May 31, 2021. Cox proportional hazards models were used to estimate associations between SWB and incident CVD. The relative importance of SWB in terms of predicting outcomes was measured by explained R 2 values. Results: During a median follow-up of 11.3 years, there were 11,662 incident CVD events (8,474 coronary heart disease [CHD] cases and 1,804 ischemic strokes). Individuals with low SWB had an approximately 2-fold higher risk of CVD compared to those with high SWB (Hazard Ratio [95% Confidence Interval], 1.99 [1.75-2.27] for CVD, 1.98 [1.71-2.30] for CHD, and 1.90 [1.34-2.69] for ischemic stroke) after adjusting for traditional risk factors. Of 12 factors examined, SWB was ranked as the fourth-strongest CVD risk factor, following hypertension, smoking, and body mass index ( Figure ). SWB was ranked as the sixth- and third-strongest risk factor for CHD and ischemic stroke, respectively. Conclusions: Our study indicates that SWB is robustly associated with the risk of incident CVD, potentially as one of the strongest modifiable risk factors for CVD prediction.

Higher ultra-processed food intake is associated with an increased incidence risk of cardiovascular disease: the Tehran lipid and glucose study

BackgroundCardiovascular disease (CVD) is a major cause of death worldwide, although limited data are currently available regarding the impact of consuming ultra-processed food (UPF) on its incidence. Given the increased consumption of UPF in Iran, we aimed to investigate the association between UPF intake and CVD risk.MethodsIndividuals without CVD (n = 2050) aged ≥ 30 years old were recruited from the Tehran Lipid and Glucose Study (TLGS). Dietary data were collected using a validated food frequency questionnaire (FFQ) and UPF intakes were assessed based on the Nova food classification. Multivariable Cox proportional hazard models adjusted for potential confounders were used to estimate the hazard ratio (HR) and 95% confidence intervals (95% CI) for the risk of CVD across tertiles of UPF intake.ResultsA 10.1% incidence of CVD occurred over a median follow-up of 10.6 years, with a 22% increase in CVD risk per each 50 g/day UPF intake. Participants with the highest intake of UPF had a 68% greater incidence of CVD compared to those with the lowest intake (HR = 1.68, 95% CI=1.14–2.48) after controlling for potential confounders. Regarding sub-groups of UPF, participants in the 3rd tertile compared to the reference had a significantly increased risk of CVD (HR = 1.56, 95% CI=1.04–2.34). Nevertheless, intake of bread, fast food, sweetened beverages, sweets and desserts, high-fat dairy products, and other UPFs were not associated with greater CVD risk.ConclusionOur findings support the hypothesis that the incidence of CVD is enhanced with the higher consumption of UPF in a representative sample of the Iranian population.

Abstract P538: Relations of Left Ventricular Mass With Long-Term Cardiovascular and Health Outcomes: The Framingham Heart Study

Introduction: Although elevated left ventricular mass (LVM) is associated with increased risk for cardiovascular disease (CVD) events over short-term follow-up, limited data exists regarding echocardiographic assessments in relation to long-term health outcomes. Hypothesis: We assessed the associations of LVM to the risk of incident all-cause mortality, CVD, dementia, hypertension, diabetes, and chronic kidney disease (CKD) over 20 years of follow-up. Methods: We evaluated up to 3 serial echocardiographic observations (1991-2008) for up to 8218 Framingham Heart Study participants. We modeled LVM as indexed to height 2.7 , logarithmically transformed then standardized. Utilizing multivariable-adjusted time-dependent and interval-censored Cox proportional hazards models, we related log-LVMI to the incidence of CVD and other health outcomes through the end of 2019 by updating LVM and all covariates at multiple examinations. Results: Over a median follow-up of 17 years (max 29 years), our study participants (mean age 47 years, 54% women) experienced 1353 events for all-cause mortality, 948 for CVD, 293 for dementia, 1631 for hypertension, 492 for diabetes, and 627 for CKD. Higher log-LVMI was significantly associated with increased incident all-cause mortality and CVD, including its respective components: coronary heart disease, heart failure (with reduced and preserved ejection fraction), and stroke. Results were consistent for incident hard and atherosclerotic CVD. Higher LVMI was also significantly associated with increased incidence of dementia, hypertension, diabetes, and CKD (defined as eGFR&lt;60 mL/min/1.73 m 2 and defined with urine albumin-to-creatinine ratio ≥30). Conclusions: In our large prospective community-based sample higher LVMI carries an adverse prognosis for multiple health outcomes over two decades of follow-up. These findings underscore the importance of maintaining an optimal LVM over the life course with control of its key determinants such as blood pressure and glycemia.

Abstract MP73: The Association of Urinary Metals With Cardiovascular Disease Incidence and All-Cause Mortality in the Multi-Ethnic Study of Atherosclerosis (MESA)

Background: Environmental exposure to metals is widespread yet preventable and has been associated with cardiovascular disease (CVD) endpoints, although evidence from prospective studies with racial and ethnic diversity is limited. Objective: We assessed the prospective association of urinary metals with incident coronary heart disease (CHD) and CVD and all-cause mortality in a diverse population of adults from the Multi-Ethnic Study of Atherosclerosis (MESA). Methods: We included 6,638 MESA participants (mean (SD) age 62.1(10.2) years, 53% female, 39% non-Hispanic white, 27% non-Hispanic Black, 22% Hispanic/Latino, 12% Chinese). Urinary non-essential metals (cadmium, tungsten, and uranium), and essential metals (cobalt, copper, and zinc) were assessed at baseline (2000-2001). We used Cox proportional hazards regression to estimate adjusted (table footnote) hazard ratios (HR) for the association between urine metals with incident CHD, CVD, and all-cause mortality through 2019. Results: Over 17.7 years median follow up (IQR: 12.4, 18.5), 749 (11%) participants developed CHD, 1,162 (17%) developed CVD, and 1,844 (28%) died. In the models adjusted by sociodemographic and behavioral factors (Table 1, [Model 1]), one IQR increase in urinary cadmium, tungsten, cobalt, copper, and zinc at baseline was significantly associated with higher risk of incident CHD, incident CVD and all-cause mortality. Uranium levels were significantly associated with all-cause mortality and incident CVD, but not CHD. The magnitude of the association was attenuated when adjusting the models for clinical risk factors (Table 1, [Model 2]). A linear trend was identified for cadmium and copper and all endpoints. Conclusion: Our findings among a large and ethnically diverse US population support that metal exposure is associated with incident CVD and premature mortality. These findings can inform the development of novel preventive strategies to improve cardiovascular health.

Abstract P384: Longitudinal Associations of Deprived Neighborhoods With Incident Cardiovascular Disease and Cardiovascular Mortality Among UK Biobank Participants

Introduction: In 2019, the global prevalence of cardiovascular disease (CVD) reached 523 million, and CVD resulted in 18.6 million deaths. Despite well-documented associations between social determinants of health and CVD, sparse data exist on the associations between living in deprived neighborhoods and incident CVD and mortality. Hypothesis: Living in deprived neighborhoods increases the risk of CVD incidence and mortality. Methods: We analyzed the UK Biobank prospective cohort, excluding prevalent CVD cases at baseline (n=297,950, mean age=55.5 years, female=53.2%). The primary exposure was the neighborhood deprivation index (NDI), defined as an area-level proximity measure of neighborhood socioeconomic status. A higher score indicates more deprived neighborhoods (expressed in quartiles). The primary outcomes were incident CVD and CVD-related mortality, including 1) overall CVD, 2) ischemic heart disease (IHD), and 3) cerebrovascular disease (CeVD). Cox proportional-hazard regression models were used to examine associations between NDI and CVD outcomes, adjusting for covariates and reported hazard ratios (HRs) with 95% confidence intervals (CIs). Results: During a median follow-up of 14.3 years (4,261,877 person-years), 20,113 incidents and 12,619 deaths were included in the analysis. In comparison to those living in the lowest NDI quartile (least deprived), those in the highest NDI quartile (most deprived) had a 20%, 15%, and 34% greater risk of developing overall CVD, IHD, and CeVD incidence, respectively ( Table ). Moreover, they exhibited a 33%, 34%, and 35% greater risk of mortality for overall CVD, IHD, and CeVD, respectively. Conclusions: Our study demonstrates that living in highly deprived neighborhoods increased the risk for CVD, IHD, and CeVD incidence and mortality in the UK Biobank cohort. Future research should consider analyzing such linkages by sex and race and reducing CVD risk via local efforts to invest in deprived neighborhoods to alleviate the burden of CVD.