Hazard Ratios For Cardiovascular Disease Research Articles

The long-term effects of blood urea nitrogen levels on cardiovascular disease and all-cause mortality in diabetes: a prospective cohort study.

The long-term effects of blood urea nitrogen(BUN) in patients with diabetes remain unknown. Current studies reporting the target BUN level in patients with diabetes are also limited. Hence, this prospective study aimed to explore the relationship of BUN with all-cause and cardiovascular mortalities in patients with diabetes. In total, 10,507 participants with diabetes from the National Health and Nutrition Examination Survey (1999-2018) were enrolled. The causes and numbers of deaths were determined based on the National Death Index mortality data from the date of NHANES interview until follow-up (December 31, 2019). Multivariate Cox proportional hazard regression models were used to calculate the hazard ratios (HRs) and 95% confidence interval (CIs) of mortality. Of the adult participants with diabetes, 4963 (47.2%) were female. The median (interquartile range) BUN level of participants was 5 (3.93-6.43) mmol/L. After 86,601 person-years of follow-up, 2,441 deaths were documented. After adjusting for variables, the HRs of cardiovascular disease (CVD) and all-cause mortality in the highest BUN level group were 1.52 and 1.35, respectively, compared with those in the lowest BUN level group. With a one-unit increment in BUN levels, the HRs of all-cause and CVD mortality rates were 1.07 and 1.08, respectively. The results remained robust when several sensitivity and stratified analyses were performed. Moreover, BUN showed a nonlinear association with all-cause and CVD mortality. Their curves all showed that the inflection points were close to the BUN level of 5 mmol/L. BUN had a nonlinear association with all-cause and CVD mortality in patients with diabetes. The inflection point was at 5 mmol/L.

Higher cardiovascular disease risks in people living with HIV: A systematic review and meta-analysis.

The prognosis of AIDS after active antiretroviral therapy (ART) and the quality of life of people living with HIV (PLWH) are both affected by non-AIDS-related diseases such as cardiovascular disease (CVD). However, the specific risk ratios between PLWH and individuals negative for HIV are poorly understood. We aimed to systematically review and investigate the CVD risk factors associated with HIV. We searched PubMed, Embase, Web of Science, and Cochrane Library databases between 1 January 2015, and 12 May 2023 for articles reported the prevalence and risk factors of CVD such as hypertension, dyslipidaemia, coronary artery disease (CAD), and myocardial infarction (MI). Due to the high heterogeneity, we used a random-effects model to analyse the data. All statistical analyses were performed using Stata/MP 17.0 with 95% confidence intervals (CIs). We analysed 31 eligible studies including 312 913 PLWH. People living with HIV had higher risks of dyslipidaemia (hazard ratio (HR) = 1.53; 95% CI = 1.29, 1.82), CAD (HR = 1.37; 95% CI = 1.24, 1.51), and MI (HR = 1.47; 95% CI = 1.28, 1.68) compared to individuals without HIV. However, there were no significant differences in the prevalence of hypertension between groups (HR = 1.17; 95% CI = 0.97, 1.41). Subgroup analysis revealed that men with HIV, PLWH who smoked and the elderly PLWH had a high prevalence of CVD. Moreover, the disease prevalence patterns varied among regions. In the USA and Europe, for instance, some HRs for CVD were higher than in other regions. Active ART initiation after 2015 appears to have a lower risk of CVD (hypertension, hyperlipidaemia, CAD). All outcomes under analysis showed significant heterogeneity (I2>70%, P < 0.001), which the available study-level variables could only partially account for. People living with HIV had a higher CVD risk than the general population; thus, CVD prevention in PLWH requires further attention. Rapid initiation of ART may reduce the incidence of CVD in PLWH. For timely screening of CVD high-risk individuals and thorough disease management to prevent CVD, further studies are required to evaluate the risk factors for CVD among PLWH, such as age, region, etc. PROSPERO (CRD42021255508).

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.

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.

Loneliness, social isolation, and cardiovascular disease among nonveteran and veteran women

We examined the prospective associations of social isolation and loneliness with incident cardiovascular disease (CVD) among aging nonveteran and veteran women, and effect modification by veteran status. Participants with no history of myocardial infarction (MI), stroke, coronary heart disease (CHD), or coronary heart failure from the Women’s Health Initiative Extension Study II self-reported social isolation, loneliness, health behaviors, health status, and veteran status. CVD and CVD subevents were physician adjudicated. Hazard ratios (HR) and 95% confidence intervals (CI) for the Interquartile Range (IQR) in social isolation (IQR = 1) and loneliness (IQR=.33) were calculated using Cox proportional hazard models adjusting for sociodemographic, health behavior, and health status characteristics. Veteran status was tested as an effect modifier. Among 52,442 women (Mean age = 79 ± 6.1; veterans n = 1023; 89.2% non-Hispanic White), 3579 major CVD events occurred over an average 5.8 follow-up years. Compared to nonveterans, veteran women reported higher levels of social isolation (p < .01) and loneliness (p < .01). The CVD HR was 1.07 (95% CI, 1.04–1.10) for the IQR in social isolation and 1.03 (95% CI, 1.10–1.06) for the IQR in loneliness. The HR for the IQR in both social isolation and loneliness was 1.10 (95% CI, 1.05–1.15). Social isolation was associated with CHD (HR = 1.12; 95% CI, 1.03–1.21). The CHD HR for the IQR in social isolation was 1.12 (95% CI, 1.03–1.21). Associations did not differ by veteran status (all p-interactions > 0.08). Findings suggest that the adverse associations of social isolation and loneliness with CVD are similar among veteran and nonveteran women.

Sugar-sweetened or artificially-sweetened beverage consumption, physical activity, and risk of cardiovascular disease in adults: a prospective cohort study

BackgroundWhether physical activity could mitigate the adverse impacts of sugar-sweetened beverages (SSBs) or artificially sweetened beverages (ASBs) on incident cardiovascular disease (CVD) remains uncertain. ObjectivesThis study aimed to examine the independent and joint associations between SSB or ASB consumption and physical activity and risk of CVD, defined as fatal and nonfatal coronary artery disease and stroke, in adults from 2 United States-based prospective cohort studies. MethodsCox proportional hazards models were used to calculate hazard ratios (HRs) and 95% CIs between SSB or ASB intake and physical activity with incident CVD among 65,730 females in the Nurses’ Health Study (1980–2016) and 39,418 males in the Health Professional’s Follow-up Study (1986–2016), who were free from chronic diseases at baseline. SSBs and ASBs were assessed every 4-y and physical activity biannually. ResultsA total of 13,269 CVD events were ascertained during 3,001,213 person-years of follow-up. Compared with those who never/rarely consumed SSBs or ASBs, the HR for CVD for participants consuming ≥2 servings/d was 1.21 (95% CI: 1.12, 1.32; P-trend < 0.001) for SSBs and 1.03 (95% CI: 0.97, 1.09; P-trend = 0.06) for those consuming ≥2 servings/d of ASBs. The HR for CVD per 1 serving increment of SSB per day was 1.18 (95% CI: 1.10, 1.26) and 1.12 (95% CI: 1.04, 1.20) for participants meeting and not meeting physical activity guidelines (≥7.5 compared with <7.5 MET h/wk), respectively. Compared with participants who met physical activity guidelines and never/rarely consumed SSBs, the HR for CVD was 1.47 (95% CI: 1.37, 1.57) for participants not meeting physical activity guidelines and consuming ≥2 servings/wk of SSBs. No significant associations were observed for ASB when stratified by physical activity. ConclusionsHigher SSB intake was associated with CVD risk regardless of physical activity levels. These results support current recommendations to limit the intake of SSBs even for physically active individuals.

Genetic and Environmental Factors and Cardiovascular Disease Risk in Adolescents

Cardiovascular risk factors in youth have been associated with future cardiovascular disease (CVD), but conventional observational studies are vulnerable to genetic and environmental confounding. To examine the role of genetic and environmental factors shared by full siblings in the association of adolescent cardiovascular risk factors with future CVD. This is a nationwide cohort study with full sibling comparisons. All men who underwent mandatory military conscription examinations in Sweden between 1972 and 1995 were followed up until December 31, 2016. Data analysis was performed from May 1 to November 10, 2022. Body mass index (BMI), cardiorespiratory fitness, blood pressure, handgrip strength, and a combined risk z score in late adolescence. The primary outcome was fatal or nonfatal CVD, as recorded in the National Inpatient Register or the Cause of Death Register before 2017. A total of 1 138 833 men (mean [SD] age, 18.3 [0.8] years), of whom 463 995 were full brothers, were followed up for a median (IQR) of 32.1 (26.7-37.7) years, during which 48 606 experienced a CVD outcome (18 598 among full brothers). All risk factors were associated with CVD, but the effect of controlling for unobserved genetic and environmental factors shared by full siblings varied. In the sibling analysis, hazard ratios for CVD (top vs bottom decile) were 2.10 (95% CI, 1.90-2.32) for BMI, 0.77 (95% CI, 0.68-0.88) for cardiorespiratory fitness, 1.45 (95% CI, 1.32-1.60) for systolic blood pressure, 0.90 (95% CI, 0.82-0.99) for handgrip strength, and 2.19 (95% CI, 1.96-2.46) for the combined z score. The percentage attenuation in these hazard ratios in the sibling vs total cohort analysis ranged from 1.1% for handgrip strength to 40.0% for cardiorespiratory fitness. Consequently, in the sibling analysis, the difference in cumulative CVD incidence at age 60 years (top vs bottom decile) was 7.2% (95% CI, 5.9%-8.6%) for BMI and 1.8% (95% CI, 1.0%-2.5%) for cardiorespiratory fitness. Similarly, in the sibling analysis, hypothetically shifting everyone in the worst deciles of BMI to the middle decile would prevent 14.9% of CVD at age 60 years, whereas the corresponding number for cardiorespiratory fitness was 5.3%. In this Swedish national cohort study, cardiovascular risk factors in late adolescence, especially a high BMI, were important targets for CVD prevention, independently of unobserved genetic and environmental factors shared by full siblings. However, the role of adolescent cardiorespiratory fitness in CVD may have been overstated by conventional observational studies.

Abstract 16444: Gut Microbiota Derived Metabolite, Ursodeoxycholic Acid, and the Risk of Cardiovascular Disease

Introduction: Gut microbial metabolites have been recognized as risk factors for cardiometabolic diseases. The associations between plasma levels of the gut microbiota derived metabolites with cardiovascular disease (CVD) have not been comprehensively examined. Our objective was to investigate the association between 6 secondary bile acids including ursodeoxycholic acid and CVD. Ursodeoxycholic acid is used to dissolve cholesterol gall stones to treat cholestatic liver diseases. Hypothesis: Gut microbiota derived metabolites are associated with CVD. Methods: We performed a secondary analysis of data from the cross-sectional Metabolic Syndrome in Men (METSIM) cohort. Our study included 915 men aged 45-73 years (age = 54.94 ± 5.04 years, BMI = 27.31 ± 3.44), randomly selected from the population register of Kuopio, Eastern Finland, from 2005 to 2010. The associations between 6 secondary bile acids (ursodeoxycholic acid, glycoursodeoxycholate, glycolithocholate sulfate, taurocholenate sulfate, taurochenodeoxycholate, and glycocholenate sulfate) and the risk of CVD were investigated. Kaplan-Meier analysis with Cox proportional-hazards regressions were conducted for the time-to-event analysis to determine hazard ratios (HR) and 95% confidence intervals (CI) for CVD. Adjustments were made for traditional cardiovascular risk factors (age, systolic blood pressure, low-density and high-density lipoprotein cholesterol levels, triglyceride levels, smoking status, high-sensitivity C-reactive protein, estimated glomerular filtration rate, and alcohol consumption). Results: Participants were stratified into groups according to quartile metabolites levels and CVD. During a median follow-up of 16 years, n = 62 (7%) of patients experienced CVD. Only ursodeoxycholic acid was significantly associated with CVD risk. Cox regression analyses showed that the adjusted HR for CVD was higher in patients in quartile 4 (HR: 2.8, 95% [CI]: 1.35-4.6; p =0.008) than in quartile 1. The Kaplan-Meier analysis indicated that patients in quartile 4 had a significantly lower event-free survival (p = 0.037) compare to quartile 1. Conclusions: Ursodeoxycholic acid, a secondary bile acid, was positively associated with an increased risk of CVD.

Long-Term Cumulative Exposure to High γ-Glutamyl Transferase Levels and the Risk of Cardiovascular Disease: A Nationwide Population-Based Cohort Study.

Elevated γ-glutamyl transferase (γ-GTP) levels are associated with metabolic syndrome. We investigated the association of cumulative exposure to high γ-GTP with the risk of cardiovascular disease (CVD) in a large-scale population. Using nationally representative data from the Korean National Health Insurance system, 1,640,127 people with 4 years of consecutive γ-GTP measurements from 2009 to 2012 were included and followed up until the end of 2019. For each year of the study period, participants were grouped by the number of exposures to the highest γ-GTP quartile (0-4), and the sum of quartiles (0-12) was defined as cumulative γ-GTP exposure. The hazard ratio for CVD was evaluated using the Cox proportional hazards model. During the 6.4 years of follow-up, there were 15,980 cases (0.97%) of myocardial infarction (MI), 14,563 (0.89%) of stroke, 29,717 (1.81%) of CVD, and 25,916 (1.58%) of death. Persistent exposure to high γ-GTP levels was associated with higher risks of MI, stroke, CVD, and death than those without such exposure. The risks of MI, stroke, CVD, and mortality increased in a dose-dependent manner according to total cumulative γ-GTP (all P for trend <0.0001). Subjects younger than 65 years, with a body mass index <25 kg/m2, and without hypertension or fatty liver showed a stronger relationship between cumulative γ-GTP and the incidence of MI, CVD, and death. Cumulative γ-GTP elevation is associated with CVD. γ-GTP could be more widely used as an early marker of CVD risk, especially in individuals without traditional CVD risk factors.

Fatty Liver Index and mortality after myocardial infarction: A prospective analysis in the Alpha Omega Cohort.

Accumulating evidence shows that NAFLD might play a role in the etiology and progression of CVD, but little is known on the association of NAFLD and CVD mortality in patients with a history of a myocardial infarction (MI). Therefore, we studied the relationship of Fatty Liver Index (FLI), as indicator for non-alcoholic fatty liver disease (NAFLD), with 12-year risk of cardiovascular disease (CVD) and all-cause mortality in post-MI patients. We included 4165 Dutch patients from the Alpha Omega Cohort aged 60-80 years who had an MI ≤10 years prior to study enrolment. NAFLD was defined as FLI ≥60. Patients were followed for cause-specific mortality from enrolment (2002-2006) through December 2018. Hazard ratios for CVD and all-cause mortality were obtained by multivariable Cox regression using FLI <30 (indicating absence of NAFLD) as the reference. Baseline FLI as a continuous measure was studied with mortality using restricted cubic splines analyses. The median (IQR) FLI was 68 (48-84). Sixty percent of the patients had FLI ≥60, who were more likely to be male and more often had diabetes, high blood pressure, and high serum cholesterol levels. During 12 years of follow-up, 2042 deaths occurred of which 846 from CVD. Patients with NAFLD were at increased risk of CVD mortality (HR: 1.55 [1.19, 2.03]) and all-cause mortality (HR: 1.21 [1.03; 1.41]) compared to patients without NAFLD. Results remained consistent after excluding patients with obesity and diabetes. To conclude, the adverse association of FLI with CVD mortality was stronger in female than in male patients with conventional cut-off points. FLI ≥60, indicating NAFLD, was a predictor for CVD and all-cause mortality in post-MI patients, independent of other cardiometabolic risk factors. However, cut-off points might differ between male and female patients for predicting CVD mortality.

Sex-specific associations of γ-glutamyltransferase to HDL-cholesterol ratio and the incident risk of cardiovascular disease: three Korean longitudinal cohorts from different regions.

The combination of gamma-glutamyl transferase (GGT) and high-density lipoprotein cholesterol (HDL-C) (GGT/HDL-C) is a novel noninsulin-based marker for assessing the risk of nonalcoholic fatty liver disease and type 2 diabetes mellitus. However, whether the GGT/HDL-C ratio is related to the risk of incident cardiovascular disease (CVD) risk is not well known. Therefore, we aimed to investigate the longitudinal effect of GGT/HDL-C ratio on incident CVD risk in three large cohorts of Korean men and women. Data were assessed from 27,643 participants without CVD from the Korean Genome and Epidemiology Study (KoGES), Health Risk Assessment Study (HERAS), and Korea Health Insurance Review and Assessment (HIRA) (HERAS-HIRA) datasets. The participants were divided into four groups according to the GGT/HDL-C quartiles. We prospectively assessed hazard ratios (HRs) with 95% confidence intervals (CIs) for CVD using multivariate Cox proportional-hazard regression models over a 50-month period following the baseline survey. During the follow-up period, 949 patients (3.4%; 529 men and 420 women) developed CVD. The HRs of CVD for GGT/HDL-C quartiles 2-4 were 1.36 (95% CI, 0.91-2.02), 1.54 (95% CI, 1.05-2.26), and 1.66 (95% CI, 1.12-2.47) after adjusting for metabolic parameters in women, but GGT/HDL-C did not show a trend toward increases in incident CVD in men. Regional discrepancies were evident in the results; the increase in HR in the metropolitan hospital cohort was more pronounced than that in the urban cohort, and the risk was not increased in the rural cohort. GGT/HDL-C ratio may be a useful predictive marker for CVD in women. Furthermore, the prevalence of CVD was strongly correlated with the GGT/HDL-C ratio in metropolitan areas, and this correlation was more significant than that observed with GGT or HDL-C in isolation.

Determining the association of rurality and cardiovascular disease among prostate cancer survivors

PurposeRural disparities in prostate cancer survivorship and cardiovascular disease remain. Prostate cancer treatment also contributes to worse cardiovascular disease outcomes. Our objective was to determine whether rural-urban differences in cardiovascular outcomes contribute to disparities in prostate cancer survivorship. Materials and MethodsData were collected from the Utah Population Database. Rural and urban prostate cancer survivors were matched by diagnosis year and age. Cox proportional hazards models were used to estimate hazard ratios for cardiovascular disease (levels 1–3) based on rural-urban classification, while controlling for demographic and socioeconomic characteristics. We identified 3,379 rural and 16,253 urban prostate cancer survivors with a median follow-up of 9.3 years. ResultsResults revealed that rural survivors had a lower risk of hypertension (HR 0.90), diseases of arteries (HR 0.92), and veins (HR 0.92) but a higher risk of congestive heart failure (HR 1.17). Interactions between level 2 cardiovascular diseases and rural/urban status, showed that diseases of the heart had a distinct between-group relationship for all-cause (P = 0.005) and cancer-specific mortality (P = 0.008). ConclusionsThis study revealed complex relationships between rural-urban status, cardiovascular disease, and prostate cancer. Rural survivors were less likely to be diagnosed with screen-detected cardiovascular disease but more likely to have heart failure. Further, the relationship between cardiovascular disease and survival was different between rural and urban survivors. It may be that our findings underscore differences in healthcare access where rural patients are less likely to be screened for preventable cardiovascular disease and have worse outcomes when they have a major cardiovascular event.

Examining the Relationship Between Multilevel Resilience Resources and Cardiovascular Disease Incidence, Overall and by Psychosocial Risks, Among Participants in the Jackson Heart Study, the Multi-Ethnic Study of Atherosclerosis, and the Mediators of Atherosclerosis in South Asians Living in America (MASALA) Study.

We examined relationships between resilience resources (optimism, social support, and neighborhood social cohesion) and cardiovascular disease (CVD) incidence and assessed potential effect-measure modification by psychosocial risk factors (e.g., stress, depression) among adults without CVD in 3 cohort studies (2000-2018): the Jackson Heart Study, the Multi-Ethnic Study of Atherosclerosis, and the Mediators of Atherosclerosis in South Asians Living in America (MASALA) Study. We fitted adjusted Cox models accounting for within-neighborhood clustering while censoring at dropout or non-CVD death. We assessed for effect-measure modification by psychosocial risks. In secondary analyses, we estimated standardized risk ratios using inverse-probability-weighted Aalen-Johansen estimators to account for confounding, dropout, and competing risks (non-CVD deaths) and obtained 95% confidence intervals (CIs) using cluster bootstrapping. For high and medium (versus low) optimism (n=6,243), adjusted hazard ratios (HRs) for incident CVD were 0.94 (95% CI: 0.78, 1.13) and 0.90 (95% CI: 0.75, 1.07), respectively. Corresponding HRs were 0.88 (95% CI: 0.74, 1.04) and 0.92 (95% CI: 0.79, 1.06) for social support (n=7,729) and 1.10 (95% CI: 0.94, 1.29) and 0.99 (95% CI: 0.85, 1.16) for social cohesion (n=7,557), respectively. Some psychosocial risks modified CVD HRs. Secondary analyses yielded similar findings. For optimism and social support, an inverse relationship was frequently most compatible with the data, but a positive relationship was also compatible. For neighborhood social cohesion, positive and null relationships were most compatible. Thus, specific resilience resources may be potential intervention targets, especially among certain subgroups.

1381-P: Effect of Dietary Potassium Intake and Its Interaction with Sodium Intake on Risk of Developing Cardiovascular Disease (CVD) in Persons with Type 2 Diabetes (T2D)—Japan Diabetes Complication and Its Prevention Prospective Study (JDCP Study)

Many guidelines recommend increased potassium intake. However, the relationship between dietary potassium intake and incidence of CVD in persons with T2D has not been explored, nor is it known if this relationship varies with sodium intake in such persons. Therefore, we investigated these relationships as part of the JDCP study, a nationwide study launched in 2007. A total of 1477 persons with T2D aged 40-75 years completed a brief self-administered Diet History Questionnaire at baseline, and resultant data were analyzed. Primary outcome was the 7-year risk of a CVD event. Hazard ratios (HRs) for CVD according to tertiles of dietary potassium and sodium intake were estimated by Cox regression adjusted for confounders in addition to a stratified analysis of tertiles of sodium intake. Mean daily potassium and sodium intakes in tertiles 1 to 3 were 1.9, 2.6, and 3.5 g and 3.3, 4.2, and 5.3 g, respectively. HbA1c, BMI, triglycerides, and blood pressure were well controlled. No significant associations between potassium and sodium intakes and incidence of CVD were shown for the second and third tertiles relative to the first tertile (potassium: 0.64 [95% CI, 0.34-1.23] and 0.59 [0.28-1.25]; sodium: 1.02 [0.51-2.04] and 1.15 [0.58-2.30]). In the stratified analysis of tertiles of sodium intake, in the high sodium intake groups (T2 and T3) HRs for CVD in the high potassium intake group were significantly lower compared to the low potassium intake group (T2: 0.40 [0.12-1.35] and 0.06 [0.01-0.69]; T3: 0.23 [0.07-0.82] and 0.26 [0.07-0.88]). Associations of potassium intake with CVD in those with low sodium intake (T1) were not significant. Findings suggested that high potassium intake under high sodium intake is associated with a deceased incidence of CVD in persons with T2D although potassium intake under low sodium intake was not associated with incident CVD. Disclosure C.Horikawa: None. H.Shimano: None. J.Satoh: None. Y.Hayashino: Advisory Panel; Novo Nordisk A/S, Ono Pharmaceutical Co., Ltd., Speaker's Bureau; Boehringer Ingelheim Japan, Inc., Sumitomo Dainippon Pharma Co., Ltd., Santen, Daiichi Sankyo, Kowa Company, Ltd. N.Tajima: None. R.Nishimura: Speaker's Bureau; Sanofi K.K., Medicure Inc., Boehringer Ingelheim Inc., Takeda Pharmaceutical Company Limited, Kissei Pharmaceutical Co., Ltd., Novartis Pharma K.K., Eli Lilly Japan K.K., Novo Nordisk, Merck &amp; Co., Inc., Abbott Japan Co., Ltd., Astellas Pharma Inc., Teijin Pharma Limited, Taisho Pharmaceutical Holdings Co., Ltd., Ono Pharmaceutical Co., Ltd., AstraZeneca. Y.Yamasaki: None. H.Sone: Research Support; Novo Nordisk, Astellas Pharma Inc., Kyowa Kirin Co., Ltd., Taisho Pharmaceutical Holdings Co., Ltd., Ono Pharmaceutical Co., Ltd., Eisai Co., Ltd., Takeda Pharmaceutical Co., Ltd. Jdcp study group: n/a. M.Takahara: None. N.Katakami: Speaker's Bureau; Abbott Japan Co., Ltd., Daiichi Sankyo, MSD, Mitsubishi Tanabe Pharma Corporation, Kowa Company, Ltd., Ono Pharmaceutical Co., Ltd., Novo Nordisk, Sumitomo Dainippon Pharma Co., Ltd., Bayer Inc., Lilly, Teijin Pharma Limited, Kyowa Kirin Co., Ltd., Boehringer Ingelheim Japan, Inc., Sanofi. Y.Takeda: None. M.Takeuchi: None. K.Fujihara: None. H.Suzuki: None. K.Tsuda: None. N.Yoshioka: None.

Association of Normal Serum Uric Acid Level and Cardiovascular Disease in People Without Risk Factors for Cardiac Diseases in China.

Background Healthy individuals with normal level of serum uric acid (SUA) may not be truly at the lowest risk of cardiovascular disease (CVD). This study aimed to assess the association of SUA levels with CVD and its subtypes in people without CVD risk factors and determine a suitable target of SUA to prevent CVD. Methods and Results We enrolled 25 284 participants who were free of CVD, absent of CVD risk factors, and with an SUA level between 180 and 359 μmol/L (3-6 mg/dL) at baseline from the Kailuan study. Cox proportional hazards models were applied to calculated adjusted hazard ratio (HR) and 95% CI for the risk of CVD and its subtypes. During a median follow-up of 12.97 years (interquartile range, 12.68-13.16 years), we identified 1007 cases of CVD. There was an increase in the risk of incident CVD with increasing SUA levels (Ptrend=0.0011). Compared with participants with SUA levels of 180 to 239 μmol/L (3-4 mg/dL), the HR of CVD was 1.12 (95% CI, 0.96-1.31) and 1.28 (95% CI, 1.08-1.52) for SUA levels of 240 to 299 μmol/L (4-5 mg/dL) and 300 to 359 μmol/L (5-6 mg/dL), respectively. A multivariable-adjusted spline regression model showed a J-shaped association between SUA and the risk of CVD. Similar results were observed for stroke and myocardial infarction. Conclusions The risk of incident CVD increased with elevating SUA levels among individuals without hyperuricemia or other traditional CVD risk factors. These findings highlighted the importance of primordial prevention for SUA level increase along with other traditional CVD risk factors.

Abstract P673: Intima-Media Thickness at the Near or Far Wall of the Common-Carotid-Artery in Cardiovascular Risk Assessment

Background: Current guidelines recommend measuring carotid intima-media thickness (IMT) at the far wall of the common-carotid-artery (CCA). Objectives: To reliably quantify associations of near vs. far wall CCA-IMT with cardiovascular risk and their added predictive values. Methods: We analyzed participant-level data of 16 prospective studies from the Proof-ATHERO consortium. We pooled study-specific hazard ratios for cardiovascular disease (CVD, defined as coronary heart disease or stroke) using random-effects meta-analysis. Results: Individual records were available for 41,941 participants (mean age 61 years [SD=11]; 53% female; 16% with history of CVD; 10,423 CVD events, median follow-up 9.3 years). Mean baseline values of near and far wall CCA-IMT were 0.83 (SD=0.28) and 0.82 (SD=0.27) mm, differed by a mean of 0.02 mm (95% limits of agreement: -0.40 to 0.43) and were moderately correlated (r=0.44; 95% CI: 0.39-0.49). Near and far wall CCA-IMT were both approximately linearly associated with CVD risk. The respective hazard ratios per SD higher value were 1.18 (95% CI: 1.14-1.22; I 2 =30.7%) and 1.20 (1.18-1.23; I 2 =5.3%) when adjusted for age, sex, and history of CVD, and 1.09 (1.07-1.12; I 2 =8.4%) and 1.14 (1.12-1.16; I 2 =1.3%) in a multivariable adjusted model (all P&lt;0.001). Assessing CCA-IMT at both walls provided a greater C-index improvement than assessing CCA-IMT at one wall only (+0.0046 vs. +0.0023 for near [P&lt;0.001] or +0.0037 for far wall [P=0.006]). Conclusions: The associations of near and far wall CCA-IMT with incident CVD were positive, approximately linear, and similarly strong. Improvement in risk discrimination was highest when CCA-IMT was measured at both walls.

The association of dietary resistance starch intake with all-cause and cause-specific mortality.

Several studies have estimated daily intake of resistant starch (RS), but no studies have investigated the relationship of RS intake with mortality. We aimed to examine associations between RS intake and all-cause and cause-specific mortality. Data from US National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018 with 24-h dietary recall data was used in current study. The main exposure in this study was RS intake, and the main outcome was the mortality status of participants until December 31, 2019. The multivariable Cox proportional hazards regression models were developed to evaluate the hazard ratios (HRs) and 95% confidence interval (95% CI) of cardiovascular disease (CVD), cancer, and all-cause mortality associated with RS intake. A total of 42,586 US adults [mean (SD) age, 46.91 (16.88) years; 22,328 (52.43%) female] were included in the present analysis. During the 454,252 person-years of follow-up, 7,043 all-cause deaths occurred, including 1,809 deaths from CVD and 1,574 deaths from cancer. The multivariable-adjusted HRs for CVD, cancer, and all-cause mortality per quintile increase in RS intake were 1 (95%CI, 0.97-1.04), 0.96 (95%CI, 0.93-1), and 0.96 (95%CI, 0.95-0.98), respectively. The associations remained similar in the subgroup and sensitivity analyses. Higher RS intake is significantly associated with lower cancer and all-cause mortality, but not significantly with CVD mortality. Future studies focusing on other populations with different food sources of RS and RS subtypes are needed to access the dose-response relationship and to improve global dietary recommendations.

Progression of Chronic Kidney Disease Risk Categories and Risk of Cardiovascular Disease and Total Mortality: Coronary Artery Risk Development in Young Adults Cohort.

Background Previous studies of worsening chronic kidney disease (CKD) based on declining estimated glomerular filtration rate (eGFR) or increasing urine albumin-creatinine ratio (UACR) are limited to later middle-age and older adults. We examined associations of CKD progression and incident cardiovascular disease (CVD) and mortality in younger adults. Methods and Results We studied 4382 adults in CARDIA (Coronary Artery Risk Development in Young Adults) initially aged 27 to 41 years and prospectively over 20 years. Five-year transition probabilities across CKD risk categories were based on eGFR and UACR measured at each exam. Proportional hazards models predicted incident CVD and all-cause mortality by time-varying CKD risk category, adjusting for demographics and CVD risk factors. Progression of CKD risk categories over 20 years occurred in 28.7% (1256/4382) of participants, driven by increases in UACR, but including 5.8% (n=255) with eGFR<60 mL/min per 1.73 m2 or UACR ≥300 mg/g. Compared with eGFR ≥60 and UACR <10, demographic and smoking-adjusted hazard ratios for CVD were 1.62 (95% CI, 1.21-2.18) for low CKD risk (eGFR ≥60 with UACR 10-29) and 13.65 (95% CI, 7.52-24.79) for very high CKD risk (eGFR <30 or eGFR 30-44 with UACR 30-299; or eGFR 30-59 with UACR ≥300). Corresponding hazard ratios for all-cause mortality were 1.42 (95% CI, 1.08-1.88) and 14.75 (95% CI, 9.97-21.82). Although CVD associations were attenuated after adjustment for mediating CVD risk factors, all-cause mortality associations remained statistically significant. Conclusions Among young to middle-aged adults, progression to higher CKD risk category was common. Routine monitoring eGFR and UACR holds promise for prevention of CVD and total mortality.

Association between sedentary behavior, physical activity, and cardiovascular disease-related outcomes in adults-A meta-analysis and systematic review.

Sedentary behavior (SB) and physical activity (PA) are modifiable risk factors for cardiovascular disease (CVD); however, previous research on the effects of PA and SB on CVD has been relatively homogeneous. Our study investigated the association between PA, SB, and CVD-related outcomes. A comprehensive search strategy was conducted in the MEDLINE, Embase, Cochrane Library, and Web of Science databases from their inception to September 2022. We identified eligible studies according to PICOS: the populations comprised healthy adults, the interventions or exposures were PA or SB, the outcomes were CVD-related outcomes, and the study designs were randomized controlled trials (RCTs) and longitudinal studies (LS). Outcomes were pooled using fixed or random effects models, and the quality of individual studies was assessed by the Cochrane Risk of Bias Instrument and the Newcastle Ottawa Scale. A total of 148 RCTs and 36 LS were included, comprising a total of 75,075 participants. The study quality was rated as low to moderate. We found an increased hazard ratio (HR) for CVD in the population with SB (HR = 1.34; 95% confidence interval [CI]: 1.26 to 1.43; I2 = 52.3%; Pheterogeneity < 0.001, random model) and a decreased HR for CVD in those who performed long-term PA (HR = 0.71; 95% CI: 0.66 to 0.77; I2 = 78.0%, Pheterogeneity < 0.001, random model). Long-term PA improved the lipid profiles in healthy adults; participants in this group exhibited increased high-density lipoprotein (weighted mean difference [WMD] = 2.38; 95% CI: 1.00 to 3.76; I2 = 84.7%; Pheterogeneity < 0.001, random model), decreased triglycerides (WMD = -7.27; 95% CI: -9.68 to -4.87; I2 = 0%, Pheterogeneity = 0.670, fixed model), and lower total-cholesterol (WMD = -6.84; 95% CI: -9.15 to -4.52; I2 = 38.4%, Pheterogeneity < 0.001, random model). Long-term SB increases the risk of CVD in healthy adults, whereas PA reduces the risk of CVD and improves indicators associated with CVD. However, the ability of PA to improve blood lipids appeared to be limited. The detailed association of SB and PA on CVD needs to be further investigated in the future.

Effect of Chronic Kidney Disease or Anemia or Both on Cardiovascular Mortality in a 25-Year Follow-Up Study of Japanese General Population (From NIPPON DATA90)

The relation between chronic kidney disease (CKD) and cardiovascular disease (CVD) in the general population is well elucidated. In patients with CKD, anemia is associated with adverse outcomes. However, the effects of CKD and anemia on CVD in the general population remains poorly explored, especially in Asian populations. This study aimed to investigate the effect of CKD and/or anemia on CVD mortality in a long-term cohort study involving Japanese community dwellers. We assessed 7,339 participants (aged ≥30 years) with no CVD history. These participants were divided into 4 categories according to their CKD (estimated glomerular filtration rate <60 or urine protein >1+ by dipstick qualitative test) and/or anemia (hemoglobin: <13 g/100 ml [men], <12 g/100 ml [women]) statuses. For each category, we calculated the hazard ratios (HRs) of CVD mortality by using the Cox proportional hazards model after adjusting for age, body mass index, hypertension, diabetes, dyslipidemia, smoking, and alcohol drinking. Within 25 years of follow-up, 637 participants died because of CVD. The HRs of CVD in patients with CKD only, anemia only, and both were 1.27, 1.59, and 2.60 (95% confidence intervals [CI] 1.06 to 1.53, 1.34 to 1.90, and 1.80 to 3.76) in men and 1.42, 1.08, and 2.00 (95% CI 1.19 to 1.69, 0.99 to 1.18, and 1.54 to 2.60) in women, respectively. In conclusion, CKD with anemia is associated with an increased risk for CVD mortality in a general population in Japan.