Cardiovascular Disease Subtypes Research Articles

Fibroblast Growth Factor 23 and Incident Cardiovascular Disease and Mortality in Middle-Aged Adults.

BackgroundHigher circulating fibroblast growth factor 23 (FGF23) associates with greater risk of cardiovascular disease (CVD) and mortality in older adults. The association of FGF23 with cardiovascular outcomes in younger populations has been incompletely explored.Methods and ResultsWe measured C‐terminal FGF23 (cFGF23) and intact FGF23 (iFGF23) in 3151 middle‐aged adults (mean age, 45±4) who participated in the year 20 examination of the CARDIA (Coronary Artery Risk Development in Young Adults) study. We used separate Cox proportional hazards models to examine the associations of cFGF23 and iFGF23 with incident CVD and mortality, adjusting models sequentially for sociodemographic, clinical, and laboratory factors. A total of 157 incident CVD events and 135 deaths occurred over a median 7.6 years of follow‐up (interquartile range, 4.1–9.9). In fully adjusted models, there were no statistically significant associations of FGF23 with incident CVD events (hazard ratio per doubling of cFGF23: 1.14, 95%CI 0.97,1.34; iFGF23: 0.76, 95%CI 0.57,1.02) or all‐cause mortality (hazard ratio per doubling of cFGF23, 1.17; 95% CI, 1.00–1.38; iFGF23, 0.86; 95% CI, 0.64–1.17). In analyses stratified by CVD subtypes, higher cFGF23 was associated with greater risk of heart failure hospitalization (hazard ratio per doubling of cFGF23, 1.52; 95% CI, 1.18–1.96) but not coronary heart disease or stroke, whereas iFGF23 was not associated with CVD subtypes in any model.ConclusionsIn middle‐aged adults with few comorbidities, higher cFGF23 and iFGF23 were not independently associated with greater risk of CVD events or death. Higher cFGF23 was independently associated with greater risk of heart failure hospitalization.

Dynamic Changes of Metabolic Syndrome Alter the Risks of Cardiovascular Diseases and All-Cause Mortality: Evidence From a Prospective Cohort Study.

Background: Metabolic syndrome (MetS) at baseline increases the risks of cardiovascular diseases (CVD) and all-cause mortality. However, MetS status is changeable during follow-up. The associations of dynamic changes of MetS with CVD and all-cause mortality remain unclear.Methods: Thirty-one thousand four hundred eighty-one eligible subjects were included from the Kailuan cohort. Dynamic changes of MetS were divided into four patterns as MetS-free, MetS-developed, MetS-recovery and MetS-stable. The outcomes were CVD, all-cause mortality, and the subtypes of CVD as myocardial infarction (MI), stroke and heart failure. Multiple Cox regression models were used to calculate the adjusted hazard ratios (HRs) and confidence intervals (95% CIs).Results: Altered risks of CVD, the subtypes of CVD, and all-cause mortality were observed among different dynamic patterns of MetS. Compared with the MetS-free group, MetS-developed group increased the risks of CVD (HR = 1.78, 95% CI = 1.51–2.11), MI (HR = 1.54, 95% CI = 1.01–2.34), stroke (HR = 1.78, 95% CI = 1.45–2.18), and heart failure (HR = 1.63, 95% CI = 1.11–2.39). MetS-recovery group decreased these risks with the HRs of 0.59 (95% CI = 0.48–0.72) for CVD, 0.62 (95% CI = 0.41–0.96) for MI, 0.59 (95% CI = 0.46–0.75) for stroke, and 0.56 (95% CI = 0.34–0.91) for heart failure compared with the MetS-stable group. However, the increased risk in the MetS-developed group and the decreased risk in the MetS-recovery group were not significant for all-cause mortality. When stratified by the onset age of MetS status change, early development of MetS (<50 years) had higher risks of CVD (HR = 2.20, 95% CI = 1.58–3.05), MI (HR = 2.35, 95% CI = 1.00–5.50), stroke (HR = 2.05, 95% CI = 1.38–3.05), heart failure (HR = 2.63, 95% CI = 1.15–6.04), and all-cause mortality (HR = 1.61, 95% CI = 1.13–2.30) than late development (≥50 years). Early recovery of MetS had lower risks with the HRs of 0.38 (95% CI = 0.24–0.59) for CVD, 0.43 (95% CI = 0.18–1.06) for MI, 0.37 (95% CI = 0.21–0.64) for stroke, 0.30 (95% CI = 0.09–1.04) for heart failure, and 0.68 (95% CI = 0.43–1.06) for all-cause mortality than late recovery.Conclusion: Dynamic changes of MetS altered the risks of CVD and all-cause mortality, especially in individuals with an early onset age. These findings highlight the importance of dynamic changes of MetS and onset age on the prevention and control for CVD.

Human Cytomegalovirus and Risk of Incident Cardiovascular Disease in United Kingdom Biobank.

BackgroundPrevious studies have yielded conflicting results on the association between human cytomegalovirus (HCMV) and cardiovascular disease (CVD). This study examined associations between HCMV and incident CVD, ischaemic heart disease (IHD) and stroke.MethodsThis study included 8531 women and men of predominantly white ethnic background, aged 40–69 without prevalent CVD from the population-based UK Biobank study, recruited between 2006–2010 with HCMV antibody levels measured. CVD was ascertained via linkage to health administrative records collected until 2020. Multivariate Cox proportional-hazards models were used to determine associations between HCMV seropositivity and incident CVD, IHD and stroke. HCMV seropositive antibody levels in tertiles were used to assess dose-response associations.ResultsOver a mean follow-up period of 10.2 years, HCMV seropositivity was not significantly associated with CVD (Cases = 626, Hazard Ratio [HR] =1.01, 95% confidence interval [CI], .86–1.20), IHD (Cases = 539, HR=1.03, 95% CI, .87–1.24) or stroke (Cases = 144, HR = 0.96, 95% CI, .68–1.36). There was no evidence of dose-response associations with any outcome.ConclusionsWe found no significant association between HCMV seropositivity and risk of CVD, IHD or stroke. Further research within understudied populations, such as those of non-white ethnicity, and CVD subtypes is warranted.

Sleep and physical activity in relation to all-cause, cardiovascular disease and cancer mortality risk

ObjectivesAlthough both physical inactivity and poor sleep are deleteriously associated with mortality, the joint effects of these two behaviours remain unknown. This study aimed to investigate the joint association of...

Association of Lipoprotein (a) variants with risk of cardiovascular disease: a Mendelian randomization study

BackgroundThere is a well-documented empirical relationship between lipoprotein (a) [Lp(a)] and cardiovascular disease (CVD); however, causal evidence, especially from the Chinese population, is lacking. Therefore, this study aims to estimate the causal association between variants in genes affecting Lp(a) concentrations and CVD in people of Han Chinese ethnicity.MethodsTwo-sample Mendelian randomization analysis was used to assess the causal effect of Lp(a) concentrations on the risk of CVD. Summary statistics for Lp(a) variants were obtained from 1256 individuals in the Cohort Study on Chronic Disease of Communities Natural Population in Beijing, Tianjin and Hebei. Data on associations between single-nucleotide polymorphisms (SNPs) and CVD were obtained from recently published genome-wide association studies.ResultsThirteen SNPs associated with Lp(a) levels in the Han Chinese population were used as instrumental variables. Genetically elevated Lp(a) was inversely associated with the risk of atrial fibrillation [odds ratio (OR), 0.94; 95% confidence interval (95%CI), 0.901–0.987; P = 0.012)], the risk of arrhythmia (OR, 0.96; 95%CI, 0.941–0.990; P = 0.005), the left ventricular mass index (OR, 0.97; 95%CI, 0.949–1.000; P = 0.048), and the left ventricular internal dimension in diastole (OR, 0.97; 95%CI, 0.950–0.997; P = 0.028) according to the inverse-variance weighted method. No significant association was observed for congestive heart failure (OR, 0.99; 95% CI, 0.950–1.038; P = 0.766), ischemic stroke (OR, 1.01; 95%CI, 0.981–1.046; P = 0.422), and left ventricular internal dimension in systole (OR, 0.98; 95%CI, 0.960–1.009; P = 0.214).ConclusionsThis study provided evidence that genetically elevated Lp(a) was inversely associated with atrial fibrillation, arrhythmia, the left ventricular mass index and the left ventricular internal dimension in diastole, but not with congestive heart failure, ischemic stroke, and the left ventricular internal dimension in systole in the Han Chinese population. Further research is needed to identify the mechanism underlying these results and determine whether genetically elevated Lp(a) increases the risk of coronary heart disease or other CVD subtypes.

Recent trends in cardiovascular disease deaths: a state specific perspective

BackgroundThe rate of decline in cardiovascular disease (CVD) mortality has lessened nationally. How these findings apply to specific states or causes of CVD deaths is not known. Examining these trends at the state level is important to plan local interventions.MethodsWe analyzed CVD mortality trends in Minnesota (MN) using the U.S. Centers for Disease Control and Prevention (CDC) Wide-ranging ONline Data for Epidemiologic Research (WONDER). Trends were analyzed by age, sex, type of CVD and location of death.ResultsCVD mortality rates in MN declined in 2000–2009 and then leveled off in 2010–2018, paralleling national rates. Age- and sex-adjusted CVD mortality decreased by 3.7% per year in 2000–2009 (average annual percent changes [AAPC]: -3.7; 95% CI: − 4.8, − 2.6) with no change observed in 2010–2018. Those aged 65–84 years had the most rapid early decline in CVD mortality (AAPC: -5.9, 95% CI: − 6.2, − 5.7) and had less improvement in 2010–2018 (AAPC: -1.8, 95% CI: − 2.2, − 1.5), and the younger age group (25–64 years) now experiences the most adverse trends (AAPC: 1.2, 95% CI: 0.7–1.8). Coronary heart disease (CHD) and cerebrovascular disease had the largest relative decreases in mortality in 2000–2009 (CHD AAPC: -5.2; 95% CI: − 6.5,-3.9; cerebrovascular disease AAPC: -4.4, 95% CI: − 5.2, − 3.6) with no change 2010–2018. Heart failure (HF)/cardiomyopathy followed similar trends with a 2.5% decrease (AAPC 95% CI: − 3.5, − 1.5) per year in 2000–2009 and no change in 2010–2018. Deaths from other CVD also decreased in the early time period (AAPC: -1.6, 95% CI: − 2.7, − 0.5) but increased in 2010–2018 (AAPC: 1.9, 95% CI: 0.5, 3.3). In- and out-of-hospital death rates improved in 2000–2009 with a slowing in improvement for in-hospital death and no further improvement for out-of-hospital death in 2010–2018.ConclusionConcerning CVD mortality trends occurred in MN. In the most recent decade (2010–2018) mortality from all CVD subtypes plateaued or even increased. CVD mortality among the younger age groups increased as well. These data are congruent with adverse national trends supporting their generalizability. These adverse trends underscore the urgent need for CVD prevention and treatment, as well as continued surveillance to assess progress at the state and national level.

High Burden of Subclinical and Cardiovascular Disease Risk in Adults With Metabolically Healthy Obesity: The Atherosclerosis Risk in Communities (ARIC) Study.

It is controversial whether adults who are obese but "metabolically healthy" have cardiovascular disease (CVD) risk comparable with that of normal-weight adults. High-sensitivity cardiac troponin T (hs-cTnT), a biomarker of myocardial damage, is useful in characterizing subclinical CVD. We categorized obesity phenotypes and studied their associations with subclinical and clinical CVD and CVD subtypes, including heart failure (HF). We conducted cross-sectional and prospective analyses of 9,477 adults in the Atherosclerosis Risk in Communities (ARIC) study. We used the Adult Treatment Panel III criteria and BMI to define obesity phenotypes as follows: metabolically healthy normal weight, metabolically healthy overweight, metabolically healthy obese, metabolically unhealthy normal weight, metabolically unhealthy overweight, and metabolically unhealthy obese. At baseline (1990-1992), mean age was 56 years, 56% were female, 23% were Black, and 25% had detectable hs-cTnT (≥6 ng/L). Over a median of 17 years of follow-up, there were 2,603 clinical CVD events. Those with the metabolically healthy obese (hazard ratio [HR] 1.38, 95% CI 1.15-1.67), metabolically unhealthy normal weight (HR 1.51, 95% CI 1.30-1.76), metabolically unhealthy overweight (HR 1.60, 95% CI 1.41-1.82), and metabolically unhealthy obese (HR 2.14, 95% CI 1.88-2.44) phenotypes had higher CVD risks in comparison with metabolically healthy normal weight. Detectable hs-cTnT (≥6 ng/L) was associated with higher CVD risk, even among metabolically healthy normal-weight adults. Metabolically healthy obese adults had higher HF risk (HR 1.65, 95% CI 1.30-2.09) in comparison with metabolically healthy normal weight. The metabolically healthy obese phenotype was associated with excess burden of clinical CVD, primarily driven by an excess risk of HF. hs-cTnT was useful in stratifying CVD risk across all obesity phenotypes, even among obese individuals who appear otherwise metabolically healthy.

Cardiovascular disease subtypes, physical disability and workforce participation: A cross-sectional study of 163,562 middle-aged Australians

Workforce participation is reduced among people with cardiovascular disease (CVD). However, detailed quantitative evidence on this is limited. We examined the relationship of CVD to workforce participation in older working-age people, by CVD subtype, within population subgroups and considering the role of physical disability. Questionnaire data (2006-2009) for participants aged 45-64 years (n = 163,562) from the population-based 45 and Up Study (n = 267,153) were linked to hospitalisation data through the Centre for Health Record Linkage. Prior CVD was from self-report or hospitalisation. Modified Poisson regression estimated adjusted prevalence ratios (PRs) for non-participation in the workforce in people with versus without CVD, adjusting for sociodemographic factors. There were 19,161 participants with CVD and 144,401 without. Compared to people without CVD, workforce non-participation was greater for those with CVD (40.0% vs 23.5%, PR = 1.36, 95%CI = 1.33-1.39). The outcome varied by CVD subtype: myocardial infarction (PR = 1.46, 95%CI = 1.36-1.55); cerebrovascular disease (PR = 1.92, 95%CI = 1.80-2.06); heart failure (PR = 1.83, 95%CI = 1.68-1.98) and peripheral vascular disease (PR = 1.76, 95%CI = 1.65-1.88). Workforce non-participation in those with CVD versus those without was at least 21% higher in all population subgroups examined, with PRs ranging from 1.75 (95%CI = 1.65-1.85) in people aged 50-55 years to 1.21 (95%CI = 1.19-1.24) among those aged 60-64. Compared to people with neither CVD nor physical functioning limitations, those with physical functional limitations were around three times as likely to be out of the workforce regardless of CVD diagnosis; participants with CVD but without physical functional limitations were 13% more likely to be out of the workforce (PR = 1.13, 95%CI = 1.07-1.20). While many people with CVD participate in the workforce, participation is substantially lower, especially for people with cerebrovascular disease, than for people without CVD, highlighting priority areas for research and support, particularly for people experiencing physical functioning limitations.

Time-to-pregnancy and risk of cardiovascular disease among men and women

A few studies indicate that women with prolonged time-to-pregnancy (TTP) have an increased risk of cardiovascular disease (CVD). This has not been studied in men. We evaluated CVD risk by self-reported TTP among parous women (n = 64,064) and men (n = 50,533) participating in the Norwegian Mother, Father and Child Cohort Study. TTP was categorized as 0–3 (reference), 4–12 and > 12 months. CVD diagnosed between 2008 and 2017 were available from the national patient and general practitioner databases. Risk of CVD by TTP was estimated using Cox regression adjusting for baseline age, education, BMI, smoking, diabetes, and number of offspring in both sexes, and history of endometriosis, ovarian cysts, preterm birth and pre-eclampsia for women. Mean age was 33 for women and 35 for men at baseline (years). The rate of any CVD was 24 per 1000 person years among women and 22 per 1000 person years among men. Longer TTP was associated with increased rate of CVD among women, with adjusted hazard ratios (HRs) of 1.07 (95% CI: 1.03, 1.09) for TTP 4–12 months and 1.14 (1.08, 1.20) for TTP > 12 months. Among men, respective HRs for CVD were 1.06 (1.00, 1.10) for TTP 4–12 months and 1.07 (1.01, 1.14) for TTP > 12 months. We observed sex-differences in the relationship with CVD subtypes but none were statistically significant. In conclusion, both men and women with a prolonged TTP had a small increased risk of CVD, clinical significance of which is unclear. Further studies are necessary to investigate in detail what underlying causes of prolonged TTP might be reflected in the increased risk of CVD. Longer follow-up is required to confirm these preliminary findings.

Socioeconomic position and cardiovascular mortality in 63 million adults from Brazil

BackgroundIt has been suggested that cardiovascular disease exhibits a ‘social cross-over’, from greater risk in higher socioeconomic groups to lower socioeconomic groups, on economic development, but robust evidence is lacking....

Association of urinary caffeine and caffeine metabolites with cardiovascular disease risk in adults

ObjectivesStudies have shown that the consumption of a moderate amount of caffeine is associated with a reduced risk of cardiovascular disease (CVD) and may even be protective against CVD. The purpose of the current study was to evaluate the association between urinary caffeine and its related metabolites and CVD risk in a national representative sample of US adults. MethodsWe analyzed cross-sectional data from the US National Health and Nutrition Examination Survey from 2009 and 2010. The associations between the levels of urinary caffeine metabolites and self-reported CVD, including congestive heart failure, coronary heart disease, angina, heart attack, and stroke, were examined separately in men and women using multivariate logistic regression models adjusted for covariates. ResultsIn total, 1916 participants (910 men and 1006 women) were included in the analysis. Among women, the odds ratios of CVD in the highest quartiles of 1,3-dimethylxanthine and 1,3,7-trimethylxanthine were 0.33 (95% confidence interval [CI], 0.12–0.92) and 0.35 (95% CI, 0.13–0.93), respectively, compared with the lowest quartiles. Each one-unit (µmol/L) increase in theophylline concentration was associated with a 0.24-mg/dL increase in high-density lipoprotein cholesterol in the fully adjusted model. Among men, no significant association was observed between urinary caffeine metabolites and CVD. Regarding the subtypes of CVD, compared with women in the lowest quartile for 1,3-dimethylxanthine and 1,3,7-trimethylxanthine, the odds of coronary heart disease decreased by 90% (95% CI, −99% to −11%) and 97% (95% CI, −99% to −47%), respectively, in those in the highest quartile. ConclusionsUrinary 1,3-dimethylxanthine and 1,3,7-trimethylxanthine were significantly and inversely associated with CVDs in women. Additional studies are needed to further confirm the results of this study and explore the underlying mechanisms.<END ABSTRACT>

Risk of cardiovascular disease following gonadotropin-releasing hormone agonists vs antagonists in prostate cancer: Real-world evidence from five databases.

Observational studies in prostate cancer (PCa) have shown an increased risk of cardiovascular disease (CVD) following gonadotropin‐releasing hormone (GnRH) agonists, whereas randomised‐controlled trials have shown no associations. Compared to GnRH agonists, GnRH antagonists have shown less atherosclerotic effects in preclinical models. We used real‐world data from five countries to investigate CVD risk following GnRH agonists and antagonists in PCa men. Data sources included cancer registries, primary and secondary healthcare databases. CVD event was defined as an incident or fatal CVD. Multivariable Cox proportional hazard models estimated hazard ratios (HRs) and 95% confidence intervals (CIs), which were pooled using random‐effects meta‐analysis. Stratified analyses were conducted by history of CVD and age (75 years). A total of 48 757 men were on GnRH agonists and 2144 on GnRH antagonists. There was no difference in risk of any CVD for men on GnRH antagonists and agonists (HR: 1.25; 95% CI: 0.96‐1.61; I 2: 64%). Men on GnRH antagonists showed increased risk of acute myocardial infarction (HR: 1.62; 95% CI: 1.11‐2.35; I 2: 0%) and arrhythmia (HR: 1.55; 95% CI: 1.11‐2.15, I 2: 17%) compared to GnRH agonists. Having a history of CVD was found to be an effect modifier for the associations with some CVD subtypes. Overall, we did not observe a difference in risk of overall CVD when comparing GnRH antagonists with agonists—though for some subtypes of CVD we noted an increased risk with antagonists. Further studies are required to address potential confounding caused by unadjusted variables such as severity of CVD history and PCa stage.

Abstract 16174: Age, Race, and Gender Related Cardiovascular Morbidity of Patients Hospitalized With Periodontal Disease

Introduction: Periodontal disease (PD) is an acquired disorder characterized by inflammation of the gums, resulting eventually in loss of teeth. Epidemiological studies have shown a link between PD and cardiovascular diseases (CVDs). The aim of this study is to evaluate differences in the prevalence of CVD amongst US patients with PD of different age, race and sex. Method: Using the US national in-patient sample database (NIS) from 2005-2014, patients with PD and CVD were identified. Results: 155,732 hospitalizations with PD were included in the study, of which 36.5% had at least one CVD. Ischemic heart disease was the most prevalent CVD (17.6%), followed by heart failure (10.9%), atrial fibrillation/flutter (10.1%) and cerebrovascular disease (CRVD) (9.7%). The overall in-hospital mortality was higher in PD patients with CVD (2.6% vs 1.2%, p&lt;0.0001). Figure 1C highlights the prevalence of various subtypes of CVD among different gender. When stratifying hospitalized patients with PD and CVD based on race and age, there was higher prevalence of CVD among Asians and Pacific Islanders (42.4%) (Figure 1A-B) and with increasing age (≥70, 56-69, and 18-55; 67.4% vs 50.1% vs 20.3%, p&lt;0.001, respectively). Significant increase trends in the prevalence of AF, HF, and CRVD in the young, middle, and older age group was noted (P-trend&lt;0.001) (Figure1A). Conclusion: CVD is prevalent in patients with PD and is more common in males and among Asians and Pacific Islanders. Higher mortality was reported among hospitalized PD patients with CVD. An increase in trend in the prevalence of AF, HF, and CRVD was noted across all age groups. This may require age, race, and gender specific strategies in PD patients for primary prevention of different CVD.

Abstract 14678: Prevalence Of Sglt2 Inhibitor And Glp-1 Receptor Agonist Prescriptions In Patients With Comorbid Diabetes And Cardiovascular Disease In An Integrated Academic Health System

Introduction: Multiple randomized clinical trials have shown that sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide 1 (GLP1) receptor agonists reduce the risk of cardiovascular events and mortality in patients with type 2 diabetes (T2D) and cardiovascular disease (CVD). In order to inform implementation strategies, we sought to describe prescribing trends among patients with T2D in clinical practice. Methods: We developed a clinical T2D cohort using a validated computable phenotype from the electronic data warehouse of a large academic health system among patients receiving care from January 1, 2013 through December 31, 2019. We retrospectively reviewed outpatient prescribing patterns in this cohort, and stratified results by CVD subtype (heart failure [HF] and atherosclerotic CVD [ASCVD]). Results: There were 23,485 patients identified with T2D. Mean (SD) age was 67 years (13), 46% were women, 61% were white, 32% had comorbid CVD (HF or ASCVD), and the mean (SD) hemoglobin A1c was 8.0% (5.7%). The majority of SGLT2 inhibitors and GLP1 receptor agonists were first prescribed by endocrinologists, 52% and 65% respectively. The prescription rate for both medication classes was low, and though SGLT2 inhibitor use increased over time (1% in 2013 to 14% in 2019; p&lt;0.01), GLP1 receptor agonist use did not significantly change (10% in 2013 to 10% in 2019; p=0.93). Among patients with HF, SGLT2 inhibitor and GLP1 receptor agonist use increased annually by 42% and 7%, respectively, while patients with ASCVD experienced year over year growth of 63% and 13% in these categories. See Figure 1 (A and B) for more detail. Conclusions: Prescription rates of SGLT2 inhibitors and GLP1 receptor agonists remains low, especially for patients with T2D and CVD, despite a proven reduction in mortality and cardiovascular events. Strategies to increase the use of these proven medical therapies represent a major opportunity to improve outcomes in this high-risk group.

Abstract 13852: Socioeconomic Status is Associated With Recurrent Cardiovascular Disease Events in People With Prevalent Cardiovascular Disease

Introduction: While low socioeconomic status (SES) is an established risk factor for incident cardiovascular disease (CVD), there is scarce data regarding the association between SES and recurrent CVD events. Hypothesis: SES measures are associated with recurrent CVD events and mortality among those with prevalent CVD. Methods: We examined 3,031 individuals in the ARIC Study who developed CVD (either myocardial infarction [MI], heart failure [HF] or stroke) from the baseline visit (1987-1989) through 2013 to allow 5 years follow-up for recurrent CVD. SES was defined using baseline measures of income, education and area deprivation index (ADI), modeled individually and combined in a cumulative SES score. We used adjusted Cox proportional hazard regression to evaluate the associations of SES with composite and individual outcomes of first recurrent CVD and mortality. Results: Median age was 69 years, 49% were female, 29% Black. Over a median follow up of 4.6 years, 2,033 participants (67%) had a recurrent CVD event, and 2,202 (73%) died. Relative to the highest income group, being in the lowest income group was associated with higher risk for recurrent CVD (HR 1.27; 95% CI: 1.07-1.51) and mortality (HR 1.32; 95% CI: 1.12-1.56) ( Table ). Similarly, less than high school education was associated with increased risk of recurrent CVD (HR 1.25; 95% CI: 1.04-1.51) and mortality (HR 1.21; 95% CI: 1.01-1.45). No significant outcome associations were seen for ADI. Low cumulative SES was associated with approximately 20% higher risk of recurrent CVD, total mortality and the composite of recurrent CVD and mortality. Similar patterns were seen for individual subtypes of CVD, with the strongest SES-mortality associations for MI and stroke. Conclusions: In the high-risk group of individuals with existing CVD, low SES was linked to greater likelihood of recurrent CVD events and death. SES should be a focus in the design of secondary prevention efforts to improve outcomes in CVD.

Incident cardiovascular disease and particulate matter air pollution in South Korea using a population-based and nationwide cohort of 0.2 million adults

BackgroundWhile many studies reported the association between long-term exposure to particulate matter air pollution (PM) and cardiovascular disease (CVD), few studies focused on incidence with relatively high-dose exposure using a nationwide cohort. This study aimed to investigate the association between long-term exposure to PM10 and PM2.5 and incidence of CVD in a nationwide and population-based cohort in South Korea where the annual average concentration of PM2.5 is above 20 μg/m3.MethodsWe selected 196,167 adults in the National Health Insurance Service-National Sample Cohort (NHIS-NSC) constructed based on the entire South Korean population. Incidence of four CVD subtypes including ischemic heart disease (IHD), myocardial infarction, heart failure, and stroke, and total CVD including all four was identified as the first diagnosis for 2007–2015. To assess individual exposures, we used annually-updated district-level residential addresses and district-specific PM concentrations predicted by a previously developed universal kriging prediction model. We computed individual-level long-term PM concentrations for four exposure windows: previous 1, 3, and 5 year(s) and 5 years before baseline. We applied time-dependent Cox proportional hazards models to estimate hazard ratios (HRs) of incident CVDs per 10 μg/m3 increase in PM10 and PM2.5 after adjusting for individual- and area-level characteristics.ResultsDuring 1,578,846 person-year, there were 33,580 cases of total incident CVD. Average PM10 and PM2.5 concentrations for the previous 5 years were 52.3 and 28.1 μg/m3, respectively. A 10 μg/m3 increase in PM2.5 exposed for the previous 5 years was associated with 4 and 10% increases in the incidence of total CVD (95% confidence interval: 0–9%) and IHD (4–16%), respectively. HRs tended to be higher with earlier exposure for IHD and more recent exposure for stroke. The estimated shape of the concentration-response relationship showed non-linear patterns. We did not find evidence of the association for PM10.ConclusionsUsing a population-based nationwide cohort exposed to relatively high PM concentration, this study confirmed the association between PM2.5 and CVD incidence that was reported in previous studies mostly with low-dose environments. The magnitude and the shape of the association were generally consistent with previous findings.

Metabolically healthy obesity, transition to unhealthy metabolic status, and vascular disease in Chinese adults: A cohort study.

Metabolically healthy obesity (MHO) and its transition to unhealthy metabolic status have been associated with risk of cardiovascular disease (CVD) in Western populations. However, it is unclear to what extent metabolic health changes over time and whether such transition affects risks of subtypes of CVD in Chinese adults. We aimed to examine the association of metabolic health status and its transition with risks of subtypes of vascular disease across body mass index (BMI) categories. The China Kadoorie Biobank was conducted during 25 June 2004 to 15 July 2008 in 5 urban (Harbin, Qingdao, Suzhou, Liuzhou, and Haikou) and 5 rural (Henan, Gansu, Sichuan, Zhejiang, and Hunan) regions across China. BMI and metabolic health information were collected. We classified participants into BMI categories: normal weight (BMI 18.5-23.9 kg/m²), overweight (BMI 24.0-27.9 kg/m²), and obese (BMI ≥ 28 kg/m²). Metabolic health was defined as meeting less than 2 of the following 4 criteria (elevated waist circumference, hypertension, elevated plasma glucose level, and dyslipidemia). The changes in obesity and metabolic health status were defined from baseline to the second resurvey with combination of overweight and obesity. Among the 458,246 participants with complete information and no history of CVD and cancer, the mean age at baseline was 50.9 (SD 10.4) years, and 40.8% were men, and 29.0% were current smokers. During a median 10.0 years of follow-up, 52,251 major vascular events (MVEs), including 7,326 major coronary events (MCEs), 37,992 ischemic heart disease (IHD), and 42,951 strokes were recorded. Compared with metabolically healthy normal weight (MHN), baseline MHO was associated with higher hazard ratios (HRs) for all types of CVD; however, almost 40% of those participants transitioned to metabolically unhealthy status. Stable metabolically unhealthy overweight or obesity (MUOO) (HR 2.22, 95% confidence interval [CI] 2.00-2.47, p < 0.001) and transition from metabolically healthy to unhealthy status (HR 1.53, 1.34-1.75, p < 0.001) were associated with higher risk for MVE, compared with stable healthy normal weight. Similar patterns were observed for MCE, IHD, and stroke. Limitations of the analysis included lack of measurement of lipid components, fasting plasma glucose, and visceral fat, and there might be possible misclassification. Among Chinese adults, MHO individuals have increased risks of MVE. Obesity remains a risk factor for CVD independent of major metabolic factors. Our data further suggest that metabolic health is a transient state for a large proportion of Chinese adults, with the highest vascular risk among those remained MUOO.

Abstract PO-077: Use of aromatase inhibitors and risk of cardiovascular disease: A population-based study

Abstract Background: Adjuvant endocrine therapy, including aromatase inhibitors (AI) or tamoxifen, is recommended for women diagnosed with estrogen receptor- and/or progesterone receptor-positive breast cancer as it significantly reduces the risk of recurrence and breast cancer-specific mortality. AIs are the preferred treatment for postmenopausal women; however, concerns have been raised with respect to their cardiovascular safety. Some meta-analyses of randomized controlled trials report an increase in cardiovascular disease (CVD) risk with use of AIs compared to tamoxifen; however, “real-world” observational studies have yielded inconsistent findings. Objectives: We aimed to conduct a population-based study in Scotland to investigate whether breast cancer patients treated with AIs are at an increased risk of cardiovascular disease compared to patients treated with tamoxifen. Methods: Women newly diagnosed with breast cancer, from 2009 to 2017, were identified from the Scottish Cancer Registry. AI and tamoxifen use were identified from the nationwide Scottish Prescribing Information System. The primary outcome was CVD, based on incidence or death from CVD obtained from hospital admission and death records, respectively. Cox regression models calculated hazard ratios (HRs) and 95% intervals (CIs) comparing AI use to tamoxifen use and risk of CVD, using an as treated exposure definition. Analyses were adjusted for a range of potential confounders and subgroup analysis investigated risk by CVD subtypes including myocardial infarction, heart failure, ischemic stroke, venous thromboembolism, and angina. Results: The cohort contained 28,712 breast cancer patients, followed for 110,999 person years, during which there were 776 cardiovascular events. Compared to tamoxifen use, AI use was associated with an increased risk of any CVD event (adjusted HR 1.14, 95% CI: 1.02, 1.27), which was particularly marked for ischemic stroke (adjusted HR 1.27, 95% CI: 0.99, 1.63). There were no clear associations for other CVD subtypes. Conclusions: Our preliminary results suggest an increased risk of CVD, and specifically ischemic stroke, in AI users compared to tamoxifen. Additional analyses will be conducted to further investigate these associations, including dose-response. Citation Format: Lauren McVicker, Christopher Cardwell, Úna McMenamin. Use of aromatase inhibitors and risk of cardiovascular disease: A population-based study [abstract]. In: Proceedings of the AACR Virtual Meeting: COVID-19 and Cancer; 2020 Jul 20-22. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(18_Suppl):Abstract nr PO-077.

Increased serum levels of aldehydes are associated with cardiovascular disease and cardiovascular risk factors in adults

Previous studies have identified several genetic and environmental risk factors for cardiovascular disease (CVD), but little is known about the associations between serum aldehydes and CVD risk. Herein, we examined associations between serum levels of aldehydes and the risk of CVD and CVD subtypes among 1947 U.S. adults participating in the National Health and Nutrition Examination Survey (NHANES) 2013−2014. Bayesian kernel machine regression (BKMR) was used to analyze the combined effect of serum aldehydes on the overall risk of CVD. We found that isopentanaldehyde concentrations were positively associated with the odds of CVD (adjusted odds ratio (aOR): 2.17; 95 % confidence interval (95 % CI): 1.36, 3.46). The result of BKMR also indicated a positive association of mixed aldehydes with CVD risk. Isopentanaldehyde had the highest posterior inclusion probabilities (PIP = 0.90). Each one-unit (ng/mL) increase in the isopentanaldehyde concentration was associated with a 25.0 mg/dL increase in triglycerides and a 0.9 × 109/L increase in white blood cell (WBC) count in the fully adjusted model. Current evidence suggests that isopentanaldehyde may increase the risk of CVD by elevating triglycerides and WBC count.

Red Blood Cell Polyunsaturated Fatty Acids and Vascular Diseases: A Mendelian Randomization Study

Abstract Objectives To evaluate the causal association of omega-3 and omega-6 polyunsaturated fatty acids (PUFAs), as measured in red blood cells (RBC), with cardiovascular disease (CVD), cerebrovascular disease (CBVD), and peripheral vascular disease (PVD). Methods Applying a two-sample Mendelian Randomization approach, we first developed genetic instruments for RBC-PUFAs by utilizing summary statistics from previous genome-wide association study in the Framingham Heart Study. We then evaluated the association of these instrumental variables with CVD, CBVD, PVD, and their subtypes in the UK Biobank cohort. Results Strong evidence of causal association with at least one RBC-PUFAs was observed for the overall risk of PVD and three of its subtypes (aortic aneurysm and dissection, arterial embolism and thrombosis, and other PVDs), but only for two CVD subtypes (hypertensive heart disease, and chronic ischemic heart disease) and for two CBVD subtypes (stroke, and cerebral infarction). Based on their effects on all examined diseases, RBC-PUFAs clustered into two groups: a protective group with alpha-Linolenic acid (ALA), linoleic acid (LA), eicosadienoic acid (EDA), and dihomo-gamma-linolenic acid (DGLA); and the other risk group with docosapentaenoic acid (DPA), gamma-linolenic acid (GLA), arachidonic acid (AA), and adrenic acid (AdrA). PUFAs in the protective group are protective, while those in the risk group are risk-increasing, for all diseases with significant associations except for hypertensive heart diseases. In the metabolic pathway converting short-chain PUFAs into long-chain ones, the protective group is mapped to precursors of desaturases, while the risk group corresponds to their products. Conclusions Genetically regulated RBC-PUFAs are associated with the risk of PVD, and subtypes of PVD, CVD, and CBVD. Funding Sources University of Georgia Research Foundation.