Clinical Cardiovascular Disease Research Articles

#347 Long-term effectiveness of a village doctor-led multifaceted strategy on blood pressure control: a cluster randomized trial

Abstract Background and Aims We tested the effectiveness of a village doctor-led multifaceted strategy on blood pressure (BP) control over 36 months among patients with hypertension in rural China. Village doctors are community health workers who provide basic primary health care in rural China. Method 326 villages were randomly assigned to the village doctor-led intervention or usual care. Individuals aged ≥40 years with an untreated mean BP ≥140/90 mmHg (≥130/80 mmHg in individuals with clinical cardiovascular disease) or treated BP ≥130/80 mmHg were recruited. The trained village doctors initiated and titrated antihypertensive medications according to a simple stepped-care protocol with supervision from primary care physicians. They also delivered discounted and free medications to patients and conducted health coaching on lifestyle change, medication adherence, and home BP monitoring. Intention to treat analysis was conducted. Results At baseline, mean age (62.8 vs. 63.2 years), percentage of women (60.9% vs. 61.6%), mean systolic BP (157.0 vs. 155.5 mmHg), and diastolic BP (88.1 vs. 87.3 mmHg) were comparable between intervention and control groups. At 36 months, 72.5% patients in the intervention group and 11.7% patients in the control group had a BP of less than 130/80 mmHg, with a group difference of 60.8% (95% CI 59.4 to 62.2%; p<0.0001). Mean systolic BP decreased by –30.8 mmHg (95% CI –31.7 to –29.9) from baseline to 36 months in the intervention group and by –7.6 mmHg (–8.5 to –6.8) in the control group, with a group difference of –23.1 mmHg (95% CI –24.4 to –21.9 mmHg; p<0.0001). Mean diastolic BP decreased by –14.8 mmHg (–15.3 to –14.3) from baseline to 36 months in the intervention group and by –4.9 mmHg (–5.3 to –4.4) in the control group, with a group difference of –9.9 mmHg (–10.6 to –9.3 mmHg; p<0.0001). No treatment-related serious adverse events were reported in either group. Conclusion In rural China, the village doctor-led multifaceted strategy significantly reduced BP over 36 months in patients with hypertension. This proven-effective and sustainable implementation strategy could be scaled up throughout rural China and in other low- and middle-income countries for hypertension control.

Identification of Transcripts with Shared Roles in the Pathogenesis of Postmenopausal Osteoporosis and Cardiovascular Disease.

Epidemiological evidence suggests existing comorbidity between postmenopausal osteoporosis (OP) and cardiovascular disease (CVD), but identification of possible shared genes is lacking. The skeletal global transcriptomes were analyzed in trans-iliac bone biopsies (n = 84) from clinically well-characterized postmenopausal women (50 to 86 years) without clinical CVD using microchips and RNA sequencing. One thousand transcripts highly correlated with areal bone mineral density (aBMD) were further analyzed using bioinformatics, and common genes overlapping with CVD and associated biological mechanisms, pathways and functions were identified. Fifty genes (45 mRNAs, 5 miRNAs) were discovered with established roles in oxidative stress, inflammatory response, endothelial function, fibrosis, dyslipidemia and osteoblastogenesis/calcification. These pleiotropic genes with possible CVD comorbidity functions were also present in transcriptomes of microvascular endothelial cells and cardiomyocytes and were differentially expressed between healthy and osteoporotic women with fragility fractures. The results were supported by a genetic pleiotropy-informed conditional False Discovery Rate approach identifying any overlap in single nucleotide polymorphisms (SNPs) within several genes encoding aBMD- and CVD-associated transcripts. The study provides transcriptional and genomic evidence for genes of importance for both BMD regulation and CVD risk in a large collection of postmenopausal bone biopsies. Most of the transcripts identified in the CVD risk categories have no previously recognized roles in OP pathogenesis and provide novel avenues for exploring the mechanistic basis for the biological association between CVD and OP.

Protective Mechanisms of SGLTi in Ischemic Heart Disease.

Ischemic heart disease (IHD) is a common clinical cardiovascular disease with high morbidity and mortality. Sodium glucose cotransporter protein inhibitor (SGLTi) is a novel hypoglycemic drug. To date, both clinical trials and animal experiments have shown that SGLTi play a protective role in IHD, including myocardial infarction (MI) and ischemia/reperfusion (I/R). The protective effects may be involved in mechanisms of energy metabolic conversion, anti-inflammation, anti-fibrosis, ionic homeostasis improvement, immune cell development, angiogenesis and functional regulation, gut microbiota regulation, and epicardial lipids. Thus, this review summarizes the above mechanisms and aims to provide theoretical evidence for therapeutic strategies for IHD.

Vascular function and skeletal fragility: A study of tonometry, brachial hemodynamics, and bone microarchitecture.

Osteoporosis and cardiovascular disease frequently occur together in older adults; however, a causal relationship between these two common conditions has not been established. By the time clinical cardiovascular disease develops, it is often too late to test whether vascular dysfunction developed before or after the onset of osteoporosis. Therefore, we assessed the association of vascular function, measured by tonometry and brachial hemodynamic testing, with bone density, microarchitecture, and strength, measured by high-resolution peripheral quantitative computed tomography (HR-pQCT), in 1391 individuals in the Framingham Heart Study. We hypothesized that decreased vascular function (pulse wave velocity, primary pressure wave, brachial pulse pressure, baseline flow amplitude and brachial flow velocity) contributes to deficits in bone density, microarchitecture and strength, particularly in cortical bone, which is less protected from excessive blood flow pulsatility than the trabecular compartment. We found that individuals with increased carotid-femoral pulse wave velocity had lower cortical volumetric bone mineral density (tibia: -0.21 [-0.26,-0.15] standardized beta [95% confidence interval], radius: -0.20 [-0.26,-0.15]), lower cortical thickness (tibia: -0.09 [-0.15,-0.04], radius: -0.07 [-0.12,-0.01]) and increased cortical porosity (tibia: 0.20 [0.15,0.25], radius: 0.21 [0.15,0.27]). However, these associations did not persist after adjustment for age, sex, height, and weight. These results suggest that vascular dysfunction with aging may not be an etiologic mechanism that contributes to the co-occurrence of osteoporosis and cardiovascular disease in older adults. Further study employing longitudinal measures of HR-pQCT parameters is needed to fully elucidate the link between vascular function and bone health.

Epicardial Adipose Tissue and Left Ventricular Systolic Function in Rheumatoid Arthritis Assessed by Two-Dimensional Speckle Tracking Echocardiography.

Introduction Epicardial adipose tissue (EAT) is an emerging cardiovascular biomarker. Subclinical left ventricular (LV) systolic dysfunction is common in rheumatoid arthritis (RA). The aim of this study was to assess LV systolic function using two-dimensional speckle tracking echocardiography (2D-STE) and investigate its association with EAT in RA patients without clinical cardiovascular disease (CVD). Methods 60 RA patients without manifestations of CVD and 60 age- and gender-matched healthy controls have been recruited for the study. We assessed LV systolic function and EAT in all subjects using conventional echocardiography and 2D-STE. EAT was measured as the relative echo-free region between the free wall of the right ventricle and the visceral layer of the pericardium at end-systole. Results Global longitudinal strain (GLS) was decreased and EAT was increased in the RA group compared to the control group. GLS was reduced as EAT increased in RA patients (r=-0.273, P=0.035). After adjusting for confounders, multivariate linear regression analysis revealed a weakened correlation between EAT and GLS.Age and disease activity scores28 were independent factors influencing GLS in RA. Conclusion RA patients have significantly thickened EAT compared with controls. 2D-STE can detect early LV myocardial systolic dysfunction in RA, as shown by lower GLS.Accumulation of EAT is associated with lower GLS, but older age and higher disease activity may play a greater role in LV myocardial systolic dysfunction in RA.

Objectively Measured Hot Flashes and Moderate-Vigorous Activity Predict Arterial Stiffness in Healthy Perimenopausal Women

Perimenopause is the period of transition when midlife women experience increases in cardiovascular disease (CVD) risk. Arterial stiffness (AS) is a preclinical CVD risk factor that precedes the manifestation of clinical CVD. Hot flashes (HF) are bothersome symptoms of menopause which are correlated with some subclinical CVD risk factors, but the exact relationship between HF and CVD risk factors remain equivocal. Habitual physical activity (PA) is effective in the prevention and treatment of CVD in many populations. However, the relationship between PA and CVD risk remains unclear for perimenopausal women. Therefore, the objective of our study was to determine the effects of HF and PA on AS in healthy perimenopausal women. We hypothesized that HFs would be associated with AS and PA would influence the association between HFs and AS. There were 61 participants (age 43-54) free from CVD risk factors included in this analysis. Arterial stiffness was measured via augmentation index (AIx), backwards wave (PB, mmHg), and reflection magnitude (RM, %). Hot flashes were measured objectively for 24 hours using ambulatory sternal skin conductance monitoring. Objective HF rate was calculated by normalizing HF count to wear time. Habitual PA activity was quantified objectively as average daily minutes of waking moderate-vigorous PA (MVPA) over 7-day using actigraphy and the R package GGIR. All statistical analyses were performed using R (version 4.2.3) and RStudio (2023.06.2+561). Pearson’s correlation and multiple regression were used to evaluate the associations between dependent and outcome variables. Age and body mass index (BMI) were controlled, and assumption testing was completed for all models. Objective HF rate was significantly positively correlated with PB, r(53) = 0.38, p < 0.01, and RM, r(53) = 0.35, p <0.01. Objective MVPA was significantly negatively associated with AIx, r(61) = -0.45, p <0.001, PB, r(61) = -0.29, p <0.05, and RM, r(61) = -0.34, p < 0.01. Objective HF rate significantly predicted arterial stiffness variables, AIx (β = 14.58, p =0.05; adjR2 = 0.38), PB (β = 6.48, p<0.01; adjR2 = 0.24), and RM (β = 17.79, p <0.01; adjR2 = 0.39). Objective MVPA significantly predicted AIX (β = -0.12, p <0.01; adjR2 = 0.41), and RM (β = -0.06, p = 0.05; adjR2 = 0.29). When HF and MVPA were added in the same model, HF and MVPA were both significant predictors of RM (βHF = 16.25, p <0.01, βMVPA = -0.06, p <0.05; adjR2 = 0.42), MVPA only was significant with AIx (βHF = 11.38, p = 0.10, βMVPA = -0.13, p <0.01; adjR2 = 0.49), and HF only was significant with PB (βHF = 6.11, p <0.01, βMVPA = -0.02, p = 0.212; adjR2 = 0.25). Adding the interaction between HF and MVPA did not help explain variation in any AS variable. In conclusion, our data showed that more objectively-measured HF were associated with negative AS outcomes and that greater MVPA may be worth considering in decreasing arterial stiffness in perimenopausal women. Contrary to our hypothesis, MVPA did not help to explain the effects of HF on AS. Future studies should focus on understanding the mechanisms behind the negative relationship between hot flashes and arterial stiffness in midlife women. NIH NHLBI R15 Grant 1R15HL145650-01A1 (Witkowski); Smith College McKinley Honors Fellowship (Tha Ra Wun). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Association of the trimethylamine N-oxide with cardiovascular risk and vascular alterations in middle-aged patients with risk factors for cardiovascular diseases.

Trimethylamine N-oxide (TMAO) is synthesized by the intestinal microbiota and is an independent predictor of cardiovascular disease (CVD). However, its underlying mechanisms remain unclear. We investigated TMAO levels across different CVD-risk patient groups, and evaluated associations between TMAO and vascular alterations (e.g., arterial stiffness, intima-media thickness (IMT), and the presence and grade of carotid artery plaques (CAPs)).Methods: We examined 95 patients (58.5 ± 7.3 years): 40 with clinical atherosclerotic cardiovascular disease (ASCVD), 40 with atherosclerosis risk factors (RF), and 15 controls. Arterial stiffness was measured by Carotid-Femoral Pulse Wave Velocity (C-F PWV). B-mode ultrasound was used to evaluate the presence and grade of CAPs and carotid IMT (CIMT). TMAO was measured by high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) and results were presented as the median (interquartile range).Results: TMAO levels were higher in patients with ASCVD (251.5 (164.5) µg/l) when compared to patients with RFs (194.0 (174) µg/l, p = 0.04) and controls (122.0 (77) µg/l, p < 0.001). A significant correlation was observed between TMAO and PWV (r = 0.31, p = 0.003), which was not confirmed after adjustment for RFs. TMAO levels were significantly correlated with plaque score (r = 0.46, p < 0.001) and plaque height (r = 0.41, p = 0.003), and were independent predictors for grade III plaques (odds ratio (OR) = 1.002, confidence interval (CI) 95%: 1.000047-1.003, p = 0.044).Conclusions: TMAO levels are increased with expanded CVD risk. Across different types of vascular damage, TMAO is associated with atherosclerotic changes.

Non–High-Density Lipoprotein Cholesterol Levels From Childhood to Adulthood and Cardiovascular Disease Events

Elevated non-high-density lipoprotein cholesterol (non-HDL-C; a recommended measure of lipid-related cardiovascular risk) is common in children and increases risk of adult cardiovascular disease (CVD). Whether resolution of elevated childhood non-HDL-C levels by adulthood is associated with reduced risk of clinical CVD events is unknown. To examine the associations of non-HDL-C status between childhood and adulthood with incident CVD events. Individual participant data from 6 prospective cohorts of children (mean age at baseline, 10.7 years) in the US and Finland. Recruitment took place between 1970 and 1996, with a final follow-up in 2019. Child (age 3-19 years) and adult (age 20-40 years) non-HDL-C age- and sex-specific z scores and categories according to clinical guideline-recommended cutoffs for dyslipidemia. Incident fatal and nonfatal CVD events adjudicated by medical records. Over a mean length of follow-up of 8.9 years after age 40 years, 147 CVD events occurred among 5121 participants (60% women; 15% Black). Both childhood and adult non-HDL-C levels were associated with increased risk of CVD events (hazard ratio [HR], 1.42 [95% CI, 1.18-1.70] and HR, 1.50 [95% CI, 1.26-1.78] for a 1-unit increase in z score, respectively), but the association for childhood non-HDL-C was reduced when adjusted for adult levels (HR, 1.12 [95% CI, 0.89-1.41]). A complementary analysis showed that both childhood non-HDL-C levels and the change between childhood and adulthood were independently associated with the outcome, suggesting that from a preventive perspective, both childhood non-HDL-C levels and the change into adulthood are informative. Compared with those whose non-HDL-C levels remained within the guideline-recommended range in childhood and adulthood, participants who had incident non-HDL-C dyslipidemia from childhood to adulthood and those with persistent dyslipidemia had increased risks of CVD events (HR, 2.17 [95% CI, 1.00-4.69] and HR, 5.17 [95% CI, 2.80-9.56], respectively). Individuals who had dyslipidemic non-HDL-C in childhood but whose non-HDL-C levels were within the guideline-recommended range in adulthood did not have a significantly increased risk (HR, 1.13 [95% CI, 0.50-2.56]). Individuals with persistent non-HDL-C dyslipidemia from childhood to adulthood had an increased risk of CVD events, but those in whom dyslipidemic non-HDL-C levels resolve by adulthood have similar risk to individuals who were never dyslipidemic. These findings suggest that interventions to prevent and reduce elevated childhood non-HDL-C levels may help prevent premature CVD.

Lipid-lowering therapies in patients undergoing percutaneous coronary intervention

Cardiovascular disease is the leading cause of death worldwide. Over past decades, multiple clinical trials have provided substantial evidence supporting the advantages of managing plasma lipids in individuals with coronary artery disease (CAD). A primary focus in reducing clinical atherosclerotic cardiovascular disease (ASCVD) in patients who have undergone percutaneous coronary intervention (PCI) is the regulation of blood lipids, with an emphasis on low-density lipoprotein (LDL) cholesterol. Statins represent the cornerstone of lipid-lowering therapy (LLT), with high-intensity statins consistently associated with beneficial outcomes in patients at high risk of ASCVD. Nevertheless, a notable portion of patients do not achieve their target cholesterol levels through statin monotherapy, necessitating the inclusion of complementary LLT strategies. Among these therapies are ezetimibe and proprotein convertase subtilisin/kexin type 9 inhibitors, which have also demonstrated clinical advantages by further reducing cholesterol levels. Existing guidelines recommend using these agents when maximally tolerated statin doses fall short of achieving target LDL levels. Additionally, recently introduced ATP-citrate lyase inhibitors, such as bempedoic acid, have gained approval as adjunctive treatments. Furthermore, icosapent ethyl, a purified derivative of eicosapentaenoic acid, targets hypertriglyceridemia and has shown cardiovascular benefits compared to placebo. In this article, we delve into the mechanisms of blood lipids and molecular targets in connection with CAD undergoing PCI. We also explore the current landscape of available LLT options, guidelines in practice, and the subtleties of therapy.

Lipid-lowering therapies in patients undergoing percutaneous coronary intervention

Cardiovascular disease is the leading cause of death worldwide. Over past decades, multiple clinical trials have provided substantial evidence supporting the advantages of managing plasma lipids in individuals with coronary artery disease (CAD). A primary focus in reducing clinical atherosclerotic cardiovascular disease (ASCVD) in patients who have undergone percutaneous coronary intervention (PCI) is the regulation of blood lipids, with an emphasis on low-density lipoprotein (LDL) cholesterol. Statins represent the cornerstone of lipid-lowering therapy (LLT), with high-intensity statins consistently associated with beneficial outcomes in patients at high risk of ASCVD. Nevertheless, a notable portion of patients do not achieve their target cholesterol levels through statin monotherapy, necessitating the inclusion of complementary LLT strategies. Among these therapies are ezetimibe and proprotein convertase subtilisin/kexin type 9 inhibitors, which have also demonstrated clinical advantages by further reducing cholesterol levels. Existing guidelines recommend using these agents when maximally tolerated statin doses fall short of achieving target LDL levels. Additionally, recently introduced ATP-citrate lyase inhibitors, such as bempedoic acid, have gained approval as adjunctive treatments. Furthermore, icosapent ethyl, a purified derivative of eicosapentaenoic acid, targets hypertriglyceridemia and has shown cardiovascular benefits compared to placebo. In this article, we delve into the mechanisms of blood lipids and molecular targets in connection with CAD undergoing PCI. We also explore the current landscape of available LLT options, guidelines in practice, and the subtleties of therapy.

Primary and secondary prevention of stroke and cardiovascular events using evolocumab and alirocumab: Meta-analysis of randomized controlled trials.

Although the clinical role of protein convertase subtilisin kexin type 9 (PCSK9) inhibitors for cholesterol management is increasing, the post-marketing period of use is short compared to other lipid-lowering drugs, so there is still insufficient evidence for their efficacy and safety. In this meta-analysis, we evaluated preventive effects of stroke and cardiovascular (CV) events using evolocumab and alirocumab. We assessed the relative risk of stroke and CV events after alirocumab or evolocumab treatment in individuals with or without clinical CV diseases compared with that in controls. In addition, we evaluated the relative risk of hemorrhagic stroke. A total of 25 articles were included (median of study duration = 52 weeks). The risk of stroke was significantly decreased after treatment with alirocumab or evolocumab (primary prevention in patients without CV diseases: RR = 0.733; 95% CI, 0.618-0.870; secondary prevention in patients with CV diseases: RR = 0.703; 95% CI, 0.562-0.880). The risk of CV events also significantly decreased in patients treated with alirocumab or evolocumab (primary prevention: RR = 0.818; 95% CI, 0.777-0.861; secondary prevention: RR = 0.725; 95% CI, 0.578-0.910). The relative risk of hemorrhagic stroke was not significantly different between PCSK9 inhibitor-treated patients and controls (RR=1.041; 95% CI, 0.690-1.573). Our findings indicate that evolocumab and alirocumab are significantly effective without increasing the risk of hemorrhagic stroke. Based on this, the PCSK9 inhibitors can be highly recommended for cholesterol management.

Identification of apolipoprotein B-reactive CDR3 motifs allows tracking of atherosclerosis-related memory CD4+T cells in multiple donors.

Atherosclerosis is a major pathological condition that underlies many cardiovascular diseases (CVDs). Its etiology involves breach of tolerance to self, leading to clonal expansion of autoreactive apolipoprotein B (APOB)-reactive CD4+T cells that correlates with clinical CVD. The T-cell receptor (TCR) sequences that mediate activation of APOB-specific CD4+T cells are unknown. In a previous study, we had profiled the hypervariable complementarity determining region 3 (CDR3) of CD4+T cells that respond to six immunodominant APOB epitopes in most donors. Here, we comprehensively analyze this dataset of 149,065 APOB-reactive and 199,211 non-reactive control CDR3s from six human leukocyte antigen-typed donors. We identified 672 highly expanded (frequency threshold > 1.39E-03) clones that were significantly enriched in the APOB-reactive group as compared to the controls (log10 odds ratio ≥1, Fisher's test p < 0.01). Analysis of 114,755 naïve, 91,001 central memory (TCM) and 29,839 effector memory (TEM) CDR3 sequences from the same donors revealed that APOB+ clones can be traced to the complex repertoire of unenriched blood T cells. The fraction of APOB+ clones that overlapped with memory CDR3s ranged from 2.2% to 46% (average 16.4%). This was significantly higher than their overlap with the naïve pool, which ranged from 0.7% to 2% (average 1.36%). CDR3 motif analysis with the machine learning-based in-silico tool, GLIPHs (grouping of lymphocyte interactions by paratope hotspots), identified 532 APOB+ motifs. Analysis of naïve and memory CDR3 sequences with GLIPH revealed that ~40% (209 of 532) of these APOB+ motifs were enriched in the memory pool. Network analysis with Cytoscape revealed extensive sharing of the memory-affiliated APOB+ motifs across multiple donors. We identified six motifs that were present in TCM and TEM CDR3 sequences from >80% of the donors and were highly enriched in the APOB-reactive TCR repertoire. The identified APOB-reactive expanded CD4+T cell clones and conserved motifs can be used to annotate and track human atherosclerosis-related autoreactive CD4+T cells and measure their clonal expansion.

Abstract P129: Risk of COVID-19 Hospitalization or Death by the AHA's Life’s Essential 8: The Collaborative Cohort of Cohorts for COVID-19 Research (C4R)

Background: It is unknown how cardiovascular health (CVH) relates to severe Covid-19 illness in adults without clinical cardiovascular disease (CVD). We hypothesized that more optimal Life’s Essential 8 (LE8)-quantified CVH is associated with lower risk of severe Covid-19 among US adults without clinical CVD. Methods: C4R is ascertaining Covid-19 events in 14 NIH cohorts via questionnaires, serosurvey, and medical record adjudication. We included cohorts with pre-pandemic LE8 measures of body mass index (BMI), blood pressure (BP), lipids, diet, glucose, physical activity, smoking, and sleep in participants without clinical CVD. Covid-19 was defined as severe (hospitalization, death) or non-severe (all other events). Fine-Gray sub-distribution hazard models compared incident Covid-19 by LE8 quartiles, with non-severe and severe Covid-19 as competing risks. Models were censored at first event, stratified by cohort, and adjusted for sociodemographics and vaccinations at time of Covid-19. Results: Among 21,300 participants in 7 cohorts (mean [SD] age 67 years [14], 61% female, 2% American Indian, 4% Asian, 16% Black, 33% White, 43% Hispanic), mean (SD) LE8 was 65 (14). In 3/2020-9/2022, there were 3,034 non-severe and 488 severe Covid-19 cases. The best CVH quartile (Q) 4 had more non-severe and fewer severe Covid-19 events. The Q4 vs. Q1 aHR was 1.08 (95% CI 0.98, 1.20) for non-severe Covid-19 and 0.59 (0.45, 0.77) for severe Covid-19. Examining LE8 components separately, better status on 5 LE8 components (BMI, BP, glucose, physical activity, smoking) was associated with significantly lower risk of severe Covid-19, whereas 3 were not associated (cholesterol, diet, sleep; data not shown). Conclusions: Better LE8-quantified CVH was associated with 41% lower risk of severe Covid-19 events in adults without clinical CVD. Further research is needed to elucidate mechanisms of Covid-19 resilience and the role of CVH-directed interventions to reduce risks of severe Covid-19.

Abstract P513: Coronary Artery Calcium Burden in Rural Alabama: Initial Findings From the Risk Underlying Rural Areas Longitudinal Cohort Study

Introduction: Individuals living in rural areas have a disproportionately high rate of cardiovascular disease (CVD) mortality. Coronary artery calcium (CAC) scanning may inform CVD risk stratification. However, the prevalence of CAC in rural areas is unknown. Research Question: What is the prevalence of CAC according to age, sex, and self-reported race (Black, White) in two rural counties in Alabama? Aims: To determine the prevalence of a CAC score &gt;0, a CAC score ≥100, and premature CAC among rural persons without clinical CVD and the extent to which they differ by demographic group. Methods: We studied 789 participants between the age of 25 and 64 years in the Risk Underlying Rural Areas Longitudinal (RURAL) Cohort Study sample in Alabama who underwent CAC scoring on non-contrast cardiac computed tomography. Premature CAC was defined as CAC &gt;0 for men &lt;45 years old, and women &lt;55 years old. Multivariable logistic regression (including age, sex, race) estimated adjusted odds ratios (aOR) for CAC &gt;0 and CAC ≥100. Results: The median age was 51 years, 70% were women, and 80% were Black. Among the were 37% with CAC &gt;0 the median CAC score was 64, while 14% had CAC ≥100 and 12% had premature CAC. Significant differences in all three CAC categories were consistently observed across age and sex, but not race ( Figure ). After adjusting for age and race, women had an approximate 70% lower odds of CAC &gt;0 (aOR=0.29, 95% CI: 0.19-0.44) and CAC ≥100 (aOR=0.28, 95% CI: 0.18-0.43) compared to men. There were no significant differences in CAC &gt;0 (aOR=0.70, 95% CI: 0.43-1.12) or CAC ≥100 (aOR=0.76, 95% CI: 0.46-1.25) for Black versus White persons independent of age and sex. Conclusion(s): In a Southern rural cohort of young and middle-aged persons, approximately one in three had prevalent CAC and one in eight had premature CAC. In contrast to previously published urban cohorts, rural Black adults had a similar CAC burden to their White counterparts. There is a need to explore the factors implicated in the high CAC burden within Southern rural communities.

Abstract P392: Cardiovascular-Kidney-Metabolic Syndrome Burden and Disparities in the 2011-2020 National Health and Nutrition Examination Survey

Background: Cardiovascular-kidney-metabolic (CKM) health is a new concept that reflects the interconnectedness of metabolic risk factors, chronic kidney disease (CKD), and cardiovascular disease (CVD). The differences in poor CKM health by race/ethnicity in the US population have not been completely elucidated. Objective: To examine racial/ethnic differences in CKM stages among persons in the United States using large, nationally representative data. Methods: We cross-sectionally examined ≥18 years from the 2011-2020 National Health and Nutrition Examination Survey (NHANES). The outcome of interest was CKM syndrome, which we defined as the presence of at least one metabolic risk factor, CKD, or clinical CVD, and categorized into stage 0, stage 1, stage 2-3, and stage 4; each category was computed as a binary outcome. Our exposure was self-reported race/ethnicity, categorized as non-Hispanic White, non-Hispanic Black, Hispanic, or non-Hispanic Asian adults. Survey-weighted multivariable logistic regression was used to estimate racial/ethnic differences across CKM stages, adjusted for age, sex, and socioeconomic status. Results: Among 27,662 adults, mean age was 47±16 years, 52% female, and 94% had stage 1 CKM or worse. In the fully adjusted models, Black and Hispanic adults had a significantly higher likelihood of CKM syndrome across all CKM stages compared to White adults, while Asian adults had lower odds of CKM ( Table ). Compared to White adults, the odds of stage 2-3 CKM was 2.67 (95%CI: 1.83-3.90) among Black adults and 1.58 (95%CI: 1.14-2.19) among Hispanic adults. Similarly, the odds of stage 4 CKM was 1.70 (95%CI: 1.14-2.53) among Black and Hispanic adults. Conclusion: Racial/ethnic disparities were evident across CKM stages and most pronounced for Black and Hispanic persons. These results underscore the disproportionate burden of CKM faced by Black and Hispanic populations and highlight the need for concerted efforts to address these unequal risks.

Trends and Patterns in Electronic Health Record Research (1991-2022): A Bibliometric Analysis of Australian Literature.

Electronic Heath Records (EHRs) play vital roles in facilitating streamlined service provision and governance across the Australian health system. Given the recent challenges due to the COVID-19 pandemic, an ageing population, health workforce silos, and growing inefficiencies in traditional systems, a detailed historical analysis of the use of EHR research in Australia is necessary. The aim of this study is to examine the trends and patterns in EHR research in Australia over the past three decades by employing bibliometric methods. A total of 951 articles published in 443 sources were included in the bibliometric analysis. The annual growth rate of EHR research in Australia was about 17.1%. Since 2022, the main trending topics in EHR research were COVID-19, opioid usage, and natural language processing. A thematic analysis indicated aged care, clinical decision support systems, cardiovascular disease, drug allergy, and adverse drug reaction as the "hot" themes in EHR research in Australia. This study reveals a significant uptrend in EHR research in Australia, highlighting the evolving intellectual and collaborative landscape of this interdisciplinary field. The data also provide guidance for policymakers and funding institutions in terms of the most significant contributions and key fields of research while also holding public interest.

Abstract P540: Sleep Duration, Rapid Eye Movement Sleep, and Subclinical Myocardial Damage

Introduction: Sleep is strongly linked to clinical cardiovascular disease and was added in 2022 to the AHA’s Life’s Essential 8. Optimizing sleep duration and quality may reduce the risk of cardiovascular disease. Few studies have examined self-reported sleep duration and percent time in rapid eye movement (REM) sleep measured by single night in-home polysomnography with high sensitivity cardiac troponin T (hs-troponin T), a biomarker of subclinical cardiovascular disease. Methods: We conducted a cross-sectional study of adults without a history of cardiovascular disease who participated in both the Atherosclerosis Risk in Communities (ARIC) Study and the Sleep Heart Health Study (SHHS) in 1995-1998. We used linear regression with sleep duration and percentage time of REM sleep modeled as predictors with restricted cubic splines and examined associations with the outcome, hs-troponin T. We adjusted for age, sex, body mass index, waist-to-hip ratio, alcohol intake, smoking status, systolic blood pressure, hypertension medication use, diabetes, HDL- and LDL-cholesterol, and cholesterol-lowering medication use. Results: Among 1,587 participants (mean age 63, 54% female), the mean sleep duration was 7.3 hours, and mean % REM time was 20.7. Sleep duration was not associated with hs-troponin T ( Figure, Panel A ). However, percentage REM sleep was negatively associated with hs-troponin T, but with a threshold effect; there was a negative linear association of hs-troponin T with % REM sleep but only at values &lt;15% ( Figure, Panel B ). Conclusion: While self-reported sleep duration was not associated with TnT levels, there was evidence that low % REM sleep, a specific neurophysiological sleep state, was associated with subclinical cardiovascular disease. These findings suggest that multiple sleep dimensions should be considered in efforts to optimize cardiovascular health.

Subclinical vascular composites predict clinical cardiovascular disease, stroke, and dementia: The Multi-Ethnic Study of Atherosclerosis (MESA)

Background and aimsSubclinical cardiovascular disease (CVD) measures may reflect biological pathways that contribute to increased risk for coronary heart disease (CHD) events, stroke, and dementia beyond conventional risk scores. MethodsThe Multi-Ethnic Study of Atherosclerosis (MESA) followed 6814 participants (45–84 years of age) from baseline in 2000–2002 to 2018 over 6 clinical examinations and annual follow-up interviews. MESA baseline subclinical CVD procedures included: seated and supineblood pressure, coronary calcium scan, radial artery tonometry, and carotid ultrasound. Baseline subclinical CVD measures were transformed into z-scores before factor analysis to derive composite factor scores. Time to clinical event for all-cause CVD, CHD, stroke and ICD code-based dementia events were modeled using Cox proportional hazards models reported as area under the curve (AUC) with 95% Confidence Intervals (95%CI) at 10 and 15 years of follow-up. All models included all factor scores together, and adjustment for conventional risk scores for global CVD, stroke, and dementia. ResultsAfter factor selection, 24 subclinical measures aggregated into four distinct factors representing: blood pressure, atherosclerosis, arteriosclerosis, and cardiac factors. Each factor significantly predicted time to CVD events and dementia at 10 and 15 years independent of each other and conventional risk scores. Subclinical vascular composites of atherosclerosis and arteriosclerosis best predicted time to clinical events of CVD, CHD, stroke, and dementia. These results were consistent across sex and racial and ethnic groups. ConclusionsSubclinical vascular composites of atherosclerosis and arteriosclerosis may be useful biomarkers to inform the vascular pathways contributing to events of CVD, CHD, stroke, and dementia.

Discrimination, Smoking, and Cardiovascular Disease Risk: A Moderated Mediation Analysis With MESA.

Carotid intima-media thickness (cIMT) and carotid plaque are reliable indicators of cardiovascular disease risk, and research highlights that racial and ethnic minority individuals generally exhibit higher cIMT and carotid plaque than White individuals. At present, the mechanisms driving these disparities among different racial and ethnic and biological sex groups are poorly understood. Data came from the baseline examination of MESA (Multi-Ethnic Study of Atherosclerosis). A total of 6814 participants aged 45 to 84 years free of clinical cardiovascular disease completed assessments on health behavior and perceived discrimination. Four sex-stratified moderated mediation models examined associations between discrimination, cigarette smoking, and mean cIMT and plaque. We hypothesized that cigarette use would mediate the association between discrimination and carotid artery disease features, and that these would differ by race and ethnicity. Indirect effects of discrimination on plaque were observed among Hispanic women such that discrimination was associated with cigarette use and, in turn, higher plaque (β=0.04 [95% CI, 0.01-0.08]). Indirect effects of discrimination on mean cIMT were found among Hispanic (β=0.003 [95% CI, 0.0001-0.007]) and White men (β=0.04 [95% CI, 0.01-0.08]) such that discrimination was associated with cigarette use and, in turn, higher cIMT. Finally, a positive indirect effect of discrimination on plaque was observed among Hispanic men (β=0.03 [95% CI, 0.004-0.07]). No other racial and ethnic differences were observed. To understand and address social determinants of cardiovascular disease, researchers must incorporate an intersectional framework that will allow us to understand the complex nature of discrimination and cardiovascular disease risk for individuals of varying intersecting identities and social positions.

Genetically predicted retinal vascular occlusion in relation to cardiovascular diseases: A bidirectional two-sample Mendelian randomization analysis.

Increasing evidence implicates retinal vascular occlusions as a susceptibility factor for cardiovascular diseases (CVDs), whereas inconsistent results on the relationship were reported in previous observational studies. This research using a bidirectional two-sample Mendelian randomization (MR) analysis aimed to investigate the potential association between genetically determined central/branch retinal artery and retinal vein occlusions (CRAO/BRAO/RVO) and the risk of CVD. Summary statistics of retinal vascular occlusions from the largest available genome-wide association study of European descent were used to investigate their relationship with CVDs, and vice versa. Primary analyses were conducted using the common inverse-variance weighted approach. Several complementary sensitivity analyses were performed to verify the reliability of our results. Inverse variance weighted method showed suggestive effects of genetically determined RVO on ischemic stroke (IS) (odds ratio [OR]=1.021, 95% confidence [CI]=1.004-1.037, p =0.012), a genetic liability to CRAO increased the risk of myocardial infarction (MI) (OR=1.014, 95% CI=1.006-1.023, p =7.0 × 10-4). In addition, genetic predisposition to BRAO had a positive effect on stroke (OR=1.008, 95% CI=1.002-1.013, p =0.011), IS (OR=1.007, 95% CI=1.001-1.014, p =0.022), and cardioembolic stroke (CES) (OR=1.018, 95% CI=1.006-1.031, p =0.004). The point estimates from sensitivity analyses were in the same direction. Reverse MR analyses found no significant evidence for the effect of CVDs on retinal vascular occlusions. Our MR study provides potential evidence that retinal vascular occlusions are causally linked to increased risk of CVDs including IS, MI, stroke, and CES. This supports the need for clinical CVD screening in individuals with retinal vascular occlusions. Further investigations are warranted to clarify the effects of CVDs on ocular comorbidities.