Risk Of Ischemic Heart Disease Research Articles

Elevated plasma levels of factor VIII enhance arterial thrombus formation on erosive smooth muscle cell-rich neointima but not normal intima in rabbits

BackgroundPlaque erosion, a type of coronary atherothrombosis, involves superficial injury to smooth muscle cell (SMC)-rich plaques. Elevated levels of coagulation factor VIII (FVIII) correlate with an increased ischemic heart disease risk. FVIII may contribute to thrombus formation on eroded plaques. AimsWe aimed to elucidate the role of elevated FVIII in arterial thrombus formation within SMC-rich neointima in rabbits. Methods and resultsWe assessed the effect of recombinant human FVIII (rFVIII) on blood coagulation in vitro and platelet aggregation ex vivo. An SMC-rich neointima was induced through balloon injury to the unilateral femoral artery. Three weeks after the first balloon injury, superficial erosive injury and thrombus formation were initiated with a second balloon injury of the bilateral femoral arteries 45 min after the administration of rFVIII (100 IU/kg) or saline. The thrombus area and contents were histologically measured 15 min after the second balloon injury. rFVIII administration reduced the activated partial thromboplastin time and augmented botrocetin-induced, but not collagen- or adenosine 5′-diphosphate-induced, platelet aggregation. While rFVIII did not influence platelet-thrombus formation in normal intima, it increased thrombus formation on SMC-rich neointima post-superficial erosive injury. Enhanced immunopositivity for glycoprotein IIb/IIIa and fibrin was observed in rFVIII-administered SMC-rich neointima. Neutrophil count in the arterial thrombus on the SMC-rich neointima correlated positively with thrombus size in the control group, unlike the rFVIII group. ConclusionsIncreased FVIII contributes to thrombus propagation within erosive SMC-rich neointima, highlighting FVIII's potential role in plaque erosion-related atherothrombosis.

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

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

Bangladeshi Atherosclerosis Biobank and Hub: The BANGABANDHU Study.

Genetic factors contribute significantly to the risk of ischaemic heart disease (IHD), which is the leading cause of mortality in Bangladesh. The BANGABANDHU (Bangladeshi Atherosclerosis Biobank AND Hub) study will allow a hypothesis-free genome-wide association study (GWAS) to identify genetic risk factors associated with ischaemic heart disease patients undergoing coronary artery bypass graft (CABG) surgery in Bangladesh. This is a multi-centre population-based case-control study aimed to evaluate 1500 (Fifteen Hundred) adult (≥18 years of age) people divided into 2 study groups: Case/Proband (750 IHD patients undergoing CABG surgery) and Control (750 healthy people). Spouses or family members are preferred as healthy control subjects due to their shared geographic location and similar environmental exposure. This will be the first largest DNA repository of CABG patients in Bangladesh, and identifying novel gene loci among CABG patients might help to discover novel therapeutic targets for Bangladeshi IHD patients. Further, identifying and comparing novel gene loci among CABG patients with other ancestry might help devise national guidelines for treating coronary artery disease. Promising current study results will encourage Bangladeshi researchers and pharmaceutical companies to conduct further studies into the genetic basis of Bangladeshi complex coronary artery disease, which might identify novel genes for therapeutic targets for Bangladeshi patients and strengthen the healthcare standards in Bangladesh.

Abstract 2006: Estrogen Therapy Is Associated With A Greater Risk Of Cardiovascular-kidney-metabolic Syndrome And Thrombosis In Cisgender Women, But Spares Transgender Women: A Global Retrospective Study

Despite the use of estrogen-based therapies in cisgender- and transgender-women, and the presumed cardioprotective effect of endogenous estrogen, there are no comprehensive studies investigating the risk of cardiovascular-kidney-metabolic (CKM) syndrome in patients taking exogenous estrogen. CKM syndrome is a health disorder attributable to connections among obesity, type 2 diabetes mellitus (T2DM), chronic kidney disease (CKD), and cardiovascular disease, including heart failure (HF), ischemic heart disease (IHD), and stroke. We hypothesized that cis- and trans-women would have decreased risk of CKM syndrome. We conducted a retrospective analysis using the TriNetX database, which contains patient information from 83 healthcare organizations worldwide. We identified 9,271,702 cis-women +/- estrogen and 17,729 trans-women on estrogen matched 1:1 with cis-men and separated patients into age deciles from 20-69 years. Cis-women taking estrogen showed a significantly increased risk of CKM comorbidities including dyslipidemia, HTN, T2DM, overweight/obesity (OB), HF, IHD, and CKD (p<0.0001 for all), and an elevated risk of thrombotic outcomes, such as myocardial infarction (MI), stroke, pulmonary embolism (PE), and deep vein thrombosis (DVT) compared to cis-women not taking estrogen (p<0.0001 for all). In contrast, the use of estrogen in trans-women compared to cis-men was not associated with a greater risk of MI, stroke, PE, or DVT, (except in the 60-69 year-aged cohort for DVT, p=0.0056). Trans-women taking estrogen also had a lower risk of HTN, T2DM, HF, IHD, and CKD, despite a higher risk of dyslipidemia, and OB compared to cis-men (p=0.02-<0.0001). This is the first comprehensive study revealing a significant association between exogenous estrogen use and CKM syndrome in cis-women. Additionally, our novel findings indicate that estrogen use in trans-women is associated with dyslipidemia, and OB, but is not associated with a greater overall risk for CKM syndrome or thrombosis. Given these findings, additional prospective studies are needed to confirm the risks or protections provided by estrogen therapy in cisgender and transgender women.

Looking into the Eyes to See the Heart of Chronic Kidney Disease Patients.

In patients with chronic kidney disease (CKD), the main cause of morbidity and mortality is cardiovascular disease (CVD). Both coronary artery calcium scoring by computed tomography (CT) and optical coherence tomography (OCT) are used to identify patients at increased risk for ischemic heart disease, thereby indicating a higher cardiovascular risk profile. Our study aimed to investigate the utility of these techniques in the CKD population. In patients with CKD, OCT was used to measure the choroidal thickness (CHT) and the thickness of the peripapillary retinal nerve fiber layer (pRNFL). A total of 127 patients were included, including 70 men (55%) with an estimated glomerular filtration rate (eGFR) of 39 ± 30 mL/min/1.73 m2. Lower pRNFL thickness was found to be related to high-sensitivity troponin I (r = -0.362, p < 0.001) and total coronary calcification (r = -0.194, p = 0.032). In a multivariate analysis, pRNFL measurements remained associated with age (β = -0.189; -0.739--0.027; p = 0.035) and high-sensitivity troponin I (β = -0.301; -0.259--0.071; p < 0.001). Severe coronary calcification (Agatston score ≥ 400 HU) was related to a worse eGFR (p = 0.008), a higher grade of CKD (p = 0.036), and a thinner pRNFL (p = 0.011). The ROC curve confirmed that the pRNFL measurement could determine the patients with an Agatston score of ≥400 HU (AUC 0.638; 95% CI 0.525-0.750; p = 0.015). Our study concludes that measurement of pRNFL thickness using OCT is related to the markers associated with ischemic heart disease, such as coronary calcification and high-sensitivity troponin I, in the CKD population.

Lp(a) Levels in Relatives of Patients with Acute Coronary Syndrome and Elevated Lp(a): HER(a) Study.

Background: Lipoprotein(a) [Lp(a)] is a proatherogenic particle associated with increased cardiovascular risk. It is mainly genetically determined; so, the aim of our study is to evaluate the levels of Lp(a) in the relatives of a prospective cohort of patients who have suffered from an acute coronary syndrome (ACS) with Lp(a) ≥ 50 mg/dL. Methods: We conducted a multicenter prospective study, in which consecutive patients who had suffered from an ACS and presented Lp(a) ≥ 50 mg/dL and their first-degree relatives were included. Results: We included 413 subjects, of which 56.4% were relatives of the patients. Family history of early ischemic heart disease was present in 57.5%, and only 20.6% were receiving statin treatment. The family cohort was younger (37.5 vs. 59.1 years; p < 0.001), and 4% had ischemic heart disease and fewer cardiovascular risk factors. Mean Lp(a) levels were 64.9 mg/dL, 59.4% had levels ≥ 50 mg/dL, and 16.1% had levels ≥ 100 mg/dL. When comparing the patients with respect to their relatives, the mean level of Lp(a) was lower but without significant differences regarding the levels of LDLc, ApoB, and non-HDL. However, relatives with Lp(a) ≥ 50 mg/dL, had values similar to the group of patients with ACS (96.8 vs. 103.8 mg/dL; p = 0.18). No differences were found in Lp(a) levels in relatives based on the other lipid parameters. Conclusions: Overall, 59.4% of the first-degree relatives of patients who suffered from an ACS with Lp(a) ≥ 50 mg/dL also had elevated levels. Relatives with elevated Lp(a) had similar levels as patients.

Is the risk of ischemic heart disease in women after radiotherapy for breast cancer nowadays still (linearly) associated with the mean heart dose?

Is the risk of ischemic heart disease in women after radiotherapy for breast cancer nowadays still (linearly) associated with the mean heart dose?

Shape of radiation dose response relationship for ischaemic heart disease mortality and its interpretation: analysis of the national registry for radiation workers (NRRW) cohort

Statistically significant increases in ischemic heart disease (IHD) mortality with cumulative occupational external radiation dose were observed in the National Registry for Radiation Workers (NRRW) cohort. There were 174 541 subjects in the NRRW cohort. The start of follow up was 1955, and the end of the follow-up for each worker was chosen as the earliest date of death or emigration, their 85th birthday or 31 December 2011. The dose-response relationship showed a downward curvature at a higher dose level >0.4 Sv with the overall shape of the dose-response relationship best described by a linear-quadratic model. The smaller risk at dose >0.4 Sv appears to be primarily associated with workers who started employment at a younger age (<30 years old) and those who were employed for more than 30 years. We modelled the dose response by age-at-first exposure. For the age-at-first exposure of 30+ years old, a linear dose-response was the best fit. For age-at-first exposure <30 years old, there was no evidence of excess risk of IHD mortality for radiation doses below 0.1 Sv or above 0.4 Sv, excess risk was only observed for doses between 0.1–0.4 Sv. For this age-at-first exposure group, it was also found that the doses they received when they were less than 35 years old or greater than 50 years old did not contribute to any increased IHD risk.

Case report: Young onset stroke from familial hypercholesterolemia

Introduction. Familial hypercholesterolemia (FH) is a medical condition that leads to extremely high levels of low-density lipoprotein (LDL) cholesterol, increasing the risk of ischemic heart disease, including myocardial infarction. However, the link between FH and ischemic stroke is still debatable. In this case, we report a young adult female who had FH and high levels of LDL and suffered from an early-onset ischemic stroke. Case presentation. A 38-year-old female presented with acute numbness and weakness in her right limb, as well as speech difficulty. She had no history of hypertension, migraine, or diabetes, but did have a history of eyelid xanthoma. The results of the neurological examination confirmed a slightly gradual response, a mild weakness in her right limb, and a slightly reduced response to touch and pain. Laboratory tests showed very high cholesterol and LDL levels, as well as an increased CRP level. Radiological examination via a CT scan revealed lesions within the left frontotemporal region. The patient was prescribed dual antiplatelet therapy and vascular risk factor medication, and after 6 days of treatment, was discharged to go home. Conclusion. We present a case of ischemic stroke in a young patient with clinically diagnosed FH, highlighting the possibility of FH in those with early-onset cerebrovascular disease.

Association between Head and Neck Cancer and Increased Risk of Ischemic Heart Disease: A Retrospective Cohort Study Using National Population Data.

Although cancer and ischemic heart disease (IHD) frequently manifest in the same individual, the risk of IHD events in cancer, especially head and neck cancer (HNC), remains unclear. We aimed to examine the incidence and risk of IHD events in patients with HNC using a population-based cohort dataset in South Korea (2002-2013). Through rigorous propensity score matching, we compared data from 2816 individuals without HNC and 704 individuals with HNC. Key independent variables were matched between groups, and the Charlson Comorbidity Index was used to match comorbidities. The Kaplan-Meier method depicted the cumulative probability of IHD throughout the follow-up period for both the study and control groups. The overall IHD incidence was significantly higher (19.93) in patients with HNC than in those without HNC (14.81), signifying an augmented IHD risk in the HNC cohort. Subsequent temporal analysis revealed a significant surge in IHD risk commencing 4 years after HNC diagnosis and persisting throughout the follow-up period. Subgroup analysis revealed an increased IHD risk in men with HNC and patients with cancers affecting the oral and sinonasal regions. This retrospective cohort study provides valuable scientific insights into the nuanced relationship between HNC and IHD, underscoring the need for tailored monitoring protocols and specialized care for susceptible individuals.

Long-term cardiovascular outcome in women with preeclampsia in Korea: a large population-based cohort study and meta-analysis

Recent studies reported the long-term cardiovascular risk of preeclampsia. However, only a few studies have investigated the association between preeclampsia and long-term cardiovascular disease in Asian populations, although there could be racial/ethnic differences in the risk of cardiovascular diseases. Therefore, we aimed to evaluate the long-term effects of preeclampsia on cardiovascular disease in an Asian population. This study included 68,658 parous women in the Health Examinees Study (HEXA) cohort of South Korea and compared the risk of long-term cardiovascular disease, including ischemic heart disease and stroke, according to the history of preeclampsia. We also performed a meta-analysis combining current study data with data from existing literature in the Asian population. Among the study population, 3413 (5.23%) women had a history of preeclampsia, and 767 (1.12%) and 404 (0.59%) women developed ischemic heart disease and stroke for 22 years. Women with a history of preeclampsia were at a higher risk for both ischemic heart disease (adjusted hazard ratio 1.66 [1.19–2.04]) and stroke (adjusted hazard ratio 1.48 [1.02–2.16]) than those without. In the meta-analysis, the pooled hazard ratio of ischemic heart disease and stroke were also increased in women with a history of preeclampsia (ischemic heart disease 1.65 [1.51–1.82]; stroke 1.78 [1.52–2.10]).

Abstract 3462: Mendelian randomization analysis of 27 cardiometabolic trait related polygenic scores identifies genetic risk for cardiometabolic and cardiovascular events in a large prospective study of breast cancer survivors

Abstract Background: CVD is the most common cause of non-cancer death in breast cancer patients. Due to cancer treatment-related cardiotoxicities, breast cancer survivors are at increased risk of cardiometabolic disease (CMD) and cardiovascular disease (CVD). In addition to treatment-related factors, behavioral risk factors such as diet, smoking, and obesity are shared between CVD and breast cancer. While clinical factors influencing the risk of CVD in breast cancer patients are well studied, the effects of genetic factors are less known. Methods: To investigate genetic factors contributing to risk of CMD and CVD in women with a history of breast cancer, we performed a Mendelian randomization analysis to explore the relationships between 27 polygenic scores (PGS) for CMD and CVD phenotypes selected from the PGS Catalog and literature and 13 incident CMD and CVD events in a large prospective cohort of 3,699 breast cancer survivors in the Pathways Study. Fine-Gray sub-distribution hazard ratios (HRs) and 95% confidence intervals (CIs) associated with one standard deviation of PGS were derived with adjustment for epidemiologic, clinical, and treatment factors. The time scale was defined as time since date of breast cancer diagnosis to first of incident event, health plan disenrollment, death, or end of study (12/31/2019). The proportional hazards assumption was tested using Schoenfeld residuals, and no violation was found. Results: We identified 19 PGS-CMD/CVD associations that met Bonferroni significance (P&amp;lt;1.17 × 10−4). Five PGS were associated with increased risk of dyslipidemia: apolipoprotein B (HR=1.52, 95% CI,1.38-1.65), LDL cholesterol (1.49, 1.36-1.63), total cholesterol (1.43, 1.31-1.56), triglyceride levels (1.24, 1.14-1.34), and coronary artery disease (1.22, 1.13-1.33). Four PGS were associated with increased risk of hypertension: systolic blood pressure (1.36, 1.25-1.48), diastolic blood pressure (1.21, 1.11-1.32), fasting glucose adjusted for BMI (1.19, 1.09-1.30), and hypertension (1.41, 1.29-1.54). PGS for atrial fibrillation was associated with increased risk of arrhythmia (1.40, 1.25-1.57) and any cardiovascular disease (1.22, 1.12-1.32). PGS for coronary artery disease and myocardial infarction were both associated with increased risk of ischemic heart disease (1.43, 1.21-1.70 and 1.38, 1.17-1.62, respectively). Conclusion: Our study provides strong evidence for the potential use of PGS to predict the risk of CVD and CMD in women with a history of breast cancer. Future studies may explore the use of PGS to identify women with breast cancer at high risk of CVD-related outcomes and strategies to mitigate this risk. Citation Format: Peter N. Fiorica, Haiyang Sheng, Cecile A. Laurent, Janise M. Roh, Valerie S. Lee, Alexa Zimbalist, Isaac J. Ergas, Qianqian Zhu, Richard K. Cheng, Eileen Rillamas-Sun, Carlos Iribarren, Jamal S. Rana, Mai Nguyen-Huynh, Dawn L. Hershman, Lawrence H. Kushi, Christine B. Ambrosone, Marilyn L. Kwan, Heather Greenlee, Song Yao. Mendelian randomization analysis of 27 cardiometabolic trait related polygenic scores identifies genetic risk for cardiometabolic and cardiovascular events in a large prospective study of breast cancer survivors [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 3462.

Cerebrovascular Complications in Spinal Fusion Surgery: A Nationwide 8-year Follow-up Study in South Korea.

This retrospective study investigated the long-term incidence and risk of postoperative complications following spinal fusion. This study included 640,366 participants from a National Health Examination cohort in the Republic of Korea. Among them, 11,699 individuals underwent spinal fusion, and 56,667 individuals who underwent non-fusion spinal procedures served as controls. Propensity score matching was used to account for patient characteristics including demographic factors, comorbidities, and other relevant variables. The participants were followed for 8 years to assess the occurrence of cerebrovascular disease (CVD), hemorrhagic infarction (HA), ischemic infarction (II), occlusion and stenosis, and ischemic heart disease (IHD). The incidence rates of CVD and IHD were found to be 27.58 and 31.45 per 1,000 person-years in the spinal fusion group compared to 18.68 and 25.73 per 1,000 person-years in the control group (p < .001), respectively. Patients who underwent spinal fusion had a higher risk of CVD, HA, and IHD than those in the control group (all p < .001). In the subgroup analysis, thoracolumbar and noncervical spinal fusion were associated with a higher risk of CVD, II, and IHD (all p < .005). Patients undergoing thoracolumbar fusion may have an increased association with CVD, II in cerebral arteries, and IHD. This suggests a need for careful consideration of vascular risks in such patient populations.

Genetic evidence for T-wave area from 12-lead electrocardiograms to monitor cardiovascular diseases in patients taking diabetes medications.

Aims Many studies indicated use of diabetes medications can influence the electrocardiogram (ECG), which remains the simplest and fastest tool for assessing cardiac functions. However, few studies have explored the role of genetic factors in determining the relationship between the use of diabetes medications and ECG trace characteristics (ETC). Methods Genome-wide association studies (GWAS) were performed for 168 ETCs extracted from the 12-lead ECGs of 42,340 Europeans in the UK Biobank. The genetic correlations, causal relationships, and phenotypic relationships of these ETCs with medication usage, as well as the risk of cardiovascular diseases (CVDs), were estimated by linkage disequilibrium score regression (LDSC), Mendelian randomization (MR), and regression model, respectively. Results The GWAS identified 124 independent single nucleotide polymorphisms (SNPs) that were study-wise and genome-wide significantly associated with at least one ETC. Regression model and LDSC identified significant phenotypic and genetic correlations of T-wave area in lead aVR (aVR_T-area) with usage of diabetes medications (ATC code: A10 drugs, and metformin), and the risks of ischemic heart disease (IHD) and coronary atherosclerosis (CA). MR analyses support a putative causal effect of the use of diabetes medications on decreasing aVR_T-area, and on increasing risk of IHD and CA. ConclusionPatients taking diabetes medications are prone to have decreased aVR_T-area and an increased risk of IHD and CA. The aVR_T-area is therefore a potential ECG marker for pre-clinical prediction of IHD and CA in patients taking diabetes medications.

Abstract P441: Alcohol Consumption and Incident Heart Failure, Ischemic Heart Disease and Atrial Fibrillation Among Current Drinkers: The All of Us Research Program

Background: The Alcohol Use Disorders Identification Test (AUDIT-C) is a clinically validated assessment tool with components that quantify last-year frequency of alcohol use, quantity consumed per drinking day and frequency of binge drinking. We determined the associations between AUDIT-C scores, their components and risks of heart failure (HF), ischemic heart disease (IHD) and atrial fibrillation (AF). Methods: In the NIH-sponsored ‘All of Us’ Research Program, we followed participants free of HF, IHD and AF who had consumed alcohol in the past year. We created Cox proportional hazards models for incident HF, IHD and AF that simultaneously adjusted for all 3 components of the AUDIT-C, sociodemographic factors, prevalent diseases and smoking status. We also created restricted cubic splines (RCS) regression models to determine the dose-response relationships between AUDIT-C scores and incident HF, IHD and AF. Results: The final sample size was 133,025 adults with a mean age of 50 years. There were 1,411 HF, 3793 IHD and 1072 AF cases over a median follow-up of 45 months. RCS demonstrated a J-shape association between total AUDIT-C scores and HF, an L-shaped association with IHD and a positive but non-significant association with AF. For AUDIT-C components, frequency of intake was associated with incident HF and IHD. Compared to drinking monthly or less, drinking 2-4 times/month, 2-3 times/week and 4 or more times per week were all associated with lower risk of incident IHD. Drinking 2-4 times/month and 2-3 times/week were negatively associated with incident HF. We observed no comparable associations of drinking quantity or binge drinking with risk of HF, IHD or AF. Conclusion: The AUDIT-C provides a quick, straightforward, and informative assessment of alcohol consumption. Among current drinkers, drinking frequency is associated with lower risk of HF and IHD but not AF. Greater quantity consumed per drinking day and episodes of binge drinking are not associated with lower risk of major cardiac diseases and should be discouraged.

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

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

Visualization of the Internal Thoracic Arteries in Giant Cell Arteritis on 18 F-FDG Semiconductor PET/CT.

A 72-year-old woman presented with the fever and the pain of skull and face for 2 weeks. 18 F-FDG PET/CT equipped with semiconductor detectors revealed strong uptake not only in the temporal, cervical, subclavian arteries, and aorta, but also in the bilateral internal thoracic arteries. The diagnosis of giant cell arteritis was made. Semiconductor PET can visualize small arteries such as the internal thoracic artery. The patients with giant cell arteritis are at a high risk of ischemic heart disease, and inflammatory involvement of the internal thoracic arteries may affect the outcome of coronary artery bypass grafting.

Statin administration ameliorates ischemia-induced overactive bladder with improvement of blood flow and anti-inflammatory effects in rats.

Statins are widely used to treat dyslipidemia and have been shown to reduce the risk of ischemic heart disease and cerebrovascular disease. The effects of statins on ischemia-induced overactive bladder (OAB) and the associated mechanisms were investigated in a rat model of chronic pelvic ischemia. A pelvic ischemia model was created by iliac arterial injury (AI) and a high-fat diet using male Sprague-Dawley rats. Rats were assigned to 3 groups: control group, AI group, and AI + statin group. The control group underwent sham operation and was fed a normal diet. The AI group underwent AI surgery and was fed a high-cholesterol diet. The AI + statin group was administered a statin for 4 weeks. Cystometry was performed for 8 weeks after surgery. Blood flow was evaluated by laser meter. Thickness of the iliac arteries was measured, and microvascular density in the lamina propria was evaluated by immunostaining for CD31. Expressions of inflammatory cytokines in the bladder were measured by real-time PCR. Cystometry showed a significantly shorter voiding interval and lower bladder capacity in the AI group than in the control group. The AI + statin group showed improvement of these findings. The AI group showed decreased bladder blood flow, increased iliac arterial wall thickening, and decreased microvascular density compared to the control group. Statin administration improved blood flow. Iliac arterial wall thickening was suppressed, and microvascular density was increased by statin administration, though not significantly. Real-time PCR showed significantly higher expressions of inflammatory cytokines (IL-6, IL-8, and TNF-α) in the AI group than in the control group, and IL-6 and IL-8 expressions were lower in the AI + statin group than in the AI group. The present results suggest that statins are effective in OAB caused by arteriosclerosis and ischemia. The mechanism of their effects involves improved bladder blood flow and decreased bladder inflammation.

Association between osteoarthritis and cardiovascular disease in elderly in Japan: an administrative claims database analysis

ObjectiveTo investigate whether osteoarthritis (OA) is a risk factor for cardiovascular disease (CVD); whether there are differences concerning ischaemic heart disease (IHD), congestive heart failure (CHF) and stroke; and whether...

Genetic Variants Linked to Myocardial Infarction in Individuals with Non-Alcoholic Fatty Liver Disease and Their Potential Interaction with Dietary Patterns.

In recent studies, non-alcoholic fatty liver disease (NAFLD) has been associated with a high risk of ischemic heart disease. This study aimed to investigate a genetic variant within a specific gene associated with myocardial infarction (MI) among patients with NAFLD. We included 57,205 participants from a Korean genome and epidemiology study. The baseline population consisted of 45,400 individuals, with 11,805 identified as patients with NAFLD. Genome-wide association studies were conducted for three groups: the entire sample, the healthy population, and patients with NAFLD. We defined the p-value < 1 × 10-5 as the nominal significance and the p-value < 5 × 10-2 as statistically significant for the gene-by-nutrient interaction. Among the significant single-nucleotide polymorphisms (SNPs), the lead SNP of each locus was further analyzed. In this cross-sectional study, a total of 1529 participants (2.8%) had experienced MI. Multivariable logistic regression was performed to evaluate the association of 102 SNPs across nine loci. Nine SNPs (rs11891202, rs2278549, rs13146480, rs17293047, rs184257317, rs183081683, rs1887427, rs146939423, and rs76662689) demonstrated an association with MI in the group with NAFLD Notably, the MI-associated SNP, rs134146480, located within the SORCS2 gene, known for its role in secreting insulin in islet cells, showed the most significant association with MI (p-value = 2.55 × 10-7). Our study identifies candidate genetic polymorphisms associated with NAFLD-related MI. These findings may serve as valuable indicators for estimating MI risk and for conducting future investigations into the underlying mechanisms of NAFLD-related MI.