Risk Of Ischemic Heart Disease Research Articles

Associations of the serum n-6 PUFA concentrations with exercise-induced myocardial ischaemia in middle-aged and older men.

n-6 PUFA, especially linoleic acid (LA) but also arachidonic acid (AA), have been inversely associated with CHD. However, mechanisms underlying these associations are not fully known. We investigated the associations of the serum concentrations of total n-6 PUFA, LA, AA, γ-linolenic acid (GLA) and dihomo-γ-linolenic acid (DGLA), with the odds of myocardial ischaemia during exercise, a predictor of future cardiac events. A total of 1871 men without a history of CHD from the Kuopio Ischaemic Heart Disease Risk Factor Study (KIHD) aged 42-60 years were included. All participants performed a maximal symptom-limited exercise stress test, using an electrically braked bicycle ergometer. Multivariable-adjusted logistic regression was used to assess the OR for exercise-induced myocardial ischaemia in quartiles of the serum n-6 PUFA concentrations. After multivariable adjustment, men in the highest v. the lowest serum AA concentration had 50 % lower odds for exercise-induced myocardial ischaemia (OR 0·50, 95 % CI 0·34, 0·76; P-trend across quartiles < 0·001). For the other PUFA, the OR (95 % CI) were 1·00 (0·69, 1·46; P-trend = 0·89) for LA, 1·07 (0·75, 1·53; P-trend = 0·40) for GLA and 0·74 (0·51, 1·07; P-trend = 0·16) for DGLA. Among the n-6 PUFA, higher serum concentration of AA was associated with lower odds for myocardial ischaemia during an exercise test in middle-aged and older men. This may provide one mechanism for the previously observed possible cardioprotective properties of AA. Our findings also suggest that n-6 PUFA should not be considered as one homogenous group.

Non-fermented and fermented milk intake in relation to risk of ischemic heart disease and to circulating cardiometabolic proteins in swedish women and men: Two prospective longitudinal cohort studies with 100,775 participants

BackgroundThe effect of milk on the risk of ischemic heart disease (IHD) and acute myocardial infarction (MI) is unclear. We aimed to examine the association between non-fermented and fermented milk consumption on these endpoints and investigate the relationship between milk intake and cardiometabolic-related proteins in plasma.MethodsOur study is based on two Swedish prospective cohort studies that included 59,998 women and 40,777 men without IHD or cancer at baseline who provided repeated measures of diet and lifestyle factors and plasma proteomics data in two subcohorts. Through registry linkage, 17,896 cases with IHD were documented during up to 33 years of follow-up, including 10,714 with MI. We used time-updated multivariable Cox regression analysis to examine non-fermented or fermented milk intake with time to IHD or MI. Using high-throughput multiplex immunoassays, 276 cardiometabolic plasma proteins were measured in two subcohorts. We applied multivariable-adjusted regression models using a discovery-replication design to examine protein associations with increasing consumption of non-fermented or fermented milk.ResultsThe results for non-fermented milk differed by sex (p-value for interaction = 0.01). In women, we found a pattern of successively greater risk of IHD and MI at non-fermented milk intake levels higher than 1.5 glasses/day. Compared with an intake of 0.5 glass/day (100 mL/day), non-fermented milk intake of 2 glasses/day in women conferred a multivariable-adjusted hazard ratio (HR) of 1.05 (95% CI 1.01–1.08) for IHD, an intake of 3 glasses/day an HR of 1.12 (95% CI 1.06–1.19), and an intake of 4 glasses/day an HR of 1.21 (95% CI 1.10–1.32). Findings were similar for whole, medium-fat, and low-fat milk. We did not detect higher risks of IHD with increasing milk intakes in men. Fermented milk intake was unrelated to the risk of IHD or MI in either sex. Increasing non-fermented milk intake in women was robustly associated with a higher concentration of plasma ACE2 and a lower concentration of FGF21.ConclusionsWe show a positive association between high amounts of non-fermented milk intake and IHD in women but not men. We suggest metabolic pathways related to ACE2 and FGF21 potentially underlie the association.Graphical abstractOur analysis of two large cohort studies involving 100,775 participants and 17,896 clinically confirmed IHD events supports a dose–response positive association between non-fermented milk intake higher than 300 mL/day with higher rates of IHD (and acute MI specifically) in women, but not in men. The higher risk of IHD with high milk intake in women was evident, irrespective of the fat content of the milk. Fermented milk intake was unrelated to the risk of IHD in both women and men. Non-fermented milk intake was associated in different directions with circulating levels of ACE2 and FGF21 in women—two essential cardiometabolic proteins, also related to IHD in women in our study.

Causal Pathways Between Breast Cancer and Cardiovascular Disease Through Mediator Factors: A Two-Step Mendelian Randomization Analysis.

The causal relationship of breast cancer (BC) with cardiovascular disease (CVD) and the underlying mediating pathways remains elusive. Our study endeavors to investigate the causal association between BC and CVD, with a focus on identifying potential metabolic mediators and elucidating their mediation effects in this causality. In this study, we conducted two-sample Mendelian randomization (MR) to estimate the causal effect of BC (overall BC, ER+ BC, ER- BC) from the Breast Cancer Association Consortium (BCAC) on CVD including coronary heart disease (CHD), hypertensive heart disease (HHD), ischaemic heart disease (IHD), and heart failure (HF) from the FinnGen consortium. Then, we used two-step MR to evaluate 18 metabolic mediators of the association and calculate the mediated proportions. Genetically predicted ER+ BC was causally associated with an increased risk of CVD including CHD (OR = 1.034, 95% CI: 1.004-1.065, p = 0.026), HHD (OR = 1.061, 95% CI: 1.002-1.124, p = 0.041), IHD (OR = 1.034, 95% CI: 1.007-1.062, p=0.013), and HF (OR = 1.055, 95% CI: 1.013-1.099, p = 0.010), while no causality was observed for overall BC and ER- BC. Furthermore, high-density lipoprotein cholesterol (HDL-C) was identified as a mediator of the association between ER+BC and CVD, including CHD (with 15.2% proportion)) and IHD (with 15.5% proportion), respectively. This study elucidates the potential causal impact of ER+ BC on subsequent risk of CVD, including CHD, HHD, IHD, and HF. We also outline the metabolic mediator HDL-C as a priority target for preventive measures to reduce excessive risk of CVD among patients diagnosed with ER+BC.

Cardiovascular disease risk after breast cancer treatment in patients with a BRCA1/2 pathogenic variant.

Breast cancer (BC) treatment can induce adverse events, such as cardiovascular disease (CVD). Defective DNA repair, as in carriers of BRCA1/2 pathogenic variants (BRCA1/2pv), may contribute to CVD risk. We aimed to study if female BRCA1/2pv carriers are more sensitive to develop CVD after BC treatment than BC patients without a known BRCA1/2pv. In a hospital-based cohort of 17,300 female BC patients, we identified 509 BRCA1/2pv carriers. Cardiovascular morbidity and mortality were assessed through hospital charts and general practitioner questionnaires. We performed Cox regression analyses comparing BRCA1/2pv carriers with all other BC patients, adjusting for age, radiotherapy regimen, chemotherapy regimen, and smoking status. Median follow-up time since BC treatment was 14years. In total, 1108 women experienced ischemic heart disease (IHD), of whom 20 (1.8%) were BRCA1/2pv carriers. Heart failure (HF) was diagnosed in 638 women, of whom 10 (1.6%) were BRCA1/2pv carriers. BRCA1/2pv carriership was associated with a slight not statistically significant increase of IHD (adjHR 1.51, 95%CI 0.93; 2.42), but not with risk of HF (adjHR 0.86, 95%CI 0.44; 1.69). The association between radiotherapy and IHD risk was not significantly different between BRCA1/2pv carriers [HR 2.30 (95%CI 0.79; 6.66)] and other BC patients (HR 1.50, 95%CI 1.30; 1.73). Associations between anthracycline-based chemotherapy and HF risk also did not differ between carriers and other BC patients (HRs of 4.02 (95%CI 1.02; 15.77) and 2.31 (95%CI 1.77; 3.01), respectively). In BRCA1/2pv BC patients, we found no evidence for a higher risk of BC treatment-related CVD than in other BC patients.

Using Genetics to Assess the Role of Acetate in Ischemic Heart Disease, Diabetes, and Sex-Hormone-Related Cancers: A Mendelian Randomization Study.

Acetate, a short-chain fatty acid, has gained attention for its contrasting roles, with evidence suggesting it may offer cardiovascular protection but also promote cancer, particularly those involving sex hormones. However, these influences have been scarcely assessed in epidemiological research. To investigate the relationship between acetate and ischemic heart disease (IHD), diabetes, and cancers related to sex hormones. Mendelian randomization (MR) was used to assess potential causal effects, selecting genetic variants without linkage disequilibrium (r2 < 0.001) and with genome-wide significance for acetate (p < 5 × 10-8). These variants were applied to large genome-wide association studies (GWAS) for ischemic heart disease (IHD; up to 154,373 cases), diabetes (109,731 cases), and five sex-hormone-related cancers (breast, colorectal, prostate, ovarian, and endometrial cancers, ranging from 8679 to 122,977 cases). We employed various methods for analysis, including penalized inverse variance weighting (pIVW), inverse variance weighting, weighted mode, and weighted median. This study indicates that acetate may be associated with a lower risk of ischemic heart disease (IHD), with an odds ratio (OR) of 0.62 per standard deviation (SD) increase in acetate and a 95% confidence interval (CI) of 0.39 to 0.98. Additionally, acetate was linked to a higher breast cancer risk, with an OR of 1.26 and a 95% CI ranging from 1.08 to 1.46. This association remained robust across multiple sensitivity analyses. Acetate, along with factors that influence its activity, may serve as possible targets for breast cancer treatment and possibly IHD, offering opportunities for new drug development.

Relationship between lipoprotein(a) and endogenous fibrinolytic status in patients with STEMI

Abstract Background The risk of myocardial infarction is at least doubled in individuals with lipoprotein(a) (Lp[a]) levels &amp;gt;90th percentile.[1] Lp(a) may exert pro-thrombotic effects by impairing fibrinolysis. Lp(a) has a high degree of homology to plasminogen and can competitively inhibit tissue plasminogen activator (tPA)-mediated plasminogen activation and tPA-mediated clot lysis.[2] Furthermore, Lp(a) stimulates the activity of plasminogen activator inhibitor-1, the major inhibitor of the fibrinolytic system. In patients with ST-segment elevation myocardial infarction (STEMI), impaired endogenous fibrinolysis is a strong, independent risk factor for recurrent cardiovascular events,[3] but the drivers of this are not fully understood. Whether impaired endogenous fibrinolysis is related to increased Lp(a) levels in patients with STEMI, is not known. Purpose We aimed to assess the relationship between Lp(a) and endogenous fibrinolysis in patients with STEMI. Methods In a prospective, observational study, venous blood samples were drawn from patients presenting with STEMI immediately before revascularisation, after dual antiplatelet therapy but before heparin administration. Endogenous fibrinolysis was measured immediately in non-anticoagulated whole blood using the point-of-care Global Thrombosis Test, which measures the time for occlusive thrombus formation under high shear (occlusion time) and the time for spontaneous lysis of the thrombus (lysis time).[3] Assessment of Lp(a) levels, measured by particle enhanced immunoturbidimetric assay, was performed with paired plasma samples, standardized against the International Federation of Clinical Chemistry reference material SRM2B for nmol/L. Lp(a) &amp;gt;32 nmol/L is associated with increased risk of ischaemic heart disease. Results A total of 80 patients were included (age 64±14y, 25% females and 86% Caucasian). There was a positive correlation between Lp(a) level and lysis time (r = 0.330, P = 0.003) (Figure 1). Lysis time was significantly longer in patients with Lp(a) &amp;gt;32 nmol/L (2782 [1626-3683] vs. 1725 [1259-2955] s, P = 0.044). Using a cut-point of lysis time ≥2500 s previously associated with a significantly increased cardiovascular risk in patients with STEMI, we showed that Lp(a) was significantly higher in patients with lysis time ≥2500 s (40 (22-111) vs. 18 (7-73) nmol/L, P = 0.045). Table 1 shows the relationship between clinical characteristics and Lp(a) and lysis time. Lp(a) level was higher in non-Caucasian patients. There was no correlation between Lp(a) and occlusion time (r = 0.156, P = 0.168). Conclusion In patients with STEMI, longer endogenous fibrinolysis time is related to higher Lp(a) level. Raised Lp(a) levels may, in part, contribute to impaired endogenous fibrinolysis. Future studies are required to assess whether reduction in Lp(a) with novel therapies currently in phase 3 trials can favourably modulate fibrinolysis and improve clinical outcomes.Figure 1

Antibodies against phosphorylcholine in prediction of cardiovascular disease among women: a population-based prospective cohort study

Abstract Background and aims Antibodies against phosphorylcholine (anti-PC) have been reported as associated with protection against atherosclerosis, cardiovascular disease (CVD) and other chronic inflammatory diseases. Underlying potential mechanisms have been demonstrated and include anti-inflammatory, clearance of dead cells and inhibition of oxidized low-density lipoprotein-effects. The aim is to study the role of IgM anti-PC and incident CVD among women, where less is known than among men in the general population. Methods In a total of 932 women, 66 ± 6 years old at baseline, from the population-based Swedish Mammography Cohort IgM anti-PC levels of sera were measured using ELISA. Prospective associations with any first CVD, ischemic heart disease (IHD), myocardial infarction (MI) and ischemic stroke were assessed using Cox proportional hazard regression, generating hazard ratios (HR) and 95% confidence intervals (CI). The model was adjusted for potential confounding factors. Results Over the course of 16 years (14,900 person-years), we identified 113 cases of composite CVD, - 69 cases of ischemic heart disease (IHD), 44 cases of myocardial infarction (MI) and 50 cases of ischemic stroke. IgM antiPC was statistically significantly inversely associated with risk of CVD, IHD and MI, but not with ischemic stroke. Comparing the highest tertile with lowest, we observed multivariable-adjusted HR of 0.26 (95% CI: 0.10–0.66; p-trend &amp;lt;0.01) for MI. Conclusions IgM anti-PC may play an active role in inhibition of CVD development in women, especially MI. Elevating anti-PC concentration through immunization, may be a future development in CVD prevention.

Association Between TTV Viremia, Chronic Inflammation, and Ischemic Heart Disease Risk: Insights From MARK-AGE and Report-Age Projects.

The implication of Torquetenovirus (TTV) in ischemic heart disease (IHD) has not been thoroughly explored. This study investigated the association between TTV viremia, pro-inflammatory cytokines, and IHD risk in an aging population. This cross-sectional study included 900 non-IHD subjects and 86 individuals with IHD (aged 55-75 years) selected from the MARK-AGE project. Results were verified in another independent Report-Age cohort, including 94 inpatients with chronic IHD and 111 inpatients with non-IHD (aged 65-96 years). Multivariable logistic regression in the MARK-AGE cohort revealed that male sex, TTV viremia ≥4log, Cu/Zn ratio, diabetes, hypertension, and smoking were significant IHD predictors. Notably, TTV viremia ≥4log independently increased the IHD risk (odds ratio [OR]: 2.51, 95% confidence interval [CI]: 1.42-4.43), confirmed in the Report-Age cohort (OR: 4.90, 95% CI: 2.32-10.39). In a RASIG subgroup, individuals with TTV viremia ≥4 log, both with and without IHD, exhibited increased plasma pro-inflammatory cytokine levels (IFN-γ, IL-1β, IL-6, IL-10, IL-12p70, TNF-α) compared to those with TTV viremia <4 log. No significant difference in cytokine production was observed between IHD patients and non-IHD with TTV viremia ≥4 log. A positive correlation between TTV viremia and DNA methylation estimator of leukocyte telomere length was observed in Report-Age patients. Additionally, IHD Report-Age patients with TTV viremia ≥4 log displayed higher NLR and SIRI index than those with TTV viremia <4 log. In conclusion, a high TTV viremia is associated with an elevated IHD risk in the older population, potentially arising from an augmented pro-inflammatory response and immunosenescence.

Association of left ventricular ejection fraction with risk of cardiovascular diseases: a prospective cohort study

Left ventricular ejection fraction (LVEF) is the most ubiquitous parameter in cardiac imaging examinations, we aimed to investigate the associations between subtle changes of LVEF and risk of common cardiovascular diseases. This is a prospective cohort study based on UK Biobank. LVEF was obtained from cardiac magnetic resonance. Incident cardiovascular disease was the outcome, including heart failure, atrial fibrillation, ischemic heart disease, and myocardial infarction. Cox proportional hazard model was the main method. A U-shaped relationship was observed between quantified LVEF and cardiovascular events risk with the nadir at the LVEF of 55–64%. As compared to moderate LVEF (55–64%), both low (40–54%) and high LVEF ( ≥ 5%) were related to higher risk of cardiovascular diseases after adjusting for confounders (HRlow = 1.15, 95%CI = 1.02–1.30; HRhigh = 1.34, 95%CI = 1.05–1.72). Specifically, low LVEF was associated with increased risk of heart failure while high LVEF predominantly predicted elevated risk of ischemic heart diseases, both low and high LVEF were related to a borderline higher incidence of atrial fibrillation. Besides, associations with specific cardiovascular diseases varied by age, sex or comorbidities. There was a U-shaped relationship between LVEF and cardiovascular events risk with the nadir at the LVEF of 55–64%, while these associations were disease-specific and varied by age, sex or comorbidities.

Differences in the Adverse Event Profiles of Sodium-Glucose Cotransporter 2 Inhibitors used in Patients with DiabetesMellitus and Heart Failure: An Analysis Using the Japanese Adverse Drug Event Report Database.

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have recently become a standard treatment for heart failure and renal failure. The number of patients using these drugs is expected to increase further. However, no adverse drug event profiles have been published for the use of SGLT2i in patients without diabetes. To analyze and clarify the differences in adverse event profiles associated with the use of SGLT2i in patients with diabetes or heart failure using the Japanese Adverse Drug Event Report (JADER) database, a Japanese reporting system for adverse events. The JADER database, containing reports submitted between April 2004 and January 2024, was used. Our study focused on patients with diabetes or heart failure, analyzing adverse events associated with empagliflozin and dapagliflozin. The reporting odds ratio (ROR) and 95% confidence interval (CI) were calculated for signal detection. We identified risks of adverse drug events such as ketoacidosis, urinary tract infection, dehydration, and acidosis in both patient groups. However, the risks of cerebral infarction and ischemic heart disease were identified only in patients with diabetes, while risks of renal dysfunction, hypoglycemia, and sepsis were identified only in those with heart failure. Adverse events should be managed appropriately for patients using SGLT2i, as the adverse event profiles differ between those with diabetes and those with heart failure. Understanding these differences is crucial for improving patient safety and optimizing treatment outcomes.

Proteomic Signature of BMI and Risk of Cardiovascular Disease.

Obesity, defined by body mass index (BMI) alone, is a metabolically heterogeneous disorder with distinct cardiovascular manifestations across individuals. This study aimed to investigate the associations of a proteomic signature of BMI with risk of major subtypes of cardiovascular disease (CVD). A total of 40 089 participants from UK Biobank, free of CVD at baseline, had complete data on proteomic data measured by the Olink assay. A BMI-proteomic score (pro-BMI score) was calculated from 67 pre-identified plasma proteins associated with BMI. A higher pro-BMI score was significantly associated with higher risks of ischemic heart disease (IHD) and heart failure (HF), but not with risk of stroke. Comparing the highest with the lowest quartiles, the adjusted hazard ratio (HR) for IHD was 1.49 (95% CI, 1.32-1.67) (P-trend < 0.001), and the adjusted HR for HF was 1.52 (95% CI, 1.25-1.85) (P-trend < 0.001). Further analyses showed that the association of pro-BMI score with HF risk was largely driven by the actual BMI, whereas the association of the pro-BMI score with IHD risk was independent of actual BMI and waist-to-hip ratio (WHR). The association between pro-BMI score and IHD risk appeared to be stronger in the normal BMI group than other BMI groups (P-interaction = 0.004) and stronger in the normal WHR group than the high WHR group (P-interaction = 0.049). Higher pro-BMI score is significantly associated with higher IHD risk, independent of actual BMI levels. Our findings suggest that plasma proteins hold promise as complementary markers for diagnosing obesity and may facilitate personalized interventions.

Major Adverse Cardiovascular Events Following Coronary Artery Stenting by History of Hypertensive Disorder of Pregnancy.

A history of hypertensive disorders of pregnancy is associated with at least twice the risk of incident ischemic heart disease. Whether the long-term outcome following treatment with coronary artery stenting is associated to the history of hypertensive disorders of pregnancy is unknown. We included 8364 women (age ≤65 years) undergoing first coronary artery stenting 2006 to 2022 following their first delivery in 1973 or later, linking nationwide data on percutaneous coronary intervention and delivery history. In total, 1122 women (13.4%) had a history of hypertensive disorders of pregnancy. The main outcome, a major adverse cardiovascular event, was defined as any incident myocardial infarction, ischemic heart disease, cardiac arrest, arrhythmias, angina pectoris, heart failure, cerebral infarction, or sudden death. During a median follow-up time of 5 years, 258 women with a history of hypertensive disorders of pregnancy had a major adverse cardiovascular event, compared with 1465 women without a history of hypertensive disorders of pregnancy (23% versus 20.2%, P=0.028 for log-rank test). Estimates adjusted for patient- and procedural characteristics in proportional hazards regression models suggested that the hazard rate increased only after 4-8 years of follow-up (hazard ratio [HR], 1.36 [95% CI, 1.05-1.78]) and was primarily driven by women with history of gestational hypertension (HR, 2.15 [95% CI, 1.49-3.11]). Women with a history of hypertensive disorders of pregnancy have an increased risk of a major adverse cardiovascular event following coronary artery stenting compared with other parous women. A history of hypertensive disorders of pregnancy warrants further attention in the secondary prevention setting of coronary artery disease.

Pioglitazone increases risk of ischemic heart disease in patients with type 2 diabetes receiving insulin

AimStudies evaluating the cardiovascular safety of pioglitazone show inconsistent results and ischemic heart disease (IHD) risks associated with different anti-diabetic drugs added to metformin uncontrolled type 2 diabetes mellitus (T2DM) are not assessed. This study aimed to evaluate IHD risk associated with pioglitazone and/or insulin added to patients with metformin uncontrolled T2DM. MethodsData were extracted from the National Health Insurance Research Database of Taiwan. A total of 19,952 patients with T2DM uncontrolled on metformin received pioglitazone and/or insulin added to metformin were included. ResultsCompared to those who never received pioglitazone and/or insulin, patients receiving both insulin and pioglitazone had higher cumulative risk of IHD (adjusted HR [aHR] = 1.911, 95 % confidence interval [CI]: 1.506–2.351), pioglitazone alone (aHR = 1.446, 95 % CI: 1.111–1.775), and insulin alone (aHR = 1.351, 95 % CI: 1.1052–1.684) (all, p < 0.05). Patients who received both pioglitazone and insulin had a higher cumulative risk of IHD than those who received insulin or pioglitazone as well as a similar result in the cumulative defined daily dose (cDDD) of the drugs. ConclusionAdministering pioglitazone plus insulin to patients with T2DM uncontrolled on metformin may increase the risk of IHD, suggesting that other second-line anti-diabetes drugs may be a better choice for patients with T2DM uncontrolled on metformin.

Luteinizing hormone is independently associated with high-sensitive cardiac troponin T elevation in postmenopausal T2DM patients: A cross-sectional study.

It is known that the risk of ischemic heart disease increases in patients with type 2 diabetes mellitus (T2DM). For female patients, the incidence of heart disease can be even greater after menopause, accompanied by dramatic changes in sex hormones. We investigated the correlations between sex hormones and markers of ischemic heart diseases in postmenopausal females with T2DM patients. This cross-sectional study collected data from 324 hospitalized postmenopausal females with T2DM. Multiple linear regression analyses were conducted to determine the correlations between sex hormones and cardiac markers including high-sensitive cardiac troponin T (hs-cTnT) and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) levels. Multiple linear regression analyses revealed that luteinizing hormone (LH) was positively and independently associated with hs-cTnT concentrations in postmenopausal females with T2DM (β = 0.189, p = 0.002). Postmenopausal females with T2DM and subclinical myocardial injury had higher LH levels than those without subclinical myocardial injury (29.67 vs. 25.08 mIU/mL, p < 0.001). A multivariate logistic regression analysis confirmed an independent and significant association between elevated LH and subclinical myocardial injury in postmenopausal females with T2DM (adjusted odds ratio [OR] = 1.077, 95% confidence interval [CI], 1.033-1.124; p < 0.001). As another gonadotropin, the follicle-stimulating hormone did not show independent correlations with hs-cTnT or NT-proBNP (p > 0.05). Neither estrogen nor testosterone was correlated with cardiac markers. Elevated LH levels were positively and independently associated with increased hs-cTnT levels in postmenopausal women with T2DM. Our findings suggest that LH could serve as a potential marker for assessing the risk of subclinical myocardial injury in postmenopausal females with T2DM.

Progressive T1 high-intensity plaques in carotid stenosis: Comparative MRI analyses in asymptomatic and symptomatic phases of low-grade stenosis

Background and PurposeCarotid artery stenosis, particularly the progression from asymptomatic to symptomatic lesions, is a key factor in cerebrovascular events. This study identifies predictors of symptom development in low-grade carotid stenosis (<50%), focusing on intraplaque hemorrhage (IPH) and dynamic plaque changes. Materials and MethodsWe conducted a retrospective study analyzing 30 cases of symptomatic low-grade carotid stenosis, using carotid MRI before and after symptom onset. Key measures included relative plaque signal intensity (rSI) and high-intensity plaque (HI plaque) volume. Stepwise regression analysis examined the influence of these factors on Symptomatic rSI, Symptomatic plaque volume, and NIHSS scores. ResultsSignificant increases were observed in rSI (1.32 ± 0.32 to 1.69 ± 0.25, p < 0.001) and HI plaque volume (296.4 ± 362.7 mm³ to 717.5 ± 554.9 mm³, p < 0.001) from asymptomatic to symptomatic phases. Past smoking (p = 0.008) and statin use (p = 0.04) were associated with higher Symptomatic rSI, while poor risk factor control (p = 0.03) was negatively associated. Female sex (p = 0.007) and current smoking (p = 0.009) were linked to smaller Symptomatic plaque volumes, while ischemic heart disease (p = 0.0002) and poor risk factor control (p = 0.002) predicted larger plaque volumes. Larger plaques were correlated with higher NIHSS scores (p = 0.002). ConclusionsIPH and plaque volume are key markers of progression in low-grade carotid stenosis. Poor control of cardiovascular risk factors and a history of ischemic heart disease contribute to plaque burden and stroke severity. Continuous monitoring and strict risk management are essential in reducing stroke severity in these patients.

Long-Term Exposure to Arsenic in Community Water Supplies and Risk of Cardiovascular Disease among Women in the California Teachers Study.

Inorganic arsenic in drinking water (wAs) is linked to atherosclerosis and cardiovascular disease. However, risk is uncertain at lower levels present in US community water supplies (CWS), currently regulated at the federal maximum contaminant level of . We evaluated the relationship between long-term wAs exposure from CWS and cardiovascular disease in the California Teachers Study cohort. Using statewide health care administrative records from enrollment through follow-up (1995-2018), we identified fatal and nonfatal cases of ischemic heart disease (IHD) and cardiovascular disease (CVD). Participants' residential addresses were linked to a network of CWS boundaries and annual wAs concentrations (1990-2020). Most participants resided in areas served by a CWS (92%). Exposure was calculated as a time-varying, 10-year moving average up to a participant's event, death, or end of follow-up. Using Cox models, we estimated hazard ratios (HRs) and 95% confidence intervals (95% CIs) for the risk of IHD or CVD. We evaluated wAs exposure categorized by concentration thresholds relevant to regulation standards (, 1.00-2.99, 3.00-4.99, 5.00-9.99, ) and continuously using a log2-transformation (i.e., per doubling). Models were adjusted for baseline age, neighborhood socioeconomic status, race/ethnicity, body mass index (BMI), and smoking status. We also stratified analyses by age, BMI, and smoking status. Our analysis included 98,250 participants, 6,119 IHD cases, and 9,936 CVD cases. The HRs for IHD at concentration thresholds (reference, ) were 1.06 (95% CI: 1.00, 1.12), 1.05 (95% CI: 0.94, 1.17), 1.20 (95% CI: 1.02, 1.41), and 1.42 (95% CI: 1.10, 1.84) for , , , and , respectively. HRs for every doubling of wAs exposure were 1.04 (95% CI: 1.02, 1.06) for IHD and 1.02 (95% CI: 1.01, 1.04) for CVD. We observed statistically stronger risk among those vs. years of age at enrollment ( and 0.012 for IHD and CVD, respectively). Long-term wAs exposure from CWS, at and below the regulatory limit, may increase cardiovascular disease risk, particularly IHD. https://doi.org/10.1289/EHP14410.

Association between Metabolic Syndrome and the Severity of Ischemic Heart Disease

Ischemic Heart Disease (IHD) was a leading cause of mortality worldwide, often complicated by metabolic syndrome, which includes hypertension, hyperglycemia, and dyslipidemia. Objective: To investigate the association between metabolic syndrome and the severity of ischemic heart disease. Methods: Data were collected from the cohort’s existing records, including clinical assessments, laboratory tests, and self-reported questionnaires. Metabolic syndrome components were evaluated using the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) criteria. Participants were classified as having metabolic syndrome if they met three or more of the following criteria: abdominal obesity, elevated blood pressure, elevated fasting glucose, high triglycerides, and low HDL cholesterol. IHD incidence was determined through medical records, hospital admissions, and mortality data, defined as non-fatal myocardial infarction, unstable angina, or coronary revascularization. Statistical analysis included calculating the incidence rate of IHD for participants with and without metabolic syndrome, expressed as IHD cases per 1,000 person-years. Cox proportional hazards regression models were used to assess the association between metabolic syndrome and IHD incidence, adjusting for confounders such as age, sex, smoking status, physical activity, and family history of cardiovascular disease. Hazard Ratios (HRs) with 95% Confidence Intervals (CIs) were reported. Results: The incidence of IHD was significantly higher in participants with metabolic syndrome. Cox regression showed metabolic syndrome was associated with increased IHD incidence (HR: 2.70, 95% CI: 1.50–4.80, p &lt; 0.001). Conclusion: Metabolic syndrome was significantly associated with IHD incidence. Early identification and management were essential to reduce IHD risk.

Association Between Triglyceride Glucose Index and Triglyceride Glucose-Obesity Composite Indices and the Risk of Ischemic Heart Disease

To explore the association between the triglyceride-glucose index (TyG) and TyG-obesity composite indices, including TyG-waist circumference (TyG-WC), TyG-body mass index (TyG-BMI), and TyG-waist-to-height ratio (TyG-WHtR), and the risk of ischemic heart disease (IHD), and to provide reference for the prevention of IHD. The sample of this study was derived from the West China Elderly Preventive and Treatment Merging Cohort, from which 9628 elderly individuals from the retrospective cohort were selected. Cox regression models were used to analyze the association between TyG-related indices and the risk of IHD. Receiver operating characteristic (ROC) curves were plotted to assess and compare the performance of TyG-related indices in predicting the occurrence of IHD. The participants were followed up for a median of 2.82 years, with 7.2% (694/9628) of the participants experiencing IHD events. Multivariate Cox regression showed that after controlling for the covariates, including sex, age, educational attainment, smoking, drinking, exercise, dietary habits, medication history, and whether the participant had hypertension, every time TyG, TyG-WC, TyG-BMI and TyG-WHtR increased by one standard deviation (SD), the risk of IHD increased by 12% (hazard ratio [HR]=1.12, 95% confidence interval [CI]: 1.04-1.20), 21% (HR=1.21, 95% CI: 1.12-1.31), 20% (HR=1.20, 95% CI: 1.12-1.29), and 19% (HR=1.19, 95% CI: 1.10-1.28), respectively. Both the TyG index and TyG-obesity composite indices were positively correlated with IHD risk, showing a linear relationship (P<0.05). TyG-WC (area under the curve[AUC]=0.680, 95% CI: 0.660-0.700, P<0.001), TyG-BMI (AUC=0.674, 95% CI: 0.654-0.695, P<0.001), and TyG-WHtR (AUC=0.678, 95% CI: 0.658-0.698, P<0.001) demonstrated better predictive performance than TyG did (AUC=0.669, 95% CI: 0.648-0.689, P<0.001). Elevated levels of TyG and TyG-obesity composite indices were associated with a higher risk for IHD, and combining TyG with BMI, WC, and WHtR may lead to better performance in risk assessment for IHD than using TyG alone.

Adherence to cardiovascular medications and risk of cardiovascular disease in breast cancer patients: A causal inference approach in the Pathways Heart Study

Purpose Women with breast cancer (BC) are at high risk of developing cardiovascular disease (CVD). We examined adherence to CVD medications and their association with major CVD events over 14 years of follow-up in the Pathways Heart Study, a prospective study of 4,776 stage I-III BC patients diagnosed from 2005–2013. Methods Eligibility included being alive 6 months post-BC diagnosis, with dyslipidemia, hypertension, or diabetes at diagnosis along with ≥1 prior outpatient order or dispensing for a statin, anti-hypertensive, or diabetes medication, respectively, in the 30 months prior. Medication adherence was measured from pharmacy data to calculate cumulative average adherence (CAA). Incident heart failure (HF), ischemic heart disease (IHD), and stroke were determined via validated diagnosis and procedure codes. Working marginal structural models (MSM) fitted with inverse probability weighting evaluated the effect of adherence regimens on the hazards for each CVD event, while controlling for baseline and time-varying confounders. MSM parameterizations included: 1) CAA&lt;100% versus CAA = 100% (ref), 2) CAA&lt;80% versus CAA≥80% (ref) and 3) CAA&lt;80% versus 80%≤CAA&lt;100% versus CAA = 100%. Results Poor statin adherence (CAA&lt;80%) was associated with higher risk of composite CVD (HR = 2.54; 95% CI: 1.09, 5.94) versus CAA≥80%. Poor statin adherence was also associated with a higher risk of stroke (HR = 8.13; 95% CI: 2.03, 32.51) but not risk of IHD and HF. Further, compared with perfect adherence (CAA = 100%), good adherence (80%≤CAA&lt;100%) was associated with lower risk (HR = 0.35; 95% CI: 0.13, 0.92) while poor adherence (CAA&lt;80%) was associated with higher risk of composite CVD (HR = 2.45; 95% CI: 1.05, 5.70). Levels of adherence to anti-hypertensives and diabetes medications had mixed or null associations with risk of CVD. Conclusions Maintaining good adherence (≥80%) to statins after BC treatment is beneficial for cardiovascular health in patients with dyslipidemia. Future studies should determine factors associated with lower adherence to statins and ways to improve adherence.

Using proteomics to identify the mechanisms underlying the benefits of statins on ischemic heart disease

Ischemic heart disease (IHD) is the single leading cause of mortality globally. Statins are the mainstay for IHD treatment. However, the specific mechanisms underlying statins’ benefits on IHD have not been clarified. To examine the mechanisms through proteins, we used two-step Mendelian randomization (MR) approach. First, we examined the associations of genetically mimicked statins with 2923 proteins using genome-wide association of proteins from the UK Biobank Pharma Proteomics Project (UKB-PPP) to identify the proteins affected by statins, and replicated the findings using deCODE. Then we examined the associations of selected proteins with IHD risk using CARDIoGRAMplusC4D using MR, and replicated using FinnGen, and using another set of genetic instruments from deCODE. We selected proteins decreased or increased IHD risk and meanwhile increased or lowered by statins. We further examined the role of the selected protein(s) on common IHD comorbidities, including diabetes, chronic kidney disease (CKD), and kidney function (measured by estimated glomerular filtration rate (eGFR)). Nine proteins were affected by statins, including four proteins (PLA2G7, FGFBP1, ANGPTL1, and PTPRZ1) lowered by statins, and five proteins (EFNA4, COL6A3, ASGR1, PRSS8 and PCOLCE) increased by statins. Among these, PLA2G7 was related to higher risk of IHD after controlling for multiple testing. The associations were robust to different analytic methods and replication using another set of genetic instrument from deCODE, and using another GWAS of IHD from FinnGen. Genetically predicted PLA2G7 had null association with diabetes, CKD, and eGFR. We identified 9 proteins affected by statins, including 7 novel proteins which were not reported previously. PLA2G7 is on the pathway underlying statins’ benefits on IHD. The clarification of statins’ mechanisms had close relevance to precision medicine, and provided insights to the development of new treatment strategies.