Cardiovascular Disease Risk Factors Research Articles

Independent Relationship of Lipoprotein(a) and Carotid Atherosclerosis With Long-Term Risk of Cardiovascular Disease.

Lipoprotein(a) (Lp(a)) is considered to be a causal risk factor of atherosclerotic cardiovascular disease (ASCVD), but whether there is an independent or joint association of Lp(a) and atherosclerotic plaque with ASCVD risk remains uncertain. This study aims to assess ASCVD risk independently or jointly conferred by Lp(a) and carotid atherosclerotic plaque. A total of 5471 participants with no history of cardiovascular disease at baseline were recruited and followed up for ASCVD events (all fatal and nonfatal acute coronary and ischemic stroke events) over a median of 11.5 years. Independent association of Lp(a), or the joint association of Lp(a) and carotid plaque with ASCVD risk, was explored using Cox proportional hazards models. Overall, 7.6% of the participants (60.0±7.9 years of age; 2649 [48.4%] men) had Lp(a) ≥50 mg/dL, and 539 (8.4/1000 person-years) incident ASCVD events occurred. Lp(a) concentrations were independently associated with long-term risk of total ASCVD events, as well as coronary events and ischemic stroke events. Participants with Lp(a) ≥50 mg/dL had a 62% higher risk of ASCVD incidence (95% CI, 1.19-2.21) than those with Lp(a) <10 mg/dL, and they exhibited a 10-year ASCVD incidence of 11.7%. This association exists even after adjusting for prevalent plaque. Moreover, participants with Lp(a) ≥30 mg/dL and prevalent plaque had a significant 4.18 times higher ASCVD risk than those with Lp(a) <30 mg/dL and no plaque. Higher Lp(a) concentrations are independently associated with long-term ASCVD risk and may exaggerate cardiovascular risk when concomitant with atherosclerotic plaque.

Cardiovascular disease: extraintestinal manifestation of inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a spectrum of diseases characterized by the interplay of the aberrant immune system, genetic factors, environmental factors, and intestinal microbiota, resulting in relapsing inflammation of the gastrointestinal tract. Underlying pro-inflammatory state and immune dysregulation act as a catalyst for increasing the likelihood of developing extraintestinal manifestations, including cardiovascular diseases (CVD) like atherosclerosis, pericarditis, myocarditis, venous and arterial thromboembolism, arrhythmias, despite a lower prevalence of classic CVD risk factors, like high body mass index or dyslipidemia compared to the general population. Chronic inflammation damages endothelium resulting in the recruitment of inflammatory cells, which induce cytotoxicity, lipoprotein oxidation, and matrix degradation, which increases the risk of atherosclerosis. Additionally, intestinal dysbiosis disrupts the intestinal mucosal barrier, releasing endotoxins and lipopolysaccharides into circulation, further exaggerating the atherosclerotic process. Abnormal collagen metabolism and alteration of nitric oxide-mediated vasodilation lead to blood pressure dysregulation in patients with IBD. Therefore, it is essential to make lifestyle modifications like smoking cessation, dietary changes, and increasing physical activity with adherence to medication to mitigate the risk of developing CVD in patients with IBD. This article reviews the potential links between IBD and the increased risk of CVD in such individuals.

Understanding the spectrum of cardiovascular risk in women - A primer for prevention.

Cardiovascular disease (CVD) is the leading cause of death in women worldwide and the lifetime risk of CVD in women is similar to men. However, the pathophysiology of CVD varies between women and men necessitating a sex-specific understanding of cardiovascular (CV) risk. A belief that women have a lower CVD risk than men, and an underrepresentation in clinical research for many years has led to a paucity of evidence in the prevention and management of CVD in women. Many recent efforts have tried to bridge the gap. As a result, we now know that traditional risk factors impact CVD risk differently in women when compared with men. There are also numerous sex-specific and pregnancy related risk factors that modify the risk and can predict the future development of CVD in women. This is important as risk calculators, in general, tend to misclassify risk in young women with nontraditional CVD risk factors. To address this, guidelines have introduced the concept of risk enhancers that can suggest a higher risk. The use of coronary artery calcium score can further accurately delineate risk in these women, leading to an appropriate matching of therapy to underlying risk. This review discusses implementation strategies that are essential to mitigate disparities in CVD outcomes and optimizing CVD risk in women.

Acoustic Delivery of Plasma Low-Density Lipoprotein into Liver via ApoB100-Targeted Microbubbles Inhibits Atherosclerotic Plaque Growth.

Atherosclerosis is the main risk factor for cardiovascular disease, which accounts for the majority of mortality worldwide. A significantly increased plasma level of low-density lipoprotein cholesterol (LDL-C), surrounded by a monolayer of phospholipids, free cholesterol, and one apolipoprotein B-100 (ApoB-100) in the blood, plays the most significant role in driving the development of atherosclerosis. Commercially available cholesterol-lowering drugs are not sufficient for preventing recurrent cardiovascular events. Developing alternative strategies to decrease the plasma cholesterol levels is desirable. Herein, we develop an approach for reducing LDL-C levels using gas-filled microbubbles (MBs) that were coated with anti-ApoB100 antibodies. These targeted MBApoB100 could selectively capture LDL particles in the bloodstream through forming LDL-MBApoB100 complexes and transport them to the liver for degradation. Further immunofluorescence staining and lipidomic analyses showed that these LDL-MBApoB100 complexes may be taken up by Kupffer cells and delivered to liver cells and bile acids, greatly inhibiting atherosclerotic plaque growth. More importantly, ultrasound irradiation of these LDL-MBApoB100 complexes that accumulated in the liver may induce acoustic cavitation effects, significantly enhancing the delivery of LDL into liver cells and accelerating their degradation. Our study provides a strategy for decreasing LDL-C levels and inhibiting the progression of atherosclerosis.

Blood pressure responses to handgrip exercise but not apnea or mental stress are enhanced in women with a recent history of preeclampsia.

Preeclampsia is a risk factor for future cardiovascular diseases. However, the mechanisms underlying this association remain unclear, limiting effective prevention strategies. Blood pressure responses to acute stimuli may reveal cardiovascular dysfunction not apparent at rest, identifying individuals at elevated cardiovascular risk. Therefore, we compared blood pressure responsiveness to acute stimuli between previously preeclamptic (PPE) women (34±5yr, 13±6 months postpartum) and women following healthy pregnancies (CTRL; 29±3yr, 15±4 months postpartum). Blood pressure (finger photoplethysmography calibrated to manual sphygmomanometry-derived values; PPE: n=12, CTRL: n=12) was assessed during end-expiratory apnea, mental stress, and isometric handgrip exercise protocols. Integrated muscle sympathetic nerve activity (MSNA) was assessed in a subset of participants (peroneal nerve microneurography; PPE: n=6, CTRL: n=8). Across all protocols, systolic blood pressure (SBP) was higher in PPE than CTRL (main effects of group all P<0.05). Peak changes in SBP were stressor-specific: peak increases in SBP were not different between PPE and CTRL during apnea (+8±6 vs. +6±5mmHg, P=0.32) or mental stress (+9±5 vs. +4±7mmHg, P=0.06). However, peak exercise-induced increases in SBP were greater in PPE than CTRL (+11±5 vs. +7±7mmHg, P=0.04). MSNA was higher in PPE than CTRL across all protocols (main effects of group all P<0.05), and increases in peak MSNA were greater in PPE than CTRL during apnea (+44±6 vs. +27±14burst/100hb, P=0.04) and exercise (+25±8 vs. +13±11burst/100hb, P=0.01) but not different between groups during mental stress (+2±3 vs. 0±5burst/100hb, P=0.41). Exaggerated pressor and sympathetic responses to certain stimuli may contribute to the elevated long-term risk for cardiovascular disease in PPE.

More People, More Active, More Often for Heart Health - Taking Action on Physical Activity.

Physical inactivity is a leading contributor to increased cardiovascular morbidity and mortality. Almost 500 million new cases of preventable noncommunicable diseases (NCDs) will occur globally between 2020 and 2030 due to physical inactivity, costing just over US$300 billion, or around US$ 27 billion annually (WHO 2022). Active adults can achieve a reduction of up to 35% in risk of death from cardiovascular disease. Physical activity also helps in moderating cardiovascular disease risk factors such as high blood pressure, unhealthy weight and type 2 diabetes. For people with cardiovascular disease, hypertension, type 2 diabetes and many cancers, physical activity is an established and evidence-based part of treatment and management. For children and young people, physical activity affords important health benefits. Physical activity can also achieve important cross-sector goals. Increased walking and cycling can reduce journeys by vehicles, air pollution, and traffic congestion and contribute to increased safety and liveability in cities.

Drivers of access to cardiovascular health care for rural Indigenous Peoples: a scoping review.

M&#257;ori (the Indigenous Peoples of Aotearoa New Zealand) are disproportionately represented in cardiovascular disease (CVD) prevalence, morbidity and mortality rates, and are less likely to receive evidence-based CVD health care. Rural M&#257;ori experience additional barriers to treatment access, poorer health outcomes and a greater burden of CVD risk factors compared to Non-M&#257;ori and M&#257;ori living in urban areas. Importantly, these inequities are similarly experienced by Indigenous Peoples in other nations impacted by colonisation. Given the scarcity of available literature, a systematic scoping review was conducted on literature exploring barriers and facilitators in accessing CVD health care for rural M&#257;ori and other Indigenous Peoples in nations impacted by colonisation. The review was underpinned by Kaupapa M&#257;ori Research methodology and was conducted utilising Arksey and O'Malley's (2005) methodological framework. A database search of MEDLINE (OVID), PubMed, Embase, SCOPUS, CINAHL Plus, Australia/New Zealand Reference Centre and NZResearch.org was used to explore empirical research literature. A grey literature search was also conducted. Literature based in any healthcare setting providing care to adults for CVD was included. Rural or remote Indigenous Peoples from New Zealand, Australia, Canada, and the US were included. Literature was included if it addressed cardiovascular conditions and reported barriers and facilitators to healthcare access in any care setting. A total of 363 articles were identified from the database search. An additional 19 reports were identified in the grey literature search. Following screening, 16 articles were included from the database search and 5 articles from the grey literature search. The literature was summarised using the Te Tiriti o Waitangi (Treaty of Waitangi) Framework principles: tino rangatiratanga (self-determination), partnership, active protection, equity and options. Themes elucidated from the literature were described as key drivers of CVD healthcare access for rural Indigenous Peoples. Key driver themes included input from rural Indigenous Peoples on healthcare service design and delivery, adequate resourcing and support of indigenous and rural healthcare services, addressing systemic racism and historical trauma, providing culturally appropriate health care, rural Indigenous Peoples' access to family and wellbeing support, rural Indigenous Peoples' differential access to the wider social determinants of health, effective interservice linkages and communication, and equity-driven and congruent data systems. The findings are consistent with other literature exploring access to health care for rural Indigenous Peoples. This review offers a novel approach to summarising literature by situating the themes within the context of equity and rights for Indigenous Peoples. This review also highlighted the need for further research in this area to be conducted in the context of Aotearoa New Zealand.

Exploring machine learning strategies for predicting cardiovascular disease risk factors from multi-omic data

BackgroundMachine learning (ML) classifiers are increasingly used for predicting cardiovascular disease (CVD) and related risk factors using omics data, although these outcomes often exhibit categorical nature and class imbalances. However, little is known about which ML classifier, omics data, or upstream dimension reduction strategy has the strongest influence on prediction quality in such settings. Our study aimed to illustrate and compare different machine learning strategies to predict CVD risk factors under different scenarios.MethodsWe compared the use of six ML classifiers in predicting CVD risk factors using blood-derived metabolomics, epigenetics and transcriptomics data. Upstream omic dimension reduction was performed using either unsupervised or semi-supervised autoencoders, whose downstream ML classifier performance we compared. CVD risk factors included systolic and diastolic blood pressure measurements and ultrasound-based biomarkers of left ventricular diastolic dysfunction (LVDD; E/e' ratio, E/A ratio, LAVI) collected from 1,249 Finnish participants, of which 80% were used for model fitting. We predicted individuals with low, high or average levels of CVD risk factors, the latter class being the most common. We constructed multi-omic predictions using a meta-learner that weighted single-omic predictions. Model performance comparisons were based on the F1 score. Finally, we investigated whether learned omic representations from pre-trained semi-supervised autoencoders could improve outcome prediction in an external cohort using transfer learning.ResultsDepending on the ML classifier or omic used, the quality of single-omic predictions varied. Multi-omics predictions outperformed single-omics predictions in most cases, particularly in the prediction of individuals with high or low CVD risk factor levels. Semi-supervised autoencoders improved downstream predictions compared to the use of unsupervised autoencoders. In addition, median gains in Area Under the Curve by transfer learning compared to modelling from scratch ranged from 0.09 to 0.14 and 0.07 to 0.11 units for transcriptomic and metabolomic data, respectively.ConclusionsBy illustrating the use of different machine learning strategies in different scenarios, our study provides a platform for researchers to evaluate how the choice of omics, ML classifiers, and dimension reduction can influence the quality of CVD risk factor predictions.

The impact of lifestyle, measured with the HLPCQ questionnaire on the prevalence of metabolic syndrome in Poland: a multicenter study

Metabolic syndrome is one of the most common health problems for people around the world. The aim of our study was to assess the prevalence of metabolic syndrome among adults without prior diagnosis of cardiovascular disease, diabetes, and chronic kidney disease. We also plan to assess the influence of certain lifestyle components on prevalence of metabolic syndrome. The study involved cardiovascularly healthy patients undergoing lab tests, measurements, and the HLPCQ questionnaire (The Healthy Lifestyle and Personal Control Questionnaire). The data were used to diagnose metabolic syndrome. Out of 1044 patients from 10 primary care facilities, 23.3% met the metabolic syndrome criteria, showing a strong link with increased blood pressure, cholesterol, and fasting glucose. Lower scores in the Organized physical exercise subscale of the HLPCQ questionnaire were noted in those with metabolic syndrome. Comparing the subscale of HLPCQ questionnaire, the lower results in Organized physical exercise subscale were found among the participants with metabolic syndrome, both male and females. Metabolic syndrome, a significant risk factor for cardiovascular disease, should be screened for actively, even in apparently healthy populations. Results obtained in our study from analysis of HLPCQ show that screening for metabolic syndrome should be preceded by prevention based on regular physical activity and proper eating habits.

Abstract PO3-09-02: Identifying risk factors for trastuzumab-induced cardiotoxicity among multi-ethnic women with HER2-positive early-stage breast cancer

Abstract Introduction: While trastuzumab, a HER2-targeted therapy for patients with HER2-positive breast cancer, has been shown to improve disease-free and overall survival rates, it also confers the risk of significant morbidity in the way of trastuzumab-induced cardiotoxicity (TIC). TIC may present as asymptomatic decline in left ventricular ejection fraction (LVEF) or as symptomatic heart failure. Given that racial/ethnic minorities are at higher risk for cardiovascular disease (CVD) compared to non-Hispanic Whites, our objective was to assess racial/ethnic differences in TIC and LVEF recovery among multi-ethnic patients with HER2-positive early-stage breast cancer. Methods: We conducted a retrospective cohort study including patients diagnosed with stage I-III HER2-positive breast cancer between 2007-2022 who had received adjuvant trastuzumab therapy at Columbia University Irving Medical Center (CUIMC) in New York, NY. TIC was defined as &amp;gt;10% decrease in LVEF to an overall LVEF&amp;lt; 50% and was confirmed by a minimum of two serial echocardiograms, whereas LVEF recovery was defined as a return to a LVEF &amp;gt;50%. Descriptive statistics, univariate and multivariate logistic regression analyses were conducted to estimate odds ratios (OR) and 95% confidence intervals (CI) for the associations between sociodemographic factors, tumor characteristics, treatment regimens, and CVD risk factors with the main outcome of TIC. Results: In the final cohort (N=500), median age was 53 years (IQR: 45.0-62.0) with 36.6% non-Hispanic White (NHW), 15.8% non-Hispanic Black (NHB), 27.8% Hispanic, and 19.8% Asian/Pacific Islander/Other. About 68.2% of patients received adjuvant radiation therapy, 30.2% were treated with anthracyclines, 37.8% with pertuzumab, 4.6% with T-DM1 and 69.0% with endocrine therapy. Fifty-three (10.6%) patients developed TIC, half of which experienced LVEF recovery. Compared to NHW, NHB patients had a higher rate of TIC (9.3% vs. 17.7%, respectively) and lower rate of LVEF recovery (70.6% vs. 21.4 % in those with TIC, respectively). On multivariable analysis, increasing age, lower LVEF at baseline, anthracycline exposure, and coronary artery disease (CAD) were associated with TIC (see Table). We found no association between TIC and use of pertuzumab or T-DM1. Discussion: In our racially/ethnically diverse study population, we found an incidence of TIC comparable to previous clinical studies. NHB patients had double the incidence of TIC and a lower incidence of LVEF recovery when compared to NHW patients. Given the observed racial disparities in TIC and LVEF recovery, NHB patients may require closer cardiac monitoring and restricted use of anthracyclines with adjuvant trastuzumab treatment. More research on cardiotoxicity associated with newer forms of HER2-targeted therapies is necessary. Table: Multivariable logistic regression model with outcome of TIC Citation Format: Leila Mishalani, Anna Vaynrub, Katherine Crew. Identifying risk factors for trastuzumab-induced cardiotoxicity among multi-ethnic women with HER2-positive early-stage breast cancer [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 PO3-09-02.

Metal mixture exposures and serum lipid levels in childhood: the Rhea mother-child cohort in Greece.

Growing evidence suggests that cardiovascular disease develops over the lifetime, often beginning in childhood. Metal exposures have been associated with cardiovascular disease and important risk factors, including dyslipidemia, but prior studies have largely focused on adult populations and single metal exposures. To investigate the individual and joint impacts of multiple metal exposures on lipid levels during childhood. This cross-sectional study included 291 4-year-old children from the Rhea Cohort Study in Heraklion, Greece. Seven metals (manganese, cobalt, selenium, molybdenum, cadmium, mercury, and lead) were measured in whole blood using inductively coupled plasma mass spectrometry. Serum lipid levels included total cholesterol, triglycerides, high-density lipoprotein (HDL) cholesterol, and low-density lipoprotein (LDL) cholesterol. To determine the joint and individual impacts of child metal exposures (log2-transformed) on lipid levels, Bayesian kernel machine regression (BKMR) was employed as the primary multi-pollutant approach. Potential effect modification by child sex and childhood environmental tobacco smoke exposure was also evaluated. BKMR identified a positive association between the metal mixture and both total and LDL cholesterol. Of the seven metals examined, selenium (median 90.6 [IQR = 83.6, 96.5] µg/L) was assigned the highest posterior inclusion probability for both total and LDL cholesterol. A difference in LDL cholesterol of 8.22 mg/dL (95% CI = 1.85, 14.59) was observed when blood selenium was set to its 75th versus 25th percentile, holding all other metals at their median values. In stratified analyses, the positive association between selenium and LDL cholesterol was only observed among boys or among children exposed to environmental tobacco smoke during childhood. Growing evidence indicates that cardiovascular events in adulthood are the consequence of the lifelong atherosclerotic process that begins in childhood. Therefore, public health interventions targeting childhood cardiovascular risk factors may have a particularly profound impact on reducing the burden of cardiovascular disease. Although growing evidence supports that both essential and nonessential metals contribute to cardiovascular disease and risk factors, such as dyslipidemia, prior studies have mainly focused on single metal exposures in adult populations. To address this research gap, the current study investigated the joint impacts of multiple metal exposures on lipid concentrations in early childhood.

Abstract PO2-11-01: Prevalence of Nonadherence to Endocrine Therapy and Cardiovascular Medications Among Breast Cancer Survivors

Abstract Background: Cardiovascular disease (CVD) and cancer are the two leading causes of death in the U.S, and breast cancer (BC) is the most common cancer among women. Most survivors of early-stage BC are prescribed adjuvant endocrine therapy (ET) to decrease their BC recurrence risk; many of them are also on statins and/or antihypertensives to manage concurrent CVD risk factors. Nonadherence to ET or CVD medications is associated with decreased survival and other poor outcomes, yet little is known about how best to identify nonadherence to multiple classes of medications in BC survivors. Methods: We reviewed pharmacy fill data from our electronic health record (EHR) for a diverse cohort of patients seen in our breast oncology clinic with prescriptions for ET and CVD medications (statin and/or antihypertensive(s)). Patients were excluded if their pharmacy data did not show both an active ET order and an active CVD order or fill. Nonadherence to any medication was defined as proportion of days covered (PDC) &amp;lt; 80% over the previous 180 days. A subset of patients also responded to a patient-reported nonadherence screener administered through our EHR at appointment registration starting in 2/2022. Descriptive statistics were used to determine the prevalence of nonadherence to all medications (defined as PDC&amp;lt; 80% for either ET and/or CVD medications) and for each class of medication separately. We also compared the PDC-based combined nonadherence to the self-reported nonadherence. Results: We identified a total of 1,015 BC survivors on ET and CVD medications last seen in clinic between 2/1/2020 and 6/6/2023 (mean age 69 yo; 23.6% non-Hispanic White, 11.3% non-Hispanic Black, and 38.9% Hispanic). Of these, 567 (55.9%) were prescribed ET and statins, and 745 (73.4%) were prescribed ET and antihypertensives. With nonadherence defined as PDC&amp;lt; 80% for any medication (ET and/or CVD medications), the nonadherence prevalence was 38.4%. The nonadherence prevalence by medication class was slightly lower for ET (20.7%) than for statins (25.9%) and antihypertensives (25.0%). Among patients on ET and statins, 10.1% were nonadherent to both medications and 24.3% were nonadherent to only 1 class of medications; the proportion of patients nonadherent to ET only was almost half that of patients nonadherent to statins only (8.5% vs 15.9%). A similar trend was observed among patients on ET and antihypertensives: 10.3% were nonadherent to both classes of medications and 26.2% were nonadherent to only 1 class of medications, with 11.5% of patients nonadherent to ET only and 14.6% nonadherent to antihypertensives only. Of the 1,015 patients, 390 (38.4%) responded to the nonadherence screener between 2/16/2022 and 6/6/2023, of which 93 (23.8%) reported any level of medication nonadherence. Among these, 57 (61.3%) had PDC≥ 80% and thus were categorized as adherent under our PDC-based adherence determination. Of the 297 patients who self-reported adherence to all medications on the screener, 32.3% had PDC&amp;lt; 80% for any medication. When combining nonadherence by PDC and self-report, the overall nonadherence rate for the 390 patients who responded to the screener was considerably higher at 48.5% (vs 33.8% by PDC only and 23.8% by self-report only). Conclusions: EHR-based screening can identify patients with or at risk for medication nonadherence for targeted interventions. Using a combined approach of pharmacy fill data and patient reports, close to 50% of patients were identified as having nonadherence to at least 1 medication. Nonadherence to statins and antihypertensives was more common than nonadherence to ET, which is concerning as early-stage BC survivors are more likely to die from CVD than BC. Interventions to improve adherence to multiple classes of medications are warranted in this population. Citation Format: Claire Sathe, David DeStephano, Shing Lee, Melissa Beauchemin, Nadia Liyanage-Don, Melissa Accordino, Katherine Crew, Ian Kronish, Dawn Hershman. Prevalence of Nonadherence to Endocrine Therapy and Cardiovascular Medications Among Breast Cancer Survivors [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 PO2-11-01.

Endothelial dysfunction in breast cancer survivors on aromatase inhibitors: changes over time

BackgroundBreast cancer is estimated to comprise about 290,560 new cases in 2022. Aromatase inhibitors (AIs) are recommended as adjuvant treatment for estrogen-receptor positive (ER+) breast carcinoma in postmenopausal women, which includes approximately two-thirds of all women with breast cancer. AIs inhibit the peripheral conversion of androgens to estrogen by deactivation of the aromatase enzyme, leading to a reduction in serum estrogen level in postmenopausal women with ER+ breast carcinoma. Estrogen is known for its cardiovascular (CV) protective properties through a variety of mechanisms including vasodilation of blood vessels and inhibition of vascular injury resulting in the prevention of atherosclerosis. In clinical trials and prospective cohorts, the long-term use of AIs can increase the risk for hypertension and hyperlipidemia. Studies demonstrate mixed results as to the impact of AIs on actual CV events and overall survival.MethodsA single arm longitudinal study of 14 postmenopausal women with ER+ breast cancer prescribed adjuvant AIs at the University of Minnesota (UMN). Subjects with a history of known tobacco use, hypertension, hyperlipidemia, and diabetes were excluded to eliminate potential confounding factors. Participants underwent routine labs, blood pressure assessments, and vascular testing at baseline (prior to starting AIs) and at six months. Vascular assessment was performed using the EndoPAT 2000 and HDI/PulseWave CR-2000 Cardiovascular Profiling System and pulse contour analysis on two occasions as previously described. Vascular measurements were conducted by one trained vascular technician. Assessments were performed in triplicate, and the mean indices were used for analyses. All subjects were on an AI at the follow-up visit. The protocol was approved by the UMN Institutional Review Board and all participants were provided written informed consent. Baseline and follow-up characteristics were compared using Wilcoxon signed-rank tests. Analyses were performed using R version 3.6.1 (R Foundation for Statistical Computing, Vienna, Austria).ResultsAfter six months of AI treatment, EndoPAT® ratio declined to a median 1.12 (Q1: 0.85, Q3: 1.86; p = 0.045; Figure 1) and median estradiol levels decreased to 2 pg/mL (Q1: 2, Q3: 3; p=0.052). There was no evidence of association between change in EndoPAT® and change in estradiol level (p = 0.91). There were no statistically significant changes in small or large arterial elasticity.ConclusionsWe hypothesize that long-term use of AI can lead to persistent endothelial dysfunction, and further investigation is necessary. In our study, patients were on AI for approximately 5-10 years. As a result, we do not have data on whether these changes, such as EndoPAT® ratio and the elasticity of small and large arterial, are reversible with discontinuation of AI. These findings set the stage for a larger study to more conclusively determine the association between AI exposure and cardiovascular outcomes. Further studies should evaluate for multivariate associations withmodifiable risk factors for CV disease.

Cardiovascular Disease Risk Factors Among Rural Dwelling Older African American Women

Cardiovascular Disease Risk Factors Among Rural Dwelling Older African American Women

Circulating interleukin 17A and other inflammatory proteins may predict cardiovascular disease in early rheumatoid arthritis.

The objective of this study was to investigate the impact of 92 inflammatory proteins on the risk of cardiovascular disease (CVD) in patients with early RA. This study included consecutive patients with early RA recruited 1995-2002. Stored plasma samples were analyzed for 92 inflammatory proteins. CVD diagnoses were retrieved from national in-patient and cause-of-death registries. Statistical analyses were pre-designated as hypothesis-driven or exploratory. For the latter, proteins were selected based on principal component analysis (i.e., factor loading >0.5 within main components). Potential predictors of CVD and coronary artery disease (CAD) were assessed using Cox regression. Data on baseline levels of proteins and CVD were available for 163 patients. As hypothesized, levels of IL-17A were associated with CVD [hazard ratio 1.35; 95% confidence interval 1.02-1.78, adjusted for age, sex, hypertension, diabetes, smoking and ESR], while not significantly with CAD. Osteoprotegerin (OPG) levels were significantly associated with both outcomes but only in crude models. No associations were observed for IL-6, TNF-α, monocyte chemotactic protein (MCP)-1 or IL-8. In the exploratory analyses, particularly MCP-3 had significant associations with both outcomes in crude models. Circulating IL-17A at RA diagnosis predicted future CVD, although we cannot exclude that this finding is due to multiple testing. The association was independent of traditional CVD risk factors, and of ESR at the time of diagnosis. Furthermore, OPG may be a predictor of CVD. We also identified some novel potential biomarkers for CVD in RA.

Clinical Benefit of Fixed-Dose Combination of Amlodipine and Potent Atorvastatin in Patients With Concomitant Hypertension and Hypercholesterolemia.

Hypertension and hypercholesterolemia are important risk factors for cardiovascular disease, and treatment with fixed-dose combination (FDC) regimens is recommended by current guidelines. However, the clinical outcomes of different FDC dosages remain unknown. This study aimed to examine the clinical outcomes of FDC regimens and the free combination of amlodipine and atorvastatin at different dosages. Patients with concurrent hypertension and hypercholesterolemia treated daily with an FDC of 5 mg amlodipine and 10 mg atorvastatin (5/10 fixed group), and FDC of 5 mg amlodipine and 20 mg atorvastatin (5/20 fixed group), or free combination of 5 mg amlodipine and 20 mg atorvastatin (5/20 free group) were identified from the National Health Insurance Research Database of Taiwan. The primary outcome was the composite cardiovascular outcomes, including cardiovascular death, acute myocardial infarction, stroke, and coronary intervention. A total of 9095 patients were eligible for inclusion. The incidence of primary outcome per 1000 person-years was 16.6 in the 5/10 fixed group, 12.6 in the 5/20 fixed group, and 16.5 in the 5/20 free group (5/20 fixed versus 5/20 free: hazard ratio [HR], 0.76 [95% CI, 0.64-0.91]; 5/20 fixed versus 5/10 fixed: HR, 0.76 [95% CI, 0.63-0.90]). Among patients with concomitant hypertension and hypercholesterolemia, treatment with an FDC of amlodipine and high-dose atorvastatin led to a lower risk of a composite of cardiovascular outcomes than treatment with the free combination or a similar FDC with a lower dose of atorvastatin.

Evaluation of left ventricular function in normotensive type-2 dm patients by echocardiography

The prevalence of diabetes mellitus (DM) is increasing globally. Indians are also believed to have a greater degree of insulin resistance and a stronger genetic predisposition to diabetes. Type II DM is a risk factor for cardiovascular disease and cardiovascular complications and these are a major cause of mortality and morbidity in diabetic patients. Left ventricular dysfunction, increased left ventricular wall thickness, increased left ventricular mass, and specific diabetic cardiomyopathy are some of the cardiovascular complications associated with diabetes. So the present study was performed to assess normotensive diabetic patients by echocardiography to evaluate their left ventricular function. A case control cross sectional study was conducted on 40 normotensive type 2 diabetes mellitus patients. 40 patients who were non-diabetic, non-hypertensive were taken as a control. A standard 2D echocardiography with M mode and Doppler was performed on case and control. In our study among 40 cases, 55% were male and 45% were female with mean age of case population being 47.5±7.24 year and among 40 controls, 50% were male and 50% were female with mean age 48.03±7.14 year. Mean BMI in case group was 29.49±2.37 kg/m2 and in control group 29.36±2.46 kg/m2. In our study we found that LVDD was present in 57.5% cases, 47.5% of cases had grade 1 LVDD whereas 10% had grade 2 LVDD. In comparison, only 10% of controls had LVDD with all of them having grade 1 LVDD. Also LV Systolic dysfunction, LVM and LVMI were higher in cases as compared to controls. Thus we concluded that the prevalence of left ventricular diastolic dysfunction in asymptomatic, normotensive patients with type 2 DM without significant coronary artery disease is much higher than previously suspected as evidenced by the results of this study and also of similar other studies and it increases with the duration of Diabetes. Left ventricular systolic dysfunction, LVM and LVMH prevalence were also higher in cases as compared to controls and they also correlate with duration of Diabetes.

Exploring the potential of pomegranate (Punica granatum) peel extract and punicalagin as novel anti-hypercholesterolemic agents

Background: Hypercholesterolemia, characterized by elevated low-density lipoprotein (LDL) cholesterol levels, is a significant risk factor for cardiovascular diseases. Familial and behavioral factors contribute to its onset, and while lifestyle changes offer some benefits, medical interventions are essential to manage this condition effectively. Statins, the primary medications used to lower LDL cholesterol, have limitations, including the unintended upregulation of proprotein convertase subtilisin/kexin type 9 (PCSK9). Therefore, exploring alternative approaches to enhance LDL receptor expression while targeting PCSK9 is crucial, with herbal medicine showing promise in this endeavor. Objective: This study investigates the potential of pomegranate peel extract and punicalagin, a key pomegranate component, in lowering LDL cholesterol in HepG2 cells. The research explores their effects on LDL receptor (LDLR) expression, LDL uptake, and proprotein convertase subtilisin/kexin type 9 (PCSK9) gene expression. Methods: HepG2 cells were treated with different concentrations of pomegranate peel extract (37.5, 75, 150, and 300 μg/ml) and punicalagin (12.5, 25, 50, and 100 μg/ml). Next, the viability of HepG2 cells, the protein levels of LDL receptors and LDL uptake, and the expression levels of PCSK9 were measured. Results: Pomegranate peel extract (37.5, 75, 150, and 300 μg/ml) and punicalagin (12.5, 25, 50, and 100 μg/ml) did not exhibit significant cytotoxicity and significantly increased LDLR protein levels (P-value= 0.00, after 24 hours) and LDL cholesterol uptake (P-value= 0.00, after 24 hours). Furthermore, they exhibited a dose-dependent reduction in the expression of PCSK9 (pomegranate: P-value= 0.01; punicalagin: P-value= 0.00).  Conclusion: These findings suggest that pomegranate peel extract and punicalagin have the potential to serve as effective agents in managing hypercholesterolemia by enhancing LDL receptor expression and reducing PCSK9 expression in HepG2 cells. Further research is required to explore their effects on transcription factors and PCSK9 function. Keywords: Pomegranate; Punicalagin; HepG2 cell; LDL; Cardiovascular; Punica granatum

Echocardiographic characterization of age- and sex-associated differences in cardiac function and morphometry in nonhuman primates.

Aging per se is a major risk factor for cardiovascular diseases and is associated with progressive changes in cardiac structure and function. Rodent models are commonly used to study cardiac aging, but do not closely mirror differences as they occur in humans. Therefore, we performed a 2D echocardiographic study in non-human primates (NHP) to establish age- and sex-associated differences in cardiac function and morphometry in this animal model. M mode and 2D echocardiography and Doppler analyses were performed cross-sectionally in 38 healthy rhesus monkeys (20 females and 18 males), both young (age 7-12years; n = 20) and old (age 19-30years; n = 18). The diameters of the cardiac chambers did not differ significantly by age group, but males had larger left ventricular diameters (2.43 vs 2.06cm in diastole and 1.91 vs 1.49cm in systole, p = 0.0004 and p = 0.0001, respectively) and left atrial diameter (1.981 vs 1.732cm; p = 0.0101). Left ventricular mass/body surface area did not vary significantly with age and sex. Ejection fraction did not differ by age and females presented a higher ejection fraction than males (54.0 vs 50.8%, p = 0.0237). Diastolic function, defined by early to late mitral peak flow velocity ratio (E/A), was significantly lower in old rhesus monkeys (2.31 vs 1.43, p = 0.0020) and was lower in females compared to males (1.595 vs 2.230, p = 0.0406). Right ventricular function, evaluated by measuring the Tricuspid Annular Plane Systolic Excursion, did not differ by age or sex, and Right Ventricular Free Wall Longitudinal Strain, did not differ with age but was lower in males than in females (-22.21 vs -17.95%, p = 0.0059). This is the first echocardiographic study to evaluate age- and sex-associated changes of cardiac morphometry and function in young and old NHP. The findings of this work will provide a reference to examine the effect of age and sex on cardiac diseases in NHP.

Prevalence and Correlates of Self-Reported Erectile Dysfunction among Adult Male Patients Receiving Cardiovascular Care in Southern Nigeria

Abstract Background: The global incidence of erectile dysfunction (ED) is on the rise, with an estimated 152 million men currently affected. Cardiovascular risk factors are strongly linked to the occurrence of ED, particularly in men with cardiovascular disease (CVD). In countries like Nigeria, where it is not typically viewed as life-threatening, ED often receives less attention. Consequently, there is limited data on selfreported ED among patients seeking cardiovascular care in cardiac clinics. Therefore, this study aims to determine the prevalence of self-reported ED among adult patients with CVD visiting a cardiac center. Materials and Method: A retrospective hospital-based study of self-reported ED patients carried out in a cardiac center among males (31-82 years) in Port Harcourt, Southern Nigeria, over a one-year period (October 2022 to January 2024). Participants’ demographic data and medical history were retrieved and analyzed. Results: The study had a total of 23 male subjects. Majority of the participants were between 50-69 years old (47.8%), 65.2% took alcohol and 21.7% smokes cigarette. 82.6% had a history of hypertension and (73.9%) were on antihypertensive, (34.8%) had diabetes mellitus, (17.4%) were on antidiabetic while (60.9%) were on other forms of medication. Overweight and obesity account for 34.8% and 52.2% of the subjects respectively. Beta-blocker (23.5%) was the frequently used medication and angiotensinconverting enzyme (ACE) inhibitors was the least accounting for (5.9%). Conclusions: The increasing incidence of ED among patients with CVD risk factors and an aging population suggest that patients should be screened. ED may become a significant public health problem and closer attention needs to be paid to control these patients to reduce further complications. Keyword: Erectile dysfunction, cardiovascular risk factor, cardiac Centre, self-reported, Good Heart medical consultants’ Hospital.