High Risk Of Cardiovascular Disease Research Articles

The link between serum neuregulin-1 and atherogenic index in type 2 diabetes mellitus.

Neuregulin-1(NRG-1) is a protein that belongs to the group of epidermal growth factors. It plays vital roles in anti-fibrotic effects on the myocardium. The current paper explores the role of NRG-1 in type 2 diabetes mellitus (T2DM) and its relation to atherogenic index as a factor for increasing cardiovascular disease(CVD) risk. In this study, 79 diabetes mellitus patients are independent insulin. These patients consisted of 53 females and 26 males their age were ranged 40-67 years. They were divided into two groups depending on the atherogenic index of plasma (AIP). Group I including48 diabetic patient with high risk of CVD and group II including 31 diabetic patients without risk CVD. Forty healthy individuals were included as control. When compared to the control group, the serum levels of NRG-1 were significantly lower (p = 0.01). Additionally, group I had a much lower NRG-1level than group II. The results of multiple stepwise regression showed that the only independent predictor for NRG-1 level prediction was AIP (β = - 0.600, P = 0.040). When comparing the diabetic patients with high risk factors for CVD to the healthy subject group, the AUC was outstanding (AUC = 0.889, P = 0.001) and had a high diagnosis. We proved low NRG-1 levels in diabetic patients and the association of highest NRG-1 amounts to a better AIP. Moreover, the measurement of NRG-1 levels could be beneficial as laboratory markers to monitor for increasing CVD risk in type 2 diabetes mellitus.

Examining the association of hysterectomy with and without oophorectomy on cardiovascular disease and all-cause, cardiovascular or cancer mortality: A systematic review and meta-analysis.

The associations between hysterectomy and cardiovascular disease (CVD) and mortality remains unlcear and a meta-analysis with cohort studies is lacking. This study aimed to conduct a systematic review and meta-analysis of cohort studies to investigate the relationship between hysterectomy and CVD, coronary heart disease (CHD), stroke, heart failure, and all-cause, cardiovascular and cancer mortality. We further explored the effect of oophorectomy on the association between hysterectomy and these health outcomes. PubMed, EMBASE and Web of Science were searched up to 24 July 2023. Cohort studies. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were pooled using a random-effects model. We used I2 to assess the heterogeneity between studies. Forty-three studies were included in the meta-analysis. Hysterectomy was significantly associated with an increased risk of CVD (pooled HR 1.11, 95% CI 1.09-1.13; n = 6; I2 = 0) and stroke (HR 1.09, 95% CI 1.04-1.14; n = 7; I2 = 52%), but with a decreased risk of cancer mortality (HR 0.93, 95% CI 0.86-1.00; n = 4; I2 = 81%). No significant association was observed between hysterectomy and CHD (n = 10; I2 = 83%), all-cause mortality (n = 8; I2 = 81%) or cardiovascular mortality (n = 7; I2 = 89%). Hysterectomy with and without oophorectomy was significantly associated with CVD and stroke risk, but showed a larger effect size for hysterectomy with oophorectomy. A significantly increased risk of CHD was observed in the subgroup of hysterectomy with oophorectomy, but not for the subgroup of hysterectomy alone. Hysterectomy may increase the risk of CVD, CHD and stroke, but not all-cause, cardiovascular or cancer mortality. Hysterectomy with oophorectomy may have a higher risk of CVD, CHD and stroke than hysterectomy alone. However, the results on CHD and mortality related to hysterectomy should be interpreted cautiously because of the high level of heterogeneity and unstable subgroup analyses.

The association between energy‐adjusted dietary inflammatory index and 10‐year cardiovascular risk: Fasa adult cohort study

AbstractA healthy diet is dominant in cardiovascular disease (CVD) prevention. Inflammation is pivotal for CVD development. This study aimed to evaluate the association between the pro‐inflammatory diet and the CVD risk. This cross‐sectional study involved 10,138 Fasa adult cohort study participants. After excluding participants with missing data, the Energy‐Adjusted Dietary Inflammatory Index (E‐DII) was calculated to assess the inflammatory potential of diet using the recorded Food Frequency Questionnaire. Framingham risk score (FRS) was used to predict the 10‐year risk of CVD. The association between E‐DII and high risk for CVD was investigated using multinominal regression. After exclusion, the mean age of studied individuals (n = 10,030) was 48.6 ± 9.6 years, including 4522 men. Most participants were low risk (FRS <10%) for CVD (87.6%), while 2.7% of them were high risk (FRS ≥20%). The median FRS was 2.80 (1.70, 6.30). The E‐DII ranged from −4.22 to 4.49 (mean E‐DII = 0.880 ± 1.127). E‐DII was significantly associated with FRS. This result persisted after adjusting for confounding factors and in both genders. This study revealed that the pro‐inflammatory diet significantly increases the CVD risk. Consequently, reducing the inflammatory potential of diet should be considered an effective dietary intervention in CVD prevention.

Cardiometabolic factors and population risks of cardiovascular disease in community-dwelling adults with varied blood pressure statuses.

To examine the differential associations between cardiometabolic risk factors and cardiovascular disease (CVD), and to evaluate the population-attributable fractions (PAFs) for CVD among community-dwelling adults with varied blood pressure (BP) statuses. This prospective cohort study included participants without prevalent CVD from a subcohort of the China Patient-Centred Evaluative Assessment of Cardiac Events Million Persons Project. Participants were divided into four BP groups according to the American College of Cardiology/American Heart Association guidelines. The study exposure comprised the selected cardiometabolic risk factors, including waist circumference (WC), body mass index, (BMI) heart rate, fasting blood glucose (FBG), low-density lipoprotein cholesterol, and remnant cholesterol. The outcome was hospitalizations for CVD. Cox proportional hazard models were conducted, and the PAFs were calculated in the analysis. Among the 94 183 participants (39.0% were men, mean age: 54.2 years), 26.6% had Stage 1 hypertension and 30.8% had Stage 2 hypertension. A total of 6065 hospitalizations for CVD were captured after a median follow-up of 3.5 years. BP (per 1-standard deviation [SD]: hazard ratio [HR] 1.34, 95% confidence interval [CI] 1.29, 1.40), FBG (per 1-SD: HR 1.16, 95% CI 1.14, 1.19) and WC (per 1-SD: HR 1.41, 95% CI 1.36, 1.47) were three major contributors to CVD events. BP status significantly modified the associations of abdominal obesity, suboptimal BMI, suboptimal heart rate and abnormal FBG with CVD, with stronger associations with CVD observed in optimal BP groups compared to hypertensive groups (p for risk factor-by-BP group interaction <0.05). Participants with all cardiometabolic risk factors were at the highest risk for CVD, accounting for 35.6% (95% CI 30.0, 40.8) of the PAF for CVD. Among the risk factors, BP control explained the highest PAF for CVD (15.1%, 95% CI 8.2, 21.4) The overall PAFs of cardiometabolic risk factors for CVD were higher among the normotensive participants compared to the hypertensive participants. The awareness and control rates of hypertension were extremely low among Southern Chinese adults. BP status significantly modified the associations between cardiometabolic risk factors and CVD, and the overall PAFs for CVD were higher among people with normal BP. Dedicated efforts are needed to improve the management of cardiometabolic factors.

Clinical epidemiology of cardiovascular disease in advanced chronic kidney disease prior to dialysis to a tertiary care centre in Bangladesh

Background: Patients with advanced CKD stages exhibit a markedly elevated risk of cardiovascular disease. Patients with chronic kidney disease (CKD) exhibit an elevated cardiovascular risk manifesting as coronary artery disease, heart failure, arrhythmias, and sudden cardiac death .The main objective of this study was to observe the clinical epidemiology of cardiovascular disease in advanced stages of CKD prior to dialysis to a tertiary care centre in Bangladesh. Methods: This was a cross-sectional observational study on 150 cases of diagnosed advanced stages (4&amp;5) of CKD patients in the indoor Department of Medicine of Sir Salimullah Medical College Mitford Hospital, Dhaka, Bangladesh from July 2022to January2023 for 6 months. Data was analyzed SPSS 25. Results: Out of the total group, 62.0% are male, 38.0% are female, and the average (mean) age of the entire group was 55.2 ±10.3. Patients are compared in terms of their relative percentages and the associated cardiovascular disease (CVD) risk, with the hypothesis that lower hemoglobin levels (&lt;9 mg/dL), common in advanced CKD, may be associated with higher CVD risk. A statistically significant P-value (0.036) indicates a significant association between lower hemoglobin levels and increased risk of CVD. Hypertension is the most common risk factor in both stages showing (80%) in stage 4 and 86.6% in Stage -5 of CKD respectively that increasing prevalence as stages of CKD increases . Other factors like diabetes 50.6%) and 53.3% , dyslipidemia 61.3% and 66.7% , and family history of cardiovascular disease (CVD) 40% and 46.6% also in prevalence from Stage 4 to Stage 5. However, the differences in the prevalence of these risk factors between the two stages are not statistically significant, as indicated by the P-values. The prevalence of Congestive Heart Failure rises from 44% in Stage 4 to 52% in Stage 5, and a similar trend is observed in Coronary Artery Disease from 40% in Stage 4 to 48% in Stage 5 and for other diseases, albeit with lesser increments. The provided pvalues, which assess statistical significance, indicate that the differences in disease prevalence between the two stages are not statistically significant, suggesting that the progression from Stage 4 to Stage 5. Conclusion: This study stated that increased prevalence and progression of cardiovascular risks in advanced CKD stages. Bangladesh J Medicine 2024; 35: 96-100

Prognostic Value of Cardiovascular Biomarkers in the Population.

Identification of individuals at high risk for atherosclerotic cardiovascular disease within the population is important to inform primary prevention strategies. To evaluate the prognostic value of routinely available cardiovascular biomarkers when added to established risk factors. Individual-level analysis including data on cardiovascular biomarkers from 28 general population-based cohorts from 12 countries and 4 continents with assessments by participant age. The median follow-up was 11.8 years. Measurement of high-sensitivity cardiac troponin I, high-sensitivity cardiac troponin T, N-terminal pro-B-type natriuretic peptide, B-type natriuretic peptide, or high-sensitivity C-reactive protein. The primary outcome was incident atherosclerotic cardiovascular disease, which included all fatal and nonfatal events. The secondary outcomes were all-cause mortality, heart failure, ischemic stroke, and myocardial infarction. Subdistribution hazard ratios (HRs) for the association of biomarkers and outcomes were calculated after adjustment for established risk factors. The additional predictive value of the biomarkers was assessed using the C statistic and reclassification analyses. The analyses included 164 054 individuals (median age, 53.1 years [IQR, 42.7-62.9 years] and 52.4% were women). There were 17 211 incident atherosclerotic cardiovascular disease events. All biomarkers were significantly associated with incident atherosclerotic cardiovascular disease (subdistribution HR per 1-SD change, 1.13 [95% CI, 1.11-1.16] for high-sensitivity cardiac troponin I; 1.18 [95% CI, 1.12-1.23] for high-sensitivity cardiac troponin T; 1.21 [95% CI, 1.18-1.24] for N-terminal pro-B-type natriuretic peptide; 1.14 [95% CI, 1.08-1.22] for B-type natriuretic peptide; and 1.14 [95% CI, 1.12-1.16] for high-sensitivity C-reactive protein) and all secondary outcomes. The addition of each single biomarker to a model that included established risk factors improved the C statistic. For 10-year incident atherosclerotic cardiovascular disease in younger people (aged <65 years), the combination of high-sensitivity cardiac troponin I, N-terminal pro-B-type natriuretic peptide, and high-sensitivity C-reactive protein resulted in a C statistic improvement from 0.812 (95% CI, 0.8021-0.8208) to 0.8194 (95% CI, 0.8089-0.8277). The combination of these biomarkers also improved reclassification compared with the conventional model. Improvements in risk prediction were most pronounced for the secondary outcomes of heart failure and all-cause mortality. The incremental value of biomarkers was greater in people aged 65 years or older vs younger people. Cardiovascular biomarkers were strongly associated with fatal and nonfatal cardiovascular events and mortality. The addition of biomarkers to established risk factors led to only a small improvement in risk prediction metrics for atherosclerotic cardiovascular disease, but was more favorable for heart failure and mortality.

Prognostic value of metabolic dysfunction-associated steatotic liver disease over coronary computed tomography angiography findings: comparison with no-alcoholic fatty liver disease

BackgroundMetabolic dysfunction-associated steatotic liver disease (MASLD) is the proposed name change for non-alcoholic fatty liver disease (NAFLD). This study aimed to investigate the association of cardiovascular disease risk with MASLD and NAFLD in patients who underwent clinically indicated coronary computed tomography angiography (CCTA).MethodsThis retrospective study included 2289 patients (60% men; mean age: 68 years) with no history of coronary artery disease who underwent CCTA. The steatotic liver was defined as a hepatic-to-spleen attenuation ratio of < 1.0 on CT just before CCTA. MASLD is defined as the presence of hepatic steatosis along with at least one of the five cardiometabolic risk factors. Adverse CCTA findings were defined as obstructive and/or high-risk plaques. Major adverse cardiac events (MACE) encompassed composite coronary events, including cardiovascular death, acute coronary syndrome, and late coronary revascularization.ResultsMASLD and NAFLD were identified in 415 (18%) and 368 (16%) patients, respectively. Adverse CCTA findings were observed in 40% and 38% of the patients with MASLD and with NAFLD, respectively. Adverse CCTA findings were significantly associated with MASLD (p = 0.007) but not NAFLD (p = 0.253). During a median follow-up of 4.4 years, 102 (4.4%) MACE were observed. MASLD was significantly associated with MACE (hazard ratio 1.82, 95% CI 1.18–2.83, p = 0.007), while its association with NAFLD was not significant (p = 0.070). By incorporating MASLD into a prediction model of MACE, including the risk score and adverse CCTA findings, global chi-squared values significantly increased from 87.0 to 94.1 (p = 0.008).ConclusionsPatients with MASLD are likely to have a higher risk of cardiovascular disease than those with NAFLD. Concurrent assessment of MASLD during CCTA improves the identification of patients at a higher risk of cardiovascular disease among those with clinically indicated CCTA.

Effects of the COVID-19 associated United Kingdom lockdown on physical activity in older adults at high risk of cardiovascular disease: a mixed methods perspective from the MedEx-UK multicenter trial

IntroductionPhysical inactivity and sedentary behaviour are linked to increased risk of cardiovascular disease, infections and dementia, as well as placing a significant economic burden on healthcare systems. The implementation of COVID-19 pandemic lockdown measures aimed at reducing virus transmission posed challenges to the opportunity to be physically active. This study investigates how the first UK COVID-19 lockdown affected objectively measured physical activity in older adults at higher risk of cardiovascular disease.MethodsWe studied 48 individuals aged 55-74 years (81.3% female) with self-reported PA levels &amp;lt; 90 min/week and a QRISK2 score ≥ 10 (indicative of a ≥ 10% risk of a major cardiovascular event in the next 10 years) without mild cognitive impairment or dementia. Physical activity data was collected using objective wrist-based activity monitors and analysed across three time periods, usual activity (pre-pandemic), the precautionary phase when the UK began advising on limiting social contact and finally during the first UK lockdown period was collected (27 January 2020 and 07 June 2020). Data was analysed using linear mixed effects model was used to investigate PA levels over the measured 12-week period. Effects of BMI, age, deprivation score and baseline PA levels on PA across the three measurement periods were also examined. Focus-group and individual interviews were conducted, and data were thematically analysed.ResultsAverage daily step count (−34% lower, p &amp;lt; 0.001) and active energy expenditure (−26% lower, p &amp;lt; 0.001) were significantly lower during the precautionary period compared with the usual activity period. Physical activity remained low during the UK lockdown period. Participants with a lower BMI engaged in significantly more (+45% higher daily steps p &amp;lt; 0.001) physical activity and those over 70 years old were more physically active than those under 70 years across the 12-week period (+23% higher daily steps p &amp;lt; 0.007). The risk of COVID-19 infection and restrictions because of lockdown measures meant some individuals had to find alternative methods to staying physical active. Participants described a lack of access to facilities and concerns over health related to COVID-19 as barriers to engaging in physical activity during lockdown. For some, this resulted in a shift towards less structured activities such as gardening or going for a walk.DiscussionThe data presented shows that lockdown measures during the COVID-19 pandemic significantly reduced physical activity among older individuals at risk of cardiovascular disease, particularly those with a higher body mass index. To support this population group in staying active during future lockdowns, a multifaceted strategy is needed, emphasizing psychosocial benefits and home-based physical activity. The MedEx-UK study was pre-registered with ClinicalTrials.gov (NCT03673722).

Incidence of cardiovascular mortality among head and neck cancer patients.

While treatment advancements have prolonged the lives of patients with head and neck cancer, the subgroups of these patients at higher risk for cardiovascular disease (CVD) mortality remain unclear. We analyzed data from the Surveillance, Epidemiology, and End Results (SEER) database for patients diagnosed with head and neck cancer from 2000 to 2019. We compared their CVD mortality against the general US population using standardized mortality ratios (SMRs). Our analysis included 474,366 patients, identifying that 14% of deaths were due to CVD, with an SMR of 1.19. Notably, patients under the age of 39 had a CVD SMR increase of over 100-fold. Those with distant tumor stages showed the highest CVD SMR of 1.52 (95% CI 1.50-1.54). An upward trend in SMR to 2.53 (95% CI 2.51-2.56) was observed from 2011 to 2019. Within the initial 5-year post-diagnosis, the SMR for CVD was 3.17 (95% CI 3.14-3.20), which exceeded the general population's rates but declined in the 5-20-year range after diagnosis. Patients who did not any therapy had the greatest CVD SMR of 2.26 (95% CI 2.24-2.28). Hypopharyngeal cancer patients exhibited the highest CVD SMR of 1.54 (95% CI 1.52-1.56). The study highlights that head and neck cancer patients, especially younger individuals and those with advanced disease stages, face substantial CVD mortality risks. The CVD SMR peaks within 5years following diagnosis. Patients abstaining from treatment bear the highest risk of CVD mortality. Cardioprotective measures should be considered critical for this patient population.

Left ventricular global longitudinal strain is worse in BRCA mutation positive breast cancer patients prior to cancer treatment and premature menopause.

Breast cancer patients with mutations in human tumor suppressor genes BRCA1 and BRCA2 are at higher risk of cardiovascular disease (CVD) than the general population, as they are frequently exposed to cardiotoxic chemotherapy, anti-estrogen therapy, radiation, and/or oophorectomy for cancer-related treatment and prophylaxis. Animal and cell culture models suggest that BRCA mutations may play an independent role in heart failure. We sought to evaluate cardiac structure and function in female BRCA1 and BRCA2 mutation carriers with breast cancer compared to BRCA wildtype women with breast cancer. We performed a 1:2 age- and hypertension-matched retrospective cohort study comparing BRCA1 and BRCA2 mutation carriers (n = 38) versus BRCA wildtype controls (n = 76) with a new diagnosis of breast cancer. Echocardiographic data were obtained within 6months of breast cancer diagnosis and prior to chemotherapy, anti-estrogen therapy, radiation, or oophorectomy. Left ventricular global longitudinal strain (LV-GLS), a highly sensitive marker of LV function, was measured using QLab 15 (Philips Healthcare). In the total cohort of 114 patients with a new diagnosis of breast cancer, the median age was 45 ± 11years and the prevalence of hypertension was 8%. There were no differences in traditional cardiovascular disease risk factors between cases and controls. BRCA carriers had lower LV-GLS (-18.1% ± 4.7% vs. -20.1% ± 3.8%, p = 0.02) and greater right atrial area (12.9cm2 ± 2.7cm2 vs. 11.8cm2 ± 2.0cm2, p = 0.04) compared to controls; however, both LV-GLS and right atrial area were within the normal range. Compared to controls, BRCA carriers had a trend toward worse LV posterior wall thickness (0.89cm ± 0.15cm vs. 0.83cm ± 0.16cm, p = 0.06) although not statistically significant. In women with newly diagnosed breast cancer and prior to treatment, LV-GLS was worse in BRCA1 and BRCA2 mutation carriers compared to those with BRCA wildtype. These findings suggest that BRCA mutations may be associated with subtle changes in cardiac function. Whether differences in GLS translate to increased cardiovascular risk in women with BRCA mutations needs to be further characterized.

The interaction of choline and one-carbon / folate metabolism derangements on the cardiac remodeling process with or without diabetes

Proper nutrition helps protect from illness and disease. Choline (Ch), an essential molecule of substantial importance for the optimal development and function of several biological systems, plays a crucial role in the pathway of one-carbon metabolism. On the other hand, Ch-deprivation (CD) has been linked with abnormal fat metabolism, insulin resistance, and myocardial dysfunction. The Ch-deficiency setting is an established experimental model of non-alco¬holic steatohepatitis that resembles the human non-alcoholic fatty liver disease (NAFLD); a disease with constantly increasing incidence and prevalence. NAFLD, commonly associated with metabolic comorbidities such as obesity and type 2 diabetes mellitus, consists a high risk for cardiovascular disease. Experimental data of dietary CD through the administration of a Ch-deficient diet to rodents have revealed myocardial monocyte infiltration along with cardiac interstitial oedema and fibrosis, as well as a deleterious effect on cardiac valves that could lead to impaired heart mechanical properties which resemble to a restrictive pattern of cardiomyopathy characterised mainly by diastolic dysfunction. In a Ch-deprived diabetic experimental model, the diastolic heart failure has been characterized by a concentric hypertrophied myocardium, a left ventricular cavity with a thinner wall, and an increased left ventricular diastolic diameter, in addition to a left atrial dilatation that could also exert functional derangement and provoke arrhythmogenesis, thereby jeopardising cardiac output.

Different cardiovascular risks associated with elevated creatinine-based eGFR and cystatin C-based eGFR

To compare the association of elevated estimated glomerular filtration rate (eGFR) based on creatinine (eGFRcr) and cystatin C (eGFRcys) with the risk of cardiovascular diseases (CVD) and chronic kidney diseases (CKD). 372,060 participants free of CVD and CKD in the UK Biobank were included. Participants were categorized into low, normal and high eGFR groups according to the age- and sex-specific 5th and 95th percentiles of eGFR. The primary outcome was incident CVD, defined as a combination of ischemic heart disease, stroke, heart failure, and atrial fibrillation. Thresholds for high eGFR varied with age and sex, ranging from 96.5 to 116.0 mL/min/1.73 m2 and 100.3 to 120.1 mL/min/1.73 m2 for eGFRcr and eGFRcys, respectively. During a median follow-up of 12.4 years, 39,855 (10.7%) participants developed CVD. Compared with normal eGFR levels, high eGFRcr levels were associated with a higher risk of CVD (HR, 1.19; 95% CI: 1.14–1.25), while high eGFRcys levels were associated with a lower risk of CVD (HR, 0.90; 95% CI: 0.85–0.95). Compared to normal eGFR levels, both high eGFRcr and high eGFRcys levels were related to a lower risk of CKD. Elevated eGFRcr levels were associated with a higher risk of CVD, and elevated eGFRcys levels were associated with a lower risk of CVD.

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.

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.

Early detection of severe hypertriglyceridemia using teleconsultation in a clinical laboratory setting

BackgroundTeleconsultation in the context of clinical laboratories is a valuable tool for the early detection of dyslipidemia and prevention of cardiovascular risk. Here, we describe a patient who was referred to the Lipid Unit of the Virgen Macarena Hospital due to an alert for severe hypertriglyceridemia through its teleconsultation program. Case presentationA comprehensive clinical and biochemical study of the patient was carried out, and genetic testing was performed on the patient and his family. The proband and his family showed mild to severe hypertriglyceridemia and various secondary factors, together with a genetic background associated with a triglyceride-raising effect. ConclusionThis extensive study has identified a family at high risk of cardiovascular disease and acute pancreatitis. These findings can help maximize lifestyle changes and improve the clinical management of their dyslipidemia.

The correlation between liver fibrosis and the 10‐year estimated risk of cardiovascular disease in adults with metabolic‐associated fatty liver disease: A cross‐sectional study in Vietnam

AbstractBackground and AimsMetabolic‐associated fatty liver disease (MAFLD) emerged as a novel term replacing nonalcoholic fatty liver disease (NAFLD) in 2020. While most MAFLD patients are asymptomatic, long‐term hepatic fat accumulation may lead to liver fibrosis and cardiovascular disease (CVD). Nevertheless, the relationship between MAFLD and cardiovascular (CV) risk factors remains unclear. This study aimed to assess the 10‐year estimated CVD risk in individuals diagnosed with MAFLD.MethodsBetween January 2022 and August 2023, this cross‐sectional study enrolled 139 MAFLD patients. We employed the systematic coronary risk evaluation 2 (SCORE2) and the systematic coronary risk evaluation 2–older persons (SCORE2‐OP) scoring systems to evaluate and categorize the 10‐year CV risk. Liver fibrosis was assessed using biochemical parameters (FIB‐4, AST/ALT, and APRI), and their correlation with CV risk was examined.ResultsMost MAFLD patients were categorized as having high or very high CV risk based on the SCORE2 and SCORE2‐OP. Liver fibrosis, measured by the FIB‐4 score, significantly differed among the various CV risk groups. Moreover, FIB‐4 correlated positively with SCORE2 and SCORE2‐OP (r = 0.588, p &lt; 0.001), indicating its substantial predictive ability for identifying individuals at very high CV risk (AUC = 0.765, 95% CI: 0.686–0.845, p &lt; 0.001). A FIB‐4 score of 1.275 demonstrated 81% sensitivity and 64% specificity in predicting very high CV risk among MAFLD patients.ConclusionPatients with MAFLD predominantly face high or very high CV risks, with elevated liver fibrosis associated with increased 10‐year estimated CVD risk. The FIB‐4 score exhibits promising predictive value for identifying MAFLD patients at very high risk of CV disease.

Mechanistic insights into cardiovascular effects of ultrafine particle exposure: A longitudinal panel study

BackgroundUltrafine particle (UFP) has been linked with higher risks of cardiovascular diseases; however, the biological mechanisms remain to be fully elucidated. ObjectivesThis study aims to investigate the cardiovascular responses to short-term UFP exposure and the biological pathways involved. MethodsA longitudinal panel study was conducted among 32 healthy, non-smoking young adults in Shanghai, China, who were engaged in five rounds of follow-ups between December 2020 and November 2021. Individual exposures were calculated based on the indoor and outdoor real-time measurements. Blood pressure, arterial stiffness, targeted biomarkers, and untargeted proteomics and metabolomics were examined during each follow-up. Linear mixed-effect models were applied to analyze the exposure and health data. The differential proteins and metabolites were used for pathway enrichment analyses. ResultsShort-term UFP exposure was associated with significant increases in blood pressure and arterial stiffness. For example, systolic blood pressure increased by 2.10 % (95 % confidence interval: 0.63 %, 3.59 %) corresponding to each interquartile increase in UFP concentrations at lag 0–3 h, while pulse wave velocity increased by 2.26 % (95 % confidence interval: 0.52 %, 4.04 %) at lag 7–12 h. In addition, dozens of molecular biomarkers altered significantly. These effects were generally present within 24 h after UFP exposure, and were robust to the adjustment of co-pollutants. Molecular changes detected in proteomics and metabolomics analyses were mainly involved in systemic inflammation, oxidative stress, endothelial dysfunction, coagulation, and disturbance in lipid transport and metabolism. DiscussionThis study provides novel and compelling evidence on the detrimental subclinical cardiovascular effects in response to short-term UFP exposure. The multi-omics profiling further offers holistic insights into the underlying biological pathways.

Obicetrapib on Top of Maximally Tolerated Lipid-Modifying Therapies in Participants With or at High Risk for Atherosclerotic Cardiovascular Disease: Rationale and Designs of BROADWAY and BROOKLYN

Obicetrapib, a novel, selective cholesteryl ester transfer protein (CETP) inhibitor, reduces low-density lipoprotein cholesterol (LDL-C), LDL particles, apolipoprotein (Apo) B, and lipoprotein(a) [Lp(a)] and increases high-density lipoprotein cholesterol (HDL-C) when added to statins with or without ezetimibe. By substantially reducing LDL-C, obicetrapib has the potential to lower atherogenic lipoproteins in patients with atherosclerotic cardiovascular disease (ASCVD) or heterozygous familial hypercholesterolemia (HeFH) whose LDL-C levels remain high despite treatment with available maximally tolerated lipid-modifying therapies, addressing an unmet medical need in a patient population at high risk for cardiovascular events. BROADWAY (NCT05142722) and BROOKLYN (NCT05425745) are ongoing placebo-controlled, double-blind, randomized Phase III trials designed to examine the efficacy, safety, and tolerability of obicetrapib as an adjunct to dietary intervention and maximally tolerated lipid-modifying therapies in participants with a history of ASCVD and/or underlying HeFH whose LDL-C is not adequately controlled. The primary efficacy endpoint was the percent change in LDL-C from baseline to day 84. Other endpoints included changes in Apo B, non-HDL-C, HDL-C, Apo A1, Lp(a) and triglycerides in addition to parameters evaluating safety, tolerability, and pharmacokinetics. BROADWAY also included an adjudicated assessment of major adverse cardiovascular events, measurements of glucose homeostasis, and an ambulatory blood pressure monitoring substudy. A total of 2532 participants were randomized in BROADWAY and 354 in BROOKLYN to receive obicetrapib 10 mg or placebo (2:1) for 365 days with follow-up through 35 days after the last dose. Results from both trials are anticipated in 2024. These trials will provide safety and efficacy data to support the potential use of obicetrapib among patients with ASCVD or HeFH with elevated LDL-C for whom existing therapies are not sufficiently effective or well-tolerated.

Actual and Perceived Risk of Cardiovascular Disease among Sample of Iraqi Patients with Rheumatoid Arthritis

Background: Independent of conventional risk factors, patients with rheumatoid arthritis (RA) have a significantly increased risk of cardiovascular disease (CVD). Aims of the study: To evaluate the actual and perceived 10-year CVD risk among Iraqi patients with RA as well as their level of knowledge about CVD risk. Patients and methods: This cross-sectional study included 100 RA patients (85 females and 15 males) who visited Baghdad Teaching Hospital/Rheumatology Unit from January 2021 till July 2021. The Framingham Risk Score (FRS) was used to calculate the actual 10-year risk of CVD. The Heart Disease Fact-Rheumatoid Arthritis Questionnaire (HDFQ-RA) was used to assess the subjects’ cardiovascular disease knowledge. Results: Among a hundred Iraqi patients with RA, the median age was 51.23 ± 8.4 years. The findings of the study revealed that 23% had high risk for CVD and 27% &amp; 50% had moderate and low risk respectively based on FRS calculator. The risk of CVD was significantly affected by the age of disease onset and seropositivity and steroid use (p value 0.001). When the perceived risk was compared to the actual risk of cardiovascular disease, there was a weak agreement between them, only 31% had corresponding answers. Conclusions: The study showed an elevated risk of CVD in rheumatoid arthritis patients, as well as a gap between actual and perceived CVD risk.

Prevalence and distributions of severely elevated low-density lipoprotein cholesterol (LDL-c) according to age, gender and clinic location among patients in the Malaysian primary care

BackgroundAdults with severely elevated low-density lipoprotein cholesterol (LDL-c) may have familial hypercholesterolaemia (FH) and are at high risk of atherosclerotic cardiovascular disease (ASCVD). The prevalence of elevated LDL-c in primary care clinics in Malaysia is not known. Therefore, this study aimed to determine the prevalence and distributions of severely elevated LDL-c among adult patients attending public primary care clinics in Malaysia. MethodsA cross-sectional study was conducted at 11 public primary care clinics in the central states of Malaysia, among adults ≥18 years old with LDL-c recorded in the electronic medical record. Sociodemographic and LDL-c data from 2018 to 2020 were extracted. Severely elevated LDL-c was defined as ≥4 mmol/L, which were further classified into: 4.0–4.9, 5.0–5.9, 6.0–6.9 and ≥ 7 mmol/L. ResultsOut of 139,702 patients, 44,374 (31.8 %) had severely elevated LDL-c of ≥4 mmol/L of which the majority were females (56.7 %). The mean (±SD) age of patients with severely elevated LDL-c was younger at 56.3 (±13.2) years compared to those with LDL-c of <4.0 mmol/L at 59.3 (±14.5) years. In terms of LDL-c levels, 30,751 (69.3 %), 10,412 (23.5 %), 2,499 (5.6 %) and 712 (1.6 %) were in the 4.0–4.9, 5.0–5.9, 6.0–6.9 and ≥ 7 mmol/L categories, respectively. ConclusionThe prevalence of severely elevated LDL-c of ≥4.0 mmol/L among adult patients in public primary care clinics was high. These patients need to be further investigated for secondary and inherited causes such as FH. Therapeutic lifestyle modification and pharmacological management are pivotal to prevent ASCVD in these patients.