Previous Cardiovascular Disease Research Articles

Determinants of serious health outcome-free status in middle-aged and older people with dysglycaemia: Exploratory analysis of the ORIGIN trial.

To assess clinical and biochemical measurements that can identify people with dysglycaemia (i.e. diabetes or pre-diabetes) who remain free of serious outcomes during follow-up. We conducted exploratory analyses using data from the Outcomes Reduction with an Initial Glargine Intervention (ORIGIN) study to identify independent determinants of outcome-free status in 12 537 middle-aged and older adults with prediabetes and early type 2 diabetes from 40 countries. Serious outcome-free status was defined as the absence of major cardiovascular outcomes, kidney or retinal outcomes, peripheral artery disease, dementia, cancer, any hospitalization, or death during follow-up. In total, 3328 (26.6%) participants remained free of serious outcomes during a median follow-up of 6.2 years (IQR 5.8, 6.7). Independent clinical determinants of outcome-free status included younger age, female sex, non-White ethnicity, shorter diabetes duration, absence of previous cardiovascular disease, current or former smokers, higher grip strength, Mini-Mental State Examination score, and ankle-brachial index, lower body mass index and kidney disease index, and non-use of renin-angiotensin system drugs and beta-blockers. In a subset of 8401 people with baseline measurements of 238 biomarkers, growth differentiation factor 15, kidney injury molecule-1, N-terminal pro-brain natriuretic peptide, uromodulin, C-reactive protein, factor VII and ferritin were independent determinants. The combination of clinical determinants and biomarkers best identified participants who remained outcome-free (C-statistics 0.71, 95% confidence interval 0.70-0.73; net reclassification improvement 0.55, 95% confidence interval 0.48-0.58). A set of routinely measured clinical characteristics and seven protein biomarkers identify middle-aged and older people with prediabetes or early type 2 diabetes as least likely to experience serious outcomes during follow-up.

Factors influencing cardiovascular system-related post-COVID-19 sequelae: A single-center cohort study.

COVID-19 sequelae are long-term symptoms of COVID-19. Cardiovascular disease is not only a risk factor for the occurrence of COVID-19 sequelae but also a potential result directly or indirectly caused by COVID-19 infection. The aim of this study is to investigate the cardiovascular system-related symptoms of outpatients and inpatients of the Cardiovascular Department of the Affiliated Hospital of Shandong University of Traditional Chinese Medicine after recovery from novel coronavirus infection, analyze the influencing factors, and symptom characteristics of related symptoms, and thereby provide a basis for further formulating a reasonable diagnosis and treatment plan. From January 15, 2023 to February 15, 2023, 452 recovered patients with novel coronavirus infection who were admitted to the Cardiovascular Department of the Affiliated Hospital of Shandong University of Traditional Chinese Medicine due to symptoms of the cardiovascular system (complaints of chest pain and palpitations) were involved in this study. A unified questionnaire was used to record the general information, past medical history, characteristics of chest pain or palpitations, and other COVID-19-related sequelae of the selected patients. All data were statistically analyzed by SPSS 26.0 statistical software. A total of 226 patients with cardiovascular symptoms and 226 patients without cardiovascular symptoms were included in this study. After univariate and multivariate logistic regression analysis, women (OR 2.081, 95% CI = 1.358-3.189) and young people (OR 2.557, 95% CI = 1.44-4.54) had a higher risk of cardiovascular symptoms; prehypertension (OR 1.905, 95% CI = 1.091-3.329) and hypertension (OR 2.287, 95% CI = 1.433-3.649) increased the risk of cardiovascular symptoms; patients with history of previous cardiovascular disease (OR 1.862, 95% CI = 1.16-2.988) and history of diabetes (OR 2.138, 95% CI = 1.058-4.319) had a higher risk of developing cardiovascular symptoms. The main symptoms related to COVID-19 sequelae reported by all 452 patients were fatigue (76.8%), shortness of breath (54.2%), dry mouth and bitter mouth (46.0%), gastrointestinal symptoms (42.7%), sleep disturbances (37.4%), sweating (31.9%), chills (29%), dizziness (25.7%), confusion of brain fog (25.2%), and tinnitus (14.6%). Compared with patients without cardiovascular symptoms, patients with cardiovascular symptoms were more likely to have shortness of breath (OR 3.521, 95% CI = 2.226-5.472), gastrointestinal symptoms (OR 2.039, 95% CI = 1.226-3.393), and dry mouth and bitter mouth (OR 1.918, 95% CI = 1.229-2.992). The differences were statistically significant (P < 0.05). In this new coronavirus infection, women, young people, the elderly, people with prehypertension, hypertension, and patients with a history of cardiovascular disease and diabetes have a higher risk of developing cardiovascular symptoms, and patients with cardiovascular symptoms are more likely to develop other COVID-19 sequelae.

Cardiovascular Risk Profile in Master Paralympic Athletes, a High-Risk Undertreated Population: A Cross-Sectional Longitudinal Study.

Recently, European Society of Cardiology (ESC)validated aprediction model to estimate 10-year fatal and non-fatal cardiovascular disease risk (CVDR) in individuals (aged 40-60 years) without previous cardiovascular disease or diabetes(ESC-SCORE2)and to provide indications for treatment. At present, data describing the CVDR in Paralympic athletes (PAs) are scarce and inconsistent. Therefore,we sought to assess the prevalence of risk factors in PAs to estimate their CVDR through SCORE2. Weenrolled 99 PAs aged ≥40 y.o., who participated at 2012-2022 Paralympic Games, competing in 22 different sport disciplines classified according to sport type (power, skills, endurance and mixed) and disabilities: spinal cord injuries (SCI) and non-SCI. CVDR factors,anthropometric measurements and blood samples were collected. Among the 99 PAs (78% males, mean age 45.7±4.7 y.o.), 52.5% had SCI; 54% were dyslipidemic and 23% were smokers. According to ESC-SCORE2, 29% had high and 1% very-high CVDR. Women (compared to men) and endurance (compared to other sport) exhibited better CV profile. SCI showed no differences when compared with non-SCI for CVDR, excepted for a lower HDL and lower exercise performance.None of the dyslipidemic athlete was on pharmacologically treatment, despitethe altered lipid profile had already been detected at younger age. PAs are a selected population, presenting a high CV risk profile, with 30% showing either high or very-high CVDR according to ESC-SCORE2. Dyslipidemiawas the most common risk factor, underestimated and undertreated, emphasizing the need for specific preventive strategies in this special setting of athletes.

Caracterización clínica y detección de arteriosclerosis subclínica en sujetos con hiperalfalipoproteinemia extrema

Introduction and objectivesThe association between HDL cholesterol (HDL-C) levels and death from cardiovascular disease follows a U-shaped pattern, increasing at the extremes. The objective of the study was to characterize a sample of subjects with extreme hyperalphalipoproteinemia (HAE). Material and methods53 cases with HAE were recruited, 24 women (HDL-C>135mg/ dL) and 29 men (HDL-C>116mg/ dL). A detailed medical history was taken and questionnaires on adherence to the Mediterranean diet and physical activity were collected. Carotid ultrasounds were performed to detect the presence of suclinical atherosclerosis. ResultsThe most prevalent cardiovascular risk factor (CVRF) was dyslipidemia (64%) with no significant differences between men and women, unlike hypertension (21% in women, versus 55% in men, p=0.01) and others CVRF, for example, diabetes. 7% of the series had previous cardiovascular disease, women had higher LDL cholesterol (p=0.002) and HDL-C than men (without significant differences). Plaque was detected in 53% of cases, being more prevalent in men. Patients with plaque were older, drank more alcohol and smoked more (p<0.05). ConclusionsMen had a higher prevalence of CVRF than women, except for dyslipidemia. Subclinical atherosclerosis occurred in more than half of the series. Age, alcohol consumption and smoking were independently associated with the presence of plaque, however, our data do not show a significant influence of HDL-C levels.

Prognostic impact of hypertension grading

BackgroundMost Hypertension Guidelines grade hypertension according to various cut-off values. We sought to investigate the prognostic impact of Grades 1 (140–159 and/or 90–99 mmHg), 2 (160–179 and/or 100–109 mmHg) and 3 (≥180 and/or ≥110 mmHg). MethodsWe followed for an average of 10 years a cohort of 3,150 initially untreated hypertensive patients (mean age 50 years, 44 % women) with no previous cardiovascular disease at entry. All patients underwent diagnostic tests including 24-hour ambulatory blood pressure (BP) monitoring. ResultsAt entry, average clinic BP was 156/97 mmHg and average 24-hour BP was 137/87 mmHg. During follow-up, 314 patients experienced a first major cardiovascular event (composite of non-fatal myocardial infarction or stroke, cardiovascular death, or hospitalization for heart failure). Event rate was not formally dissimilar between Grade 1 and Grade 2 (0.73 vs 0.95 per 100 patient-years, respectively; p = 0.06). It was higher in Grade 3 (1.93 per 100 patient-years; p < 0.01 vs Grade 1 and Grade 2). After adjustment for a robust set of covariables, the hazard ratio was not dissimilar between Grade 1 and Grade 2 (p = 0.27), and higher in Grade 3 than in Grade 1 (p < 0.01), but the excess risk in Grade 3 was no longer significant (hazard ratio: 1.25, 95 % CI 0.87–1.78; p = 0.22) after adjustment for 24-hour ambulatory systolic BP. ConclusionsWe were unable to find a significant difference in the relative hazard of cardiovascular events tied to hypertension Grades 1 and 2. Conversely, Grade 3 (clinic BP ≥180/110 mmHg) portends a higher cardiovascular risk, which is associated with higher levels of 24-hour ambulatory BP.

Cardiovascular considerations on recreational scuba diving. SEC-Clinical Cardiology Association/SEC-Working Group on Sports Cardiology consensus document

The practice of recreational scuba diving has increased worldwide, with millions of people taking part each year. The aquatic environment is a hostile setting that requires human physiology to adapt by undergoing a series of changes that stress the body. Therefore, physical fitness and control of cardiovascular risk factors are essential for practicing this sport. Medical assessment is not mandatory before participating in this sport and is only required when recommended by a health questionnaire designed for this purpose. However, due to the significance of cardiovascular disease, cardiology consultations are becoming more frequent. The aim of the present consensus document is to describe the cardiovascular physiological changes that occur during diving, focusing on related cardiovascular diseases, their management, and follow-up recommendations. The assessment and follow-up of individuals who practice diving with previous cardiovascular disease are also discussed. This document, endorsed by the Clinical Cardiology Association of the Spanish Society of Cardiology (SEC) and the SEC Working Group on Sports Cardiology of the Association of Preventive Cardiology, aims to assist both cardiologists in evaluating patients, as well as other specialists responsible for assessing individuals’ fitness for diving practice.

Large-scale plasma proteomics in the UK Biobank modestly improves prediction of major cardiovascular events in a population without previous cardiovascular disease.

Improved identification of individuals at high risk of developing cardiovascular disease would enable targeted interventions and potentially lead to reductions in mortality and morbidity. Our aim was to determine whether use of large-scale proteomics improves prediction of cardiovascular events beyond traditional risk factors (TRFs). Using proximity extension assays, 2919 plasma proteins were measured in 38 380 participants of the UK Biobank. Both data- and literature-based feature selection and trained models using extreme gradient boosting machine learning were used to predict risk of major cardiovascular events (MACE: fatal and non-fatal myocardial infarction, stroke and coronary artery revascularisation) during a 10-year follow-up. Area under the curve (AUC) and net reclassification index (NRI) were used to evaluate the additive value of selected protein panels to MACE prediction by Systematic COronary Risk Evaluation 2 (SCORE2) or the 10 TRFs used in SCORE2. SCORE2 and SCORE2 refitted to UK Biobank data predicted MACE with AUCs of 0.740 and 0.749, respectively. data-driven selection identified 114 proteins of greatest relevance for prediction. Prediction of MACE was not improved by using these proteins alone (AUC of 0.758) but was significantly improved by combining these proteins with SCORE2 or the 10 TRFs (AUC=0.771, p<001, NRI=0.140, and AUC=0.767, p=0.03, NRI 0.053, respectively). Literature-based protein selection (113 proteins from five previous studies) also improved risk prediction beyond TRFs while a random selection of 114 proteins did not. Large-scale plasma proteomics with data-driven and literature-based protein selection modestly improves prediction of future MACE beyond TRFs.

Development and validation of a risk score nomogram model to predict the risk of 5-year all-cause mortality in diabetic patients with hypertension: A study based on NHANES data

BackgroundThe present study aimed to develop and validate a prediction nomogram model for 5-year all-cause mortality in diabetic patients with hypertension. MethodsData were extracted from the National Health and Nutrition Examination Survey (NHANES). A total of 3291 diabetic patients with hypertension in the NHANES cycles for 1999–2014 were selected and randomly assigned at a ratio of 8:2 to the training cohort (n = 2633) and validation cohort (n = 658). Multivariable Cox regression was conducted to establish a visual nomogram model for predicting the risk of 5-year all-cause mortality. Receiver operating characteristic curves and C-indexes were used to evaluate the discriminant ability of the prediction nomogram model for all-cause mortality. Survival curves were created using the Kaplan–Meier method and compared by the log-rank test. ResultsThe nomogram model included eight independent predictors: age, sex, education status, marital status, smoking, serum albumin, blood urea nitrogen, and previous cardiovascular disease. The C-indexes for the model in the training and validation cohorts were 0.76 (95% confidence interval: 0.73–0.79, p < 0.001) and 0.75 (95% confidence interval: 0.69–0.81, p < 0.001), respectively. The calibration curves indicated that the model had satisfactory consistency in the two cohorts. The risk of all-cause mortality gradually increased as the tertiles of the nomogram model score increased (log-rank test, p < 0.001). ConclusionThe newly developed nomogram model, a readily useable and efficient tool to predict the risk of 5-year all-cause mortality in diabetic patients with hypertension, provides a novel risk stratification method for individualized intervention.

Haptoglobin Phenotype and Intensive Glycemic Control for Coronary Artery Disease Risk Reduction in People With Type 2 Diabetes: The ADVANCE Study.

Intensive glycemic control reduced coronary artery disease (CAD) events among the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study participants with the haptoglobin (Hp)2-2 phenotype but not in participants without the Hp2-2 phenotype. It is unknown whether and how these results translate across different demographic/clinical characteristics and treatment strategies. Haptoglobin phenotype was measured in available samples from the Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE) biomarker case-cohort study. Weighted multivariable-adjusted Cox regression models were used to evaluate the association between intensive glycemic control (HbA1c target of ≤6.5%) versus standard therapy (based on local guidelines) and major CAD events among participants with (n = 1,327) and without (n = 2,077) the Hp2-2 phenotype separately and within prespecified stratifications by sex, race, previous cardiovascular disease (CVD), diabetes duration, and HDL-cholesterol. While the hazard ratios (HRs) were in the hypothesized differing directions, compared with standard therapy, intensive glycemic control was not significantly associated with risk of CAD events among participants without (1.04, 95% CI 0.82-1.32) or with (0.84, 0.63-1.14, Pinteraction = 0.27) the Hp2-2 phenotype overall. Intensive therapy was associated with lower CAD risk among participants with the Hp2-2 phenotype who had no previous CVD (0.47, 0.29-0.76, Pinteraction = 0.01). Our findings suggest that intensive glycemic control contributes to the prevention of major CAD events among ADVANCE participants with the Hp2-2 phenotype and no previous CVD and are in alignment with our hypothesis that intensive glycemic control may be beneficial in a subset of people with the Hp2-2 phenotype.

Lifetime and 10-year cardiovascular risk prediction in individuals with type 1 diabetes: The LIFE-T1D model.

To develop and externally validate the LIFE-T1D model for the estimation of lifetime and 10-year risk of cardiovascular disease (CVD) in individuals with type 1 diabetes. A sex-specific competing risk-adjusted Cox proportional hazards model was derived in individuals with type 1 diabetes without prior CVD from the Swedish National Diabetes Register (NDR), using age as the time axis. Predictors included age at diabetes onset, smoking status, body mass index, systolic blood pressure, glycated haemoglobin level, estimated glomerular filtration rate, non-high-density lipoprotein cholesterol, albuminuria and retinopathy. The model was externally validated in the Danish Funen Diabetes Database (FDDB) and the UK Biobank. During a median follow-up of 11.8 years (interquartile interval 6.1-17.1 years), 4608 CVD events and 1316 non-CVD deaths were observed in the NDR (n = 39 756). The internal validation c-statistic was 0.85 (95% confidence interval [CI] 0.84-0.85) and the external validation c-statistics were 0.77 (95% CI 0.74-0.81) for the FDDB (n = 2709) and 0.73 (95% CI 0.70-0.77) for the UK Biobank (n = 1022). Predicted risks were consistent with the observed incidence in the derivation and both validation cohorts. The LIFE-T1D model can estimate lifetime risk of CVD and CVD-free life expectancy in individuals with type 1 diabetes without previous CVD. This model can facilitate individualized CVD prevention among individuals with type 1 diabetes. Validation in additional cohorts will improve future clinical implementation.

SARS-CoV-2 testing, positivity, and factors associated with COVID-19 among people with HIV across Europe in the multinational EuroSIDA cohort.

Although people with HIV might be at risk of severe outcomes from infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; coronavirus 2019 [COVID-19]), regional and temporal differences in SARS-CoV-2 testing in people with HIV across Europe have not been previously described. We described the proportions of testing, positive test results, and hospitalizations due to COVID-19 between 1 January 2020 and 31 December 2021 in the EuroSIDA cohort and the factors associated with being tested for SARS-CoV-2 and with ever testing positive. Of 9012 participants, 2270 (25.2%, 95% confidence interval [CI] 24.3-26.1) had a SARS-CoV-2 polymerase chain reaction test during the study period (range: 38.3% in Northern to 14.6% in Central-Eastern Europe). People from Northern Europe, women, those aged <40 years, those with CD4 cell count <350 cells/mm3 , and those with previous cardiovascular disease or malignancy were significantly more likely to have been tested, as were people with HIV in 2021 compared with those in 2020. Overall, 390 people with HIV (4.3%, 95% CI 3.9-4.8) tested positive (range: 2.6% in Northern to 7.1% in Southern Europe), and the odds of testing positive were higher in all regions than in Northern Europe and in 2021 than in 2020. In total, 64 people with HIV (0.7%, 95% CI 0.6-0.9) were hospitalized, of whom 12 died. Compared with 2020, the odds of positive testing decreased in all regions in 2021, and the associations with cardiovascular disease, malignancy, and use of tenofovir disoproxil fumarate disappeared in 2021. Among study participants, 58.9% received a COVID-19 vaccine (range: 72.0% in Southern to 14.8% in Eastern Europe). We observed large heterogeneity in SARS-CoV-2 testing and positivity and a low proportion of hospital admissions and deaths across the regions of Europe.

Prognostic Impact of Previous Atherosclerotic Cardiovascular Disease on Short- and Long-Term Outcomes in Acute Myocardial Infarction

Patients with previous atherosclerotic cardiovascular disease (ASCVD) are typically managed by secondary prevention modalities, but they may experience recurrent events. In acute myocardial infarction (MI), the prognostic effect of pre-existing ASCVD on short- and long-term outcomes remains uncertain. This retrospective multicenter registry included 2475 patients with acute MI who had undergone percutaneous coronary intervention. Previous ASCVD was defined as a history of ischemic events in the coronary, cerebral, and peripheral arterial territories. Patients were divided into 2 groups according to pre-existing ASCVD. The primary endpoint was major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, recurrent MI, and ischemic stroke during hospitalization and after discharge. The bleeding outcomes were also evaluated. Of the 2475 patients, 475 (19.2%) had previous ASCVD. Patients with previous ASCVD were older and likely to have more comorbidities than those without ASCVD. During hospitalization, MACE rates were higher in the ASCVD group than in the non-ASCVD group (16.4% vs. 9.6%, p<0.001). Similarly, during a median follow-up of 542 days after discharge, patients with previous ASCVD had an increased risk of MACE than those without ASCVD (13.4% vs. 5.6%, p<0.001). Multivariable analyses identified previous ASCVD as a factor that was significantly associated with MACE after discharge. Major bleeding events occurred more frequently in the ASCVD group than in the non-ASCVD group. In conclusion, pre-existing ASCVD was often observed in patients with acute MI and was particularly associated with long-term ischemic outcomes after discharge; thus, further clinical investigations are needed in this vulnerable patient subset.

Proton Pump Inhibitor Use and the Risk of Cardiovascular Complications and Death in Older Adults with Diabetes: A Population-Based Cohort Study.

The unfavorable effect of proton pump inhibitors (PPIs) on cardiovascular (CV) outcomes and mortality was reported in the general population. We investigated the impact of PPIs on CV outcomes and total mortality in older people with diabetes mellitus (DM) for whom evidence is missing. Using administrative health databases of the Lombardy Region, we analyzed the risk of myocardial infarction (MI), ischemic stroke and total mortality in individuals with DM (≥65 years of age) exposed to PPIs in 2015 and followed up to 2021. The outcomes were analyzed using a multivariable-adjusted Cox proportional hazards model to compute hazard ratios (HRs) with 95% confidence intervals (CIs). HRs between PPI users and non-users were also estimated in selected subgroups. A sensitivity analysis was also performed in a 1:1 propensity score matching population. A total of 284,068 patients were included in the analysis (49.4% PPI users, 50.6% non-PPI users). A higher prevalence of comorbidities and medications was reported in PPI users as compared with non-users. During a median follow-up of 6.7 years, the use of PPIs was associated with a higher risk for ischemic stroke (HR 1.14, 95% CI 95% 1.08-1.20), MI (HR 1.36, 95% CI 1.31-1.41) and total mortality (HR 1.24, 95% CI 1.22-1.26). These risks were higher in PPI users regardless of the PPI type. Among sexes, previous CV diseases, and insulin subgroups, the use of PPIs was correlated with a statistically significant increased risk of ischemic stroke in men, in individuals without a history of CV disease, and in those who were not treated with insulin. A significantly higher risk of MI was associated with PPIs for all subgroups, as well as for total mortality, with the exception of patients with a previous history of CV diseases. The sensitivity analysis confirmed the results of the unmatched cohort. Our findings confirmed an increased risk of CV events and all-cause mortality in a large population of older adults with DM exposed to PPIs. This could have an important impact on public health and costs for National Health Service, therefore a regular assessment of PPI appropriateness is recommended, particularly in this population.

Cardiovascular risk assessment in Portugal's primary health care system: SCORE vs. SCORE2

Introduction and objectivesThe 2021 European Society of Cardiology guidelines on cardiovascular disease (CVD) prevention introduced the more accurate SCORE2 risk model as a replacement for the earlier SCORE, which is still used in primary care software in Portugal. Our objective is to determine whether the difference between risk assessment using SCORE and SCORE2, in the same patient population, is statistically significant. MethodsA total of 1642 patients aged 40–65 without previous CVD, from the medical records of two Family Health Units, were included in this cross-sectional study. SCORE and SCORE2 were calculated using the variables gender, age, smoking status, lipid profile and systolic blood pressure. A statistical analysis was performed on the results. ResultsUsing SCORE, 98% of the patients were in the low–moderate risk categories and 2% in the high or very high risk categories. When using SCORE2, the corresponding percentages were 55% and 45%, respectively. Reclassification with SCORE2 into higher categories was more often observed in younger (under 50 years of age) and male patients. With SCORE, 38.61% of patients were within the LDL-C target range; this figure fell to 20.28% with SCORE2. These differences are statistically significant (p<0.0001). ConclusionOur findings show that a significant number of patients in this cohort who were classified through SCORE at lower risk levels were reclassified into higher risk categories with SCORE2. Similarly, the number of patients within the LDL-C target range for LDL-C was also lower using SCORE2.

Associations of carotid atherosclerosis with cognitive function and brain health: Findings from a UK tri-ethnic cohort study (Southall and Brent Revisited)

BackgroundCognitive function has an important role in determining the quality of life of older adults. Cardiovascular disease (CVD) is common in older people and may compromise cognitive performance; however, the extent to which this is related to carotid atherosclerosis is unclear. AimWe investigated associations between carotid atherosclerosis and cognitive function and neuroimaging markers of brain health in a UK multi-ethnic community-based sample including older people of European, South Asian, and African-Caribbean ethnicity. MethodsCarotid plaques and intima-media thickness (cIMT) were assessed using ultrasound in 985 people (mean age 73.2y, 56 % male). Associations of carotid atherosclerosis with cognitive function (memory, executive function, language and CSI-D, a global measure of cognitive state) and neuroimaging measures (total brain volume, hippocampal volume, white matter (WM) lesion volume and coalescence score) were analysed using regression analyses, with and without adjustment for potential confounders using two models: 1) adjustment for age, sex, and ethnicity; 2) model 1 plus education, physical activity category, body mass index, hypertension, diabetes, total and high density lipoprotein cholesterol, atrial fibrillation, smoking, previous CVD, alcohol consumption, and presence of chronic kidney disease. ResultsPeople with carotid plaque or higher cIMT had lower CSI-D score, poorer memory poorer executive function and higher WM lesion volume and coalescence. Language was poorer in people with plaque but was not correlated with cIMT. Associations with plaque were preserved after full adjustment (model 2) but relationships for cIMT were attenuated. Associations with other plaque characteristics were generally unconvincing after adjustment. ConclusionsThis multi-ethnic cohort study provides evidence that presence of carotid plaque, is associated with poorer cognitive function and brain health.

First Report of Inclisiran Utilization for Hypercholesterolemia Treatment in Real-world Clinical Settings in a Middle East Population

Inclisiran is the first small interfering RNA-based treatment approved for reducing pro-atherogenic lipoproteins in patients with heterozygous familial hypercholesterolemia or clinical atherosclerotic cardiovascular disease, who require additional lowering of low-density lipoprotein cholesterol (LDL-C). We report the first evaluation of the effects of inclisiran in a Middle East population. We conducted a retrospective review of patients initiating inclisiran treatment at an outpatient diabetology, endocrinology, and cardiology center between May 2021 and December 2022. All patients followed up for 90 days or more, or with at least 1 lipid determination post initiation were included. Participants were categorized into primary prevention (n = 57) and secondary prevention (n = 89) groups according to previous atherosclerotic cardiovascular disease. Inclisiran was initiated in 146 patients; mean (SD) age was 54.8 (12.12) years, 82 patients (56.2%) were male, 28 patients (19.2%) had received a diagnosis of familial hypercholesterolemia, 89 patients (61%) had received a diagnosis of diabetes mellitus, and 35 patients (23.9%) had a statin intolerance. Median (interquartile range) follow-up was 137 (90 to 193) days. At 90 days, median (interquartile range) reductions in serum LDL-C and triglycerides were -37.9% (-9.5% to -51.2%) and -12.0% (-9.8% to -40.5%), respectively, in primary prevention and -54.1% (-17.1% to -71.4%) and -15.3% (-14% to -38.8%), respectively, in secondary prevention (all, P < 0.001). LDL-C goals were attained in 110 patients (75.3%). Nonattainment of LDL-C goal was attributed to system effect in 26 patients (72.2%), biological effect in 5 patients (13.9%), and discontinuation of treatment in 5 patients (13.9%). Therapy was well tolerated. This study is the first from the Middle East and North Africa region that reported the real-world efficacy and safety profile of inclisiran in a mixed-risk population of patients with heterozygous familial hypercholesterolemia and other non-familial hypercholesterolemia indications. Clinically meaningful and sustained reductions in pro-atherogenic lipids with good tolerability were observed after inclisiran initiation. Fewer AEs were reported in this predominantly Arabic population, consistent with previous safety reports for inclisiran. It is important to note that no patient stopped inclisiran treatment due to AEs. Strengths of our study included an optimal cohort, patient heterogeneity, and high retention. In addition, we were able to report mean robust effects of inclisiran and good medication tolerability, quite like randomized studies and open-label extension periods. Despite this, our study had some limitations, including selection bias due to the retrospective design and the absence of a comparative group.

Systematic review with meta-analysis: Steatosis severity and subclinical atherosclerosis in metabolic dysfunction-associated steatotic liver disease.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent liver condition recognised as an independent risk factor for cardiovascular disease (CVD). However, there is ongoing debate regarding the effective strategy for cardiovascular risk assessment in MASLD. To investigate the relationship between liver imaging, specifically focusing on the severity of steatosis and subclinical atherosclerosis. We conducted a thorough search across four databases, from 1950 to April 2023, to identify eligible studies employing imaging to explore the relationship between different degrees of steatosis and subclinical atherosclerosis among MASLD. Additionally, we conducted a quality assessment using the Newcastle Ottawa Scale, performed a meta-analysis employing the DerSimonian-Liard random-effects model, and conducted subgroup analyses for validation. In total, 19 studies, encompassing 147,411 middle-aged individuals without previous CVD (74.94% male; mean age 45.53 years [SD 10.69]; mean BMI 24.3 kg/m2 [SD 3.35]), were included. The pooled odds ratio for subclinical atherosclerosis was 1.27 (95% CI: 1.13-1.41, I2 = 76.68%) in mild steatosis and significantly increased to 1.68 (95% CI: 1.41-2.00, I2 = 89.02%) in moderate to severe steatosis. Sensitivity analysis, focusing on high-quality studies, consistently supported this finding and the results remained robust across subgroup analyses. Furthermore, meta-regression revealed that a higher mean AST and ALT, alongside a lower mean HDL, were significant moderators of this association. Even mild steatosis is associated with CVD risk, and steatosis severity further intensifies this association. These findings suggest that liver fat quantification enhances CVD risk stratification in patients with MASLD.

Females Display Lower Risk of Myocardial Infarction From Higher Estimated Cardiorespiratory Fitness Than Males: The Tromsø Study 1994-2014

ObjectiveTo examine the dose-response association between estimated cardiorespiratory fitness (eCRF) and risk of myocardial infarction (MI). Patients and MethodsAdults who attended Tromsø Study surveys 4-6 (Janurary 1,1994-December 20, 2008) with no previous cardiovascular disease were followed up through December 31, 2014 for incident MI. Associations were examined using restricted cubic splines Fine and Gray regressions, adjusted for education, smoking, alcohol, diet, sex, adiposity, physical activity, study survey, and age (timescale) in the total cohort and subsamples with hyperlipidemia (n=2956), hypertension (n=8290), obesity (n=5784), metabolic syndrome (n=1410), smokers (n=3823), and poor diet (n=3463) and in those who were physically inactive (n=6255). ResultsOf 14,285 participants (mean age ± SD, 53.7±11.4 years), 979 (6.9%) experienced MI during follow-up (median, 7.2 years; 25th-75th, 5.3-14.6 years). Females with median eCRF (32 mL/kg/min) had 43% lower MI risk (subdistributed hazard ratio [SHR], 0.57; 95% CI, 0.48-0.68) than those at the 10th percentile (25 mL/kg/min) as reference. The lowest MI risk was observed at 47 mL/kg/min (SHR, 0.02; 95% CI, 0.01-0.11). Males had 26% lower MI risk at median eCRF (40 mL/kg/min; SHR, 0.74; 95% CI, 0.63-0.86) than those at the 10th percentile (32 mL/kg/min), and the lowest risk was 69% (SHR, 0.31; 95% CI, 0.14-0.71) at 60 mL/kg/min. The associations were similar in subsamples with cardiovascular disease risk factors. ConclusionHigher eCRF associated with lower MI risk in females and males, but associations were more pronounced among females than those in males. This suggest eCRF as a vital estimate to implement in medical care to identify individuals at high risk of future MI, especially for females.

Prevalence of Cardiovascular Disease and Rate of Major Adverse Cardiovascular Events in Severe Alpha-1 Antitrypsin Deficiency COPD.

Alpha-1 antitrypsin deficiency is an autosomal co-dominant condition that predisposes individuals to early-onset emphysema. As with COPD, AATD-COPD is associated with pulmonary exacerbations, which impacts on overall mortality and quality of life. Though there is evidence that COPD is associated with a higher prevalence of cardiovascular disease and major adverse cardiovascular events (MACE), it is unclear if this is true for patients with AATD-COPD. Prevalence of cardiovascular disease was determined in two separate severe AATD cohorts: AlphaNet, USA and the Birmingham AATD registry, UK. All patients had preexisting lung disease. Cardiovascular disease was defined as presence of any of the following: heart failure, ischaemic heart disease, atrial fibrillation, stroke, and myocardial infarction. A Cox proportional hazards model was used to assess the impact of prior cardiovascular disease and frequent exacerbator phenotype on risk of future MACE. Out of 3493 patients with severe AATD, 14.7% had prior cardiovascular disease, including stroke (2.3%), myocardial infarction (2.2%), and heart failure (2.5%). Frequent exacerbators were more likely to have preexisting cardiovascular disease compared with those with one or no exacerbations in the preceding year (63% vs 44.8%, p = 0.001). There was increased risk of future MACE in frequent exacerbators (HR 1.85, 95% CI 1.24 to 2.75), former and current smokers (HR 1.80, 95% CI 1.07 to 3.02, p = 0.026, and HR 4.04, 95% CI 1.44 to 11.32, p = 0.008, respectively), and those with prior cardiovascular disease (HR 3.81, 95% CI 2.60 to 5.58, p < 0.001). In severe AATD-COPD, MACE are associated with an increased exacerbation frequency, previous cardiovascular disease, and a history of smoking.

Impact of Hyperuricemia and Urate-Lowering Agents on Cardiovascular Diseases.

The association between hyperuricemia and cardiovascular diseases has been studied for many years. Research has shown a link between high uric acid levels and increased risk of including coronary artery disease hypertension and other cardiovascular conditions. Urate-lowering therapy, particularly with xanthine oxidase inhibitors like allopurinol, has shown promising results in reducing blood pressure in individuals with hyperuricemia and hypertension. Clinical trials and studies have demonstrated significant reductions in both systolic and diastolic blood pressure with urate-lowering treatment. Urate-lowering treatment has shown a favorable effect on reducing systolic blood pressure and major adverse cardiovascular events in patients with previous cardiovascular disease. In terms of cardiovascular safety, clinical trials have indicated that xanthine oxidase inhibitors such as febuxostat are non-inferior to allopurinol and do not increase the risk of death or serious adverse events. Overall, these findings highlight the importance of managing hyperuricemia and utilizing urate-lowering therapy to mitigate the adverse cardiovascular effects associated with elevated uric acid levels.