Social disadvantage, coronary artery calcium, and their interplay in the prediction of atherosclerotic cardiovascular disease events

JAMA cardiology

ImportanceCardiovascular disease (CVD) is increased in people with HIV (PWH) and is characterized by premature noncalcified coronary plaque. In the Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE), pitavastatin reduced major adverse cardiovascular events (MACE) by 35% over a median of 5.1 years.ObjectiveTo investigate the effects of pitavastatin on noncalcified coronary artery plaque by coronary computed tomography angiography (CTA) and on inflammatory biomarkers as potential mechanisms for MACE prevention.Design, Setting, and ParticipantsThis double-blind, placebo-controlled randomized clinical trial enrolled participants from April 2015 to February 2018 at 31 US clinical research sites.PWH without known CVD who were taking antiretroviral therapy and had low to moderate 10-year CVD risk were included. Data were analyzed from April to November 2023.InterventionOral …

Circulation: Cardiovascular Imaging

Achieving optimal cardiovascular health in rural populations can be challenging for several reasons including decreased access to care with limited availability of imaging modalities, specialist physicians, and other important health care team members. Therefore, innovative solutions are needed to optimize health care and address cardiovascular health disparities in rural areas. Mobile examination units can bring imaging technology to underserved or remote communities with limited access to health care services. Mobile examination units can be equipped with a wide array of assessment tools and multiple imaging modalities such as computed tomography scanning and echocardiography. The detailed structural assessment of cardiovascular and lung pathology, as well as the detection of extracardiac pathology afforded by computed tomography imaging combined with the functional and hemodynamic …

Journal of the American College of Cardiology

BackgroundSemaglutide is associated with improved outcomes in patients with diabetes and obesity. However, potential sociodemographic and clinical heterogeneity in semaglutide eligibility, and associated mortality risk has not been assessed by obesity class on a population scale.MethodsThis study included 2013-2018 National Health Interview Survey participants≥ 45 years old with ASCVD. Using eligibility criteria for semaglutide, we classified participants into (1) SELECT group (ASCVD+ BMI≥ 27),(2) SUSTAIN group (ASCVD+ T2D), and (3) control group (ASCVD, BMI< 27, no T2D). We generated weighted estimates and examined the multivariable association between obesity class and all-cause mortality.ResultsOf 15,912 adults (11.5 million nationally) with ASCVD, 68% met eligibility criteria for semaglutide. Eligible adults in higher obesity classes were more likely to be non-elderly, female non-Hispanic …

Journal of the American College of Cardiology

BackgroundObesity is associated with high healthcare utilization. However, the association between financial toxicity (FT)-a composite measure of burden and sequelae of high healthcare costs-and all-cause mortality in adults with obesity has not been investigated on a population level in the US.MethodsThis study used data from the 2013-2018 National Health Interview Survey, linked to the National Death Index for mortality ascertainment.. FT was defined as a binary variable, composite of: difficulty paying medical bills, cost-related medication non-adherence and delayed/foregone care. Age-adjusted mortality rates (AAMR) were generated; multivariable Cox regression was used to calculate hazard ratios for mortality.ResultsOf the 60,920 adults with obesity (BMI≥ 30), 39.3% experienced FT. Those reporting FT were more likely to be younger, female and non-Hispanic Black, have public insurance and lower …

Journal of the American College of Cardiology

BackgroundThe intersection of Rheumatologic Diseases (RDs) and Atherosclerotic Cardiovascular Disease (ASCVD) augments cardiovascular risk substantially. Although statin use mitigates risk, a comparative evaluation of statin utilization in patients with ASCVD with and without RDs necessitates further exploration.MethodsThe Houston Methodist Learning Health System Outpatient Registry, an electronic medical record (EMR)-linked registry encompassing approximately 1.2 million patients, was leveraged to discern patients with confirmed ASCVD and RD's through ICD-10 codes. Statin prescriptions and dosing were assessed employing ATC codes and medication reconciliation derived from EMR data.ResultsFrom 113,021 identified ASCVD patients, 7286 (6.4%) manifested RDs. A total of 71.1% of ASCVD patients were administered statins, with utilization discernibly lower in the RD subset compared to the …

American Heart Journal

IntroductionThere is increasing prevalence of hepatic steatosis. Hepatic steatosis is increasingly recognized as the independent risk factor for cardiovascular mortality. However, there are limited options for the treatment of fatty liver. In this study we evaluated the effect of semaglutide on liver fat as measured by non-contrast cardiac CT scans.MethodsSTOP is a randomized controlled trial that evaluated semaglutide treatment effect on coronary atherosclerosis progression (STOP) in type 2 diabetes. We utilized unenhanced cardiac CT scans to quantify liver fat based on CT Hounsfield attenuation method. A total of 114 subjects qualified for this study of the 140 subjects randomized, 59 in semaglutide group and 55 in the placebo group and were followed for 12 months. Multivariate regression models were used to evaluate the change in liver fat content overtime.Results114 subjects were included in the study, 61 …

BMC Cardiovascular Disorders

ObjectiveTo assess the association between cardiovascular risk factor (CRF) profile and premature all-cause and cardiovascular disease (CVD) mortality among US adults (age < 65).MethodsThis study used data from the National Health Interview Survey from 2006 to 2014, linked to the National Death Index for non-elderly adults aged < 65 years. A composite CRF score (range = 0–6) was calculated, based on the presence or absence of six established cardiovascular risk factors: hypertension, diabetes, hypercholesterolemia, smoking, obesity, and insufficient physical activity. CRF profile was defined as “Poor” (≥ 3 risk factors), “Average” (1–2), or “Optimal” (0 risk factors). Age-adjusted mortality rates (AAMR) were reported across CRF profile categories, separately for all-cause and CVD mortality. Cox proportional hazard models were used to evaluate the association between CRF profile and all-cause …

Journal of the American College of Cardiology

BackgroundRheumatologic diseases (RDs) are well established independent risk factors (RFs) for atherosclerotic cardiovascular disease (ASCVD). Burden of ASCVD RFs in patients with RDs has not been described in large population samples. We aimed to determine the prevalence of common CV RFs in patients with vs without RDs in a large contemporary cohort.MethodsThe Houston Methodist Cardiovascular Disease Learning Health System Registry was queried to retrieve data of 1 1171 702 patients> 18 yo with at least one outpatient visit in the 2016-2022 timeframe. ICD codes and EMR data were used to identify all patients with RDs and ASCVD risk factors. Age adjusted prevalence and multivariate logistic regression were used to assess the burden of ASCVD RFs among patients with vs without RDs.ResultsA total of 39,860 patients (3.4%) with one or more RDs were identified (aged 60.5±15.6 yrs, 80.7 …

Journal of the American College of Cardiology

BackgroundSemaglutide is associated with improved outcomes in patients with diabetes and obesity. However, potential sociodemographic and clinical heterogeneity in semaglutide eligibility, and associated mortality risk has not been assessed by obesity class on a population scale.MethodsThis study included 2013-2018 National Health Interview Survey participants≥ 45 years old with ASCVD. Using eligibility criteria for semaglutide, we classified participants into (1) SELECT group (ASCVD+ BMI≥ 27),(2) SUSTAIN group (ASCVD+ T2D), and (3) control group (ASCVD, BMI< 27, no T2D). We generated weighted estimates and examined the multivariable association between obesity class and all-cause mortality.ResultsOf 15,912 adults (11.5 million nationally) with ASCVD, 68% met eligibility criteria for semaglutide. Eligible adults in higher obesity classes were more likely to be non-elderly, female non-Hispanic …

Radiology

Background Coronary artery calcium (CAC) has prognostic value for major adverse cardiovascular events (MACE) in asymptomatic individuals, whereas its role in symptomatic patients is less clear. Purpose To assess the prognostic value of CAC scoring for MACE in participants with stable chest pain initially referred for invasive coronary angiography (ICA). Materials and Methods This prespecified subgroup analysis from the Diagnostic Imaging Strategies for Patients With Stable Chest Pain and Intermediate Risk of Coronary Artery Disease (DISCHARGE) trial, conducted between October 2015 and April 2019 across 26 centers in 16 countries, focused on adult …

The Lancet Diabetes & Endocrinology

BackgroundThe EMPA-KIDNEY trial showed that empagliflozin reduced the risk of the primary composite outcome of kidney disease progression or cardiovascular death in patients with chronic kidney disease mainly through slowing progression. We aimed to assess how effects of empagliflozin might differ by primary kidney disease across its broad population.MethodsEMPA-KIDNEY, a randomised, controlled, phase 3 trial, was conducted at 241 centres in eight countries (Canada, China, Germany, Italy, Japan, Malaysia, the UK, and the USA). Patients were eligible if their estimated glomerular filtration rate (eGFR) was 20 to less than 45 mL/min per 1·73 m2, or 45 to less than 90 mL/min per 1·73 m2 with a urinary albumin-to-creatinine ratio (uACR) of 200 mg/g or higher at screening. They were randomly assigned (1:1) to 10 mg oral empagliflozin once daily or matching placebo. Effects on kidney disease …

Journal of Cardiovascular Computed Tomography

BackgroundRadiomics is expected to identify imaging features beyond the human eye. We investigated whether radiomics can identify coronary segments that will develop new atherosclerotic plaques on coronary computed tomography angiography (CCTA).MethodsFrom a prospective multinational registry of patients with serial CCTA studies at ≥ 2-year intervals, segments without identifiable coronary plaque at baseline were selected and radiomic features were extracted. Cox models using clinical risk factors (Model 1), radiomic features (Model 2) and both clinical risk factors and radiomic features (Model 3) were constructed to predict the development of a coronary plaque, defined as total PV ​≥ ​1 ​mm3, at follow-up CCTA in each segment.ResultsIn total, 9583 normal coronary segments were identified from 1162 patients (60.3 ​± ​9.2 years, 55.7% male) and divided 8:2 into training and test sets. At follow …

JACC: Advances

Background The initiation of coronary artery calcium (CAC) is an important physiologic milestone associated with increased cardiovascular disease risk. However, traditional risk factors (RF) do not perform well for predicting incident CAC among the 54 million older U.S. adults. Objectives The authors sought to assess the association between nontraditional cardiovascular disease RF and incident CAC in older persons. Methods There were 815 MESA (Multi-Ethnic Study of Atherosclerosis) participants ≥65 years of age who had CAC = 0 at Visit 1 and a follow-up CAC scan. Multivariable adjusted Cox hazards ratios (aHR) and C-statistics were calculated to examine the association of nontraditional RF with incident CAC. Results The mean age was 70.2 years and 67% were women. The median follow-up time to repeat CAC scan was 3.6 years (IQR: 2.6-9.2 years) and 45% of participants developed incident CAC …

Journal of the American College of Cardiology

BackgroundSemaglutide enhances cardiovascular outcomes in ASCVD patients. Refining phenotypes among eligible individuals can facilitate timely intervention and enhance disease management.MethodsHouston Methodist Learning Health System registry was used to identify individuals≥ 45 years with ASCVD between 2016 to 2022. Semaglutide eligibility was determined per SELECT (non-diabetes, BMI≥ 27) clinical trial criteria. K-means clustering analysis, utilizing the elbow method, was employed on the training data (60%) by incorporating demographic, clinical, and social factors. Test data was subsequently used to validate clusters stability (40%).ResultsIn the training cohort of 18,549 participants, two distinct phenotypes of ASCVD Semaglutide-eligible patients emerged. Cluster A (n= 10,160) included younger individuals with a higher BMI and a higher rate of married status, while Cluster B (n= 8,389 …

Journal of the American College of Cardiology

BackgroundThe rising incidence of major adverse cardiovascular events (MACE) in very young adults (< 40 years) warrants thorough examination, especially given the current paucity of data and the crucial role of real-world evidence in bridging research and clinical practice.MethodsData insights from very young adults (18-39 years) without atherosclerotic CVD (ASCVD) was leveraged from the Houston Methodist Cardiovascular Disease Learning Health System Registry (2016-2022). Our analysis emphasized on the impact of demographics cardiovascular risk factors, social disparities, and ensuing incidence of MACE (myocardial infarction, stroke, and heart failure) per 100 person-years (PY).ResultsOf the 352,080 very young adults analyzed (53.5% female, 39.8% NH Blacks), 1,289 (0.4%) experienced MACE over a mean period of 2.7±2.1 years. Distinctly, men, NH Blacks, smokers, substance use and those …

Journal of the American College of Cardiology

BackgroundSemaglutide, substantiated by the SUSTAIN and SELECT trials, has been spotlighted for enhancing outcomes in ASCVD patients. In light of the risk heterogeneity among those potentially qualifying for Semaglutide, enriching phenotypic characterization can significantly guide research and therapeutic initiativesMethodsUtilizing the NHIS (2013-2018), individuals≥ 45 years with ASCVD were investigated. Participants were demarcated as SUSTAIN (diabetes) and SELECT (non-diabetes, BMI≥ 27) cohorts, thus deeming them eligible for Semaglutide. K-means clustering analysis was applied within the training data (60%), incorporating demographic, clinical, and social factors. Clusters stability was subsequently validated within the test data (40%)ResultsIn the training cohort comprising 5,859 participants (representing 4, 2 million), five distinct clusters were identified, highlighting demographic and health …

The Lancet Diabetes & Endocrinology

BackgroundSodium–glucose co-transporter-2 (SGLT2) inhibitors reduce progression of chronic kidney disease and the risk of cardiovascular morbidity and mortality in a wide range of patients. However, their effects on kidney disease progression in some patients with chronic kidney disease are unclear because few clinical kidney outcomes occurred among such patients in the completed trials. In particular, some guidelines stratify their level of recommendation about who should be treated with SGLT2 inhibitors based on diabetes status and albuminuria. We aimed to assess the effects of empagliflozin on progression of chronic kidney disease both overall and among specific types of participants in the EMPA-KIDNEY trial.MethodsEMPA-KIDNEY, a randomised, controlled, phase 3 trial, was conducted at 241 centres in eight countries (Canada, China, Germany, Italy, Japan, Malaysia, the UK, and the USA), and …

Journal of the American College of Cardiology

BackgroundAlthough Randomized Clinical Trials have underscored significant weight loss (WL) with Semaglutide in patients exhibiting overweight/obesity (OO) and type 2 diabetes (T2D), a comprehensive understanding of its real-world effectiveness in large population settings remains limited so far.MethodsThe Houston Methodist CVD Learning Health System Registry (06/2016-12/2022) was utilized extract data from adults presenting a BMI≥ 27 kg/m/2 at baseline, with at least two visits spaced a minimum of three months apart and an active Semaglutide prescription at their most recent visit. Weight variations at intervals of 3, 6, and 12 months were assessed in the overall population and across specified subgroups, categorized based on indication (OO vs T2D) and baseline BMI.ResultsOf the 21,653 patients observed over median span of 46 months, 58% encountered weight loss, with average reductions of 7.6 …

Journal of the American College of Cardiology

BackgroundThe efficacy of Semaglutide in improving cardiovascular outcomes for patients with ASCVD and concurrent obesity or diabetes requires a comprehensive understanding of the demographic and health profiles of eligible US adults with ASCVD. This knowledge is crucial for informed policy-making, especially regarding budgetary and public health mattersMethodsUtilizing data from the 2013-2018 NHIS, we included adults aged≥ 45 years with ASCVD. Participants were categorized into three subgroups: SUSTAIN (ASCVD with diabetes), SELECT (ASCVD without diabetes, BMI≥ 27), and Control (ASCVD ineligible for SUSTAIN/SELECT) to facilitate comparative analysesResultsOut of 15,912 (over 11 million) adults≥ 45 years with ASCVD; a weighted population estimate of nearly 8 million (4.9% of total population and 69% of ASCVD population) were found Semaglutide eligible based on SELECT and …

Atherosclerosis

Seamus P. Whelton, Division of Cardiology, Johns Hopkins Ciccarone Center for Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine Email: seamus. whelton@ jhmi. edu X:@ seamuswhelton

Atherosclerosis

Methods: Seven KIV-2 amplicon mixtures (50% to 0.5% level, 85 differences) and 13 individuals were used for method validation. UMIs are random oligonucleotides that act as single-molecule barcodes and allow creating intramolecular consensus sequences to compensate sequencing and polymerase error rate. All KIV-2 repeats in each sample were UMI-tagged and PCR-amplified. After nanopore-sequencing (chemistries R9 and V14), reads were mapped, iteratively clustered by their UMI-tags and a consensus for each KIV-2 molecule was created. Variants were called and haplotypes extracted.Results: UMI-nanopore sequencing is comparable to NGS but retains full SNP haplotype information of each KIV-2 unit. False-positive rate per KIV-2 unit was< 1 in 5,100 bp (< 0.02%). After noise filtering, we found 1,179 of 1,191 expected SNPs with only 14 false-positives (precision and sensitivity, mean±SD: 98.9%±0 …

Atherosclerosis

Background and aimsCoronary artery calcium (CAC) is validated for risk prediction among middle-aged adults, but there is limited research exploring implications of CAC among older adults. We used data from the Atherosclerosis Risk in Communities study to evaluate the association of CAC with domains of healthy and unhealthy aging in adults aged ≥75years.MethodsWe included 2,290 participants aged ≥75years free of known coronary heart disease who underwent CAC scoring at study visit 7. We examined the cross-sectional association of CAC = 0, 1–999(reference), and ≥1000 with seven domains of aging: cognitive function, hearing, ankle-brachial index (ABI), pulse-wave velocity (PWV), forced vital capacity (FVC), physical functioning, and grip strength.ResultsThe mean age was 80.5 ± 4.3years, 38·6% male, and 77·7% White. 10·3% had CAC = 0 and 19.2% had CAC≥1000. Individuals with …

Atherosclerosis

BackgroundPatients with prior coronary artery bypass grafting (CABG) presenting with an acute coronary syndrome (ACS) have poor outcomes and the optimal treatment strategy for this population is unknown.MethodsUsing linked administrative databases, we examined patients with an ACS between 2008 and 2019, identifying patients with prior CABG. Patients were categorized by ACS presentation type and treatment strategy. Our primary outcome was the composite of death and recurrent myocardial infarction at one-year.ResultsOf 54,641 patients who presented with an ACS, 1670 (3.1%) had a history of prior CABG. Of those, 11.0% presented with an ST-elevation myocardial infarction (STEMI) of which, 15.3% were treated medically, 31.1% underwent angiography but were treated medically, 22.4% with fibrinolytic therapy and 31.1% with primary PCI. The primary outcome rate was the highest (36.8%) in …

Atherosclerosis

Background and aimsInformation on the association between dietary oily fish intake and intracranial atherosclerosis is limited and contradictory. Inconsistencies might be in part related to heterogeneous designs and differences in race/ethnicity of study populations. We aim to assess whether oily fish intake is inversely associated with intracranial artery stenosis (ICAS) in frequent fish consumers of indigenous ancestry living in coastal Ecuador.MethodsThe study included 384 participants aged ≥60 years enrolled in the Atahualpa Project Cohort. Dietary oily fish intake was quantified systematically via validated surveys and all participants received a time-of-flight MRA of intracranial vessels. Poisson regression models, adjusted for demographics, level of education, traditional risk factors and severe tooth loss, were fitted to assess the association between amounts of oily fish intake and the number of intracranial …

Atherosclerosis

Background and aimsInclisiran, an siRNA therapy, consistently reduces low-density lipoprotein cholesterol (LDL-C) with twice-yearly dosing. Potential cardiovascular benefits of implementing inclisiran at a population level, added to statins, were evaluated through simulation.MethodsFor each participant in the ORION-10 and ORION-11 trials comparing inclisiran with placebo, baseline 10-year cardiovascular risk was estimated using the SMART equation. The time-adjusted LDL-C difference from baseline observed 90–540 days after baseline was assumed to persist and used to estimate potential reduction in 10-year cardiovascular risk. Impact on 500,000 ORION-like individuals was simulated with Monte-Carlo.ResultsMean baseline LDL-C and predicted 10-year major vascular risk among patients randomized to inclisiran (n = 1288) versus placebo (n = 1264) were 2.66 mmol/L versus 2.60 mmol/L and 24.9 …

Atherosclerosis

Background and aimsSocial determinants of health (SDOH) are key for the identification of populations at increased risk of atherosclerotic cardiovascular disease (ASCVD). However, whether at the individual level SDOH improve current ASCVD risk prediction paradigms beyond traditional risk factors and the coronary artery calcium (CAC) score, is unknown. We evaluated the interplay between CAC and SDOH in ASCVD risk prediction.MethodsMESA is a prospective study of US adults free of clinical ASCVD at baseline. We used an SDOH index inclusive of 14 determinants from 5 domains. The index ranged 0–1 and was divided into quartiles, with higher ones representing worse SDOH. Cox regression was used to evaluate the adjusted associations between CAC, SDOH, their interplay, and ASCVD events. The C-statistic was computed to assess improvement in risk discrimination for prediction of ASCVD events …

Atherosclerosis

Background and aimsObesity and type 2 diabetes are significant risk factors for atherosclerotic cardiovascular disease (CVD) worldwide, but the underlying pathophysiological links are poorly understood. Neurotensin (NT), a 13-amino-acid hormone peptide, facilitates intestinal fat absorption and contributes to obesity in mice fed a high-fat diet. Elevated levels of pro-NT (a stable NT precursor produced in equimolar amounts relative to NT) are associated with obesity, type 2 diabetes, and CVD in humans. Whether NT is a causative factor in CVD is unknown.MethodsNt+/+ and Nt–/– mice were either injected with adeno-associated virus encoding PCSK9 mutants or crossed with Ldlr–/– mice and fed a Western diet. Atherosclerotic plaques were analyzed by en face analysis, Oil Red O and CD68 staining. In humans, we evaluated the association between baseline pro-NT and growth of carotid bulb thickness after 16.4 …

Atherosclerosis

BackgroundPatients with prior coronary artery bypass grafting (CABG) presenting with an acute coronary syndrome (ACS) have poor outcomes and the optimal treatment strategy for this population is unknown.MethodsUsing linked administrative databases, we examined patients with an ACS between 2008 and 2019, identifying patients with prior CABG. Patients were categorized by ACS presentation type and treatment strategy. Our primary outcome was the composite of death and recurrent myocardial infarction at one-year.ResultsOf 54,641 patients who presented with an ACS, 1670 (3.1%) had a history of prior CABG. Of those, 11.0% presented with an ST-elevation myocardial infarction (STEMI) of which, 15.3% were treated medically, 31.1% underwent angiography but were treated medically, 22.4% with fibrinolytic therapy and 31.1% with primary PCI. The primary outcome rate was the highest (36.8%) in …

Atherosclerosis

Methods: Seven KIV-2 amplicon mixtures (50% to 0.5% level, 85 differences) and 13 individuals were used for method validation. UMIs are random oligonucleotides that act as single-molecule barcodes and allow creating intramolecular consensus sequences to compensate sequencing and polymerase error rate. All KIV-2 repeats in each sample were UMI-tagged and PCR-amplified. After nanopore-sequencing (chemistries R9 and V14), reads were mapped, iteratively clustered by their UMI-tags and a consensus for each KIV-2 molecule was created. Variants were called and haplotypes extracted.Results: UMI-nanopore sequencing is comparable to NGS but retains full SNP haplotype information of each KIV-2 unit. False-positive rate per KIV-2 unit was< 1 in 5,100 bp (< 0.02%). After noise filtering, we found 1,179 of 1,191 expected SNPs with only 14 false-positives (precision and sensitivity, mean±SD: 98.9%±0 …

Atherosclerosis

Background and aimsSeveral studies have shown that endothelial dysfunction plays a role in the pathogenesis of Takotsubo syndrome (TTS). Given the potential benefit of statin therapy on endothelial dysfunction, we hypothesized that such treatment could improve outcome. Aim of our study was to evaluate clinical characteristics and outcome of TTS patients treated with statin therapy.MethodsPatients were enrolled in the international multicenter GEIST (GErman Italian Spanish Takotsubo) registry. Demographic data, clinical features and drug therapy at discharge were recorded. Primary study outcome was the occurrence of all-cause death at follow-up.ResultsStudy population included 2429 consecutive TTS patients: 1293 (53.2%) discharged on statin and 1136 (46.8%) without statin.Patients with statin were older (age 72 ± 11 vs 69 ± 13 years, p < 0.001), with higher prevalence of hypertension (74.3% vs 60.3 …

Atherosclerosis

Background and aimsAcetylcholine (ACh) provocation testing can detect vasomotor disorders in patients with ischemia and non-obstructed coronary arteries (INOCA) or myocardial infarction and non-obstructed coronary arteries (MINOCA). We aimed to derive and validate a simple risk score to predict a positive ACh test response.MethodsWe prospectively enrolled consecutive INOCA and MINOCA patients undergoing ACh provocation testing. Patients were split in two cohorts (derivation and validation) according to time of enrolment. The score was derived in 386 patients (derivation cohort) and then validated in 165 patients (validation cohort).Results551 patients were enrolled, 371 (67.3%) INOCA and 180 (32.7%) MINOCA. ACh test was positive in 288 (52.3%) patients. MINOCA, myocardial bridge (MB), C-reactive protein (CRP) and dyslipidaemia were independent predictors of a positive ACh test in the …

Atherosclerosis

Background and aimsAtherosclerosis is the primary underlying cause of myocardial infarction and stroke, which are the major causes of death globally. Heparanase (Hpse) is a pro-inflammatory extracellular matrix degrading enzyme that has been implicated in atherogenesis. However, to date the precise roles of Hpse in atherosclerosis and its mechanisms of action are not well defined. This study aims to provide new insights into the contribution of Hpse in different stages of atherosclerosis in vivo.MethodsWe generated Hpse gene-deficient mice on the atherosclerosis-prone apolipoprotein E gene knockout (ApoE−/−) background to investigate the impact of Hpse gene deficiency on the initiation and progression of atherosclerosis after 6 and 14 weeks high-fat diet feeding, respectively. Atherosclerotic lesion development, blood serum profiles, lesion composition and aortic immune cell populations were evaluated …

Atherosclerosis

Background and aimsSubclinical cardiovascular disease (CVD) measures may reflect biological pathways that contribute to increased risk for coronary heart disease (CHD) events, stroke, and dementia beyond conventional risk scores.MethodsThe Multi-Ethnic Study of Atherosclerosis (MESA) followed 6814 participants (45–84 years of age) from baseline in 2000–2002 to 2018 over 6 clinical examinations and annual follow-up interviews. MESA baseline subclinical CVD procedures included: seated and supineblood pressure, coronary calcium scan, radial artery tonometry, and carotid ultrasound. Baseline subclinical CVD measures were transformed into z-scores before factor analysis to derive composite factor scores. Time to clinical event for all-cause CVD, CHD, stroke and ICD code-based dementia events were modeled using Cox proportional hazards models reported as area under the curve (AUC) with 95 …

Atherosclerosis

Background and aimsReproductive risk factors are associated with increased risk of cardiovascular disease (CVD) in women. However, the combined effects of the composite reproductive risk factors on CVD are unknown. This study was performed to construct a reproductive risk score (RRS) to measure reproductive status, examine the association between RRS and CVD, and explore the modification effect of healthy lifestyle on the association in women in the UK Biobank cohort.MethodsThe RRS was constructed in 74 141 female participants with data about the items derived for the RRS in the UK Biobank. The RRS was derived from 17 baseline variables, all of which indicated women’s reproductive health status. We defined four categories of RRS status: low-risk group (score 0–1); low-intermediate group (score 2–3); high-intermediate group (score 4–5); and high-risk group (score 6–13). We also constructed a …

Atherosclerosis

Background and aimsPrognosis and management differ between Familial chylomicronaemia syndrome (FCS), a rare autosomal recessive disorder, and multifactorial chylomicronaemia syndrome (MCS) or severe mixed hyperlipidaemia. A clinical scoring tool to differentiate these conditions has been devised but not been validated in other populations. The objective of this study was to validate this score in the UK population and identify any additional factors that might improve it.MethodsA retrospective validation study was conducted using data from 151 patients comprising 75 FCS and 76 MCS patients. All participants had undergone genetic testing for genes implicated in FCS. Validation was performed by standard methods. Additional variables were identified from clinical data by logistic regression analysis.ResultsAt the recommended FCS score threshold of ≥10 points, the sensitivity and specificity of the score …

Atherosclerosis

Background and aimsSeveral studies have shown that endothelial dysfunction plays a role in the pathogenesis of Takotsubo syndrome (TTS). Given the potential benefit of statin therapy on endothelial dysfunction, we hypothesized that such treatment could improve outcome. Aim of our study was to evaluate clinical characteristics and outcome of TTS patients treated with statin therapy.MethodsPatients were enrolled in the international multicenter GEIST (GErman Italian Spanish Takotsubo) registry. Demographic data, clinical features and drug therapy at discharge were recorded. Primary study outcome was the occurrence of all-cause death at follow-up.ResultsStudy population included 2429 consecutive TTS patients: 1293 (53.2%) discharged on statin and 1136 (46.8%) without statin.Patients with statin were older (age 72 ± 11 vs 69 ± 13 years, p < 0.001), with higher prevalence of hypertension (74.3% vs 60.3 …

Atherosclerosis

Methods: We performed two new GWAS in the Estonian Biobank (2451 cases and 192521 controls) and the UK Biobank (2359 cases and 405762 controls) and combined these results with FinnGen (3022 cases and 195144 controls) in a genome-wide association meta-analysis totalling 7832 cases and 793427 controls. We then performed a series of inverse variance-weighted MR analyses using 123 metabolites derived from a GWAS of> 24,000 Europeans as study exposures. From there, we performed sensitivity analyses using MR-PRESSO and contamination mixture tests to account for horizontal pleiotropy and assess the validity of our instruments, respectively.Results: Our GWAS meta-analysis identified genome-wide significant variants (p< 5e-8) at two known AP loci (ABCG8 and SPINK1) as well as at one new locus (TRPV6). Out of the 123 metabolites tested, only the amino-acid glycine (beta [95% CI]=-0 …

Atherosclerosis

Background and aimsIn the COMPASS trial, low-dose rivaroxaban with aspirin improved cardiovascular outcomes in patients with atherosclerotic cardiovascular disease (ASCVD). We aimed to assess the potential clinical implications of this therapy in a generalizable population.Methods and resultsA retrospective cohort of adults with ASVCD was formed using healthcare administrative databases in Alberta, Canada (Population 4.4 million). Patients with a new diagnosis between 2008 and 2019 formed the epidemiological cohort (n = 224,600) and those with long-term follow-up (>5 years) formed the outcomes cohort (n = 232,460). The primary outcome of major adverse cardiovascular events (MACE) was assessed and categorized based on the COMPASS trial eligibility. In the outcomes cohort, 77% had only coronary artery disease, 15% had only peripheral artery disease, and 8% had both. Of those, 37% met …

Atherosclerosis

Background and aimsRemnant cholesterol (RC) and insulin resistance (IR) have been independently associated with cardiovascular risk. Here, we evaluated the role of IR and RC on cardiovascular disease (CVD) mortality.MethodsWe conducted an analysis of 16,113 individuals ≥20 years without diabetes from the National Health and Nutrition Examination Survey (NHANES-III/IV). RC levels were calculated using total cholesterol, non-HDL-c, and LDL-c; IR was defined as HOMA2-IR≥2.5 and CVD mortality as a composite of cardiovascular and cerebrovascular mortality. Multiple linear regression was used to assess the relationship between HOMA2-IR and RC and Cox regression models to assess their joint role in CVD mortality. Causally ordered mediation models were used to explore the mediating role of IR in RC-associated CVD mortality.ResultsWe identified an association between higher HOMA2-IR and …