Atherosclerotic Cardiovascular Disease Research Articles

Abstract 4131951: The Safety Profile Of Inclisiran In Patients With Dyslipidemia And Intermediate To High Atherosclerotic Cardiovascular Disease Risk: A Systematic Review And Meta-Analysis

Introduction: Inclisiran is a novel drug that employs ribonucleic acid (RNA) interference to lower levels of the proprotein convertase subtilisin/kexin type 9 (PCSK9) protein, thereby improving the clearance of low-density lipoprotein (LDL) cholesterol from the bloodstream. It is given through subcutaneous injections at specified intervals and significantly reduces LDL cholesterol levels in patients with dyslipidemia and with intermediate to high risk of atherosclerotic cardiovascular disease (ASCVD). Goal: We aim to evaluate the safety of the use of inclisiran in patients with dyslipidemia and intermediate to high ASCVD risk. Methods: Three electronic databases of MEDLINE, Web of Science, and Embase were searched from inception to May 5th 2024 to identify relevant randomized controlled trials (RCTs) comparing safety profiles of inclisiran versus the control group . The primary outcome was all-cause mortality. Secondary outcomes were major adverse cardiovascular events (MACE), injection-site reaction and all treatment-emergent adverse events (TEAE). The effect estimates of outcomes were assessed using risk ratio (RR) with a 95% confidence interval (CI). Random-effects meta-analysis was conducted using the restricted maximum likelihood method given the inter-study variance was inevitable. The subgroup analysis was performed based on different dosing regimens. Results: We included 7 RCTs enrolling 4790 patients (63.8 ± 9.7 years, 66.8 % males) who received inclisiran. Compared to the control group, the use of inclisiran did not yield a significant effect on all-cause mortality (RR, 0.92; 95% CI, 0.54 to 1.54; I 2 = 0%), MACE (RR, 0.98; 95% CI, 0.82 to 1.17; I 2 = 0%), and TEAE (RR, 1.76; 95% CI, 0.74 to 4.15; I 2 = 74%). However, inclisiran use significantly increased injection-site reaction (RR, 7.08; 95% CI, 3.42 to 14.64; I 2 = 27%). Results are illustrated in the accompanying figure. Conclusions: Inclisiran use significantly increased injection-site reaction, with no increase in mortality and TEAE. Further trials are required to comprehensively assess the safety of inclisiran in the management of dyslipidemia in patients with ASCVD risk.

Prediabetes is associated with elevated risk of clinical outcomes even without progression to diabetes.

Prediabetes (HbA1c 39-47 mmol/mol [5.7-6.4%] or fasting glucose 5.6-6.9 mmol/l) is associated with elevated risks of microvascular and macrovascular complications. It is unknown to what extent these risks in prediabetes remain after accounting for progression to diabetes. In 10,310 participants from the Atherosclerosis Risk in Communities (ARIC) Study (aged 46-70 years, ~55% women, ~20% Black adults) without diabetes at baseline (1990-1992), we used Cox regression to characterise age- and sex-adjusted associations of prediabetes with ~30 year incidence of complications (composite and separately), including atherosclerotic CVD (ASCVD), heart failure, chronic kidney disease (CKD) and all-cause mortality before and after accounting for intervening incidence of diabetes, modelled as a time-varying variable. We calculated the excess risk of complications in prediabetes remaining after accounting for progression to diabetes. Of the 60% of adults with prediabetes at baseline, ~30% progressed to diabetes (median time to diabetes, 7 years). Over the maximum follow-up of ~30 years, there were 7069 events (1937 ASCVD, 2109 heart failure, 3288 CKD and 4785 deaths). Prediabetes was modestly associated with risk of any complication (HR 1.21 [95% CI 1.15, 1.27]) vs normoglycaemia. This association remained significant after accounting for progression to diabetes (HR 1.18 [95% CI 1.12, 1.24]) with 85% (95% CI 75, 94%) of the excess risk of any complication in prediabetes remaining. Results were similar for the individual complications. Progression to diabetes explained less than one-quarter of the risks of clinical outcomes associated with prediabetes. Prediabetes contributes to the risk of clinical outcomes even without progression to diabetes.

Abstract 4114406: Galectin-3 and Progression of Kidney Disease in Patients With Type 2 Diabetes Mellitus: Analyses From the DECLARE-TIMI 58 Trial

Background: Galectin-3 (Gal-3) is a circulating biomarker of fibrosis, with higher levels having been associated with an increased risk of progression of kidney disease. Patients with type 2 diabetes mellitus (T2DM) are at increased risk for kidney disease with fibrosis. Aims: To study the association of Gal-3 with chronic kidney disease progression, and the effect of the SGLT2-inhibitor dapagliflozin in pts with T2DM. Methods: DECLARE-TIMI 58 was a randomized, placebo-controlled trial of dapagliflozin in pts with T2DM with or at high risk for atherosclerotic cardiovascular (CV) disease and creatinine clearance ≥60ml/min. In a nested biomarker substudy, Gal-3 was measured at baseline (Alinity, Abbott Diagnostics) in the TIMI Clinical Trials Laboratory (Boston, MA). The prespecified kidney-specific composite endpoint (Kidney-EP) was a sustained ≥40% decrease in eGFR to <60 mL/min, initiation of renal replacement therapy or confirmed sustained eGFR <15 mL/min, or adjudicated renal death. Cox models were adjusted for baseline eGFR, urine albumin-creatinine ratio (UACR), patient characteristics, CV risk factors, NTproBNP and hs-cTnT. Results: Among 14,530 pts, median Gal-3 was 14.9 ng/mL [IQR, 11.9, 18.4]. Gal-3 was weakly associated with UACR (r = 0.098, p < 0.0001) and eGFR (r = -0.27, p<0.001) at baseline. Gal-3 was independently associated with the incidence of the Kidney-EP (adj-HR 1.15 [95% CI 1.03, 1.28] per 1-SD log(Gal-3), p = 0.013). Upon stratification by quartiles, there was a gradient of higher adjusted risk of the Kidney-EP with higher Gal-3 ( Fig., A ; p-trend <0.0001). There were 111 (1.5%) and 203 (2,8%) Kidney-EPs in the dapagliflozin and placebo groups, respectively. Dapagliflozin significantly and similarly reduced the relative risk of the Kidney-EP across quartiles of Gal-3 (overall HR 0.45 [95%CI 0.23, 0.85], p<0.0001; p-interaction = 0.97, Fig., B ). However, there was greater absolute benefit of dapagliflozin with higher Gal-3 (ARR Q4 1.9 [95% CI 0.6, 3.2] vs. Q1 0.6% [-0.1, 1.3], ARR p-trend 0.048). Conclusion: Plasma Gal-3 is associated with progression of kidney dysfunction in patients with T2DM independently of patient characteristics, including baseline kidney function. Moreover, Gal-3 identified an increasing gradient of absolute benefit of dapagliflozin for reducing kidney disease progression.

Devouring Atherosclerotic Plaques: The Engineered Nanorobot Rousing Macrophage Efferocytosis by a Two‐Pronged Strategy

AbstractInvestigating the potential of macrophage efferocytosis has led to a growing interest in exploiting macrophage in immunotherapy. Macrophage‐specific nano‐medicines are currently being developed to stimulate the phagocytic clearance of apoptotic debris in atherosclerosis; however, these unnatural nanoparticles exhibit poor biocompatibility and limited efferocytosis activation ability. Here a pro‐efferocytosis biomimetic nanorobot UM‐EVLipo is developed based on nano‐motor and extracellular vesicles (EVs) hybridized with plaque double‐targeted liposomes. An elegant procedure with only 4 steps is integrated to prepare and purify these hybrid nanovesicles. It is first demonstrated that the EVs derived from bone marrow macrophages stimulated with IL‐4 can promote the transformation of M0 and M1 macrophages into M2, an efferocytosis phenotype. Furthermore, the EVs hybridized with SHP‐1 siRNA‐liposomes blocked the “don't eat me” signal from apoptotic debris by intervening CD47‐SIRPα‐SHP‐1 axis. This two‐pronged strategy of resetting phenotype and blocking checkpoints furthest activates macrophage efferocytosis. Importantly, the urease motor increased the swimming speed of nanovesicles in the blood by 12.4 times, making it easier for them to penetrate the endothelial barrier. The UM‐EVLipo accumulated within the atherosclerotic plaque, reactivate lesioned efferocytosis and reduce the plaque area in the carotid and coronary, which demonstrates the potential of a two‐pronged strategy to prevent atherosclerotic cardiovascular disease.

Abstract 4136289: Aortic Valve Calcium as a Predictor of Chronic Kidney Disease in a Multi-Ethnic Cohort: The MESA Study

Background: Aortic valve calcium (AVC) is associated with an increased risk of cardiovascular disease, non-cardiovascular disease such as dementia, and all-cause mortality. Traditional atherosclerotic cardiovascular disease risk factors are associated with both AVC and chronic kidney disease (CKD), but whether there is an association between AVC and CKD is unknown. Objectives: To ascertain whether AVC quantified by cardiac CT scanning is independently associated with the long-term risk of incident CKD among individuals without a previous history of cardiovascular disease. Methods: We examined 6,346 Multi-Ethnic Study of Atherosclerosis (MESA) participants who underwent cardiac CT scanning at Visit 1 (2000-02) and had an eGFR of ≥ 60 mL/min/1.73 m 2 . AVC was quantified using the Agatston method and categorized as 0, 1-99, and ≥100. Incident CKD was defined as an eGFR < 60 mL/min/1.73 m 2 accompanied with an at least 40% decline in eGFR from baseline, and/or a diagnosis of CKD and indicators of end stage renal disease extracted from hospital records using the International Classification of Disease (ICD) codes. We performed Kaplan-Meier survival curve analyses along with multivariable Cox proportional hazard regression models, adjusted for age, gender, race/ethnicity, highest level of education and traditional cardiovascular risk factors along with coronary artery calcium (CAC), lipoprotein (a) (Lp[a]), and the APOE-ε4 genotype to examine the association between AVC (categorical and log-transformed) and incident CKD. Results: Participants had a mean age 62.2±10.1 years, 53% were women, and AVC >0 was present in 795 (12%) participants. During a median follow-up time of 16.9 years, 982 (15%) participants developed incident CKD. AVC examined as a continuous variable was associated with a significantly increased risk of developing CKD (per log-unit [AVC+1] HR 1.06 [95% CI: 1.02-1.10]; p = 0.005). There was a stepwise increased risk for CKD with higher AVC levels ( Figure ). Similarly, in the multivariable adjusted Cox models, participants with AVC ≥100 had a higher risk of incident CKD, compared with the AVC=0 group (HR 1.48 [95% CI: 1.15-1.89]; p = 0.002). The observed associations remained after further adjusting for CAC score ( p = 0.024), Lp (a) ( p = 0.004), and the APOE-ε4 genotype ( p = 0.004). Conclusions: In a multi-ethnic cohort of participants free of CKD at baseline, AVC was independently associated with a higher risk of incident CKD.

Abstract 4137058: Clinical Characteristics and Outcomes of South Asians Presenting with Acute Coronary Syndrome

Background: Patients of South Asian descent have a higher incidence of atherosclerotic cardiovascular disease and are affected by clinically significant coronary artery disease at an earlier age when compared to the general population. As a result, they have been shown to have a higher rate of cardiovascular events. This at-risk population has not been well studied as it pertains to acute coronary syndrome. Methods: Out of 1610 patients who presented to one of two tertiary care centers between 2021-2022 with a diagnosis of acute coronary syndrome and underwent coronary angiography, 240 patients were identified as being South Asian and were included in the study. 480 non-South Asian patients were randomly selected as controls. A retrospective analysis was conducted to study the demographics, risk factors, clinical presentation, diagnostic features, and outcomes of the two groups. Results: South Asian patients who were diagnosed with acute coronary syndrome and underwent coronary angiography were significantly younger than non-South Asian patients (61 vs 65 years, p < 0.001). Though they were less likely to be smokers, they were significantly more likely to have other known risk factors including hypertension, dyslipidemia, and a history of prior myocardial infarction (p < 0.001). South Asians had mean lower HDL (p = 0.02), higher triglycerides (0.006), and higher Hgb A1C (p < 0.001). Surprisingly, rates of multivessel disease (defined as stenosis of 50% or greater in two or three vessels) were similar between the two groups. South Asians were more likely to be referred for CABG after initial coronary angiography most likely due to diffuse disease (p = 0.014). Clinical outcomes including pre-discharge LVEF, and 2-year mortality were similar between the groups. Conclusions: South Asians are a notoriously high-risk group when it comes to early-onset and more severe coronary artery disease. The pathophysiology behind this disproportionate manifestation of cardiovascular disease is not entirely understood, but several efforts to delineate this are ongoing. Our data demonstrate that this is at least in part, due to a higher prevalence of conventional modifiable and nonmodifiable risk factors in South Asian patients.

Abstract 4140126: Comparison of Clinical Risk Calculators for Atherosclerotic Cardiovascular Diseases: PREVENT, Pooled Cohort Equations, and QRISK3

Introduction: The cardio-kidney-metabolic pathway has a crucial role in ASCVD, motivating development of the PREVENT equation. There is a need for external validation of the PREVENT equation and assessment of its performance in independent cohorts to assess generalizability across diverse populations. Aim: To compare predictive performance of the PREVENT equation with previously developed risk calculators; pooled cohort equations (PCE), and QRISK3. Methods: We used data from 500k participants of the United Kingdom Biobank (UKB). ASCVD was defined as the composite outcome of fatal and non-fatal myocardial infarction, coronary revascularization, and stroke. We ascertained demographic and clinical covariates required to calculate ASCVD risk, using the base model of PREVENT, PCE, and QRISK3, at the time of recruitment. Those with a diagnosis of ASCVD at the time of recruitment or missing data on age, sex, or ethnicity were excluded. We used the area under the ROC curve (AUC) and calibration plots for analysis. Results: Of 459,681 participants (mean age 56.3±8.1 years, 44.4% male, and 94.7% White), 24,514 (5.4%) participants had a new diagnosis of ASCVD during a 10-year follow-up. The median [interquartile range] of estimated 10-y ASCVD risk was 3.7% [1.9% - 6.1%] for PREVENT, 5.6% [2.4% - 11.3%] for PCE, and 8.0% [3.9% - 13.8%] for QRISK3 (Figure 1A). The calibration slope (95% CI) was 1.71 (1.66 – 1.76) for PREVENT, 0.64 (0.63 – 0.66) for PCE, and 0.66 (0.64 – 0.67) for QRISK3 (Figure 1B). The AUC for ASCVD prediction was 0.741 (0.738 - 0.744) for PREVENT, 0.744 (0.741 – 0.747) for PCE, and 0.751 (0.749 – 0.755) for QRISK3 (Figure 1C). Conclusion: In the UKB cohort, the PREVENT equation underpredicted while the PCE and QRISK3 overpredicted ASCVD risk, with a similar discrimination. Consequently, fewer individuals would be eligible for primary prevention with statins, based on the actionable thresholds of 7.5% or 10% when considering ASCVD risk based on PREVENT. Therefore, the external application of the PREVENT equation requires recalibration and context-specific interpretation.

Abstract 4143225: Carotid Artery Ultrasound Grayscale and Incident Dementia: The Multi-Ethnic Study of Atherosclerosis (MESA)

Introduction: Vascular contributions to cognitive impairment and dementia are potentially modifiable. Early detection of reversible arterial injury may improve dementia risk stratification and provide an opportunity for treatment monitoring. We hypothesized that carotid ultrasound grayscale-median (GSM), a novel imaging biomarker of early arterial injury, would predict incident all-cause dementia in the Multi-Ethnic Study of Atherosclerosis (MESA). Methods: The MESA enrolled adults aged 45-84 years old who were free of atherosclerotic cardiovascular disease at baseline. Common carotid artery GSM (grayscale units) was measured at baseline. Incident all-cause dementia events were identified by hospital and death records. Adjusted Cox proportional hazards models with natural cubic splines allowing for non-linear effects investigated the associations of baseline GSM and incident all-cause dementia. Results: The 1,788 participants were a mean (standard deviation) 63.1 (10.3) years old (53% female). Over a median of 13.7 years, 157 all-cause dementia events occurred. Lower (worse) carotid GSM independently predicted incident all-cause dementia (Hazard Ratio [HR] 1st to 3rd tertile, 1.39 [95% Confidence Intervals, 1.08-1.80], p =0.04). In models adjusting additionally for carotid IMT there was no attenuation of the association of GSM and incident all-cause dementia (HR 1.63 [95% CI 1.13-2.35], p=0.033) (Figure 1). Conclusions: Lower GSM predicts incident all-cause dementia independent of carotid intima-media thickness, suggesting it may serve as an early marker of dementia risk.

Abstract 4138304: Macrophage ZIP8 Enhances Efferocytosis and Mitigates Atherosclerosis by Modulating cellular Manganese (Mn) Homeostasis

Introduction: ZIP8, also known as SLC39A8, is a transmembrane transporter responsible for the movement of various divalent metal ions. Multiple genome-wide association studies (GWAS) have revealed a significant association between a mutation in ZIP8 (rs13107325; Ala391Thr) and cardiovascular diseases. While its physiologic role is incompletely understood, recent studies implicate that Zn2+ influx into monocytes regulated by ZIP8 is a novel factor determining their adhesion and recruitment to atherosclerotic lesions. The potential role of ZIP8 in modulating macrophage function and thereby influencing the development of atherosclerosis warrants further investigation. Methods and Results: Using an ApoE -/- ZIP8 A393T missense mutation mouse model, we quantified atherosclerotic plaque burden and lipid profiles following induction of atherosclerosis. The presence of the ZIP8 A393T missense mutation resulted in increased necrotic regions and plaque load in the atherosclerosis mouse model, while having no impact on total cholesterol (TC) or low-density lipoprotein cholesterol (LDL-C) levels. Confocal microscopy and flow cytometry to investigate how reduced ZIP8 expression affects macrophage efferocytosis. When siRNA was used to knock down ZIP8 in vitro, macrophage efferocytosis was reduced. Subsequently, Macrophage-specific ZIP8 knockout mice (ZIP8 LysM ) demonstrated a decrease in the efferocytosis index in primary macrophage. Additionally, in vivo thymic and peritoneal efferocytosis assays showed an impaired efferocytosis phenotype in ZIP8 LysM mice. Confocal microscopy showed ZIP8 LysM mice have no effect on macrophage binding to apoptotic cells. The lack of or incompleteness of the F-ACTIN ring formed by macrophages surrounding apoptosis in the ZIP8 LysM mice, and the prolonged duration of phagocytosis ring formation suggests that the internalization process is compromised. The role of ZIP8 ion transport in the efferocytosis impairment mechanism was also investigated.The regulation of macrophage efferocytosis via the metabolism of D-galactose, glutamine, glutamate, and Zn 2+ is unaffected by ZIP8. Mn 2+ was identified as a vital regulatory factor in the efferocytosis function of ZIP8 in macrophages. Conclusions: ZIP8 influences the efferocytotic capacity of macrophages and regulates the clearance of apoptotic cells through Mn 2+ , suggesting that ZIP8 and Mn 2+ hold promise as a key therapeutic targets for the treatment of atherosclerotic cardiovascular diseases.

Abstract 4132341: Systematic Examination of the AHA PREVENT Equations

Background: The novel AHA Predicting Risk of CVD Events (PREVENT) equations newly incorporate predictors (estimated glomerular filtration rate [eGFR]) and outcomes (heart failure [HF]) relevant to the novel construct of cardiovascular-kidney-metabolic (CKM) syndrome. Aims: We sought to characterize the intrinsic properties of the PREVENT equations by simulating different risk profiles across the age and CKM risk spectrum. Methods: We applied the PREVENT base equations to estimate 10-year predicted risk for total CVD, which includes atherosclerotic CVD and HF. First, we calculated risk estimates for a hypothetical individual varying age from 30-79 years with an average risk factor profile (mean population risk factor levels based on National Health and Nutrition Examination Survey 2011-2020 data without diabetes, not on anti-hypertensive or statin medication, and who does not smoke). Second, we examined at which age a hypothetical individual would exceed the previously defined intermediate risk threshold ≥7.5% established by national guidelines. Lastly, we examined the differences in predicted risk with or without diabetes and/or Stage 3 CKD (defined as eGFR 44.5 mL/min/1.73m 2 ). Results: For hypothetical individuals aged 30-79 years with average risk factor levels, predicted 10-year CVD risk is shown in the figure for females (Panel A) and males (Panel B). The predicted risk would exceed the intermediate risk threshold at age 68 years if female and 63 years if male. If the individual had Stage 3 CKD, the predicted risk would exceed the intermediate risk threshold at 60 if female and 55 years if male. If the individual had diabetes, the predicted risk would exceed the intermediate risk threshold at 59 if female and 52 years if male. If both diabetes and Stage 3 CKD were present, the predicted risk would exceed the intermediate risk threshold at age 42 years if female and 35 years if male. Conclusions: The PREVENT equations enable more granular differentiation of risk among individuals with varying CKM profiles. Understanding risk estimates across the spectrum of age and CKM can support interpretability among clinicians and patients.

Metabolic Surgery: Progenitor of Effective Therapy for Atherosclerotic Cardiovascular Disease, Cancer, Type 2 Diabetes, and Obesity.

Metabolic surgery - operating on a normal organ for a beneficial metabolic gain - is not only an emerging discipline of surgery but the progenitor of therapy for the major global afflictions of atherosclerotic cardiovascular disease, cancer, type 2 diabetes, and obesity, as well as at least 18 other disease entities.

Association between the weight-adjusted-waist index and Familial hypercholesterolemia: a cross-sectional study

ObjectiveThe weight-adjusted-waist index (WWI) is a novel obesity measurement indicator, and this study aims to determine the relationship between WWI and Familial hypercholesterolemia (FH).MethodsUsing data from the National Health and Nutrition Examination Survey (NHANES) from 2017 to March 2020, cross-sectional data from 3698 participants were analyzed. The study examined the correlation between WWI and FH using multivariate logistic regression and smooth curve fitting, and conducted subgroup analysis and interaction tests.ResultsThe study sample consisted of 3698 subjects for whom the overall probable prevalence of FH was 5.43% and increased with WWI tertile (quantile 1: 4.00%; quantile 2: 4.94%; quantile 3: 7.34%); individuals with the highest WWI tertile were significantly more likely to have FH than those with the lowest tertile (OR = 4.60,95% CI: 2.00-10.60). Subgroup analysis and interaction tests showed significant significance between WWI and personal history of early Atherosclerotic cardiovascular disease (ASCVD), family history of early ASCVD and probable prevalence of FH (p < 0.05).ConclusionThis study demonstrates a nonlinear positive correlation between WWI and FH. This may provide new ideas for the prevention and treatment of FH in the future.

Racial and ethnic disparities in the uptake of SGLT2is and GLP-1RAs among Medicare beneficiaries with type 2 diabetes and heart failure, atherosclerotic cardiovascular disease and chronic kidney disease, 2013-2019.

The aim of this study was to investigate racial and ethnic disparities in the use of sodium-glucose cotransporter 2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor antagonists (GLP-1RAs) among older adults with type 2 diabetes and cardiorenal conditions. Using Medicare fee-for-service data (2013-2019), this retrospective cohort study identified older adults (≥65 years) with type 2 diabetes initiating second-line therapies (SGLT2is, GLP1-RAs, dipeptidyl peptidase-4 inhibitors [DPP4is] and sulfonylureas [SUs]) with (1) heart failure (HF), (2) atherosclerotic cardiovascular disease (ASCVD), (3) chronic kidney disease (CKD) and (4) no recorded cardiorenal conditions. Participants were classified as non-Hispanic White, non-Hispanic Black and Hispanic. Multinomial regressions, adjusting for sociodemographic, clinical and county-level characteristics, were used to model the odds of initiating SGLT2is or GLP-1RAs within each cohort. Black participants with HF, ASCVD, CKD or no recorded cardiorenal conditions had 35% (adjusted OR 0.65 [95% CI 0.61, 0.68]), 33% (0.67 [0.64, 0.69]), 32% (0.68 [0.64, 0.72]) and 24% (0.76 [0.74, 0.79]) lower odds of initiating SGLT2is, respectively, than White participants. Disparities ameliorated from 50-60% lower odds in 2013 to 17-18% in 2019. Similar patterns were observed for GLP-1RA uptake among Black participants. By contrast, Hispanic participants had similar odds of SGLT2i initiation in the HF and CKD cohorts as White participants, but 6% (0.94 [0.91, 0.98]) lower odds in the ASCVD cohort. Notable disparities for Hispanic participants compared with White participants were observed for GLP-1RA uptake in the HF, ASCVD, CKD and no cardiorenal conditions cohorts: 11% (0.89 [0.84, 0.94]), 16% (0.84 [0.81, 0.87]), 16% (0.84 [0.80, 0.89]) and 25% (0.75 [0.72, 0.78]) lower odds, respectively. Participants had greater odds than White participants of initiating DPP4is, which confer no cardiorenal benefits, across all cohorts (HF 1.25 [1.19, 1.31]; ASCVD 1.36 [1.32, 1.40]; CKD 1.32 [1.26, 1.38). Adjustment for social determinants of health did not meaningfully change the study findings. Compared with White participants, disparities in the uptake of SGLT2is were evident for Black participants, and in the uptake of GLP-1RAs for both Black and Hispanic participants. This study highlights how type 2 diabetes management is evolving, while underscoring historical imbalances that have shown signs of abatement.

Influence of sleep on physiological systems in atherosclerosis.

Sleep is a fundamental requirement of life and is integral to health. Deviation from optimal sleep associates with numerous diseases including those of the cardiovascular system. Studies, spanning animal models to humans, show that insufficient, disrupted or inconsistent sleep contribute to poor cardiovascular health by disrupting body systems. Fundamental experiments have begun to uncover the molecular and cellular links between sleep and heart health while large-scale human studies have associated sleep with cardiovascular outcomes in diverse populations. Here, we review preclinical and clinical findings that demonstrate how sleep influences the autonomic nervous, metabolic and immune systems to affect atherosclerotic cardiovascular disease.

The Role of Lipid Metabolism in Dyslipidemias and Atherosclerosis

Atherosclerotic cardiovascular disease is a major burden of morbidity and, despite recent therapeutic advances, is the leading cause of mortality worldwide [...]

Osteocalcin and Chinese visceral adiposity index are associated with the risk of ASCVD and arterial stiffness in patients with T2DM

This study aims to discover the association between serum osteocalcin, the Chinese visceral adiposity index (CVAI), and atherosclerotic cardiovascular disease (ASCVD) risk, and their impact on arterial stiffness in T2DM patients. We included 639 T2DM patients aged 30 and older who received the assessment of ASCVD risk using the China-PAR equation, Osteocalcin and arterial stiffness in this cross-sectional study. We found that osteocalcin and CVAI as independent risk factors for both medium–high-risk ASCVD (osteocalcin: men, OR,0.96, 95% CI 0.92, 1.00; women, OR, 0.93, 95% CI 0.8, 1.08, respectively)(CVAI: men, OR,1.01,95% CI 1.00,1.02; women: OR, 1.08, 95% CI 1.02,1.14, respectively) and arterial stiffness (osteocalcin: men, OR, 0.98, 95% CI 0.94,1.01; women, OR, 0.98, 95% CI 0.90,1.06, respectively)(CVAI: men, OR,1.0, 95% CI 0.99,1.01; women, OR, 1.02, 95% CI 1.00,1.04, respectively) in both men and women patients with T2DM. Combining osteocalcin levels and CVAI improved the prediction accuracy of arterial stiffness in men patients with T2DM (difference of AUC(Model 4 vs. Model 1):1.5%, NRI: 0.06 [0.0,0.4]). All P-values were < 0.05. The results suggested that osteocalcin levels and CVAI are independent risk factors for ASCVD risk and arterial stiffness in T2DM. Combining osteocalcin and CVAI can enhance the early detection of atherosclerosis through male patients with T2DM.

Gene-Based Targeting for Treatment of Hypercholesterolemia and Prevention of Atherosclerotic Cardiovascular Disease

Familial hypercholesterolemia, characterized by high levels of LDL cholesterol is a monogenic metabolic disorder linked to atherosclerotic cardiovascular disease. Several genetic mutations in genes such as LDLR and PSK9 are thought to cause familial hypercholesterolemia. This ultimately causes dysfunction of the LDLR pathway, increasing circulating LDL levels. Current treatment revolves around decreasing LDL cholesterol levels in the blood. Statins are the current gold standard while sterol absorption inhibitors (ezetimibe) and PCSK9 inhibitors (evolocumab) are either used as primary treatment in individuals with statin intolerance, or supplementary treatment otherwise. However, CRISPR-Cas9 offers an upstream therapeutic intervention, inducing mutations in pathogenic genes (such as LDLR) to upregulate or downregulate gene expression and subsequently reduce LDL cholesterol levels. This technology thus has great potential as a two-fold treatment option, offering an effective solution for familial hypercholesterolemia, while simultaneously diminishing the risk of atherosclerotic cardiovascular disease. A limitation to current research exists in the sole analysis of monogenic factors in genetic screening, thus polygenic, multifactorial analyses are required to assess more holistic treatment plans. Furthermore, there exist current limitations to CRISPR-Cas9 including ethical limitations and social considerations revolving around the perpetuation of social inequities through technology necessitating future research on global health policies.

In HF, T2D, CKD, or atherosclerotic CVD, SGLT2 inhibitors reduce HF hospitalizations and CV mortality.

Usman MS, Bhatt DL, Hameed I, et al. Effect of SGLT2 inhibitors on heart failure outcomes and cardiovascular death across the cardiometabolic disease spectrum: a systematic review and meta-analysis. Lancet Diabetes Endocrinol. 2024;12:447-461. 38768620.

Cardiovascular Disease in Acute Cocaine Compared to Acute Fentanyl Intoxication Deaths.

Cocaine is the most common stimulant drug that causes death in Connecticut. Unlike opioid intoxication deaths, which largely correlate with dose/concentration, cocaine deaths occur more idiosyncratically, with mechanisms of death often related to underlying cardiovascular disease. We examined 78 sole acute cocaine and 306 sole acute fentanyl intoxication deaths to assess their association with cardiovascular disease. In the cocaine cohort, 87% (68/78) had atherosclerotic and/or hypertensive cardiovascular disease while 40% (122/306) in the fentanyl cohort did. Cocaine was detected in 40% of all accidental drug intoxication deaths, 41% of all accidental drug intoxication deaths involving fentanyl, and 37% of all drug intoxication deaths involving heroin. The relatively low number of sole cocaine deaths compared to the much higher proportion of cocaine/opioid deaths may be explained by the synergistic effects encountered in many mixed drug intoxications, the contributory role of cardiovascular disease in sole cocaine deaths, and/or the increased prevalence and potency of fentanyl. The high number of sole cocaine deaths in which the decedents had co-existing heart disease compared to those from sole fentanyl deaths (P < 0.001) suggests that heart disease plays a mechanistic role in sole cocaine deaths, whereas the potency of fentanyl is the dominant mechanism in fentanyl deaths.

Integrating the Polysocial Risk Score: Enhancing Comprehensive Healthcare Delivery.

Social determinants of health (SDOH) are known to determine a significant portion of a person's health, influencing downstream outcomes and widespread disparities. Screening for SDOH in clinical practice can improve efficacy of medical care, highlighting the potential for polysocial risk scores (PsRS) to help evaluate a patient's risk of developing atherosclerotic cardiovascular disease and other conditions. This review highlights existing research about the efficacy of PsRS in practical risk assessment, current gaps in the literature, and opportunities to refine the design and implementation of PsRS in real-world clinical settings. PsRS present unique opportunities to improve traditional risk prediction models for heart disease and other conditions, particularly if they examine both individual and area-level SDOH. Future studies should assess novel methods for extracting SDOH data from patients' medical records as well as PsRS implementation strategies that promote efficiency and patient confidentiality in real-world clinical settings.