High Atherosclerotic Cardiovascular Disease Research Articles

Cardiovascular disease, brain glucose metabolism and neurocognitive decline in People With HIV

Abstract Background Cardiovascular disease (CVD) and neuroinflammation are thought to exacerbate neurocognitive dysfunction in treated people with HIV (PWH). Here, we longitudinally measured brain glucose metabolism as a measure of neuronal integrity in treated PWH using [18F]Fluorodeoxyglucose (FDG) PET/CT in correlation with atherosclerotic cardiovascular disease (ASCVD) scores, CSF neuroinflammatory markers, neurocognitive outcomes and other clinical/laboratory variables (CLVs). Methods Well-controlled PWH (n=36) underwent baseline and follow-up FDG PET/CT obtained 3.5 years apart on average. Longitudinal changes in whole brain (WB) and regional relative FDG uptake, brain volumes, CLVs, CSF cytokines and neuropsychological measures were measured. A variable selection model identified baseline variables related to future brain metabolic changes while multivariable models explored neuropsychological implications of brain metabolism and volumetric. Results High ASCVD scores predicted future decreased thalamic uptake (slope=-0.0068, p=0.027) and decreasing thalamic uptake correlated with worsening cognition (slope=15.80, p=0.020). Despite longitudinal greater than expected gray matter loss, WB FDG uptake did not change over the follow-up period. Most CSF cytokines decreased longitudinally but were not predictive of FDG changes. Conclusions We found that high ASCVD scores in a group of treated PWH were related to thalamic hypometabolism, which in turn correlated with neurocognitive decline. Our findings support the contribution of CVD to neurocognitive dysfunction. More proactive CVD management may have a role in mitigating progression of cognitive impairment. Lack of change in global brain glucose metabolism despite documented accelerated gray matter volume loss over the same period suggests that FDG PET might underestimate neuronal injury in PWH compared to structural MRI.

Thoracic versus coronary calcification for atherosclerotic cardiovascular disease events prediction

This study compared the prognostic value of quantified thoracic artery calcium (TAC) including aortic arch on chest CT and coronary artery calcium (CAC) score on ECG-gated cardiac CT.MethodsA total of...

Cardiovascular disease risk and associated physical activity factors in gastrointestinal cancer survivors

IntroductionAlthough the risk of CVD is increased in cancer survivors, few studies have investigated the CVD risk in survivors of gastrointestinal (GI) cancer. Therefore, we evaluated the CVD risk using the 10-year atherosclerotic cardiovascular disease (ASCVD) risk score for GI cancer survivors and associated physical activity factors.MethodsUsing the 2014–2019 Korean National Health and Nutrition Examination Surveys, data were collected for 262 GI cancer survivors and 1,310 cancer-free controls matched at a 1:5 ratio based on age and sex. The International Physical Activity Questionnaire Short-Form was used to assess physical activity, and the Euro QoL Questionnaire 5-Dimensional Classification (EQ-5D) was used to assess the health-related quality of life.ResultsA multiple logistic regression analysis demonstrated a lower risk of ASCVD in GI cancer survivors than in controls (adjusted odds ratio [aOR] = 0.73, 95% confidence interval [CI] = 0.55-0.97). Moreover, the risk of having a high ASCVD score was significantly lower in individuals who performed sufficient aerobic physical activity (aOR = 0.59, 95% CI = 0.47-0.75) and those with an EQ-5D score 1 or 2 (aOR = 0.36, 95% CI = 0.20-0.65 and aOR = 0.31, 95% CI = 0.16-0.58, respectively).ConclusionsThis population-based study demonstrated that engaging in sufficient physical activity can reduce the ASCVD risk among GI cancer survivors.

Effectiveness of a nurse-led management intervention on systolic blood pressure among type 2 diabetes patients in Uganda: a cluster randomized trial

BackgroundHypertension (HT) is an orchestrator of atherosclerotic cardiovascular disease (ASCVD) in people living with type 2 diabetes (T2D). Control of systolic blood pressure (SBP) and HT as a whole is suboptimal in diabetes, partly due to the scarcity of doctors. While nurse-led interventions are pragmatic and cost-effective in the control of HT in primary health care, their effectiveness on SBP control among patients with T2D in Uganda is scantly known.AimWe evaluated the effectiveness of a nurse-led management intervention on SBP among T2D patients with a high ASCVD risk in Uganda.MethodsA two-armed cluster randomized controlled trial compared the nurse-led management intervention with usual doctor-led care. The intervention involved training nurses to provide structured health education, protocol-based HT/CVD management, 24-h phone calls, and 2-monthly text messages for 6 months. The primary outcome was the mean difference in SBP change among patients with T2D with a high ASCVD risk in the intervention and control groups after 6 months. The secondary outcome was the absolute difference in the number of patients at target for SBP, total cholesterol (TC), fasting blood glucose (FBG), glycated hemoglobin (HbA1C), low-density lipoprotein (LDL), triglycerides (TG), and body mass index (BMI) after the intervention. The study was analyzed according to the intention-to-treat principle. Generalized estimating equations were used to assess intra-cluster effect modifiers. Statistical significance was set at 0.05 for all analyses.ResultsEight clinics (n = 388 patients) were included (intervention 4 clinics; n = 192; control 4 clinics; n = 196). A nurse-led intervention reduced SBP by -11.21 ± 16.02 mmHg with a mean difference between the groups of -13.75 mmHg (95% CI -16.48 to -11.02, p < 0.001). An increase in SBP of 2.54 ± 10.95 mmHg was observed in the control group. Diastolic blood pressure was reduced by -6.80 ± 9.48 mmHg with a mean difference between groups of -7.20 mmHg (95% C1 -8.87 to -5.48, p < 0.001). The mean differences in the change in ASCVD score and glycated hemoglobin were -4.73% (95% CI -5.95 to -3.51, p = 0.006) and -0.82% (95% CI -1.30 to -0.35, p = 0.001), respectively. There were significant absolute differences in the number of patients at target in SBP (p = 0.001), DBP (p = 0.003), and TC (p = 0.008).ConclusionA nurse-led management intervention reduces SBP and ASCVD risk among patients with T2D. Such an intervention may be pragmatic in the screening and management of HT/ASCVD in Uganda.Trial registrationPan African Clinical Trial Registry, PACTR202001916873358, registered on 6th October 2019.

Abstract 1020: Comparative Assessment Of Hscrp And Apolipoprotein B As Ascvd Risk Biomarkers

According to the American Heart Association, the accumulation of plaque in the walls of arteries is identified as the primary cause of atherosclerotic cardiovascular disease (ASCVD). Currently, ASCVD-related conditions remain the leading cause of morbidity and mortality globally. Apolipoprotein B has been identified as a more precise cardiovascular risk marker than LDL-C, while hsCRP has shown potential as a cardiovascular disease indicator. This study aims to investigate the diagnostic performance and routine screening cut-off of hsCRP for early atherosclerosis vascular diseases (ASCVD) risk in adult patients, comparing it with Apo B. Objective: To compare the diagnostic performance of high-sensitivity C-reactive protein (hsCRP) with apolipoprotein B in assessing ASCVD risk. Method: A sample of 494 individuals from the NHANES 2015-2016 laboratory dataset, with a mean age greater than 17 years, was used for this study. ASCVD risk was measured by non-HDL-C, categorized into low and high risk based on the Mayo Clinic reference range. Predictors included Apo B, and hs-CRP. Binomial logistic regression and ROC curve analyses were conducted using the generalised linear models and pROC packages in RStudio IDE. Hypotheses were validated at p≤0.05, and diagnostic performance metrics such as ROC AUC, sensitivity, and specificity were measured on a scale of 0-1. Result: The findings revealed that for every 1g/L increase in apo B concentration, the odds of high ASCVD risk were approximately 3.8 х1011 times higher. Additionally, the model indicated that the odds of high ASCVD risk were 1.03 times higher for every 1mg/L increase in hsCRP concentration. However, this indicate that hsCRP level was not associated with odds of ASCVD risk. The ROC AUC for apo B and hsCRP were approximately 0.9739 and 0.6165, respectively, with cut-off values (sensitivity, specificity) of approximately 0.9g/L (0.927, 0.897) and 2.4 mg/L (0.596, 0.601), respectively. Thus, levels above these thresholds for both apo B and hsCRP are associated with high ASCVD risk. Conclusion: The study demonstrates that apo B exhibits high discriminatory and diagnostic accuracy, making it a suitable ASCVD risk biomarker compared to hsCRP. While hsCRP shows moderate diagnostic accuracy, it is not sufficient as a standalone ASCVD risk diagnostic marker. Therefore, apo B could serve as a replacement for LDL-C, while hsCRP could possibly serve as an add-on test in ASCVD risk assessment.

MAFLD predicts cardiovascular disease risk better than MASLD.

Metabolic dysfunction-associated steatotic liver disease (MASLD) has been proposed as an alternative for the validated definition of metabolic dysfunction-associated fatty liver disease (MAFLD). We compared the abilities of MAFLD and MASLD to predict the risk of atherosclerotic cardiovascular disease (ASCVD). Six thousand and ninety sixparticipants from the 2017 to 2020 National Health and Nutrition Examination Survey cohort who received a thorough medical health check-up were chosen for the study. The associations between fatty liver status and coronary risk surrogates, such as 10-year ASCVD risk and self-reported cardiovascular events, were analysed. MAFLD and MASLD were identified in 2911 (47.7%) and 2758 (45.2%) patients, respectively. MAFLD (odds ratio [OR]: 2.14, 95% confidence interval [CI], 1.78-2.57, p < .001) was more strongly independently associated with high ASCVD risk than MASLD (OR: 1.82, 95% CI, 1.52-2.18, p < .001) was in comparison with the absence of each condition. However, compared with MAFLD, MASLD alone was not associated with increased ASCVD risk. Multiple logistic regression revealed that MAFLD alone was significantly more strongly associated with a high risk of ASCVD (OR: 2.82; 95% CI: 1.13-7.01; p < .03) than MASLD alone. Although both MAFLD and MASLD were associated with different ASCVD risks, MAFLD predicted the ASCVD risk better than MASLD. The higher predictive ability of MAFLD compared to MASLD was attributed to metabolic dysfunction rather than moderate alcohol use.

Abstract MP28: Declines in Plasma Levels of Nonnutritive Sweetener Erythritol Are Related to Two-Year Improvements in Atherosclerotic Cardiovascular Disease Risk Estimates Among Adults With Overweight and Obesity

Background: A potential adverse relationship between the consumption of low-calorie sweeteners and cardiovascular disease (CVD) risk has been proposed. High levels of circulating erythritol, a sugar alcohol (polyol) used as one of the non-nutritive sweeteners, have been recently linked to increased risks of major adverse cardiovascular events. However, associations of temporal changes in plasma erythritol and other polyols with cardiometabolic risk remain unclear. Hypothesis: We tested whether changes in plasma levels of non-nutritive sweetener erythritol and other polyols in response to weight-loss dietary interventions were associated with improved atherosclerotic cardiovascular disease (ASCVD) risk estimates and atherogenic lipoproteins among adults with overweight and obesity. Methods: This study included 804 adults (mean BMI: 32.7 [SD 3.9] kg/m 2 ) without diabetes or unstable CVD at baseline who participated in a 2-year intervention of weight-loss diets, the POUNDS Lost trial. Metabolomic profiling was performed to measure plasma erythritol and its precursor erythronate, other sugar alcohols, and low-calorie sweeteners at baseline and 6 months after randomization. The primary outcome was the change in 10-year ASCVD risk scores calculated by the validated pooled cohort equations. Two-year changes in lipid profiles and cholesterol [Chol] in lipoprotein subfractions defined by the presence or absence of apolipoprotein CIII (apoCIII) were analyzed as secondary outcomes. Results: The mean estimated value of the 10-year ASCVD risk was 4.0% at baseline; 16% of the participants were at intermediate or high ASCVD risk (score ≥7.5%). Higher levels of erythritol (per 1 SD increment: β 1.1% [SE 0.2%], p &lt;.0001) and erythronate (β 1.3% [0.2%], p &lt;.0001), as well as other sugar alcohols, such as mannitol-sorbitol, myoinositol, arabitol-xylitol ( p &lt;.0001 for all), and low-calorie sweetener saccharin ( p = 0.02), but not acesulfame ( p =0.8), were related to a higher ASCVD risk at baseline after adjusting for BMI. There was large variability in the changes in metabolite levels across participants; greater decreases in erythritol in response to the interventions were significantly related to greater reductions in ASCVD risk estimates at 6 months (per 1 SD reduction: β -0.2% [SE 0.1%]; p =0.023) and at 2 years (β -0.3% [0.1%]; p = 0.015) after adjusting for covariates, including BMI, the initial metabolite levels, and baseline ASCVD risk. The 6-month decrease in erythritol was associated with long-term (2-year) improvements in atherogenic lipids, including Chol in VLDL+LDL with apoCIII ( p &lt;0.05). Conclusions: Higher plasma levels of erythritol and other sugar alcohols were associated with greater 10-year ASCVD risk scores among adults with overweight and obesity. Weight-loss diet-induced decreases in erythritol levels were related to improved ASCVD risk and atherogenic lipid profiles.

Nurse-Led Strategy to Improve Blood Pressure and Cholesterol Level Among People With HIV

Despite higher atherosclerotic cardiovascular disease (ASCVD) risk, people with HIV (PWH) experience unique barriers to ASCVD prevention, such as changing models of HIV primary care. To test whether a multicomponent nurse-led strategy would improve systolic blood pressure (SBP) and non-high-density lipoprotein (HDL) cholesterol level in a diverse population of PWH receiving antiretroviral therapy (ART). This randomized clinical trial enrolled PWH at 3 academic HIV clinics in the US from September 2019 to January 2022 and conducted follow-up for 12 months until January 2023. Included patients were 18 years or older and had a confirmed HIV diagnosis, an HIV-1 viral load less than 200 copies/mL, and both hypertension and hypercholesterolemia. Participants were stratified by trial site and randomized 1:1 to either the multicomponent EXTRA-CVD (A Nurse-Led Intervention to Extend the HIV Treatment Cascade for Cardiovascular Disease Prevention) intervention group or the control group. Primary analyses were conducted according to the intention-to-treat principle. The EXTRA-CVD group received home BP monitoring guidance and BP and cholesterol management from a dedicated prevention nurse at 4 in-person visits (baseline and 4, 8, and 12 months) and frequent telephone check-ins up to every 2 weeks as needed. The control group received general prevention education sessions from the prevention nurse at each of the 4 in-person visits. Study-measured SBP was the primary outcome, and non-HDL cholesterol level was the secondary outcome. Measurements were taken over 12 months and assessed by linear mixed models. Prespecified moderators tested were sex at birth, baseline ASCVD risk, and trial site. A total of 297 PWH were randomized to the EXTRA-CVD arm (n = 149) or control arm (n = 148). Participants had a median (IQR) age of 59.0 (53.0-65.0) years and included 234 males (78.8%). Baseline mean (SD) SBP was 135.0 (18.8) mm Hg and non-HDL cholesterol level was 139.9 (44.6) mg/dL. At 12 months, participants in the EXTRA-CVD arm had a clinically significant 4.2-mm Hg (95% CI, 0.3-8.2 mm Hg; P = .04) lower SBP and 16.9-mg/dL (95% CI, 8.6-25.2 mg/dL; P < .001) lower non-HDL cholesterol level compared with participants in the control arm. There was a clinically meaningful but not statistically significant difference in SBP effect in females compared with males (11.8-mm Hg greater difference at 4 months, 9.6 mm Hg at 8 months, and 5.9 mm Hg at 12 months; overall joint test P = .06). Results of this trial indicate that the EXTRA-CVD strategy effectively reduced BP and cholesterol level over 12 months and should inform future implementation of multifaceted ASCVD prevention programs for PWH. ClinicalTrials.gov Identifier: NCT03643705.

Left Main Coronary Artery Calcium and Diabetes Confer Very-High-Risk Equivalence in Coronary Artery Calcium >1,000

BackgroundAlthough a coronary artery calcium (CAC) of ≥1,000 is a subclinical atherosclerosis threshold to consider combination lipid-lowering therapy, differentiating very high from high atherosclerotic cardiovascular disease (ASCVD) risk in this patient population is not well-defined. ObjectivesAmong persons with a CAC of ≥1,000, the authors sought to identify risk factors equating with very high-risk ASCVD mortality rates. MethodsThe authors studied 2,246 asymptomatic patients with a CAC of ≥1,000 from the CAC Consortium without a prior ASCVD event. Cox proportional hazards regression modelling was performed for ASCVD mortality during a median follow-up of 11.3 years. Crude ASCVD mortality rates were compared with those reported for secondary prevention trial patients classified as very high risk, defined by ≥2 major ASCVD events or 1 major event and ≥2 high-risk conditions (1.4 per 100 person-years). ResultsThe mean age was 66.6 years, 14% were female, and 10% were non-White. The median CAC score was 1,592 and 6% had severe left main (LM) CAC (vessel-specific CAC ≥300). Diabetes (HR: 2.04 [95% CI: 1.47-2.83]) and severe LM CAC (HR: 2.32 [95% CI: 1.51-3.55]) were associated with ASCVD mortality. The ASCVD mortality per 100 person-years for all patients was 0.8 (95% CI: 0.7-0.9), although higher rates were observed for diabetes (1.4 [95% CI: 0.8-1.9]), severe LM CAC (1.3 [95% CI: 0.6-2.0]), and both diabetes and severe LM CAC (7.1 [95% CI: 3.4-10.8]). ConclusionsAmong asymptomatic patients with a CAC of ≥1,000 without a prior index event, diabetes, and severe LM CAC define very high risk ASCVD, identifying individuals who may benefit from more intensive prevention therapies across several domains, including low-density lipoprotein-cholesterol lowering.

Epidemiology and Prognostic Implications of Coronary Artery Calcium in Asymptomatic Individuals With Prediabetes: A Multicohort Study.

To describe the epidemiology and prognostic value of coronary artery calcium (CAC) in individuals with prediabetes. We pooled participants free of clinical atherosclerotic cardiovascular disease (ASCVD) from four prospective cohorts: the Multi-Ethnic Study of Atherosclerosis, Heinz Nixdorf Recall Study, Framingham Heart Study, and Jackson Heart Study. Two definitions were used for prediabetes: inclusive (fasting plasma glucose [FPG] ≥100 to <126 mg/dL and hemoglobin A1c [HbA1c] ≥5.7% to <6.5%, if available, and no glucose-lowering medications) and restrictive (FPG ≥110 to <126 mg/dL and HbA1c ≥5.7% to <6.5%, if available, among participants not taking glucose-lowering medications). The study included 13,376 participants (mean age 58 years; 54% women; 57% White; 27% Black). The proportions with CAC ≥100 were 17%, 22%, and 37% in those with euglycemia, prediabetes, and diabetes, respectively. Over a median (25th-75th percentile) follow-up time of 14.6 (interquartile range 7.8-16.4) years, individuals with prediabetes and CAC ≥100 had a higher unadjusted 10-year incidence of ASCVD (13.4%) than the overall group of those with diabetes (10.6%). In adjusted analyses, using the inclusive definition of prediabetes, compared with euglycemia, the hazard ratios (HRs) for ASCVD were 0.79 (95% CI 0.62, 1.01) for prediabetes and CAC 0, 0.70 (0.54, 0.89) for prediabetes and CAC 1-99, 1.54 (1.27, 1.88) for prediabetes and CAC ≥100, and 1.64 (1.39, 1.93) for diabetes. Using the restrictive definition, the HR for ASCVD was 1.63 (1.29, 2.06) for prediabetes and CAC ≥100. CAC ≥100 is frequent among individuals with prediabetes and identifies a high ASCVD risk subgroup in which the adjusted ASCVD risk is similar to that in individuals with diabetes.

Role of Fenofibrate Use in Dyslipidemia and Related Comorbidities in the Asian Population: A Narrative Review.

Hypertriglyceridemia and decreased high-density lipoprotein cholesterol (HDL-C) persist despite statin therapy, contributing to residual atherosclerotic cardiovascular disease (ASCVD) risk. Asian subjects are metabolically more susceptible to hypertriglyceridemia than other ethnicities. Fenofibrate regulates hypertriglyceridemia, raises HDL-C levels, and is a recommended treatment for dyslipidemia. However, data on fenofibrate use across different Asian regions are limited. This narrative review summarizes the efficacy and safety data of fenofibrate in Asian subjects with dyslipidemia and related comorbidities (diabetes, metabolic syndrome, diabetic retinopathy, and diabetic nephropathy). Long-term fenofibrate use resulted in fewer cardiovascular (CV) events and reduced the composite of heart failure hospitalizations or CV mortality in type 2 diabetes mellitus. Fenofibrate plays a significant role in improving irisin resistance and microalbuminuria, inhibiting inflammatory responses, and reducing retinopathy incidence. Fenofibrate plus statin combination significantly reduced composite CV events risk in patients with metabolic syndrome and demonstrated decreased triglyceride and increased HDL-C levels with an acceptable safety profile in those with high CV or ASCVD risk. Nevertheless, care is necessary with fenofibrate use due to possible hepatic and renal toxicities in vulnerable individuals. Long-term trials and real-world studies are needed to confirm the clinical benefits of fenofibrate in the heterogeneous Asian population with dyslipidemia.

Risk estimation for recurrent cardiovascular events using the SMART-REACH model and direct inpatient cost profiling in Indonesian ASCVD patients: a large-scale multicenter study.

With atherosclerotic cardiovascular disease (ASCVD) cases increasing in Indonesia, there is a growing need to identify high-risk patients for recurrent cardiovascular events. Risk stratification could guide optimal secondary preventive therapy. Understanding the ASCVD direct inpatient costs could further provide insight in reducing the economic burden that comes with Indonesia's high number ASCVD cases. However, there is a significant gap in Indonesian large-scale research on both of these valuable data. Employing the SMART-REACH model, we can profile the risk of recurrent cardiovascular events in Indonesian ASCVD patients. Utilize the SMART-REACH model to estimate 10-year and lifetime risk of cardiovascular events in Indonesian ASCVD patients and describe the direct inpatient cost of ASCVD. This descriptive cross-sectional study gathered data from 3,209 ASCVD patients aged 45-80 from two major cardiovascular centers using purposive sampling. Participants were patients admitted between January 2020 and March 2023 with ST-elevated myocardial infarct (STEMI), non-ST-elevated myocardial infarct (NSTEMI), and chronic coronary syndrome (CCS) requiring elective percutaneous coronary intervention (PCI). The SMART-REACH risk estimation model required clinical data upon admission, laboratory results within the first 24 h of admission, and cardiovascular medication prescribed upon discharge. The SMART-REACH model is a Fine and Gray competing risk model incorporating cardiovascular risk factors that estimates individual 10-year and lifetime risk for recurrent cardiovascular events which includes myocardial infarction, stroke, or vascular death. Direct inpatient cost profiling totaled all medical expenses incurred from ASCVD diagnosis admission to discharge. Results were reported descriptively with subgroup analyses. The cohorts (mean age 60.15 ± 8.6 years) were predominantly male [n = 2,537 (79.1%)], hypertensive [n = 2,267 (70.6%)], and diagnosed with STEMI [n = 1,732 (54%)]. The SMART-REACH model calculated a mean 10-year risk of 30.2% (95% CI 29.7-30.6) and a lifetime risk of 62.5% (95% CI 62.1-62.9). The direct inpatient cost of ASCVD patients includes a median 3,033 USD, with highest median costs in the STEMI subgroup (3,270 USD). A significant number of Indonesian ASCVD patients exhibited notably high 10-year and lifetime risks of experiencing a major cardiovascular event. Combined with the direct inpatient cost, therapy optimization is crucially needed to mitigate these risks and further cost burden.

Lifestyle risk behavior and atherosclerotic cardiovascular risk: An analysis using the Korea National Health and Nutrition Examination Survey.

Clustering lifestyle risk behaviors is important for predicting cardiovascular disease risk. However, it is unclear which behavior mediates other ones to influence cardiovascular disease risk. We aimed to assess the causal inference of each lifestyle risk behavior for the atherosclerotic cardiovascular disease (ASCVD) risk of the general population. We performed a Bayesian network mediation analysis using data from the Korea National Health and Nutrition Examination Survey from 2014 to 2019. The main exposure was a combination of lifestyle risk behaviors including unhealthy weight, heavy alcohol consumption, inadequate sleep, physical inactivity, excessive sodium intake, and current smoking among subjects 40 to 79 years of age. The high risk of ASCVD (≥7.5% for the 10-year risk) was assessed using logistic regression, Bayesian networks, and structural equational models to examine the causal relationships between these six lifestyle risk behaviors. Among all participants, the most prevalent lifestyle risk behavior for those at high risk for ASCVD was excessive sodium intake (95.6%), followed by inadequate sleep (49.9%) and physical inactivity (43.8%). Older age (65-79 years) and male sex were directly associated with a high risk for ASCVD. Physical inactivity, current smoking, excessive sodium intake, and unhealthy weight indirectly mediated the effects of older age (8.2% of the older age) and male sex (39.9% of males) to high ASCVD risk. Physical inactivity, current smoking, excessive sodium intake, and unhealthy weight particularly mediated the high ASCVD risk sequentially. Heavy alcohol consumption and inadequate sleep were not directly associated with high ASCVD risk and did not indirectly mediate the effects of older age and males on the high ASCVD risk. Lifestyle risk behaviors mediated the atherosclerotic cardiovascular disease risk in a different manner. Especially, physical inactivity preceded current smoking, excessive sodium intake, and unhealthy weight in relation to high ASCVD risk, and this causal relationship was different according to age and sex. Therefore, tailored strategies according to specific target populations may be needed to effectively reduce the high ASCVD risk.

Intensity of and adherence to lipid-lowering therapy as predictors of goal attainment and major adverse cardiovascular events in primary prevention

The effectiveness of lipid-lowering therapy (LLT) for primary prevention of atherosclerotic cardiovascular disease (ASCVD) in routine care may depend on treatment intensity and adherence. Observational study of adults with newly initiated LLT for primary prevention of ASCVD in Stockholm, Sweden, during 2017-2021. Study exposures were LLT adherence [proportion of days covered (PDC)], LLT intensity (expected reduction of LDL cholesterol), and the combined measure of adherence and intensity. At each LLT fill, adherence and intensity were calculated during the previous 12 months, and the patients estimated ASCVD risk was categorized. Study outcomes were major adverse cardiovascular events (MACE) and LDL-C goal attainment. Thirty-six thousand two hundred eighty-three individuals (mean age 63 years, 47% women, median follow-up 2 years), with a baseline low-moderate (40%), high (49%), and very-high (11%) ASCVD risk started LLT. Increases in LLT adherence, intensity, or adherence-adjusted intensity of 10% over 1 year were associated with lower risks of MACE (with hazard ratios of 0.95 [95% CI, 0.93-0.98]; 0.93 [0.86-1.00]; and 0.90 [0.85-0.95], respectively) and higher odds of attaining LDL goals. Patients with good adherence (≥80%) had similar risks of MACE and similar odds ratios for LDL-C goal attainment with low-moderate and high-intensity LLT. Treatment discontinuation was associated with increased MACE risk. The relative and absolute benefits of good adherence were greatest in patients with very high ASCVD risk. In routine-care primary prevention, better adherence to LLT was associated with a lower risk of MACE across all treatment intensities. Improving adherence is especially important among patients with very high ASCVD risk.

Appendicular Skeletal Muscle Mass to Visceral Fat Area Ratio Predicts Hepatic Morbidities.

: Reports on the association between sarcopenic visceral obesity and non-alcoholic fatty liver disease (NAFLD)-associated morbidities remain scarce. We investigated the association between sarcopenia and visceral obesity, and the influence of this association on hepatic and coronary comorbidities. : The appendicular skeletal muscle mass to visceral fat area ratio (SV ratio) was evaluated using bioelectric impedance analysis. NAFLD and significant liver fibrosis were assessed using transient elastography, and high atherosclerotic cardiovascular disease (ASCVD) risk was defined as a 10-year ASCVD risk score >10%. Sarcopenia was defined as appendicular skeletal muscle mass adjusted by body mass index (<0.789 for men and <0.512 for women). : In total, 82.0% (n=1,205) of the entire study population had NAFLD, and 14.6% of these individuals (n=176) exhibited significant liver fibrosis. Individuals with the lowest SV ratio had a significantly increased risk of NAFLD, significant liver fibrosis, and high ASCVD risk (all p<0.05). Individuals with both the lowest SV ratio and sarcopenia had the highest risk of developing NAFLD (odds ratio [OR]=3.11), significant liver fibrosis (OR=2.03), and high ASCVD risk (OR=4.15), compared with those with a higher SV ratio and without sarcopenia (all p<0.05). : Low SV ratio combined with sarcopenia was significantly associated with an increased risk of NAFLD, significant liver fibrosis, and high ASCVD risk among individuals with a high risk of NAFLD.

Atherosclerotic cardiovascular disease events among adults with high predicted risk without established risk factors

ObjectiveAge is the strongest contributor to 10-year predicted atherosclerotic cardiovascular disease (ASCVD) risk. Some older adults have a predicted ASCVD risk ≥7.5 %, without established risk factors. We sought to compare ASCVD incidence among adults with predicted ASCVD risk ≥7.5 %, with and without established ASCVD risk factors, to adults with predicted risk <7.5 %. MethodsWe analyzed data from REasons for Geographic and Racial Differences in Stroke study participants, 45–79 years old, without ASCVD or diabetes, not taking statins and with low-density lipoprotein cholesterol 70–189 mg/dL. Participants were categorized into 3 groups based on their 10-year predicted ASCVD risk and presence of established risk factors: <7.5 %, ≥7.5 % with established risk factors and ≥7.5 % without established risk factors. Established risk factors included smoking, systolic blood pressure ≥130 mmHg or antihypertensive medication use, total cholesterol ≥200 mg/dL, or high-density lipoprotein cholesterol <50 mg/dL for women (<40 mg/dL for men). Participants were followed for ASCVD events. ResultsAmong 11,115 participants, 911 incident ASCVD events occurred over a median of 11.1 years. ASCVD incidence rates were 3.6, 12.8, and 9.8 per 1,000 person-years for participants with predicted risk <7.5 %, predicted risk ≥7.5 % with established risk factors and predicted risk ≥7.5 % without established risk factors, respectively. Compared to adults with predicted risk <7.5 %, hazard ratios for incident ASCVD in participants with risk ≥7.5 % with and without established risk factors were 3.58 (95 %CI 3.03 – 4.21) and 2.72 (95 %CI 1.91–3.88), respectively. ConclusionsAdults with a 10-year predicted ASCVD risk ≥7.5 % but without established risk factors had a high ASCVD incidence.

Increased Lipoprotein (a) and familial hypercholesterolemia: a dangerous combination.Data from a 12-year follow-up study

Abstract Background Lipoprotein (a)[Lp(a)] is a molecule characterized by very increased atherogenicity. Mounting evidence support the causal link between high Lp(a) concentration and atherosclerotic cardiovascular (CV) disease in the general population. Purpose The role of Lp (a) in specific categories of patients at high CV risk, such as patients with familial hypercholesterolaemia (FH), is also of special importance. The aim of our study was to investigate the prognostic role of Lp (a) regarding major adverse CV outcomes in subjects with heterozygous FH. Methods 155 patients from the outpatient lipid clinic of our hospital (56 males,mean age 41.2±14.2 years, 26% smokers, 16% with diabetes mellitus), without history of CV disease, who fulfilled the FH criteria participated in the study. Participants were evaluated for a mean follow-up period of 12.4±7.1 years with at least one annual visit. Venous blood samples were obtained at baseline in all patients for the determination of plasma glucose, lipid profile and levels of Lp(a). All subjects were on lipid-lowering medication during the follow-up period. The endpoint of our study was the composite of major CV events (coronary artery disease events and stroke). Results The incidence of the composite endpoint of major CV events during the follow-up period was 9% (n=14). In the total population, the mean baseline Lp (a) levels were 34.9±33.7 mg/dl, while 42% had increased Lp (a) levels ≥30mg/dl. The group of FH patients with new-onset CV disease had higher levels of Lp(a) at baseline compared to those without new-onset CV disease (48.1±37.3 vs 33.6±33.1 mg/dl, p=0.01). Also, those with new-onset CV disease had higher percentage of increased Lp(a) levels (≥30mg/dl) at baseline compared to those without development of CV disease (71% vs 39%, p=0.02).Multiple Cox regression analysis revealed that during the follow-up period independent predictors of major adverse CV events were:increased baseline Lp(a) levels(≥30mg/dl)(HR 5.61, 95% CI 1.51-10.92, p=0.01), male sex (HR 8.11, 95% CI 2.02-12.48, p&amp;lt;0.01), baseline low-density cholesterol levels (HR 1.01, 95% CI 1.00-1.02, p=0.04) and the presence of hypertension at baseline (HR 3.59, 95% CI 1.03-12.49, p=0.04), after adjustment for confounding factors. Conclusions In patients with FH, increased baseline Lp(a) is an independent predictor of adverse CV events, after a 12-year follow-up period. FH patients with Lp (a)levels ≥30mg/dl have an almost 5-fold greater CV risk compared to those with lower Lp (a) levels. It seems that Lp (a) reclassifies the already increased CV risk of FH subjects into an even higher level.

DAHNA-An integrated innovative mobile application for the screening and personalised management of the atherosclerotic cardiovascular disease risk

Abstract Background DAHNA (Diet According to the Healthy Heart Nutritional Approach) is an integrated and innovative mobile app that allows for: 1. Screening of atherosclerotic cardiovascular disease (ASCVD) risk; 2. A personalized healthy diet (macro- and micronutrients) based on cardiometabolic screening; 3. Long-term management of major risk factors; 4. Highly incentivizing rewards within the app. Objective To present the functionalities, mode of operation, and initial results of DAHNA through public implementation. Methods DAHNA can be downloaded on mobile phones (iOS and Android). Firstly, the app assesses the user's ASCVD risk score based on their country of residence using a "one-size-fits-all" risk calculator that combines the 2021 European Society of Cardiology (ESC) SCORE2/SCORE2-OP scores and the American Heart Association (AHA) Framingham score. For Europe, the calculation is based on the four SCORE2/SCORE2-OP tables for the four risk regions. DAHNA is not limited to healthy individuals and allows the user to indicate if they have diabetes, chronic kidney disease, or ASCVD. Secondly, based on the individual ASCVD risk score, DAHNA offers the following features: 1. Personalized healthy menus (Mediterranean diet) based on the only macro- and micronutrients proven to reduce individual ASCVD risk and in the recommended daily dose, with an automatically generated ingredient list and quantities; the user can choose to purchase the ingredients personally or order the list from suppliers; 2. Periodic follow-up of ASCVD risk outcomes; 3. Display of healthy life minutes gained by the user; 4. Notifications, reminders, rewards within the app, personalized weight loss plans, PDF reports to share with healthcare teams, and nutritional education; 5. A recommendation for a medical examination for those with high or very high risk; 6. Short movies to introduce physical activity and up-to-date medical information; 7. All data is collected in a central database. Results Between August 10th, 2022 and February 12th, 2023, 19,780 users downloaded DAHNA (mean age 48 +/- 10 years, 58% females, 11.13% with diabetes, 15.16% smokers, 16.4% with hypertension; 14% had low-to-moderate risk, 40% had high risk, and 46% had very high risk). A 100% correspondence was confirmed between the results of the DAHNA calculator and the ESC tables. Conclusion 1. DAHNA self-screening showed that 86% of users belong to the high or very high ASCVD risk group, which is consistent with statistical data showing Romania among the countries with a very high ASCVD risk. 2. This app is the first to assign a personalized healthy diet based on specific micronutrients to control ASCVD risk, provide medical recommendations for a healthy lifestyle, and allow for real-time management of major risk factors and ASCVD risk in large populations. These data should be important for adjusting health policies.

Abstract 18219: J-Shaped Association Between LDL-Cholesterol Level and Cardiovascular Events: A Longitudinal Follow-Up Study Over 2.4 Million Nationwide Primary Prevention Cohort

Introduction: Low-density lipoprotein (LDL)-cholesterol lowering treatment showed benefits in patients with high atherosclerotic cardiovascular disease (ASCVD) risk. Hypothesis: Although high LDL-cholesterol level is known to increase ASCVD risks, prognostic implications of low LDL-cholesterol level remain elusive. Methods: Using the data from a Korean Nationwide Cohort, we included 2,432,471 subjects without previous ASCVD. From 2009, subjects were followed for myocardial infarction (MI) and ischemic stroke until 2018. Subjects were stratified according to 10-year ASCVD risks (&lt;5%, 5 to &lt;7.5%, 7.5 to &lt;20%, and ≥20%) and LDL-cholesterol level (&lt;70, 70-99, 100-129, 130-159, 160-189, and ≥190 mg/dL). Results: In the overall population (median follow-up: 9.3 years), the relationship between LDL-C level and cardiovascular events showed J-shaped curve. Subjects with LDL-cholesterol &lt;70mg/dL showed increased risk of myocardial infarction compared to those with LDL-cholesterol 70 to &lt;100mg/dL after adjusting covariates in low ASCVD risk group. Similarly, subjects with LDL-cholesterol 70-99 mg/dL and 100-129 mg/dL had lower stroke risks than those with LDL-cholesterol &lt;70mg/dL in low ASCVD risk group. In contrast, LDL-cholesterol level and risks of MI and stroke showed linear association in high ASCVD risk group. Conclusions: High LDL-cholesterol level is associated with increased risk of MI or stroke, while low LDL-cholesterol level does not warrant safety from ASCVD in the primary prevention setting.

Abstract 16491: The Relationship Between Cardiovascular Health and 10-year Atherosclerotic Cardiovascular Risk in American Adults

Introduction: Life’s Essential 8 (LE8) is a metric of overall cardiovascular health (CVH) while 10-year atherosclerotic cardiovascular disease (ASCVD) risk is routinely used to guide primary prevention. Yet, the relationship between LE8 and 10-year ASCVD risk is unclear. Hypothesis: CVH has an inverse relationship with 10-year ASCVD risk in adults aged 40–75 years from the National Health and Nutrition Examination Survey 2017-2020 cycle. Methods: Adults with ASCVD and data missing to calculate 10-year ASCVD risk and LE8 scores were excluded. LE8 score was estimated from the mean of LE8 components (scored 0 to 100), with scores ≥80, 79–50, and &lt;49 grouped into ideal, intermediate, and poor CVH, respectively. 10-year ASCVD risk was estimated using pooled cohort equation, with scores &lt;5%, 5–19.9%, and ≥20% grouped as low, borderline/intermediate, and high risk, respectively. The survey weighted chi-square and ANOVA analysis was performed. Results: We included 1,550 adults representing nearly 45 million US adults with a mean age of 57.8 years, 35.3% women. Overall, 35.4%, 42.3%, and 22.3% had low, borderline/intermediate, and high 10-year ASCVD risk, respectively. Low, borderline/intermediate, and high-risk individuals had a mean LE8 score of 68.2, 61.8, and 62.6 (p-value: &lt;0.001) while 18.1%, 7.4%, and 5.6% (p-value: 0.002) had ideal CVH, respectively. Diet, nicotine exposure, body mass index (BMI), and blood lipids metrics were very low across the risk groups (figure). Additionally, the mean blood pressure metric was 41.3 among high-risk and 61.1 among intermediate/borderline-risk individuals. Conclusions: The prevalence of ideal CVH is very low across all 10-year ASCVD risk groups primarily due to poor diet, nicotine exposure, high BMI, and high blood lipids. Since ASCVD risk is predominantly age-dependent and given comparable LE8 scores among borderline/intermediate and high-risk individuals, LE8 may denote an age-independent long-term/lifetime risk.