BACKGROUND AND AIM: Current guidelines state that Systematic Coronary Risk Evaluation 2 (SCORE2) risk algorithms should not be used among persons under lipid-lowering therapy. This study investigated, among dyslipidemia-...BACKGROUND AND AIM: Current guidelines state that Systematic Coronary Risk Evaluation 2 (SCORE2) risk algorithms should not be used among persons under lipid-lowering therapy. This study investigated, among dyslipidemia-treated individuals, the effect of lipid-lowering treatment on SCORE2 calculation and on its performance in detecting high-risk individuals METHODS AND RESULTS: Analysis included middle-aged individuals (n = 417), treated for dyslipidemia, without established cardiovascular disease, diabetes and/or chronic kidney disease, recruited from screening programs in the community [mean age 59.5 ± 6.9 (SD) years, men 48.9%, statin monotherapy 67%, statin/ezetimibe combination 26%]. SCORE2 algorithms were calculated using measured and adjusted (for the lipid-lowering therapy characteristics) lipid levels. SCORE2 and adjusted-SCORE2 were 5.4 ± 2.7% and 6.6 ± 3.3% respectively (P < 0.05). Participants classified as low-moderate/high/very-high risk (age-dependent risk thresholds) were 42.2%/51.1%/6.7% with SCORE2, and 28.8%/54.4%/16.8% with adjusted-SCORE2 (agreement 76.5%, weighted kappa 0.73, P < 0.05). Using single risk thresholds (<10%, 10% to <20%, and ≥20%), the respective percentages were 93.8%/6.2%/0% and 83.9%/16.1%/0% (agreement 90.2%, kappa 0.52, P < 0.05). The agreement between carotid plaque score and SCORE2/adjusted-SCORE2 was 54% (weighted kappa 0.29, P < 0.05)/50.1% (weighted kappa 0.25, P < 0.05). CONCLUSIONS: Lipid-lowering treatment appears to have a modest effect on SCORE2 calculation and mainly on its stability to detect high-risk individuals.
BACKGROUND AND AIM: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a major contributor to chronic liver disease worldwide, yet the risk factors for carotid plaque in MASLD patients remain unclear. Th...BACKGROUND AND AIM: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a major contributor to chronic liver disease worldwide, yet the risk factors for carotid plaque in MASLD patients remain unclear. This study aimed to identify these risk factors. METHODS AND RESULTS: We performed a retrospective cross-sectional analysis of 5372 participants, of whom 2673 met the 2023 MASLD criteria. The MASLD cohort was randomly divided into a training set (70%) and a validation set (30%) to develop a predictive model for carotid atherosclerosis risk. The model's performance and goodness-of-fit were assessed via internal and external validation. Additionally, Mendelian randomization (MR) analysis was performed to investigate the causal relationships between identified risk factors and carotid atherosclerosis. MASLD was significantly associated with carotid plaque formation (P < 0.001). Multivariate analysis identified age, sex, fasting plasma glucose (FPG), and systolic blood pressure (SBP) as independent risk factors, which were used to construct a predictive model (AUC = 0.801, 95% CI: 0.782-0.821). Subgroup analysis indicated that MASLD patients with glucose metabolism abnormalities had a higher plaque risk. MR analysis provided genetic evidence suggesting that genetically proxied SBP (P = 0.018) and FPG (P = 0.004) were associated with carotid atherosclerosis. CONCLUSIONS: A novel predictive model (XY-CPRM) can identify the risk of carotid plaque in the MASLD population. Intensive management of blood glucose and blood pressure is a critical strategy to mitigate cardiovascular risk in MASLD population.
BACKGROUND AND AIMS: Metabolomic signatures representing a "healthy" and "unhealthy" dietary pattern have previously been constructed using data from a randomised controlled crossover feeding study (DQFS). The utility of...BACKGROUND AND AIMS: Metabolomic signatures representing a "healthy" and "unhealthy" dietary pattern have previously been constructed using data from a randomised controlled crossover feeding study (DQFS). The utility of these metabolomic signatures in other populations has not been evaluated. Here, we mapped changes in diet-derived plasma metabolites in a sample of rural adults screened as at elevated-cardiovascular disease (CVD) risk receiving medical nutrition therapy (MNT), against the DQFS dietary metabolite signature. METHODS AND RESULTS: A sub-sample of MNT participants (n = 11) received personalised MNT from a dietitian over 6-months. Plasma metabolites for DQFS and HRH were analysed using ultra-high performance liquid chromatography-tandem mass spectrometry. Restricted maximum likelihood mixed-effect models were used to evaluate change in metabolites and dietary intake across the MNT intervention. Principle component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) plots were used to compare metabolite profiles between both studies. Five metabolites significantly changed between baseline and either the 3- or 6-month, with two metabolites [Ethylmalonate and Glycosyl-N-stearoyl-sphingosine (d18:1/18:0)] significantly reduced at both 3- and 6-months. Diet quality significantly increased across the intervention (p < 0.001). PCA and PLS-DA plots identified that post MNT intervention 3- and 6-month metabolic signatures aligned more closely with the "healthy" dietary pattern signature. CONCLUSION: Findings demonstrated that the metabolomic signature identified in the controlled DQFS feeding study can be used to map changes in diet quality in response to an MNT intervention in people at an elevated CVD risk. Future studies in larger, independent cohorts are warranted.
BACKGROUND AND AIM: Glycogen storage disease type I (GSD I) is characterized by impaired endogenous glucose production, leading to fasting hypoglycemia and multiple metabolic complications. Cornstarch supplementation is...BACKGROUND AND AIM: Glycogen storage disease type I (GSD I) is characterized by impaired endogenous glucose production, leading to fasting hypoglycemia and multiple metabolic complications. Cornstarch supplementation is a cornerstone of dietary management, primarily to prevent fasting hypoglycemia. However, its role in modulating daytime postprandial glycemia in adults remains unclear. This study aimed to evaluate the impact of mealtime cornstarch supplementation on postprandial glucose dynamics in adults with GSD I under real-life conditions. METHODS AND RESULTS: In this cross-sectional observational study, 10 consecutive adults with genetically confirmed GSD I underwent a 7-day dietary assessment and continuous glucose monitoring (CGM). Meals were classified according to the presence or absence of cornstarch supplementation (Starch and noStarch meals). Postprandial glucose responses were analyzed over a 240-min observation window using dynamic CGM-derived metrics, including peak, nadir, time to peak, time to nadir, and incremental area under the curve (iAUC). A total of 102 meals (60 noStarch, 42 Starch) allowed for the 4-h analysis. No significant differences were observed between Starch and noStarch meals in overall 4-h glucose profiles (p = 0.209), iAUC (p = 0.234), peak and nadir glucose levels, or dynamic indices (p always >0.05). Postprandial hypoglycemia was infrequent, with only 14 events <70 mg/dL and a single event <54 mg/dL. Results remained consistent after adjustment for daily starch intake and subject-level effects. CONCLUSIONS: In adults with GSD I and stable metabolic control, mealtime cornstarch supplementation does not significantly modify postprandial glucose dynamics over 4 h. These findings support individualized, CGM-guided strategies to optimize cornstarch use.
BACKGROUND AND AIM: Vitamin K has been proposed to have a preventive effect against arterial calcification through activation of the vitamin K dependent proteins and potentially protect against progression of atheroscler...BACKGROUND AND AIM: Vitamin K has been proposed to have a preventive effect against arterial calcification through activation of the vitamin K dependent proteins and potentially protect against progression of atherosclerosis. Our aim was to assess the association between vitamin K status and vascular health in a general elderly population. METHODS AND RESULTS: In a cross-sectional study, the vitamin status was measured using the inverse biomarker, dephospho-uncarboxylated Matrix Gla Protein (dp-ucMGP). Vascular health was reflected by total coronary artery calcification (CAC) score and coronary artery stenosis estimated using a cardiac Computed Tomography scan and by arterial stiffness estimated using carotid-femoral Pulse Wave Velocity (cfPWV). A total of 2167 participants with a mean age of 68 years (48% women) were included. In the fully adjusted analyses adjusted for age, sex, lifestyle factors, waist circumference, mean arterial pressure (for cfPWV) and kidney function, a doubling in dp-ucMGP levels (indicating lower vitamin K status) were independently and significantly associated with higher cfPWV (0.30 m/s (95% CI: 0.08 to 0.52 m/s)) but not with total CAC (21% increased total CAC (95% CI -5 to 54%)) or severity of stenosis (OR 1.26 (95% CI 0.86 to 1.86) for obstructive-extensive stenoses compared to no stenosis). CONCLUSION: Lower vitamin K status was independently associated with higher arterial stiffness but not CAC nor coronary stenosis when adjusting for cardiovascular risk factors. The results point to a complex interplay between vitamin K and vascular health and the need for more research into the possible role of vitamin K in vascular health.
BACKGROUND AND AIMS: To evaluate the prognostic value of the combined assessment of hemoglobin glycation index (HGI) and stress hyperglycemia ratio (SHR) for short-term mortality in critically ill patients with heart fai...BACKGROUND AND AIMS: To evaluate the prognostic value of the combined assessment of hemoglobin glycation index (HGI) and stress hyperglycemia ratio (SHR) for short-term mortality in critically ill patients with heart failure (HF). METHODS AND RESULTS: ICU data on HF patients were retrospectively retrieved from the MIMIC-III and IV databases between 2001 and 2022. SHR and HGI were calculated at admission and stratified into tertiles. The endpoint was in-hospital and 90-day mortality. Logistic and Cox models evaluated associations between SHR, HGI, and their combination with mortality in both diabetic and non-diabetic patients. Exploratory interpretable machine learning prognostic models were developed to evaluate predictive performance. A total of 1573 HF patients were included. In-hospital and 90-day mortality rates were 14.1% and 24.3%, respectively. High SHR was independently associated with increased in-hospital mortality (OR: 2.01, 95% CI: 1.31-3.09) and 90-day mortality (HR: 1.54, 95% CI: 1.18-2.00). Higher HGI was associated with a reduced risk of in-hospital mortality (OR: 0.88, 95% CI: 0.78-0.99) and 90-day mortality (HR: 0.91, 95% CI: 0.84-0.98). High SHR and low HGI had the highest mortality risk for both in-hospital mortality (OR: 1.90, 95% CI: 1.288-2.85) and 90-day mortality (HR: 1.45, 95% CI: 1.13-1.87). The XGBoost model demonstrated optimal predictive accuracy, with an AUROC of 0.810 for in-hospital mortality and 0.808 for 90-day mortality. CONCLUSION: High SHR and low HGI are significantly associated with short-term mortality in HF patients, suggesting that their combined assessment may improve short-term prognostic assessment in critically ill patients with HF.
BACKGROUND AND AIMS: Endothelial dysfunction (ED) represents an early key event in atherogenesis. Our aim was to evaluate the efficacy of six months add-on PCSK9 monoclonal antibodies (mAbs) on endothelial function asses...BACKGROUND AND AIMS: Endothelial dysfunction (ED) represents an early key event in atherogenesis. Our aim was to evaluate the efficacy of six months add-on PCSK9 monoclonal antibodies (mAbs) on endothelial function assessed by endocan plasma levels and PWV in a cohort of HeFH subjects; furthermore, we investigated the association of endocan lowering and PWV variation. METHODS AND RESULTS: In this prospective observational study, we evaluated 30 FH subjects on high-intensity statins plus ezetimibe and with an off-target LDL-C. All patients received PCSK9 mAbs therapy and obtained biochemical analysis as well as endocan measurement and PWV evaluation at baseline and after six months of PCSK9 mAbs. After six months of add-on PCSK9 mAbs therapy, a significant reduction of TC, LDL-C, Non-HDL-C, TG, Lp(a) and ApoB was observed; moreover, both PWV and endocan significantly improved after six months of treatment. Finally, univariate linear regression analysis showed that ΔPWV was significantly associated with ΔEndocan (p value < 0.001). CONCLUSIONS: PCSK9 inhibition was associated with significant improved endocan levels and PWV in a cohort of HeFH subjects. ΔEndocan was significantly associated with ΔPWV. Our exploratory findings demonstrate endothelial benefits of PCSK9 mAbs in addition to LDL-C lowering and support endocan and PWV as complementary markers of vascular response in FH.
BACKGROUND AND AIM: Sleep disorders (SD) are a known cardiovascular risk factor, with systemic inflammation implicated as a potential pathway. However, whether inflammation mediates or modifies the association between SD...BACKGROUND AND AIM: Sleep disorders (SD) are a known cardiovascular risk factor, with systemic inflammation implicated as a potential pathway. However, whether inflammation mediates or modifies the association between SD and cardiovascular disease (CVD) remains unclear. We investigated the role of systemic inflammation in the long-term CVD mortality risk associated with SD. METHODS AND RESULTS: We analyzed 26,477 adults from the National Health and Nutrition Examination Survey (NHANES, 2005-2018) with a median follow-up of 9.5 years. Physician-diagnosed SD was assessed via questionnaires. Inflammation was quantified using log-transformed C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR), systemic immune-inflammation index (SII), and a composite inflammation score. Survey-weighted Cox models, interaction, and mediation analyses were conducted, adjusting for demographic, metabolic, and lifestyle covariates. During follow-up, 2757 all-cause deaths and 1930 CVD deaths occurred. In fully adjusted models, SD was associated with higher all-cause mortality (hazard ratio [HR] = 1.29, 95% CI: 1.09-1.54) and CVD mortality (HR = 1.23, 95% CI: 1.05-1.51). Compared with participants without SD or baseline CVD, those with SD alone showed modest, non-significant risk elevation, while participants with both SD and baseline CVD had the highest risk (all-cause HR 1.63-2.15; CVD HR 1.15-2.39). Participants with only CVD also had increased mortality. No significant SD × inflammation interactions were observed. In the baseline CVD-free subcohort, elevated CRP, NLR, and composite inflammation scores predicted fatal CVD events only in participants without SD. Mediation analysis indicated negligible indirect effects. CONCLUSION: Sleep disorders independently predict cardiovascular mortality and reshape the prognostic value of systemic inflammation-inflammatory markers are only predictive in individuals without sleep disorders. Integrating sleep health is essential for inflammation-based CVD risk assessment.
BACKGROUND AND AIMS: Malnutrition, sarcopenia, and frailty are increasingly recognized as relevant determinants of outcomes in heart failure (HF), yet comprehensive evaluation of body composition and circulating biomarke...BACKGROUND AND AIMS: Malnutrition, sarcopenia, and frailty are increasingly recognized as relevant determinants of outcomes in heart failure (HF), yet comprehensive evaluation of body composition and circulating biomarkers is still not routinely implemented. We aimed to characterize body composition, physical function, and selected novel biomarkers in patients with HF and to compare these findings with those of healthy controls. METHODS AND RESULTS: In this single-centre, observational, cross-sectional study, consecutive patients admitted with acute HF between July 2020 and May 2021 were prospectively enrolled. Participants underwent a comprehensive assessment including dual-energy X-ray absorptiometry (DEXA) for bone mineral density and body composition, isometric handgrip dynamometry, the Short Physical Performance Battery (SPPB), and measurement of circulating Klotho and growth differentiation factor-15 (GDF-15). Healthy individuals served as the control group. Of 202 enrolled patients, 39 completed the full evaluation (mean age 66.3 years; 33.3% women). Frailty prevalence was 46.2%. Frail HF patients showed lower bone mineral density (p = 0.016) and reduced handgrip strength (p = 0.002) compared with non-frail HF patients. Trends toward lower Klotho and higher GDF-15 were also observed. Relative to controls, HF patients exhibited higher GDF-15 (p < 0.001), lower Klotho (p < 0.01), and poorer physical performance, whereas differences in muscle strength did not reach statistical significance. CONCLUSION: This multimodal evaluation suggests a substantial burden of frailty and metabolic-nutritional alterations in HF. Integrating DEXA-derived metrics with emerging biomarkers such as Klotho and GDF-15 may help refine frailty characterization and inform future hypothesis-generating interventional studies.
Makri R, Evangelou I, Vlachava M
… +15 more, Dafoulas GE, Bargiota A, Karaglani E, Drympeta I, Votis K, Georga EI, Fotiadis DI, Lupiáñez-Villanueva F, Folkvord F, Pecchia L, Fico G, Panagiotakos D, Androutsos O, Manios Y, GATEKEEPER-study (Greek Use Case 1) group
BACKGROUND AND AIM: Hypertension is a leading cardiovascular risk factor with substantial global impact on morbidity, mortality, and healthcare costs. While lifestyle interventions remain central to management, mHealth t...BACKGROUND AND AIM: Hypertension is a leading cardiovascular risk factor with substantial global impact on morbidity, mortality, and healthcare costs. While lifestyle interventions remain central to management, mHealth technologies offer promising adjunctive support, though their clinical effectiveness remains uncertain. This study evaluated whether combining dietetic counseling with digital tools improves hemodynamic markers in adults aged ≥55 years with increased cardiometabolic risk. METHODS AND RESULTS: This 3-month RCT (NCT05031299) included 954 adults with at least one metabolic syndrome risk factor, allocated 1:1:1 to Standard Care (dietetic counseling), Platform (counseling plus web-based platform), or Platform + Devices (counseling plus platform plus wearables). Outcomes included anthropometrics, lifestyle characteristics, blood pressure, pulse pressure, and estimated pulse wave velocity, analyzed using linear mixed-effects models adjusted for age and sex. All groups improved over 3 months. Waist circumference decreased by -6.29, -4.92, and -4.69 cm across Standard Care, Platform, and Platform + Devices groups respectively, and systolic blood pressure declined by -4.84 to -7.15 mmHg across groups. The Platform + Devices group showed greater increases in physical activity (94.62 MET-min/week; 95% CI 66.49 to 122.76) and greater reductions in pulse pressure (-3.90 mmHg; -6.58 to -1.22) versus Standard Care. Weight loss was associated with lower odds of hypertension (OR 0.4; 95% CI 0.2-0.7), greater likelihood of hypertension reversal (OR 3.6; 1.2-10.3), and higher probability of achieving normal pulse pressure (OR 1.8; 1.1-3.1). CONCLUSIONS: Dietary lifestyle intervention improved cardiometabolic outcomes, with limited added benefit from digital tools. Weight loss was the primary driver of hemodynamic improvement.
BACKGROUND AND AIM: Data on the link between metabolic dysfunction-associated fatty liver disease (MAFLD) and subclinical atherosclerosis (SA) assessed at multiple vascular sites are limited.This study aimed to evaluate...BACKGROUND AND AIM: Data on the link between metabolic dysfunction-associated fatty liver disease (MAFLD) and subclinical atherosclerosis (SA) assessed at multiple vascular sites are limited.This study aimed to evaluate the association of MAFLD and its subtypes with multiple territorial extents of SA. METHODS AND RESULTS: This cross-sectional study included 3,539 health check-up participants. All subjects were categorized into four groups: non-MAFLD, diabetes mellitus (DM)-MAFLD, overweight/obese (OW)-MAFLD and lean-MAFLD. Polyvascular plaques were assessed, with vascular ultrasound for the carotid, subclavian, abdominal aorta and iliofemoral arteries (4 sites) and brachial-ankle pulse wave velocity for central and peripheral muscular artery stiffness (1 site). The extent of the SA was defined according to the number of these five vascular sites affected. Compared with those in the non-MAFLD group, the odds ratios (95% confidence intervals) for MAFLD with a greater number of plaques were 1.69 (1.41-2.02), 1.65 (1.41-1.93), 1.75 (1.45-2.11) and 1.57 (1.32-1.87) in the carotid, subclavian, abdominal aorta and iliofemoral arteries, respectively; greater artery stiffness was 1.96 (1.63-2.35) in the central and peripheral muscular arteries. The extent of polyvascular SA showed the same pattern. Participants with lean-MAFLD or DM-MAFLD had a greater extent of focal (1 site affected) and multiterritorial (≥2 sites affected) SA than those with OW-MAFLD did. Additionally, the presence of liver fibrosis was significantly associated with increased multiterritorial SA risk in each MAFLD subtype. CONCLUSION: Polyvascular SA differed across MAFLD subtypes. Classifying MAFLD subtypes on the basis of metabolic phenotypes and liver fibrosis might aid in cardiovascular risk stratification.
BACKGROUND AND AIMS: Heart failure (HF) is a severe complication in type 2 diabetes mellitus (T2DM), but current risk stratification scores have limited predictive accuracy. We aimed to develop novel prediction tools int...BACKGROUND AND AIMS: Heart failure (HF) is a severe complication in type 2 diabetes mellitus (T2DM), but current risk stratification scores have limited predictive accuracy. We aimed to develop novel prediction tools integrating clinical variables with proteomics to improve risk stratification of hospitalization for HF in T2DM. METHODS AND RESULTS: In this study, we included 2111 UK Biobank participants with T2DM but no prior HF, and profiled 2920 proteins to predict 10-year incident HF hospitalization. Participants were randomly divided into training (70%), tuning (10%), and validation (20%) sets.Three prediction models were developed: a Clinical model based on demographic characteristics, comorbidities, medication use, and laboratory indices; a Protein model based on 40 proteins selected by the Light Gradient Boosting Machine (LGBM); and the Clinical OMics and Protein ASSessment for Heart Failure (COMPASS-HF) model, which integrated both clinical variables and the LGBM-selected proteins. Models were evaluated for area under the curve (AUC), sensitivity, and specificity. During follow-up, 168 participants (7.96%) developed incident HF. The COMPASS-HF model showed better discrimination than the Clinical model, with an AUC of 0.897 (95% CI: 0.850-0.945) versus 0.790 (95% CI: 0.723-0.856). It also demonstrated higher sensitivity (0.882; 95% CI: 0.725-0.967) and consistent performance in subgroups. COMPASS-HF effectively stratified risk of hospitalization for HF, with cumulative incidence rates of 31.9% in the high-risk group and 1.2% in the low-risk group. CONCLUSIONS: By combining clinical and proteomic variables, we developed a high-performance HF prediction model for T2DM, enabling precise risk stratification and informing early intervention strategies.
AIMS: Frailty is highly associated with morbidity and mortality in type 2 diabetes mellitus (T2DM). This viewpoint article reviews the importance of considering frailty in T2DM and cardiometabolic risk factor management...AIMS: Frailty is highly associated with morbidity and mortality in type 2 diabetes mellitus (T2DM). This viewpoint article reviews the importance of considering frailty in T2DM and cardiometabolic risk factor management and recommends its systematic integration into clinical practice. We propose that frailty is not merely a complication of metabolic disease, but an independent modifier of risk, treatment response, and outcomes. DATA SYNTHESIS: We conducted a literature review on the epidemiology of frailty in T2DM, bidirectional biological mechanisms linking frailty to T2DM and cardiometabolic disease, comparative utility of frailty measurement tools, and opportunities for incorporation of frailty assessments into routine T2DM and cardiometabolic care. CONCLUSIONS: Frailty is highly prevalent among individuals with T2DM and independently amplifies the risk of adverse outcomes including mortality, cardiovascular disease (CVD) events, functional decline, and hypoglycemia, beyond traditional cardiometabolic risk factors. The bidirectional relationship between frailty and dysglycemia, mediated by sarcopenia, chronic inflammation, and insulin resistance, highlights the importance of early, systematic frailty assessment in diabetes care. The Fried Frailty Phenotype and the Frailty Index are validated tools suitable for clinical and research contexts. Frailty evaluation can assist with the prioritization of interventions and the individualization of glycemic targets. Integrating frailty assessment into routine T2DM and cardiometabolic risk factor management is feasible, clinically meaningful, and can promote person-centred care for older adults.
BACKGROUND AND AIMS: Antioxidants are known to combat oxidative stress, a key factor in the development of cardiovascular diseases(CVDs) and mortality. In the current study, we aimed to prospectively investigate the rela...BACKGROUND AND AIMS: Antioxidants are known to combat oxidative stress, a key factor in the development of cardiovascular diseases(CVDs) and mortality. In the current study, we aimed to prospectively investigate the relationship between the composite dietary antioxidant index(CDAI) and the incidence of CVDs and mortality in the Iranian population. METHODS AND RESULTS: This study was conducted within the framework of the Tehran Lipid and Glucose Study(TLGS) among 5048 adults≥30 years, selected from the third and fourth phases of the TLGS. Dietary intake was assessed using a validated food frequency questionnaire, and the CDAI was calculated based on intakes of vitamins A, C, E, selenium, zinc, and manganese from food sources. A multivariable Cox proportional hazard regression model was used to estimate the risk CVDs, coronary heart disease(CHD), stroke, and mortality across CDAI tertiles. Median(interquartile) of CDAI score for all participants was -0.69(-3.12, 2.43). During 9-year follow-up period, 357 cases of CVDs(7.10%) and 131 cases of all-cause mortality(2.60%) were ascertained. In the multivariable adjusted model, the CVDs risk reduced across the tertiles of CDAI(HR = 0.60; 95%CI:0.40-0.89; P-trend = 0.013). Also, a one SD increase in CDAI score was associated with reduced risk of CVDs(HR = 0.77; 95%CI:0.64-0.93; P-trend = 0.007) and CHD(HR = 0.78; 95%CI:0.64-0.95; P-trend = 0.016). No significant associations were found between the CDAI score and the incidence risk of stroke and mortality. CONCLUSION: The findings of this study showed that a higher CDAI score is associated with a lower risk of CVDs in Iranian adults. However, there is no significant relationship between the CDAI score and risk of mortality and stroke.
BACKGROUND AND AIMS: To evaluate the association between lipid parameters and incident Cardio-Renal-Metabolic (CRM) multimorbidity in a large prospective cohort. METHODS AND RESULTS: We used multivariable Cox regression...BACKGROUND AND AIMS: To evaluate the association between lipid parameters and incident Cardio-Renal-Metabolic (CRM) multimorbidity in a large prospective cohort. METHODS AND RESULTS: We used multivariable Cox regression models to assess the association between lipid parameters and the risk of incident CRM multimorbidity, defined as the presence of ≥2 of type 2 diabetes (T2DM), cardiovascular disease (CVD), and chronic kidney disease (CKD), in individuals initially free of these conditions. Data from 5721 participants in the Tehran Lipid and Glucose Study (TLGS) (mean age 44.4 years; 3075 women) were analyzed. During a median follow-up of 15.4 years, 332 cases of CRM multimorbidity were identified. The combinations of coexisting CRM conditions, in order of frequency, were CVD and T2DM (49.2%), CKD and T2DM (19.9%), CVD and CKD (18.0%), and all three conditions (12.8%). Multivariable-adjusted hazard ratios (HRs) per standard deviation (SD) increase in TC, non-HDL-C, LDL-C, and log(TG) were 1.24 (1.12-1.37), 1.26 (1.14-1.39), 1.20 (1.08-1.34), and 1.29 (1.15-1.45), respectively. HRs per SD increase in TC/HDL-C, LDL-C/HDL-C, and log(TG/HDL-C) were 1.21 (1.10-1.33), 1.18 (1.07-1.30), and 1.26 (1.12-1.43), respectively. HDL-C was associated with a 17% lower risk (95% CI: 0.73-0.93); however, not after adjustment for metabolic risk factors. No evidence of nonlinearity was observed (all P >0.05). CONCLUSION: These findings underscore the important role of lipid abnormalities in cardio-renal-metabolic multimorbidity, particularly CVD-T2DM multimorbidity. However, they should be interpreted in light of composite heterogeneous outcomes with shared pathophysiological pathways, and the likelihood that the analytic sample represented a relatively healthier subset of the original cohort.
BACKGROUND AND AIMS: The Cardiovascular-Kidney-Metabolic (CKM) syndrome proposed by the American Heart Association (AHA) has been validated for mortality risk stratification in limited populations, but large-scale longit...BACKGROUND AND AIMS: The Cardiovascular-Kidney-Metabolic (CKM) syndrome proposed by the American Heart Association (AHA) has been validated for mortality risk stratification in limited populations, but large-scale longitudinal evidence from mainland China remains scarce. This study aimed to fill this gap by evaluating the association between CKM stages and all-cause mortality in middle-aged and older Chinese adults. METHODS AND RESULTS: We used data from the China Health and Retirement Longitudinal Study (CHARLS) spanning 2011-2020. Kaplan-Meier curves were generated, and propensity score overlap weighting was employed to balance the potential confounders. Multivariable Cox proportional hazards models were employed to examine the association of CKM stages with all-cause mortality. Restricted cubic splines (RCS) were used to explore potential nonlinear associations. Among 9223 participants (median age 58 years, 47.5% male), the prevalence of CKM stages 0-4 was 7.5%, 15.4%, 43.5%, 22.5%, and 11.0%, respectively. Over a median follow-up of 9 years, 1203 all-cause deaths were recorded. Participants in the lower CKM stages achieved relatively longer survival according to the Kaplan-Meier curves. After stratification by age and sex, compared to stage 0, stages 3 and 4 were significantly associated with increased all-cause mortality (stage 3: Hazard Ratio (HR) 1.77, 95% Confidence Interval (CI) 1.28-2.45, p < 0.001; stage 4: HR 1.46, 95% CI 1.01-2.11, p = 0.042). RCS analysis showed a nonlinear correlation between CKM stages and all-cause mortality (p-nonlinear = 0.512). CONCLUSION: Advanced CKM stages (3-4) were associated with increased all-cause mortality risk among middle-aged and older adults in China, with a significant linear dose-response relationship.
BACKGROUND AND AIMS: The effect of consuming a mix of Brazilian nuts on energy metabolism has not been explored. Thus, the present study aimed to evaluate the effects of acute and chronic consumption of mixed nuts on mar...BACKGROUND AND AIMS: The effect of consuming a mix of Brazilian nuts on energy metabolism has not been explored. Thus, the present study aimed to evaluate the effects of acute and chronic consumption of mixed nuts on markers of energy metabolism in women with overweight/obesity. METHODS AND RESULTS: This is a randomized, controlled, and parallel clinical trial with adult women. In an acute study, participants received a beverage containing mixed nuts (30 g of cashew nuts + 15 g of Brazil nuts) or a control beverage, and energy metabolism markers were assessed for up to 3 h postprandially. For the chronic study, participants received 45 g of a mix of nuts/day and a -500kcal energy-restricted diet (MNG) or only a -500kcal energy-restricted diet free of nuts (CTG) for 8 weeks, and energy metabolism was assessed before and after the intervention period. In the postprandial period, fat oxidation was higher in the MNG than in the CTG (piAUC: 47.53 ± 5.78 mg/min vs. 27.93 ± 6.98 mg/min; p = 0.048). After 8 weeks of the intervention, fasting fat oxidation increased in the MNG (+16.0 ± 7.0 mg/min) and decreased in the CTG (-5.0 ± 6.0 mg/min), with no significant difference between groups. Other acute and chronic markers also showed no significant changes between groups. CONCLUSION: The acute consumption of mixed nuts increased postprandial fat oxidation, whereas chronic intake within an energy-restricted diet did not affect energy metabolism markers in women at cardiometabolic risk. REGISTRATION NUMBER FOR BRAZILIAN REGISTRY OF CLINICAL TRIALS: RBR-3ntxrm.
AIMS: This viewpoint discusses the current role of bempedoic acid in clinical practice. DATA SYNTHESIS: Randomized clinical trials have shown bempedoic acid efficacy in both reducing LDL-C levels and major cardiovascular...AIMS: This viewpoint discusses the current role of bempedoic acid in clinical practice. DATA SYNTHESIS: Randomized clinical trials have shown bempedoic acid efficacy in both reducing LDL-C levels and major cardiovascular adverse events. This evidence has led to the inclusion of bempedoic acid among the lipid-lowering therapies with demonstrated clinical efficacy and recommended by the last update of European Society of Cardiology guidelines on dyslipidaemia management to prevent cardiovascular disease. CONCLUSIONS: Bempedoic acid is an important therapeutic option that overcomes some limitations of statins and allows to further reduce the global burden of atherosclerotic cardiovascular disease.