Search Results (9,418)

Chronic kidney disease (CKD) is associated with a significantly elevated mortality rate, primarily due to cardiovascular disease (CVD), highlighting a complex bidirectional relationship between the two conditions. Life-threatening cardiovascular events occur despite control of the traditional risk factors, emphasizing the underlying role of non-traditional risk factors. CKD, causing mineral imbalance and the accumulation of uremic toxins due to a compromised ability to excrete waste products, imposes extra pressure on the cardiovascular system. The retention of mineral and uremic toxins, in turn, aggravates the progression of CKD. This review aims to elucidate the pathophysiological connections between CKD and CVD, with a particular focus on the metabolic regulatory mechanisms influenced by minerals such as calcium and phosphate, as well as uremic toxins. We review how these factors contributed to accelerated multi-organ damage through mechanisms such as inflammation, endothelial dysfunction, oxidative stress, and vascular calcification. In addition, we discuss the therapeutic strategies for specific uremic toxins and proposed directions for future investigations. This review provides insights into the complex interplay between metabolic dysregulation and cardiovascular outcomes in CKD patients, promoting the development of innovative therapeutic interventions, ultimately improving the prognosis and quality of life for patients affected by these interconnected conditions. Full article

Aldosterone excess, particularly in the context of primary aldosteronism, is associated with adverse cardiovascular outcomes. Historically considered a condition of resistant hypertension with hypokalaemia, patients with primary aldosteronism often experienced prolonged diagnostic delay with significant end-organ damage involving the renal, cardiovascular, and central nervous systems at diagnosis. Emerging research has revealed a wide spectrum of renin-independent aldosteronism, ranging from subclinical disease with normal or mildly elevated BP to overt disease marked by resistant hypertension and cardiovascular complications. Subclinical forms of primary aldosteronism have been identified across all age groups, and it is increasingly linked to early signs of adverse cardiac remodelling, even in young adults. Notably, adverse cardiac remodelling was independent of blood pressure. Furthermore, primary aldosteronism confers excess cardiovascular morbidity and mortality compared to blood-pressure-matched essential hypertension. Importantly, these risks can be mitigated through timely diagnosis and treatment with mineralocorticoid receptor antagonists. In this narrative review, we explore the cardiovascular consequences of aldosterone excess, discuss the pathophysiological mechanisms underlying cardiac remodelling, and examine the implications of renin-independent aldosteronism for cardiovascular risk across the lifespan. Full article

Circadian rhythms are endogenous biological cycles that regulate essential cardiovascular functions, including blood pressure, heart rate, vascular tone, and metabolic homeostasis. Disruption of these rhythms due to factors such as shift work, artificial light at night, irregular sleep–wake cycles, or mistimed eating has been increasingly recognized as an independent risk factor for cardiovascular disease. A growing body of evidence links circadian misalignment to key pathophysiological mechanisms, including endothelial dysfunction, oxidative stress, inflammation, and autonomic imbalance. Melatonin, a hormone produced primarily by the pineal gland, plays a central role in circadian regulation and exhibits potent antioxidant, anti-inflammatory, and cardiometabolic properties. This narrative review synthesizes current findings on the interplay between circadian disruption and cardiovascular risk, with a particular emphasis on the mechanistic and therapeutic role of melatonin. We also highlight the potential of chronotherapeutic strategies, such as timed melatonin supplementation, antihypertensive dosing, and time-restricted eating, to restore circadian alignment and improve cardiovascular outcomes. Despite promising data, translation into clinical practice remains limited. Future research should focus on identifying practical circadian biomarkers, refining chronotherapy protocols, and integrating circadian variables into risk models and clinical workflows. Full article

Background/Objectives: Gut microbial metabolism of choline and related quaternary amines to trimethylamine (TMA) is the first step in the production of trimethylamine N-oxide (TMAO), a circulating metabolite that contributes to the development of atherosclerosis and other forms of cardiovascular disease (CVD). No data exist on regional differences in TMA production within the colon due to difficulties studying gut regions in vivo. A better understanding of TMA production by gut microbiota is needed to develop strategies to limit TMA production in the gut and TMAO levels in circulation with the goal of reducing CVD risk. Methods: We employed our novel three-compartment MiGut in vitro model, which establishes three distinct microbial ecologies mimicking the proximal, mid, and distal colon, to study conversion of choline to TMA by human gut microbiota using isotopically labelled substrate. Results: Choline-d₉ was almost completely converted to TMA-d₉ in vessels 2–3 (mimicking the mid and distal colon) within 6–8 h, but little conversion occurred in vessel 1 (mimicking the proximal colon). Abundance of cutC, part of the cutC/D gene cluster responsible for choline conversion to TMA, was highest in vessel 1 vs. 2–3, suggesting that its expression or activity may be suppressed in the proximal colon. Another possibility is that the viability/activity of bacteria expressing cutC could be suppressed in the same region. Conclusions: This novel finding suggests that while bacteria capable of converting choline to TMA exist throughout the colon, their activity may be different in distinct colon regions. The regional specificity of TMA production, if confirmed in vivo, has implications for both basic microbial ecology related to CVD and the development of strategies to control TMA and TMAO production, with the goal of lowering CVD risk. These findings warrant further study in vitro and in vivo. Full article

Metabolic syndrome (MetS) is defined by a combination of metabolic abnormalities, such as central obesity, insulin resistance, hypertension, and dyslipidemia, and significantly increases the risk of cardiovascular diseases and type 2 diabetes. The high prevalence of MetS is a public health concern, necessitating rapid identification and intervention strategies to prevent this emerging epidemic. Diagnosing MetS requires the presence of three or more of these abnormalities, underscoring the need for effective management approaches. Despite a growing body of literature, limited reviews have critically evaluated the complex interplay between metabolic dysfunction, inflammation, and coagulation, particularly in the context of dietary interventions. Therefore, this article reviews the relationship between metabolic syndrome, inflammation, and thrombotic diseases, with an emphasis on their impacts on hematological health. Furthermore, this review explores the potential role of vegetarian and vegan dietary patterns in controlling these processes and improving hematological outcomes. This narrative review aims to critically evaluate current research on the inflammatory and thrombotic implications of MetS and assess the potential modulating role of vegan and plant-based diets within this context. Full article

Background: Reduced-dose prasugrel is widely used in East Asia for acute coronary syndrome (ACS), but real-world data in diverse Asian populations are limited. This study evaluated its effectiveness and safety in Taiwanese patients. Methods: The PROMISE-TW Registry was a multicenter, retrospective study including 1167 patients with ACS or chronic coronary syndrome (CCS) treated with reduced-dose prasugrel (20 mg loading, 3.75 mg maintenance) across 13 hospitals in Taiwan from 2018 to 2022. The primary endpoint was 1-year major adverse cardiovascular events (MACEs: cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke). Secondary outcomes included composite ischemic events and major bleeding (BARC 3–5). Results: Among enrolled patients (mean age 63.9 years; 81.2% male; 83% ACS), percutaneous coronary intervention was performed in 90.8%. At one year, MACEs occurred in 1.9%, composite ischemic events in 8.2%, and major bleeding in 0.8%. Subgroup analysis identified prior stroke, diabetes, and chronic total occlusion intervention as predictors of bleeding. Male sex, chronic kidney disease, and left circumflex artery intervention predicted higher ischemic risk. Conclusions:Reduced-dose prasugrel provided effective ischemic protection and low bleeding rates in Taiwanese patients, especially those with ACS. These findings support the clinical utility of dose-adjusted prasugrel in East Asian populations and highlight the importance of individualized risk assessment. Full article

Introduction: Chronic kidney disease (CKD) affects roughly 10% of the global population and significantly increases cardiovascular risk. While renin–angiotensin system inhibitors (RASi) remain a therapeutic mainstay, recent evidence supports the renoprotective value of sodium–glucose cotransporter-2 inhibitors (SGLT2i) and finerenone. This study evaluated the real-world use of guideline-directed medical therapy (GDMT) among patients with cardiorenal disease in Greece and explored factors influencing prescribing patterns. Methods: The Hellenic Cardiorenal Morbidity Snapshots (HECMOS 1 and 2) enrolled all cardiology inpatients across Greece on 3 March, 2022, and 5 June, 2024. Comorbidities and medication data were based on self-report and chart review. CKD patients eligible for SGLT2i and finerenone were identified per guideline criteria. Multivariable logistic regression was used to identify predictors of SGLT2i use. Results: From a total of 923 and 1222 patients enrolled in HECMOS 1 and 2, CKD was present in 26% and 27%, respectively. SGLT2i use prior to hospitalization rose from 15% in HECMOS 1 to 30.4% in HECMOS 2. In HECMOS 1, diabetes mellitus was the strongest predictor of SGLT2i use (OR 12.01, 95% CI 3.31–45.56, p < 0.001), while heart failure predicted use in HECMOS 2 (OR 4.10, 95% CI 1.70–9.88, p = 0.002). Finerenone was prescribed in only 1.7% of eligible patients in HECMOS 2. RASi usage among CKD patients remained stable across both cohorts (42.1% vs. 41.7%), with renal dysfunction showing no impact on prescribing patterns. Conclusions: SGLT2i use in patients with CKD and cardiovascular disease doubled over 2 years, indicating progress in implementing GDMT. However, overall use of disease-modifying therapies remains suboptimal, underscoring the need for further improvement in real-world care. Full article

Background/Objectives: This cohort study aimed to elucidate the real-world treatment course of patients receiving low-dose olanzapine (<2.5 mg), to assess its efficacy, and to examine its metabolic side effects. This study was a cohort study using a clinical registry. Methods: The primary efficacy endpoint was effective medication adherence and appropriate dosing. The primary safety endpoint was the incidence of metabolic adverse events, including diabetes mellitus, dyslipidemia, cardiovascular events, and cerebrovascular events. Cox proportional hazards models were used to compare outcomes between groups. Results: A total of 9565 patients were prescribed olanzapine at Samsung Medical Center from 2002 to 2023, and 1629 (17%) were in the low-dose group. The median maintenance period for low-dose olanzapine was 142 days (IQR, 30–551 days), and 95.5% of patients received low-dose olanzapine with either gradual tapering or gradual dose escalation. During follow-up, the risk of diabetes mellitus (HR = 0.32, 95% CI = 0.17–0.62), dyslipidemia (HR = 0.59, 95% CI = 0.42–0.82), cardiovascular disease (HR = 0.88, 95% CI = 0.51–1.49), and cerebrovascular events (HR = 0.75, 95% CI = 0.41–1.36) was lower in the low-dose group than in the regular-dose group. Conclusions: Low doses of olanzapine have clinical benefits in providing appropriate dosing and a reduced incidence of metabolic side effects. These findings support personalized antipsychotic treatment strategies, particularly in populations with heightened metabolic vulnerability, by informing dose selection based on individual risk–benefit profiles. Full article

Background/Objectives: Diabetic sensorimotor polyneuropathy (DSPN) is a frequent microvascular complication of diabetes mellitus, associated with increased morbidity and reduced quality of life. The existing literature offers a limited understanding of sex-specific cardiovascular risk profiles and their association with DSPN, particularly within Central and Eastern European populations. Methods: A retrospective analysis was conducted using data from 621 individuals with type 1 or type 2 diabetes mellitus who underwent comprehensive neuropathy screening at the University of Debrecen between 2017 and 2021. The diagnosis of DSPN was made in accordance with international criteria, incorporating symptom scores, and electrophysiological measurements. Multivariate logistic regression was applied in order to identify independent predictors. Results: The diagnosis of DSPN was made in 444 individuals (71.5%), of whom 58.2% were female. Despite similar glycemic control (HbA1c: 7.81% in men vs. 7.65% in women, p = 0.297), men had significantly more frequent occurrences of previous myocardial infarction (11.8% vs. 5.0%, p = 0.008), peripheral vascular disease (19.9% vs. 12.7%, p = 0.041) and atherosclerosis (31.7% vs. 22.0%, p = 0.021). Multivariate analysis showed that female gender was independently associated with a lower incidence of DSPN (odds ratio [OR] = 0.592, 95% confidence interval [CI]: 0.369–0.950, p = 0.030), while diabetic retinopathy was a significant predictor (OR = 2.728, 95% CI: 1.300–5.725, p = 0.008). Electrophysiological testing revealed lower nerve conduction amplitudes in females for selected nerves. Conclusions: Our findings highlight sex-specific differences in neuropathy risk and support the implementation of individualized screening strategies in diabetic populations with region-specific risk factors. Full article

Background: Cardiovascular morbidity and mortality are alarmingly high in Bulgaria, partly due to behavioral risk factors such as smoking. Purpose: This study aimed to assess and compare smoking habits, second-hand smoke exposure, and attitudes of Bulgarian and foreign medical students to better understand smoking behavior in this population. Methods: A cross-sectional survey was conducted among 1063 medical students at the Medical University of Plovdiv (60.8% women; 53% Bulgarian). Results: More Bulgarian students were active smokers and ever-smokers than foreign students (24.7% vs. 14% and 29.3% vs. 18.8%, p < 0.001). Bulgarian women smoked nearly as much as Bulgarian men (24.1% vs. 25.6% for active smokers, p > 0.05), whereas foreign women smoked less than foreign men (15.7% vs. 23.7%, p = 0.034). Women more often replaced classic cigarettes with tobacco heating systems (THSs) than men (40.7% vs. 25.3%, p = 0.020). Nearly 85% of the respondents started smoking by the age of 19. Exposure to second-hand smoke among friends, among colleagues, and in the family was associated with a higher risk of being an ever-smoker (ORs ~8.9; 3.4 and 3.7, respectively). About 20% of students were unsure or disagreed that smoking fewer cigarettes, THSs, or e-cigarettes posed health risks. The majority (61.3%) of active smokers acknowledged negative health effects. Conclusions: These findings highlight a concerning smoking prevalence among Bulgarian medical students and emphasize the need to strengthen medical education and health policies with updated tobacco risk information and targeted prevention programs to reduce smoking and improve future physicians’ cessation counseling skills. Smoking likely contributes significantly to Bulgaria’s high cardiovascular morbidity. Full article

Background/Objectives: Normal-weight obesity describes those with a normal body mass index (BMI) and high body fat percent. Older adults with normal-weight obesity (NWO-O) are at increased risk for cardiovascular disease (CVD), but underlying mechanisms remain unclear. This pilot study examined whether NWO-O had an unfavorable cardiometabolic response to acute high-fat meal intake compared to normal BMI, low body fat percent individuals that were both older (NWL-O) and younger (NWL-Y). Methods: Participants (N = 29) with a normal BMI were grouped as follows: NWL-Y (18–35 years, low body fat percent; n = 12), NWL-O (≥60 years, low body fat percent; n = 9), and NWO-O (≥60 years, high body fat percent; n = 8). All participants completed an abbreviated fat tolerance test (75 g fat). Fasting and 4 h blood samples were collected to measure lipids (triglycerides and high-density lipoprotein cholesterol [HDL-C]), biomarkers of intestinal permeability (lipopolysaccharide binding protein [LBP] and soluble cluster of differentiation [sCD14]), and the inflammatory marker interleukin (IL)-6. Results: NWO-O had higher percent, absolute, and trunk fat compared to NWL-Y and NWL-O (p’s ≤ 0.01). Conversely, percent lean mass was lower in NWO-O versus both NWL groups (p’s ≤ 0.01). NWO-O had higher fasting triglycerides than NWL-Y (p < 0.05), but all groups were in the clinically normal range on average (≤107 mg/dL). However, NWO-O had higher 4 h triglycerides (239.4 ± 101.0 mg/dL) compared to NWL-Y and NWL-O (p < 0.01), consistent with an adverse response. The absolute change in triglycerides was higher in NWO-O relative to NWL-Y (p < 0.01), but not compared to NWL-O (p = 0.06). Fasting IL-6 was higher in NWO-O relative to NWL-Y (p < 0.05). Fasting and 4 h sCD14 were similarly higher in NWL-O and NWO-O versus NWL-Y (p’s < 0.01). Conclusions: NWO-O had an exaggerated postprandial triglyceride response compared to younger and similar-aged NWL individuals, which could reflect hepatic very low-density lipoprotein overproduction or impaired triglyceride clearance. Future work should continue to investigate the role of postprandial dyslipidemia in NWO-O’s reported CVD risk. Full article

Background and Objectives: AIDS-related mortality has significantly decreased due to antiretroviral therapy (ART), leading to a substantial increase in average lifespan. Consequently, cardiovascular diseases have become a growing concern among people living with HIV (PLWH). This study aimed to assess the cardiovascular risk profile of people living with HIV receiving ART and to explore the association between traditional and HIV-related factors with increased cardiovascular risk. Materials and Methods: We conducted a case study involving 112 PLWH receiving ART at a specialized clinic in southeastern Romania to estimate cardiovascular risk (CVR) using the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D^®) score. For participants aged 40 and above, the SCORE2 algorithm was additionally applied. Results: Most participants were male and under 40 years of age, including 34 individuals from Romania’s distinct pediatric HIV cohort. We observed a substantial cardiovascular risk burden: abdominal obesity was present in 24.1% of participants, active smoking was reported by 55.4%, and over 70% had low physical activity levels. Among participants aged 40 and above, the D:A:D^® and SCORE2 scores were strongly correlated, with an average cardiovascular age exceeding chronological age by a mean of 7.5 years. Although CVR remained similarly low among subgroups of PLWH under 40, the prevalence of metabolic syndrome was higher in patients from the pediatric cohort compared to those diagnosed later. Traditional risk factors—such as age, obesity, hypertension, dyslipidemia, smoking, and alcohol use—as well as elevated C-reactive protein levels, were significantly associated with increased CVR. Conclusions: Residual inflammation in PLWH, despite complete viral suppression in combination with metabolic syndrome, is associated with increased cardiovascular risk even in younger and clinically stable populations. Routine integration of metabolic and cardiovascular risk screening into HIV care may support timely prevention and personalized management strategies starting at an early age. Full article

Cardiovascular disease (CVD) remains the leading cause of death worldwide, with elevated low-density lipoprotein cholesterol (LDL-C) as a major risk factor. Beyond medications, dietary interventions and functional foods offer significant cholesterol-lowering potential. This article provides a comprehensive review of functional foods and nutraceutical ingredients that help to reduce cholesterol levels and introduces the novel Cholesterol-Lowering Capacity Index (CLCI), designed to quantify and communicate the efficacy of such foods. In doing so, it summarizes key functional components, including plant sterols/stanols, viscous fibers, soy protein, red yeast rice, berberine, polyphenols (e.g., bergamot extract, garlic), and others, highlighting their mechanisms of action and the typical LDL-C reductions observed in clinical studies. Strategies for the design of next-generation cholesterol-lowering foods are discussed, such as combining multiple bioactives for synergistic effects, personalized nutrition approaches, and novel food processing techniques to enhance bioavailability. Building on these strategies, the CLCI is then proposed as a practical scoring system, analogous to the glycemic index for blood sugar, that integrates the evidence-based potency of ingredients, effective dosing, and synergistic interactions into a single metric. A methodology for the calculation of the CLCI is presented, alongside potential applications in food labeling, clinical guidance, and dietary planning. Full article

Background/Objectives: Hypercholesterolemia, a metabolic disorder and major risk factor for cardiovascular disease, remains a global health concern. Although current pharmacological interventions effectively reduce cholesterol levels, their use is often associated with adverse side effects. These limitations have driven interest in alternative or complementary approaches based on natural products; however, the poor solubility, stability, and bioavailability of many natural compounds emphasize the need for innovative drug delivery systems to enhance their health-promoting potential. The extract obtained from Persea americana peels, a sustainable and underutilized by-product, has previously been reported to have cholesterol-lowering properties. Methods: The extract was encapsulated in bovine serum albumin nanoparticles. The nanoformulation was characterized for physicochemical properties and for extract stability under acid-simulated gastric digestion. Safety and biocompatibility were evaluated by in vitro cytotoxicity assays using intestinal Caco-2 and liver HepG2 cells, and in vivo toxicity using Artemia salina. The bioavailability of the extract and the nanoformulation’s capacity to reduce cholesterol absorption in a differentiated Caco-2 cell model were additionally assessed. Results: Encapsulation enhanced extract stability and bioavailability, protecting it from degradation in acid simulated gastric digestion. The nanoparticles showed favorable physicochemical properties, including a small size of less than 100 nm, and demonstrated safety and biocompatibility. In the Caco-2 model, the encapsulation of the extract resulted in reduced cholesterol permeation compared to the free extract Conclusions: These findings suggest that the nanoformulation developed may offer a safe and effective strategy for the oral delivery of P. americana peel extract, reinforcing its potential for application in hypercholesterolemia management. Full article

Background: Asymptomatic left ventricular diastolic dysfunction (LVDD) occurs in type 2 diabetes mellitus (T2DM) patients, particularly among the elderly. Aim: This study aimed to identify diastolic function changes over a 52-week follow-up and the predictive factors for LVDD in T2DM patients without atherosclerotic manifestations. Methods: Diastolic function, metabolic profile, atherogenic indexes, and subclinical inflammatory markers were assessed at baseline and after one year in 138 T2DM outpatients. All variables were compared in patients with and without LVDD across three age groups. Results: The patients were 57.86 ± 8.82 years old, 49.3% male, with a mean 5-year diabetes duration and a median HbA_1c of 7.8%. At baseline, 71 patients had grade 1 LVDD, 12 had grade 2 and 3 LVDD, and 15 had indeterminate LVDD. In the elderly group, 29 patients had LVDD. The logistic regression analysis identified age over 65 as an independent risk factor for LVDD (Exp B = 9.85, 95% CI: 1.29–75.36, p = 0.027). LVDD patients had a longer diabetes duration and a higher prevalence of diabetic neuropathy. Elderly patients had the lowest E/A, e’, lateral s’, atherogenic and Castelli risk indexes, and significantly higher E/e’, EDT, LAVI and TNF-alpha values (p < 0.05). After 52 weeks, diastolic function worsened in 27 patients, who had no significant differences compared to those with stable or improved diastolic function. Conclusions: LVDD was common in our T2DM patients without known cardiovascular disease, and age increases the LVDD risk. Echocardiographic assessment is necessary, especially in elderly T2DM patients with co-morbidities, to identify patients at risk of progression to heart failure early. Full article