Cardiovascular Disease In Individuals Research Articles

Relationship between liver and cardiometabolic health in type 1 diabetes

IntroductionType 1 diabetes (T1D) is a chronic condition marked by insulin deficiency and hyperglycemia, with an increasing global incidence, particularly among children. Despite improvements in diabetes management, individuals with T1D continue to experience higher rates of cardiovascular disease (CVD), the leading cause of mortality in this population. Traditional CVD risk factors such as dyslipidemia and poor glycemic control are insufficient to fully explain the elevated risk in T1D, prompting further investigation into additional factors. Emerging evidence suggests that metabolic dysfunction-associated steatotic liver disease (MASLD) plays a critical role in this heightened CVD risk.ObjectiveThis narrative review aims to explore the relationship between MASLD and CVD in individuals with T1D. The review focuses on the prevalence of MASLD, its contributing risk factors, and the potential impact of liver dysfunction on cardiovascular outcomes in this population.MethodsA review of existing literature was conducted, focusing on observational studies, cohort studies, and meta-analyses that investigate the prevalence of MASLD in T1D populations and its association with CVD. The review also examines the physiological mechanisms linking MASLD and CVD, including insulin resistance, systemic inflammation, and hepatic dyslipidemia. Key studies were evaluated to identify patterns in MASLD prevalence based on diagnostic modalities and to assess the independent contribution of MASLD to cardiovascular risk in T1D patients.ConclusionMASLD is increasingly recognized as a significant contributor to CVD in individuals with T1D, particularly in those with shared risk factors like obesity and insulin resistance. Evidence suggests that MASLD exacerbates hepatic and systemic metabolic dysfunction, increasing CVD risk through mechanisms such as chronic inflammation and atherogenic lipid profiles. Routine liver health assessments and tailored management strategies targeting MASLD should be incorporated into clinical care for individuals with T1D to mitigate long-term cardiovascular complications.

Abstract 4130641: The Role of Oxidized Phospholipids in Triggering Trained Immunity and Accelerating Atherosclerotic Plaque Inflammation during Cholesterol Cycling

Introduction: Oxidized phospholipids (OxPL) derived from LDL play a crucial role in the development and progression of atherosclerosis by promoting chronic inflammation and formation of foam cells. The natural antibody E06, binding to OxPL, diminishes macrophage uptake of OxLDL in vitro and decreases atherosclerosis progression in vivo. In our prior work using a model of plasma cholesterol cycling (high-low-high), resulting in atherosclerotic plaque Progression (P)-Regression (PR)-re-Progression (PRP), respectively, we observed accelerated plaque inflammation in the PRP group relative to mice with non-cycling high cholesterol. Hypothesis: OxPL promotes plaque inflammation in the cholesterol cycling model via trained immunity and that the E06 antibody will mitigate this process. Methods: We utilized transgenic "E06 mice" that expressed a single-chain variable fragment of E06 (E06-scFv) using the Apoe promoter on the Ldlr−/− background. Both E06 mice and Ldlr-/- mice were subjected to high cholesterol diets (HCD) and categorized into three groups in the cholesterol cycling model: Baseline Progression (P), PR and PRP. Plaque regression was induced by ApoB-ASO injection, which significantly lowered cholesterol levels by inhibiting LDL production. Results: As before, Ldlr-/- mice in the PRP group exhibited accelerated plaque inflammation post-regression shown by CD68 staining on aortic roots. Notably, this acceleration was significantly inhibited in the E06 mice, highlighting the protective effects of E06 against plaque re-progression. Additionally, flow cytometry of peripheral blood exhibited reduced total monocytes and Ly6Chi-monocytes (thought to become inflammatory macrophages in plaques), alongside increased Ly6Clo-monocytes (thought to become inflammation resolving macrophages in plaques) among E06 mice in the PRP group compared to Ldlr-/- mice. Ex-vivo stimulation of bone marrow cells with the inflammatory stimulus LPS demonstrated higher IL-6 levels in supernatant in Ldlr-/- mice versus E06 mice in the PRP group, suggesting OXPL-induced trained immunity in bone marrow precursors of monocytes and macrophages is involved. Conclusion: The acceleration of plaque inflammation in cholesterol cycling model was significantly inhibited in the E06 mice. These results provide insight into the increased risk of cardiovascular disease in individuals with intermittent adherence to statins who undergo cholesterol cycling.

Characteristics of pulse wave velocity and its correlation with cardiovascular disease risk factors in healthy individuals.

Cardiovascular disease (CVD) is a major cause of human mortality and has become the leading cause of death worldwide. Existing studies indicate that structural and functional damage to the main arteries represents a significant risk factor for early vascular lesions and many CVDs. This study aimed to explore characteristics of carotid-femoral pulse wave velocity (cfPWV) and its correlation with cardiovascular disease risk factors in healthy individuals. Convenience sampling was used to collect demographics, risk factors, and laboratory examinations from 501 healthy individuals who underwent health checkups at our healthcare center from August 2020 to January 2021. Pearson correlation coefficients were used to examine the correlations between cfPWV and various parameters in both sexes. Multiple linear regression analysis was used to investigate the factors potentially influencing cfPWV. A statistically significant difference in cfPWV between sexes was observed only in the age group of subjects 38-47 years old. The results of the univariate analysis showed that in males, cfPWV was positively correlated with age, blood pressure, heart rate, and alcohol consumption and was negatively correlated with tehe resistive index. In females, cfPWV was positively correlated with age, blood pressure, heart rate, alanine aminotransferase, urea, creatine, uric acid, fasting blood glucose, triglycerides, total cholesterol, and heart rate. The results of multivariable analysis indicated that age, systolic blood pressure, heart rate, and alcohol consumption were influencing factors for cfPWV in males, while age, systolic blood pressure, heart rate, and creatinine were influencing factors for cfPWV in females (P <0.05 for all). In healthy individuals, the distribution patterns of cfPWV values vary by sex and age. In the elderly population, especially elderly women, enhanced monitoring and regular follow-ups are recommended to prevent the development and progression of CVDs in high-risk individuals at an early stage.

Serum neurofilament light chain: a novel biomarker for cardiovascular diseases in individuals without hypertension

Serum neurofilament light chain (sNFL) is a biomarker for axonal injury. Previous studies have linked sNFL levels to cardiovascular risk factors such as diabetes and hypertension, but its association with cardiovascular diseases (CVD) remains unclear. This study aims to explore the association between sNFL and CVD and evaluates its predictive value. Utilizing NHANES 2013–2014 data, this study included 2,035 participants aged ≥ 20 years with measured sNFL quantified using a Siemens immunoassay. CVD was self-reported and included myocardial infarction, stroke, heart failure, coronary heart disease, or angina. Logistic regression models assessed the association between sNFL levels and CVD. The predictive value of sNFL for CVD was evaluated using area under the curve (AUC) and DeLong test. Participants with higher sNFL levels were typically older, male, non-Hispanic white, smokers, and had lower socioeconomic status, higher CVD, hypertension, and diabetes prevalence. Higher sNFL levels were significantly associated with increased odds of CVD (adjusted OR = 1.41, 95% CI: 1.05–1.88). The association was significant in non-hypertensive individuals (OR = 2.72, 95% CI: 1.61–4.62) but not in hypertensive individuals (OR = 1.13, 95% CI: 0.81–1.56). sNFL addition to traditional risk models improved predictive accuracy, especially in non-hypertensive individuals (AUC from 0.827 to 0.856). sNFL levels are significantly associated with CVD in the general population, with a strong predictive value in non-hypertensive individuals. Future longitudinal studies should validate sNFL’s efficacy in various populations and explore the underlying mechanisms of its relationship with hypertension and CVD.

Impact of addressing modifiable risk factors on the 10-year risk of cardiovascular disease in individuals with familial hypercholesterolemia: a causal analysis utilising UK biobank

Abstract Background Familial hypercholesterolemia (FH) is a prevalent autosomal dominant disorder characterised by elevated low-density lipoprotein cholesterol (LDL-C) levels from birth. These elevated LDL-C levels significantly amplify the lifetime risk of cardiovascular disease (CVD). While the impact of early and effective initiation of lipid-lowering medication (LLM) on CVD risk is well documented in genetically confirmed FH, the additional impact of addressing modifiable lifestyle risk factors (MLRF) in that patient population remains largely unquantified. Methods This study quantified the potential effects of successfully managing 4 MLRF (smoking, obesity, alcohol consumption, and low physical activity) on the 10-year incidence of a first CVD diagnosis in adults with genetically confirmed FH treated with LLM within the UK Biobank. The synthesised causal estimates of these 4 MLF were obtained using two recent causal analysis frameworks, namely the doWhy causal calculus framework and the Causal Forest Double Machine Learning Method. Results In 660 FH individuals (mean age 56±8 years; 60.15% women), smoking cessation and reducing body mass index below 30 kg/m2 delivered the most substantial risk reductions (pooled estimates, adjusted for the 3 other MLRF: -6.5% and -3.2%, respectively; both p&amp;lt;0.001), followed by initiating moderate or high physical activity (-1.7%; p&amp;lt;0.001; Figure). Notably, cessation of alcohol consumption significantly increased CVD risk (+2.5%; p&amp;lt;0.001), aligning with existing literature. Conclusion In over 10 years, reductions in CVD risk ranging from 1.7% to 6.5% were achievable through smoking cessation, BMI reduction, and enhanced physical activity in FH individuals. Leveraging causal inference methodologies facilitates the discernment of which risk factors offer the most pronounced additional benefits beyond lipid-lowering interventions in this high-risk population.Forest Plot of Causal Effect Estimates

The Influence of GLP1 on Body Weight and Glycemic Management in Patients with Diabetes—A Scientometric Investigation and Visualization Study

Diabetes medications can affect weight and cardiovascular health. Some medications can aid in weight management, while others may lead to weight gain. Patients must be monitored and receive appropriate care to manage weight and prevent cardiovascular complications. Despite advancements in diabetes treatments that can influence weight and cardiovascular outcomes, ongoing research is necessary in this intricate field. Long-term effects, individual variations, and combination therapies are still subjects of uncertainty and ongoing investigation. The major objective of the research is to evaluate the impact of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) on body weight in diabetic patients through a scientometric assessment. Methodology: Research data were gathered from the Web of Science Core Collection (WoSCC) database by searching for the keywords “Body Weight”, dulaglutide, and semaglutide, identifying 60 relevant articles in the field. While there are advantages in managing diseases in which the cardiovascular system is implicated, there are also clinical considerations for personalized medicine and shared decision-making. The scientometric analysis of the articles revealed important insights into how dulaglutide and semaglutide impact weight management and their potential benefits for managing cardiovascular diseases in individuals with diabetes. Conclusions: Semaglutide shows superior outcomes compared to other commercially available GLP-1RAs, particularly in improving blood sugar control, lowering body weight, and addressing other cardio-metabolic risk factors in individuals with type 2 diabetes (T2DM). The findings suggest that GLP-1 RAs have the potential to provide cardiovascular protection by influencing various physiological factors such as blood pressure, pulse rate, glycated hemoglobin (HbA1c) levels, and the urinary albumin-to-creatinine ratio (RAC). The development and validation of the 4GI model provides a sophisticated tool for evaluating the complex interactions involved in diabetes treatments, offering insights into the mechanisms of action of various medications.

Subclinical Hyperthyroidism and Cardiovascular Disease.

Background: In this narrative review, we assess published data on subclinical hyperthyroidism (SCHyper) and its association with cardiovascular disease (CVD) in the general population. Summary: We present data on the risk of SCHyper in relation to CVD outcomes, including atrial fibrillation (AF), heart failure, stroke, coronary heart disease (CHD), major adverse cardiac events (MACE), CVD mortality, and all-cause mortality. Evidence indicates that SCHyper is associated with an elevated risk of AF, heart failure, MACE, CVD mortality, and all-cause mortality. SCHyper appears to have little association with stroke risk and has shown conflicting results regarding CHD risk. Regarding the degree of serum TSH suppression, evidence shows a higher risk of CVD in SCHyper individuals with suppressed TSH (<0.1 mIU/L) compared with those with low TSH (0.1-0.4 mIU/L). Despite evidence that older individuals are inherently at a higher risk for CVD, no studies have yet demonstrated an age-related increase in the relative risk of CVD in SCHyper. Conclusion: The studies indicate that SCHyper is associated with an increased risk of AF, heart failure, MACE, CVD mortality, and all-cause mortality. Considering the importance of the degree of serum TSH suppression and age as risk factors for CVD, treatment decisions should be individualized based on their specific risk factors.

Pentraxin-3 marker as a predictor of cardiovascular events in obstructive sleep apnea; a cross-sectional study

Introduction A large population suffers from obstructive sleep apnea (OSA). Most of these individuals (almost 90%) are either unrecognized or untreated OSA. These patients are at increased risk of cardiovascular diseases. Aim The aim of this study was to assess the prognostic value of Pentraxin 3 (PTX3) in OSA compared with the clinically relevant biological markers (HbA1c, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), uric acid, and fibrinogen) and to evaluate the relationship between PTX3 levels and risk of cardiovascular diseases. Patients and methods This research used a cross-sectional design and enrolled 100 participants with suspected OSA. All the participants underwent a full clinical history, a STOP-Bang questionnaire, and a polysomnography (PSG) study, and the serum biomarkers were also analyzed. Results The apnea-hypopnea index (AHI) from PSG was used to measure the OSA severity, and the individuals were distributed into three groups accordingly. Our findings showed that there was a significant difference in Pentraxin 3 and fibrinogen levels between patients with mild or moderate OSA and those with severe OSA. Pentraxin 3, at a cutoff point of greater than 4.25 ng/ml, had the highest prognostic accuracy in OSA (96%), with an AUC of 0.96. Regression analysis revealed that Pentraxin 3, with a cutoff point greater than 4.25, and CRP were significant predictors of cardiovascular disease in individuals with OSA. Furthermore, Pentraxin 3 (with a cutoff point of greater than 4.25 ng/ml) and fibrinogen were significant predictors of pulmonary embolism in patients with OSA. Conclusion Serum PTX3 was higher in patients with severe OSA than in those with mild- to moderate OSA. Furthermore, we found that OSA severity as indicated by the AHI was significantly correlated with serum PTX3. PTX3 and CRP are useful markers of cardiovascular risk in OSA.

Individual and joint effects of diabetes and depression on incident cardiovascular diseases and all-cause mortality: Results from a population-based cohort study

AimsTo assess the individual and joint effects of diabetes and depression on all-cause mortality and cardiovascular disease (CVD) in the middle-aged and elderly Chinese populations. Methods9105 individuals without CVD from the China Health and Retirement Longitudinal Study (CHARLS) were included and followed up for 9 years. Participants were divided into four comparative groups: diabetes alone, depression alone, both conditions, and neither condition. Multivariate binary logistic regression models were performed to compare the risks of all-cause mortality and CVD among the four groups. ResultsWhen compared to those without diabetes and depression, the multivariate adjusted odds ratios (aORs) for CVD in individuals who had diabetes only, depression only, and both diabetes and depression were 1.245 (95 % CI 1.023 to 1.515), 1.318 (95 % CI 1.171 to 1.485) and 1.722 (95 % CI 1.361 to 2.178), respectively. The aORs for all-cause mortality were 1.366 (95 % CI 1.035–1.804) for diabetes alone, 1.082 (95 % CI 0.916–1.279) for depression alone, and 1.590 (95 % CI 1.152–2.195) for both conditions when compared with those with neither condition. ConclusionsIndividuals with both diabetes and depression had greater risk of CVD and all-cause mortality when compared to those with diabetes or depression alone, or those without either condition.

G6pdN126D Variant Increases the Risk of Developing VEGFR (Vascular Endothelial Growth Factor Receptor) Blocker-Induced Pulmonary Vascular Disease.

G6PD (glucose-6-phosphate-dehydrogenase) is a key enzyme in the glycolytic pathway and has been implicated in the pathogenesis of cancer and pulmonary hypertension-associated vascular remodeling. Here, we investigated the role of an X-linked G6pd mutation (N126D polymorphism), which is known to increase the risk of cardiovascular disease in individuals from sub-Saharan Africa and many others with African ancestry, in the pathogenesis of pulmonary hypertension induced by a vascular endothelial cell growth factor receptor blocker used for treating cancer. CRISPR-Cas9 genome editing was used to generate the G6pd variant (N126D; G6pdN126D) in rats. A single dose of the vascular endothelial cell growth factor receptor blocker sugen-5416 (SU; 20 mg/kg in DMSO), which is currently in a Phase 2/3 clinical trial for cancer treatment, was subcutaneously injected into G6pdN126D rats and their wild-type littermates. After 8 weeks of normoxic conditions, right ventricular pressure and hypertrophy, pulmonary artery remodeling, the metabolic profile, and cytokine expression were assessed. Right ventricular pressure and pulmonary arterial wall thickness were increased in G6PDN126D+SU/normoxic rats. Simultaneously, levels of oxidized glutathione, inositol triphosphate, and intracellular Ca2+ were increased in the lungs of G6PDN126D+SU/normoxic rats, whereas nitric oxide was decreased. Also increased in G6PDN126D+SU/normoxic rats were pulmonary levels of plasminogen activator inhibitor-1, thrombin-antithrombin complex, and expression of proinflammatory cytokines CCL3 (chemokine [C-C motif] ligand), CCL5, and CCL7. Our results suggest G6PDN126D increases inositol triphosphate-Ca2+ signaling, inflammation, thrombosis, and hypertrophic pulmonary artery remodeling in SU-treated rats. This suggests an increased risk of vascular endothelial cell growth factor receptor blocker-induced pulmonary hypertension in those carrying this G6PD variant.

The Efficacy of Vitamins in the Prevention and Treatment of Cardiovascular Disease.

Vitamins are known to affect the regulation of several biochemical and metabolic pathways that influence cellular function. Adequate amounts of both hydrophilic and lipophilic vitamins are required for maintaining normal cardiac and vascular function, but their deficiencies can contribute to cardiovascular abnormalities. In this regard, a deficiency in the lipophilic vitamins, such as vitamins A, D, and E, as well as in the hydrophilic vitamins, such as vitamin C and B, has been associated with suboptimal cardiovascular function, whereas additional intakes have been suggested to reduce the risk of atherosclerosis, hypertension, ischemic heart disease, arrhythmias, and heart failure. Here, we have attempted to describe the association between low vitamin status and cardiovascular disease, and to offer a discussion on the efficacy of vitamins. While there are inconsistencies in the impact of a deficiency in vitamins on the development of cardiovascular disease and the benefits associated with supplementation, this review proposes that specific vitamins may contribute to the prevention of cardiovascular disease in individuals at risk rather than serve as an adjunct therapy.

O75 INHIBITION OF PCSK9/NFAT AMELIORATES CARDIAC DYSMETABOLISM AND FIBROSIS IN EXPERIMENTAL RAT MODEL OF PCOS BY REDUCING ATHEROGENIC LIPID AND IMPROVING INSULIN SENSITIVITY

Background: Polycystic ovarian syndrome (PCOS) remains an independent risk factor of cardiovascular disease (CVD), particularly in women of child-bearing age, and contributes to global increase in the prevalence/incidence of cardiovascular mortality and morbidity in women. Proprotein convertase subtilisin/kexin type 9 (PCSK9) has emerged as a promising therapeutic target to reduce residual CVD risk. Similarly, Nuclear factor of activated T cells (NFAT) is a transcription factor that is implicated in cardiac fibrosis. However, the role of PCSK9/NFAT in PCOS-associated cardiometabolic syndrome is not clear. Short chain fatty acids (SCFAs) play a multifaceted regulatory role in metabolic health. The present study therefore investigated the role of PCSK9/NFAT in cardiometabolic syndrome associated with experimental PCOS, and the therapeutic potential of SCFAs, especially butyrate. Material and Methods: Eight-week-old female Wistar rats were allotted into four groups (n=5). Polycystic ovarian syndrome was induced by administering letrozole (1 mg/kg p.o.) once daily for 21 days, thereafter the animals were treated with 200 mg/kg (oral gavage) of sodium butyrate for six weeks. Gene expression, biochemical parameters and cardiac/ovarian morphology were evaluated with appropriate methods. Results: Rats with PCOS showed androgen excess, multiple ovarian cysts and reduced insulin sensitivity. The rats in addition displayed atherogenic dyslipidemia (triglyceride/HDLc, TC/HDLc and LDLc), hypercorticosteronemia and elevated cardiac triglyceride, inflammatory biomarkers (NF-kappaB and TNF-alpha), caspase-6, 4-hydroxynonenal, inflammasome (NLRP3), fibrosis and depleted antioxidant defense (NrF2 and glutathione) as well as increased expression of PCSK9 and NFAT when compared to the control rats. Nevertheless, these systemic and morphological alterations were ameliorated following treatment with sodium butyrate. Conclusion: The present results collectively demonstrate cardiac dysmetabolism, inflammation, fibrosis as well as apoptosis in experimental PCOS rat model, which are driven by elevated expression of PCSK9/NFAT. The results further suggest that SCFAs, butyrate alleviates cardiometabolic syndrome and its attendant cardiomorbidity by suppression of PCSK9/NFAT. The present data provide a preclinical insight to prevention and management of CVD in PCOS individuals.

Unidirectional association of clonal hematopoiesis with atherosclerosis development

Clonal hematopoiesis, a condition in which acquired somatic mutations in hematopoietic stem cells lead to the outgrowth of a mutant hematopoietic clone, is associated with a higher risk of hematological cancer and a growing list of nonhematological disorders, most notably atherosclerosis and associated cardiovascular disease. However, whether accelerated atherosclerosis is a cause or a consequence of clonal hematopoiesis remains a matter of debate. Some studies support a direct contribution of certain clonal hematopoiesis-related mutations to atherosclerosis via exacerbation of inflammatory responses, whereas others suggest that clonal hematopoiesis is a symptom rather than a cause of atherosclerosis, as atherosclerosis or related traits may accelerate the expansion of mutant hematopoietic clones. Here we combine high-sensitivity DNA sequencing in blood and noninvasive vascular imaging to investigate the interplay between clonal hematopoiesis and atherosclerosis in a longitudinal cohort of healthy middle-aged individuals. We found that the presence of a clonal hematopoiesis-related mutation confers an increased risk of developing de novo femoral atherosclerosis over a 6-year period, whereas neither the presence nor the extent of atherosclerosis affects mutant cell expansion during this timeframe. These findings indicate that clonal hematopoiesis unidirectionally promotes atherosclerosis, which should help translate the growing understanding of this condition into strategies for the prevention of atherosclerotic cardiovascular disease in individuals exhibiting clonal hematopoiesis.

Association of Life’s Essential 8 With Incident Cardiovascular Disease Among Individuals With Depression: A Prospective Study

BackgroundDepression is an increasing illness worldwide that severely diminishes the quality of life. In this study we sought to elucidate the association of the American Heart Association’s Life’s Essential 8 (LE8) metrics with the incidence of cardiovascular disease (CVD) among depression participants and further quantify the related theoretical reduction of long-term CVD burden. MethodsWe included 20,832 participants with depression from the UK Biobank. LE8, including diet quality, physical activity, nicotine exposure, sleep duration, body mass index, lipids, glucose, and blood pressure, was calculated at baseline and categorized into low, medium, and high levels. Hazard ratios (HRs) and 95% confidence interval (CI) for major cardiovascular events (MACE) were calculated using Cox models. We further quantified the population-attributable fraction (PAF) for CVD. ResultsDuring a median follow-up of 12.0 years, 658 MACE were recorded. After multi-variable adjustment, compared with participants with low LE8, people with high LE8 had a decreased risk of MACE (HR, 0.32; 95% CI, 0.22-0.47), non-fatal MACE (HR, 0.39, 0.26-0.61), myocardial infarction (HR, 0.23, 0.12-0.44), and ischemic stroke (HR, 0.52, 0.27-0.99). Overall 50.7% (95% CI, 34.5%-66.9%) of MACE and 48.0% (95% CI, 29.5%-66.4%) of nonfatal MACE were attributable to the low and medium adherence to LE8 at the 5-year follow-up, respectively. Suboptimal control of blood pressure ranked as the top contributor to all types of CVD in individuals with depression. ConclusionsOptimal adherence to LE8 was associated with lower burden of CVD in those with depression. Adopting a comprehensive lifestyle intervention might help further reduce CVD burden in those with mental disorders.

Self-reported sleep duration and quality and cardiovascular diseases among middle-aged and older Chinese: A 7-year longitudinal cohort study.

Cardiovascular disease (CVD) is a leading cause of death worldwide, and several studies have attempted to identify its risk factors. This study aimed to investigate the association between sleep duration and sleep quality, and the 7-year incidence of CVD among middle-aged and older Chinese individuals. A total of 6682 participants aged 45-90 years from the China Health and Retirement Longitudinal Study database were included in this study. The authors estimated sleep duration and quality based on self-reported data of night sleep hours and disturbance symptoms, and examined the associations between them and the composite outcome of CVD using logistic regression models. A total of 1692 participants (25.32%) reported new CVD events during follow-up. Short sleep duration (<6h/night) was significantly associated with a higher risk of CVD in all three models (p<.05). However, this was not observed for long sleep duration (>8h/night). Additionally, participants with mild sleep disturbance in all three models, and severe sleep disturbance in Models 2 and 3 had a significantly higher risk of CVD (p<.05). After stratification by age and daytime napping, we still found a significant association between short sleep duration and CVD in individuals aged 45-59 years, and between sleep disturbance and CVD in non-nappers (p<.05). However, these associations were not significant in individuals aged ≥60 years or in nappers (p>.05). In conclusion, short sleep duration and sleep disturbance are both associated with an increased risk of CVD in middle-aged and older Chinese individuals.

A linear positive association between high-sensitivity C-reactive protein and the prevalence of cardiovascular disease among individuals with diabetes

AimsTo assess the correlation between high-sensitivity C-reactive protein (Hs-CRP) and the prevalence of cardiovascular disease (CVD) among individuals with diabetes.MethodsA total of 1,555 participants from the National Health and Nutrition Examination Survey were enrolled in this cross-sectional study after excluding individuals without diabetes and those who lacked data on Hs-CRP, diabetes and CVD. All participants were divided into four groups based on quartiles of Hs-CRP: Q1 (≤ 1.20 mg/L), Q2 (1.20–2.86 mg/L), Q3 (2.86–6.40 mg/L), and Q4 (> 6.40 mg/L). Logistic regression analysis, subgroup analysis and restricted cubic spline (RCS) analysis were used to evaluate the correlation between Hs-CRP and the prevalence of CVD in individuals with diabetes.ResultsIn univariate logistic regression analysis, a higher level of Hs-CRP was associated with a higher prevalence of CVD (P < 0.05). In the multivariate logistic regression analysis adjusting for confounders, the correlation between Hs-CRP and the prevalence of CVD remained significant (Q3 vs. Q1, OR: 1.505, 95% CI: 1.056–2.147, P = 0.024; Q4 vs. Q1, OR: 1.711, 95% CI: 1.171–2.499, P = 0.006; log10(Hs-CRP), OR: 1.504, 95% CI: 1.168–1.935, P = 0.002). Further subgroup analysis showed that a higher Hs-CRP was independently associated with a higher prevalence of CVD in the < 60 years, male, non-hypertension and non-hypercholesterolemia subgroups (P < 0.05). Additionally, RCS analysis revealed a linear positive correlation between Hs-CRP and CVD prevalence (P for nonlinearity = 0.244).ConclusionA higher level of Hs-CRP was closely related to a higher prevalence of CVD in people with diabetes.

Long-term sex differences in atherosclerotic cardiovascular disease in individuals with heterozygous familial hypercholesterolaemia in Spain: a study using data from SAFEHEART, a nationwide, multicentre, prospective cohort study

Sex differences in atherosclerotic cardiovascular disease (ASCVD) in familial hypercholesterolaemia have been reported but are not fully established. We aimed to assess sex differences in the risk of ASCVD and life-time burden of ASCVD in patients with heterozygous familial hypercholesterolaemia. SAFEHEART is a nationwide, multicentre, long-term prospective cohort study conducted in 25 tertiary care hospitals and one regional hospital in Spain. Participants in the SAFEHEART study aged 18 years or older with genetically confirmed familial hypercholesterolaemia were included in our analysis. Data were obtained between Jan 26, 2004, and Nov 30, 2022. ASCVD and age at onset were documented at enrolment and at follow-up. Our aim was to investigate the differences by sex in the risk and burden of ASCVD in patients with heterozygous familial hypercholesterolaemia, over the study follow-up and over the life course. The SAFEHEART study is registered with ClinicalTrials.gov, NCT02693548. Of the 5262 participants in SAFEHEART at the time of analysis, 3506 (1898 [54·1%] female and 1608 [45·9%] male participants) met the inclusion criteria and were included in the current study. Mean age was 46·1 years (SD 15·5) and median follow-up was 10·3 years (IQR 6·4-13·0). Mean on-treatment LDL-cholesterol at follow-up was 3·1 mmol/L (SD 1·4) in females and 3·0 mmol/L (1·5) in males. LDL-cholesterol reductions over time were similar in both sexes (1·39 mmol/L [95% CI 1·30-1·47] absolute reduction in females vs 1·39 mmol/L [1·29-1·48] in males; p=0·98). At enrolment, 130 (6·8%) females and 304 (18·9%) males (p<0·0001) had cardiovascular disease. During follow-up, 134 (7·1%) females and 222 (13·8%) males (p<0·0001) had incident cardiovascular events. Median age at first ASCVD event (mostly due to coronary artery disease) was 61·6 years (IQR 50·0-71·4) in females and 50·6 years (42·0-58·6) in males (p<0·0001). The adjusted hazard ratio for ASCVD in males compared with females during follow-up was 1·90 (95% CI 1·49-2·42) and for cardiovascular death was 1·74 (1·11-2·73). Major adverse cardiovascular disease event (MACE)-free survival from birth was lower in males than females (hazard ratio 3·52 [95% CI 2·98-4·16]; p<0·0001). Median MACE-free survival time was 90·1 years (95% CI 86·5-not estimable) in females and 71·0 years (69·2-74·6) in males. The age at which 25% of female participants have had a MACE event was 74·9 years, this figure was 55·5 years in male participants. Our findings suggest that the burden and risk of ASCVD are markedly lower in females than males with familial hypercholesterolaemia. The impact of sex needs to be considered to improve risk stratification and personalised management in patients with heterozygous familial hypercholesterolaemia. Fundación Hipercolesterolemia Familiar, the Instituto de Salud Carlos III, and Next Generation EU funds from the Recovery and Resilience Mechanism Program. For the Spanish translation of the abstract see Supplementary Materials section.

Strategies for Cardiovascular Disease Prevention in Type 1 Diabetes: A Comprehensive Review.

Cardiovascular disease (CVD) is a leading cause of morbidity and mortality among individuals with type 1 diabetes (T1D), necessitating effective prevention strategies. This comprehensive review consolidates current knowledge and evidence on preventing CVD in T1D patients. It begins by exploring the pathophysiological mechanisms that link T1D to an increased risk of CVD, highlighting factors such as chronic hyperglycemia, hypertension, dyslipidemia, and inflammation. The review also examines the epidemiology and specific risk factors for CVD in this population, emphasizing the need for rigorous risk assessment and screening. Lifestyle modifications, including dietary interventions, regular physical activity, and smoking cessation, are evaluated for their effectiveness in reducing CVD risk. Additionally, the review discusses pharmacological interventions, such as insulin therapy for glycemic control, antihypertensive medications, lipid-lowering agents, and antiplatelet therapy, underscoring their critical role in CVD prevention. Emerging therapies and future research directions are explored, focusing on novel pharmacological agents, advances in insulin delivery systems, and personalized medicine approaches. The importance of integrated care models involving multidisciplinary teams and the use of technology is highlighted as essential for comprehensive management. Challenges and barriers to implementing these strategies, including healthcare system limitations, patient adherence, and socioeconomic factors, are also addressed. This review provides a detailed synthesis of current strategies and future directions for preventing CVD in individuals with T1D, serving as a valuable resource for clinicians, researchers, and policymakers dedicated to improving cardiovascular outcomes in this high-risk population.

Mechanisms of action and therapeutic applications of GLP-1 and dual GIP/GLP-1 receptor agonists.

Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are two incretins that bind to their respective receptors and activate the downstream signaling in various tissues and organs. Both GIP and GLP-1 play roles in regulating food intake by stimulating neurons in the brain's satiety center. They also stimulate insulin secretion in pancreatic β-cells, but their effects on glucagon production in pancreatic α-cells differ, with GIP having a glucagonotropic effect during hypoglycemia and GLP-1 exhibiting glucagonostatic effect during hyperglycemia. Additionally, GIP directly stimulates lipogenesis, while GLP-1 indirectly promotes lipolysis, collectively maintaining healthy adipocytes, reducing ectopic fat distribution, and increasing the production and secretion of adiponectin from adipocytes. Together, these two incretins contribute to metabolic homeostasis, preventing both hyperglycemia and hypoglycemia, mitigating dyslipidemia, and reducing the risk of cardiovascular diseases in individuals with type 2 diabetes and obesity. Several GLP-1 and dual GIP/GLP-1 receptor agonists have been developed to harness these pharmacological effects in the treatment of type 2 diabetes, with some demonstrating robust effectiveness in weight management and prevention of cardiovascular diseases. Elucidating the underlying cellular and molecular mechanisms could potentially usher in the development of new generations of incretin mimetics with enhanced efficacy and fewer adverse effects. The treatment guidelines are evolving based on clinical trial outcomes, shaping the management of metabolic and cardiovascular diseases.

Adverse childhood experience, adopting a healthy lifestyle in adulthood, and risk of cardiovascular diseases

BackgroundBoth adverse childhood experiences (ACEs) and lifestyle factors have been associated with risk of cardiovascular diseases (CVDs) in later life, but whether and to what extent adherence to a healthy lifestyle in adulthood can offset the increased cardiovascular risk associated with ACEs is unclear. We aimed to determine whether and to what extent adopting to a healthy lifestyle in adulthood can offset the risk of CVDs in individuals according to their ACEs. MethodsA prospective cohort study included 143,869 participants aged 38–72 years, free of CVDs at baseline from the UK Biobank. The history of ACEs was assessed using the Childhood Trauma Screener. Participants were divided into three risk groups based on ACEs: low (no ACEs), intermediate (one or two ACEs), and high (three or more ACEs). A healthy lifestyle score in adulthood was constructed as the sum of four modifiable lifestyle factors (no smoking, adequate physical activity, healthy diet, no obesity), and participants were then categorized into three groups based on this score (unfavorable [0–1 point], intermediate [2–3 points], favorable [4 points]). Cox proportional hazard models were conducted to investigate the association between ACEs, healthy lifestyle, and incident CVDs. ResultsDuring a median follow-up of 12.49 years, 13,373 incident cases of overall CVDs were identified. This included 7521 cases of coronary heart disease (CHD), 6175 cases of atrial fibrillation (AF) and 1813 cases of stroke. Individuals with high ACEs had a greater risk of incident overall CVDs (hazard ratio [HR] = 1.39, [95%CI = 1.29 to 1.50]), CHD (1.50 [1.36 to 1.65]) and AF (1.18 [1.05 to 1.33]) compared to those with low ACEs. The risk of CVDs decreased moving from unfavorable to favorable lifestyle categories (P for trend<0.001), with the lowest risk observed among individuals with a favorable lifestyle (0.70 [0.66 to 0.74] for overall CVDs, 0.69 [0.64 to 0.75] for CHD, and 0.71 [0.65 to 0.78] for AF). Participants with high ACEs and a favorable lifestyle had a 39 %, 40 % and 47 % lower risk of developing overall CVDs (0.61 [0.48 to 0.76]), CHD (0.60 [0.44 to 0.81], and AF (0.53 [0.36 to 0.77]) than those with high ACEs and an unfavorable lifestyle. ConclusionsHaving a healthy lifestyle in adulthood could substantially attenuate the increased risk of overall CVDs, CHD, and AF conferred by ACEs.