Cardiovascular Disease Risk Factors Research Articles

Interaction between non-alcoholic fatty liver disease and obesity on the risk of developing cardiovascular diseases

BackgroundsThis investigation seeks to explore the correlation between nonalcoholic fatty liver disease (NAFLD) and cardiovascular diseases (CVDs), and to to provide evidence for the prevention and treatment of CVDs.MethodsThis study utilized data from the Jinchang cohort platform, including 19,399 participants without pre-existing major CVDs. Based on the general population and gender stratification, Cox models were used to analyze the risk of NAFLD for CVDs. The combined effect of NAFLD and different obesity indicators on CVDs was analyzed by additive and multiplicative interaction models and subgroups.ResultsThere were 3129 NAFLD patients out of 19399 subjects, and 723 (23.11%) of them had the CVD. After adjusting for multiple confounding factors, the Cox model revealed a 1.17-fold increase in the risk of CVDs among patients with NAFLD compared to those without NAFLD. Moreover, there was no notable disparity in CVDs risk among most NAFLD patients at the same level of obesity. The results indicated no additive interaction between NAFLD and obesity concerning CVDs risk, but rather a positive multiplicative interaction. Using the normal population as a reference, it was found that people with both obesity and NAFLD significantly increased the risk of developing CVDs, with HRs and 95% CIs of 1.790 (1.508, 2.126), 1.356 (1.213, 1.517), and 1.807 (1.503, 2.174), respectively, for BMI, WC, and the combination of BMI and WC.ConclusionsNAFLD and obesity are independent risk factors for CVDs. The synergy of obesity and NAFLD implies that NAFLD patients should control weight gain. Larger BMI and WC values may increase the CVDs risk for NAFLD patients, especially women.

Impact of provision of abdominal aortic calcification results on fruit and vegetable intake: 12-week randomized phase 2 controlled trial

Provision of non-invasive vascular imaging results to individuals has been shown to improve cardiovascular disease risk factor control: its impact on diet remains uncertain. In this two-arm, single-blind, parallel, 12-week randomized controlled trial, 240 participants, 57.5% females aged 60–80 y had abdominal aortic calcification and clinical assessments performed at a hospital clinic. Participants were randomized 1:1 to receive (intervention n = 121) or not (control n = 119) their calcification results. Both groups received educational resources on cardiovascular disease risk control and were unblinded to the intervention. Outcome measures were performed at baseline and 12 weeks. The primary outcomes of the study were changes in fruit and vegetable intake measures over 12 weeks assessed using plasma carotenoid concentrations (biomarkers of FV intake) and a food frequency questionnaire. Secondary outcomes included 12-week changes in other aspects of the diet, physical activity, body weight, blood pressure, heart rate, lipid profile, glucose concentrations, estimated cardiovascular disease risk score, and medication use. Between-group differences were tested using linear mixed-effects regression. There were no between-group differences in the primary outcomes at 12 weeks: plasma carotenoids (mean difference +0.03 µg/mL [95%CI −0.06, 0.13]) and fruit and vegetable intakes (+18 g/d [−37, 72]). However, the provision of calcification results led to between-group differences in serum total (−0.22 mmol/L [−0.41, −0.04]) and non-HDL (−0.19 mmol/L [−0.35, −0.03]) cholesterol, and estimated cardiovascular disease risk score (−0.24% [−0.47, −0.02]). No between-group differences were seen for other secondary outcomes. In this work, providing vascular imaging results did not improve diet but did improve some cardiovascular disease risk factors (Australian and New Zealand Clinical Trials Registry ACTRN12618001087246).

Aging and rejuvenation of engineered cardiovascular tissues: from research to clinical application

Aging is a key contributor to the pathogenesis of cardiovascular diseases (CVDs). However, current methods and models of CVD do not include the factor of aging due to the use of premature cardiomyocytes. There is an urgent need for an engineered cardiovascular tissue (ECT) model that includes aging as the greatest CVD risk factor to facilitate drug development for aged CVD patients. Cell therapy, which transplants pluripotent stem cell-derived cardiomyocytes in patients, was proved to be effective for cardiac repair, while the cell retention rate is limited. Alternatively, implantation of ECT could enable long-term retention of cells after translation and may result in rejuvenation in aged hearts. This review summarizes the key features of aging and the influencing factors in engineered cardiovascular tissues. The applications and challenges of engineered myocardium designed for clinical use are also discussed.

Causality Between ADHD, ASD, and CVDs: A Two-Step, Two-Sample Mendelian Randomization Investigation.

While observational studies have established a connection between attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and heightened risk for cardiovascular diseases (CVD), the causal relationships are not well-defined. This study is designed to examine the causality between ASD, ADHD, and CVD risk as well as investigate the mediating factors through which ADHD and ASD influence CVD. Leveraging two-sample Mendelian randomization (MR) approaches and large scale GWAS summary stats, we examined underlying causal links between ASD and ADHD and the risk of CVDs. The analysis indicated that ADHD was related to an increased likelihood of developing coronary heart disease (OR [95% CI] 1.12 [1.03, 1.21], p = .008), heart failure (OR [95% CI] 1.14 [1.07, 1.22], p = 1.45 × 10-4), and large-artery stroke (OR [95% CI] 1.35 [1.09, 1.66], p = .005). In parallel, ASD showed a correlation with a greater atrial fibrillation risk (OR [95% CI] 1.09 [1.03, 1.16], p = .005] and heart failure (OR [95% CI] 1.11 [1.04, 1.19], p = .004). Additionally, we explored the mediating role of CVD risk factors through two-step MR and multivariable MR, highlighting the possible role of smoking, prescription opioid use, triglycerides, education, income, Townsend deprivation index, and obesity in the causal association of ADHD, ASD, on CVDs. This MR study highlights the necessity for rigorous cardiovascular surveillance and interventions to decrease adverse cardiovascular events in people with ADHD or ASD by preventing identified mediating risk factors.

Concept, study design, and baseline nighttime blood pressure control status of the WISDOM-Night Study using a wrist-type oscillometric home blood pressure monitoring device.

There is growing evidence that nocturnal hypertension is an independent risk factor for cardiovascular diseases, including heart failure. However, brachial blood pressure (BP) measurements during sleep might themselves disturb sleep quality. We initiated a nationwide, multicenter observational prospective study using a wrist-type oscillometric nighttime BP monitoring device with new algorithms to measure supine BP accurately without sleep disturbance. This study, named the Wrist ICT-based Sleep and Circadian Blood Pressure Monitoring Program-Night BP Study (WISDOM-Night Study), was designed to clarify the impact of wrist-measured daily nighttime BPs on cardiovascular prognosis (stroke, coronary artery disease, heart failure, etc.) using 7 days of BP measurements at 2:00 a.m., 3:00 a.m., 4:00 a.m., and 4 h after bedtime. A total of 2751 patients with one or more cardiovascular risk factors were recruited between March 2021 and March 2024 and are currently being followed up for 7 years. Additionally, 1416 of the WISDOM-Night Study-enrolled patients who also agreed to participate in the WISDOM-Hypertension-Mediated Organ Damage (HMOD) Study underwent echocardiography to evaluate the association between wrist-measured BP and left ventricular structure. Data from this WISDOM-Night Study should provide the prospective association between nighttime BP and cardiovascular disease and reveal the indexes of nighttime BP with clinical pathological relevance. This first report of the WISDOM-Night Study describes the study design, baseline characteristics, and BP control status.

Deep learning assists early-detection of hypertension-mediated heart change on ECG signals.

Arterial hypertension is a major risk factor for cardiovascular diseases. While cardiac ultrasound is a typical way to diagnose hypertension-mediated heart change, it often fails to detect early subtle structural changes. Electrocardiogram(ECG) represents electrical activity of heart muscle, affected by the changes in heart's structure. It is crucial to explore whether ECG can capture slight signals of hypertension-mediated heart change. However, reading ECG records is complex and some signals are too subtle to be captured by cardiologist's visual inspection. In this study, we designed a deep learning model to predict hypertension on ECG signals and then to identify hypertension-associated ECG segments. From The First Affiliated Hospital of Xiamen University, we collected 210,120 10-s 12-lead ECGs using the FX-8322 manufactured by FUKUDA and 812 ECGs using the RAGE-12 manufactured by NALONG. We proposed a deep learning framework, including MML-Net, a multi-branch, multi-scale LSTM neural network to evaluate the potential of ECG signals to detect hypertension, and ECG-XAI, an ECG-oriented wave-alignment AI explanation pipeline to identify hypertension-associated ECG segments. MML-Net achieved an 82% recall and an 87% precision in the testing, and an 80% recall and an 82% precision in the independent testing. In contrast, experienced clinical cardiologists typically attain recall rates ranging from 30 to 50% by visual inspection. The experiments demonstrate that ECG signals are sensitive to slight changes in heart structure caused by hypertension. ECG-XAI detects that R-wave and P-wave are the hypertension-associated ECG segments. The proposed framework has the potential to facilitate early diagnosis of heart change.

Predictors of trastuzumab-induced cardiotoxicity among racially and ethnically diverse patients with HER2-positive breast cancer

BackgroundWhile trastuzumab has been shown to improve disease-free and overall survival in patients with HER2-positive breast cancer, it may also cause trastuzumab-induced cardiotoxicity (TIC). Although racial and ethnic minorities are at higher risk for cardiovascular disease (CVD) compared to non-Hispanic Whites (NHW), limited data exists on TIC incidence in diverse multi-ethnic populations. Our objective was to assess racial and ethnic differences in TIC and left ventricular ejection fraction (LVEF) recovery among patients with HER2-positive breast cancer.MethodsWe conducted a retrospective cohort study including patients diagnosed with stage I-III HER2-positive breast cancer between 2007 and 2022 who had received adjuvant trastuzumab. We analyzed associations between sociodemographic factors, tumor characteristics, treatment regimens, and CVD risk factors with the primary outcomes of TIC and LVEF recovery, using multivariable logistic regression models. TIC was defined as > 10% decrease in LVEF to an overall LVEF < 50%; LVEF recovery as a return to a LVEF > 50%.ResultsAmong 496 evaluable patients, median age was 53 years (IQR: 45.0–62.0) with 36.6% NHW, 15.8% non-Hispanic Black (NHB), 27.8% Hispanic, and 19.8% Other. Fifty-three (10.6%) patients developed TIC, half of whom experienced LVEF recovery. Compared to NHW, NHB had a higher rate of TIC (9.3% vs. 17.7%, respectively) and lower rate of LVEF recovery (70.6% vs. 21.4%, respectively), however, race/ethnicity was not a significant predictor of TIC after adjusting for confounders. Increasing age, lower baseline LVEF, anthracycline use, and presence of hypertension or coronary artery disease were significantly associated with TIC in multivariable analysis.ConclusionsTIC was more common among NHB compared to NHW, however, Black race was not consistently associated with TIC after adjustment for CVD risk factors. This suggests that CVD comorbidities (e.g., hypertension) that more frequently affect racial and ethnic minorities and are modifiable may explain differences in TIC incidence and recovery.

Thrombotic, Cardiovascular, and Microvascular Complications of Myeloproliferative Neoplasms and Clonal Hematopoiesis (CHIP): A Narrative Review.

The most common causes of morbidity and mortality in the myeloproliferative neoplasms (MPNs), with the exception of myelofibrosis, are venous and arterial thrombosis, as well as more recently discovered cardiovascular disease (CVD). Clonal hematopoiesis of indeterminate potential (CHIP) is the subclinical finding in an individual of somatic mutations that are also found in clinically overt MPNs and other myeloid malignancies. The prevalence of "silent" CHIP increases with age. CHIP can transform into a clinically overt MPN at an estimated rate of 0.5 to 1% per year. It is likely, therefore, but not proven, that many, if not all, MPN patients had antecedent CHIP, possibly for many years. Moreover, both individuals with asymptomatic CHIP, as well as clinically diagnosed patients with MPN, can develop thrombotic complications. An unexpected and remarkable discovery during the last few years is that even CHIP (as well as MPNs) are significant, independent risk factors for CVD. This review discusses up-to-date information on the types of thrombotic and cardiovascular complications that are found in CHIP and MPN patients. A systemic inflammatory state (that is often subclinical) is most likely to be a major mediator of adverse reciprocal bone marrow-cardiovascular interplay that may fuel the development of progression of MPNs, including its thrombotic and vascular complications, as well as the worsening of cardiovascular disease, possibly in a "vicious cycle". Translating this to clinical practice for hematologists and oncologists who treat MPN patients, attention should now be paid to ensuring that cardiovascular risk factors are controlled and minimized, either by the patient's cardiologist or primary care physician or by the hematologist/oncologist herself or himself. This review is intended to cover the clinical aspects of thrombosis and cardiovascular complications in the MPN, accompanied by pathobiological comments.

Myeloid-Specific JAK2 Contributes to Inflammation and Salt Sensitivity of Blood Pressure.

Salt sensitivity of blood pressure (SSBP), characterized by acute changes in blood pressure with changes in dietary sodium intake, is an independent risk factor for cardiovascular disease and mortality in people with and without hypertension. We previously found that elevated sodium concentration activates antigen-presenting cells (APCs), resulting in high blood pressure, but the mechanisms are unknown. Here, we hypothesized that APC-specific JAK2 (Janus kinase 2) through STAT3 (signal transducer and activator of transcription 3) and SMAD3 (small mothers against decapentaplegic homolog 3) contributes to SSBP. We performed bulk or single-cell transcriptomic analyses following in vitro monocytes exposed to high salt and in vivo high sodium treatment in humans using a rigorous salt-loading/depletion protocol to phenotype SSBP. We also used a myeloid cell-specific CD11c+ JAK2 knockout mouse model and measured blood pressure with radiotelemetry after N-omega-nitro-L-arginine-methyl ester and a high salt diet treatment. We used flow cytometry for immunophenotyping and measuring cytokine levels. Fluorescence in situ hybridization and immunohistochemistry were performed to spatially visualize the kidney's immune cells and cytokine levels. Echocardiography was performed to assess cardiac function. We found that high salt treatment upregulates gene expression of the JAK/STAT/SMAD pathway while downregulating inhibitors of this pathway, such as suppression of cytokine signaling and cytokine-inducible SH2, in human monocytes. Expression of the JAK2 pathway genes mirrored changes in blood pressure after salt loading and depletion in salt-sensitive but not salt-resistant humans. Ablation of JAK2, specifically in CD11c+ APCs, attenuated salt-induced hypertension in mice with SSBP. Mechanistically, we found that SMAD3 acted downstream of JAK2 and STAT3, leading to increased production of highly reactive isolevuglandins and proinflammatory cytokine IL (interleukin)-6 in renal APCs, which activate T cells and increase production of IL-17A, IL-6, and TNF-α (tumor necrosis factor-alpha). Our findings reveal the APC JAK2 signaling pathway as a potential target for the diagnosis and treatment of SSBP in humans.

Association of COVID-19 risk factors with systemic fungal infections in hospitalized patients.

A new category of systemic co-infections that emerged with the COVID-19 pandemic is known as COVID-19-associated (CA) fungal infections, which include pulmonary aspergillosis (CAPA), candidiasis (CAC), and mucormycosis (CAM). We aimed to study the association between patient characteristics of hospitalized COVID-19 patients, COVID-19 comorbidities, and COVID-19 therapies with secondary non-superficial fungal infections. We performed descriptive and regression analyses of data from 4,999 hospitalized COVID-19 patients from the University of Kentucky Healthcare (UKHC) system. The patients with secondary systemic fungal infections had a 6-fold higher risk of death than those without such infections. Generally, the risk factors for severe COVID-19 (age, obesity, cardiovascular disease, diabetes, and lack of COVID-19 vaccination) were strong predictors of a secondary fungal infection. However, several characteristics had much higher risks, suggesting that a causative link may be at play: ICU admission, mechanical ventilation, length of hospital stay, and steroid use. In sum, this study found that the known risk factors for severe COVID-19 disease, age, diabetes, cardiovascular disease, obesity, ventilation, and high steroid doses were all predictors of a secondary fungal infection. Steroid therapy may need to be modified to account for a risk or a presence of a fungal infection in vulnerable patients.

Key Risk-Factors Contributing to Cardiovascular Disease: Lifestyle Modifications to Improve Cardiovascular Health

Cardiovascular disease is a preventable public health issue. The aim of this review is to identify modifiable risk-factors for cardiovascular disease and recommend lifestyle modification to prevent cardiovascular disease. PubMed, ScienceDirect, SAGE, Google Scholar, World Health Organisation websites, as well as public and community health textbooks, were hand searched and academic resources which are relevant for this review were selected for inclusion. Cardiovascular disease is leading cause of deaths in all continents of the world. While deaths from cardiovascular disease is increasing in Africa and Asia, it is decreasing in Australia and fluctuating in the USA. Premature deaths from cardiovascular disease are preeminent across middle income countries in Europe compared with high income countries. Cardiovascular disease is higher in rural areas of South America compared with urban areas. Trends in lifestyle patterns, including physical inactivity, smoking behaviour, and diets contribute to cardiovascular disease-prone conditions. Prevention includes health promotion activities that facilitate healthy living across life course and limit the initial onset of cardiovascular disease. Investment in prevention is the critical sustainable solution for the cardiovascular disease epidemic. Adopting WHO existing policies within individual countries in Africa, Asia, and middle-income countries in Europe, and ensuring robust implementation of such policies across life course and from different layers of sectors such as education and workplaces would have wider impacts in reducing risk and cardiovascular disease burden in the respective continents. Government of countries with worsening cardiovascular events should also increase health financing and focus on strengthening primary health care services for prevention and treatment of cardiovascular disease.

Serum uric acid: an independent risk factor for cardiovascular disease in Pakistani Punjabi patients

BackgroundIt is well-known that serum uric acid (SUA) can increase the risk of hypertension, diabetes, obesity and dyslipidemia. However, its independent association with the risk of cardiovascular diseases (CVD) is controversial particularly in different populations. Hence, this study was aimed to assess an independent association of SUA with CVD risk in a Punjabi Pakistani cohort.MethodsThis is a retrospective observational study in which 502 human subjects having CVD, hypertension and/or diabetes were grouped based on SUA levels as normouricemia (n = 266) and hyperuricemia (n = 236). Role of SUA was assessed in increasing the risk of CVD independent of other key confounding factors (i.e. age, gender, dyslipidemia, hypertension, diabetes, dietary and life-style habits). All clinical and biochemical data were analyzed in SPSS (ver. 20).ResultsSubjects aged 55 ± 13 years were of both genders (males: 52%). SUA levels were significantly different among clinical subtypes of CVD [i.e. acute coronary syndrome (ACS), myocardial infarction (MI) and heart failure (HF)]. Spearman correlation showed a significantly positive association between CVD and SUA (rho = 0.149, p < 0.001). Multivariate logistic regression of SUA quartiles showed that hyperuricemia is associated with CVD [3rd quartile: OR: 1.78 (CI: 1.28–2.48), p = 0.001 and 4th quartile: OR: 2.37 (CI: 1.72–3.27), p < 0.001]. Moreover, this association remained significant even after adjusting for confounding factors.ConclusionThis study showed that SUA is positively associated with CVD, thus it can act as an independent risk factor for CVD.

The Influence of Physical Activity and Diet Mobile Apps on Cardiovascular Disease Risk Factors: Meta-Review.

The literature on whether physical activity (PA) and PA and diet (PA+Diet) mobile apps improve cardiovascular disease (CVD) risk factors is promising. The aim of this meta-review is to provide an evidence synthesis of systematic reviews and meta-analyses examining the influence of PA and PA+Diet apps on the major CVD risk factors. We systematically searched 5 databases until January 12, 2022. Included systematic reviews and meta-analyses (1) reported the CVD risk factor outcomes of BMI, waist circumference, body weight, blood pressure (BP), hemoglobin A1c (HbA1c), fasting blood glucose, blood lipids, or PA; (2) enrolled healthy participants ≥18 years who may or may not have the metabolic syndrome, diabetes mellitus, or preexisting CVD risk factors; (3) reviewed PA or PA+Diet app interventions integrating behavioral change techniques (BCT) to deliver their information; and (4) had a nonapp control. In total, 17 reviews (9 systematic reviews and 8 meta-analyses) published between 2012 and 2021 qualified. Participants were middle-aged, mostly women ranging in number from 10 to 62,219. Interventions lasted from 1 to 24 months, with the most common behavioral strategies being personalized feedback (n=8), self-monitoring (n=7), and goal setting (n=5). Of the PA app systematic reviews (N=4), the following CVD risk factors improved: body weight and BMI (n=2, 50%), BP (n=1, 25%), HbA1c (n=1, 25%), and blood lipids (n=1, 25%) decreased, while PA (n=4, 100%) increased. Of the PA+Diet app systematic reviews (N=5), the following CVD risk factors improved: body weight and BMI (n=3, 60%), BP (n=1, 20%), and HbA1c (n=3, 60%) decreased, while PA (n=3, 60%) increased. Of the PA app meta-analyses (N=1), the following CVD risk factors improved: body weight decreased (-0.73 kg, 95% CI -1.45 to -0.01; P=.05) and PA increased by 25 minutes/week (95% CI 0.58-1.68; P<.001), while BMI (-0.09 kg/m2, 95% CI -0.29 to 0.10; P=.35) and waist circumference (-1.92 cm, 95% CI -3.94 to 0.09; P=.06) tended to decrease. Of the PA+Diet app meta-analyses (n=4), the following CVD risk factors improved: body weight (n=4, 100%; from -1.79 kg 95% CI -3.17 to -0.41; P=.01 to -2.80 kg 95% CI -4.54 to -1.06, P=.002), BMI (n=1, 25%; -0.64 kg/m2, 95% CI -1.09 to -0.18; P=.01), waist circumference (n=1, 25%; -2.46 cm, 95% CI -4.56 to -0.36; P=.02), systolic/diastolic BP (n=1, 25%; -4.22/-2.87 mm Hg, 95% CI -6.54 to -1.91/ -4.44 to -1.29; P<.01), and HbA1c (n=1, 25%; -0.43%, 95% CI -0.68 to -0.19; P<.001) decreased. PA and PA+Diet apps appear to be most consistent in improving PA and anthropometric measures with favorable but less consistent effects on other CVD risk factors. Future studies are needed that directly compare and better quantify the effects of PA and PA+Diet apps on CVD risk factors. PROSPERO CRD42023392359; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=392359.

Effectiveness of Lifestyle Modification to Control the Blood Pressure among Hypertensive Patient of Morang District

Background: Hypertension is a strong, independent and etiologically relevant risk factor for cardiovascular diseases and therefore, the leading cause of preventable death worldwide. The purpose of this study was to determine the effect of multifaceted lifestyle modification intervention on blood pressure among hypertensive patients. Methods: A quasi-experimental study was conducted among 67 participants in the medical OPD through convenience sampling method. The studied multifaceted intervention includes motivational interviews and 60 minutes 3 training session on dietary patterns and exercise and 4 phone call follow-ups. BP was measured before and after intervention and compared between them. Results: The differences between the mean changes in before and after intervention are systolic (-7.65 ± 4.45), and diastolic (5.74± 4.45) Conclusion: The studied multifaceted lifestyle intervention promoted and reduced systolic and diastolic BP. Thus, the use of this method as a supplementary treatment is recommended during visit to medical OPD

Sex-differential effect of waist circumference on new-onset cerebral infarction: a nationwide cohort study.

Excessive abdominal adiposity represents a cardiovascular disease risk factor. Waist circumference (WC) reflects abdominal adiposity and is known as an easy-to-measure indicator of obesity. This study aimed to evaluate the relationship between WC level and the development of cerebral infarction in Koreans. 209,442 Koreans were included among the general population registered in the National Health Information Database. Depending on the degree of WC, the possibility of cerebral infarction was tracked for 4.37 person-years. Identification of patients with cerebral infarction was confirmed through the diagnostic code ICD I63 of inpatient or outpatient. Participants' data were analyzed by sex. The hazard ratios (HRs) and confidence interval (CI) for cerebral infarction were calculated using the Cox proportional hazards model. Between 2009 and 2013, 2,403 cases (1.15%) of cerebral infarction occurred during the follow-up period of 915,223.6 person-years. The HRs (95% CI) for incident cerebral infarction in men was adjusted for multiple covariates, and comparison of WC levels second, third, and fourth quartile with the first quartile showed 1.10 (0.94-1.28), 1.11 (0.95-1.30), and 1.24 (1.07-1.45), respectively (P for trend 0.045). This association was not significant in women (P for trend 0.619). The severity of WC levels in men is significantly associated with the risk of developing cerebral infarction in Koreans. This finding indicates that other measurements for excessive adipose visceral tissue, except abdominal circumference, need to be taken into account to identify the risk of cerebral infarction in women.

The role of metabolic disorders in the development of atherosclerosis.

Atherosclerosis is a major risk factor for cardiovascular disease (CVD), which is the leading cause of death worldwide. Atherosclerosis is initiated by endothelial activation, followed by a cascade of events (accumulation of lipids, fibrous elements, and calcification) triggering vasoconstriction and activation of inflammatory pathways. This review focuses on the various stages in the development of atherosclerosis, ranging from endothelial dysfunction to plaque rupture. In addition, disorders of lipid, glucose and amino acid metabolism in atherosclerosis are considered here. The key pathological stages of metabolism disruption and their role in atherosclerosis are considered in detail which may be helpful for the more better understanding of atherosclerosis pathogenesis. Finally, some therapeutic approaches aimed at modulating lipid metabolism will also be presented which show the therapeutic targets (enzymes and transport proteins) which modulation can prevent further deterioration of patients symptoms.

The Effect of Exercise on Immune Response in Population with Increased Risk Factors for Cardiovascular Disease: A Systematic Review.

This systematic review aimed to provide information on existing interventional studies that evaluate the efficacy of exercise in populations with increased cardiovascular disease (CVD) risk factors through immune functional perspectives. A literature search was conducted in four databases: PubMed, Scopus, Taylor & Francis and ScienceDirect from January 2012 to February 2023. The articles were screened and evaluated for quality before data were extracted. The review protocol was registered at PROSPERO (CRD42022321704). In total, 18 studies were included for quality appraisal and synthesised evidence indicated that exercise contributes to enhancing the functioning of both innate and adaptive immune responses, potentially serving as an anti-immunosenescent response to exercise in individuals with elevated CVD risk factors. Furthermore, the review emphasised that exercise, irrespective of its type, intensity or mode, was well tolerated by individuals at increased risk for CVD and may have significant implications in generating anti-inflammatory effects.

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.

Prognostic factors for premature cardiovascular disease mortality in Malaysia: a modelling approach using semi-parametric and parametric survival analysis with national health and morbidity survey linked mortality data.

Cardiovascular disease (CVD) is the leading cause of premature mortality worldwide. Despite existing research on CVD risk factors, the study of premature CVD mortality in Malaysia remains limited. This study employs survival analysis to model modifiable risk factors associated with premature CVD mortality among Malaysian adults. We utilised data from Malaysia's National Health and Morbidity Survey (NHMS) conducted in 2006, 2011, and 2015, linked with mortality records. The cohort comprised individuals aged 18 to 70 during the NHMS interview. Follow-up extended to 2021, focusing on CVD-related premature mortality between ages 30 and 70. We employed six survival models: a semi-parametric Cox proportional hazard (PH) and five parametric survival models, which were Exponential, Weibull, Gompertz, log-normal and log-logistic distributions using R software. The age standardized incidence rate (ASIR) of premature CVD mortality was calculated per 1000 person-years. Among 63,722 participants, 886 (1.4%) experienced premature CVD mortality, with an ASIR of 1.80 per 1000 person-years. The best-fit models (based on AIC value) were the stratified Cox model by age (semi-parametric) and the log-normal accelerated failure time (AFT) model (parametric). Males had higher risk (Hazard Ratio, HR = 2.68) and experienced 49% shorter survival time (Event Time Ratio, ETR = 0.51) compared to females. Compared to Chinese ethnicity, Indians, Malays, and other Bumiputera had higher HR and lower survival times. Rural residents and those with lower education also faced increased HRs and reduced survival times. Diabetes (diagnosed: HR = 3.26, ETR = 0.37; undiagnosed: HR = 1.63, ETR = 0.63), hypertension (diagnosed: HR = 1.84, ETR = 0.53; undiagnosed: HR = 1.46, ETR = 0.68), and undiagnosed hypercholesterolemia (HR = 1.31, ETR = 0.80) increased risk and decreased survival times. Additionally, current smoking and abdominal obesity elevated risk (HR = 1.38, 1.60) and shortened survival (ETR = 0.81, 0.71). The semi-parametric and parametric survival models both highlight the considerable impact of socioeconomic status and modifiable risk factors on premature CVD mortality, underscoring the imperative for targeted interventions to effectively mitigate these effects.

Inflammatory Trajectory of Type 2 Diabetes: Novel Opportunities for Early and Late Treatment.

Low-grade inflammation (LGI) represents a key driver of type 2 diabetes (T2D) and its associated cardiovascular diseases (CVDs). Indeed, inflammatory markers such as hs-CRP and IL-6 predict the development of T2D and its complications, suggesting that LGI already increases before T2D diagnosis and remains elevated even after treatment. Overnutrition, unhealthy diets, physical inactivity, obesity, and aging are all recognized triggers of LGI, promoting insulin resistance and sustaining the pathogenesis of T2D. Once developed, and even before frank appearance, people with T2D undergo a pathological metabolic remodeling, with an alteration of multiple CVD risk factors, i.e., glycemia, lipids, blood pressure, and renal function. In turn, such variables foster a range of inflammatory pathways and mechanisms, e.g., immune cell stimulation, the accrual of senescent cells, long-lasting epigenetic changes, and trained immunity, which are held to chronically fuel LGI at the systemic and tissue levels. Targeting of CVD risk factors partially ameliorates LGI. However, some long-lasting inflammatory pathways are unaffected by common therapies, and LGI burden is still increased in many T2D patients, a phenomenon possibly underlying the residual inflammatory risk (i.e., having hs-CRP > 2 mg/dL despite optimal LDL cholesterol control). On the other hand, selected disease-modifying drugs, e.g., GLP-1RA, seem to also act on the pathogenesis of T2D, curbing the inflammatory trajectory of the disease and possibly preventing it if introduced early. In addition, selected trials demonstrated the potential of canonical anti-inflammatory therapies in reducing the rate of CVDs in patients with this condition or at high risk for it, many of whom had T2D. Since colchicine, an inhibitor of immune cell activation, is now approved for the prevention of CVDs, it might be worth exploring a possible therapeutic paradigm to identify subjects with T2D and an increased LGI burden to treat them with this drug. Upcoming studies will reveal whether disease-modifying drugs reverse early T2D by suppressing sources of LGI and whether colchicine has a broad benefit in people with this condition.