Coronary artery diseases (CAD) and heart failure have high mortality rate in the world, although much progress has been made in this field in last two decades. There is still a clinical need for a novel diagnostic approach and a therapeutic strategy to decrease the incidence of CAD. MicroRNAs (miRNAs) are highly conserved noncoding small RNA molecules that regulate a large fraction of the genome by binding to complementary messenger RNA sequences, resulting in posttranscriptional gene silencing. Recent studies have shown that specific miRNAs are involved in whole stage of atherosclerosis, from endothelium dysfunction to plaque rupture. These findings suggest that miRNAs are potential biomarkers in early diagnosis and therapeutic targets in CAD. In the present review, we highlight the role of miRNAs in every stage of atherosclerosis, and discuss the prospects of miRNAs in the near future.

Activated platelets play a critical role in the acute complications of atherosclerosis that cause life-threatening ischemic events at late stages of the disease. The miRNAs are a novel class of small, non-coding RNAs that play a significant role in both inflammatory and cardiovascular diseases. The miRNAs are known to be present in platelets and exert important regulatory functions. Here we systematically examine the genes that are regulated by platelet miRNAs (miRNA-223,miRNA-126,miRNA-21, miRNA-24 and miRNA-197) and the association with cardiovascular disease risks. Platelet-secreted miRNAs could be novel biomarkers associated with cardiovascular diseases.

In 2010 the American Heart Association proposed a definition of ideal health behaviors and health factors to measure cardiovascular health, from which Huffman et al. created the Cardiovascular Health Score (CVH score) to estimate these metrics on an individual level. We performed a prospective cohort study among employees of the Kailuan Group Corporation, who underwent a physical examination in 2006-2007 to investigate the relationship between the CVH score and the risk of cardiovascular disease (CVD). A total of 91,598 individuals free of stroke and myocardial infarction at baseline were included in the final analysis. We calculated baseline CVH score for each metric (poor=0, intermediate=1, ideal=2 points; range=0-14 points for all seven metrics) and categorized them into three groups: inadequate (0-4 points), average (5-9 points), and optimum (10-14 points). Incidence of total number of CVD events, myocardial infarction, and stroke was analyzed among these three groups and each incremental point on the CVH score. During an average 6.81 years of follow-up, there were 3276 CVD events, 2579 strokes and 747 myocardial infarction occurred. After adjusting for several confounding factors, each better health category of the CVH score was associated with reduced odds of 47% for all CVD events, and each point higher on the CVH score was associated with reduced odds of 18%. Similar trends were detected in the risks for myocardial infarction and stroke. A higher CVH score is therefore a protective factor for CVD, myocardial infarction, and stroke.

Infection by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is responsible for the second pandemic of the XXI century after influenza A in 2009. As of mid-June 2020, more than 4,40,000 fatal cases of SARS-CoV-2-related disease (COVID-19) have occurred worldwide. Besides its prominent expression at the level of the respiratory apparatus, COVID-19 is also characterized by a substantial degree of cardiovascular involvement, both in terms of deterioration of pre-existing conditions, and as the effect of inflammation-facilitated acute events. They include ischemic/inflammatory heart disease, ventricular arrhythmias, conduction disturbances, thrombotic events at the level of the lungs, and systemic activation of the coagulation cascade, configuring the scenario of disseminated intravascular coagulation. Herein, we summarize the main COVID-19 features of relevance for the clinicians in the cardiovascular field. The rationale, concerns, and possible side effects of specific therapeutic measures, including anticoagulants, renin-angiotensin-aldosterone system inhibitors, and anti-inflammatory/antiviral medications applied to the treatment of COVID-19 are also discussed.

RNA modifications have recently become the focus of attention due to their extensive regulatory effects in a vast array of cellular networks and signaling pathways. Just as epigenetics is responsible for the imprinting of environmental conditions on a genetic level, epitranscriptomics follows the same principle at the RNA level, but in a more dynamic and sensitive manner. Nevertheless, its impact in the field of cardiovascular disease (CVD) remains largely unexplored. CVD and its associated pathologies remain the leading cause of death in Western populations due to the limited regenerative capacity of the heart. As such, maintenance of cardiac homeostasis is paramount for its physiological function and its capacity to respond to environmental stimuli. In this context, epitranscriptomic modifications offer a novel and promising therapeutic avenue, based on the fine‑tuning of regulatory cascades, necessary for cardiac function. This review aimed to provide an overview of the most recent findings of key epitranscriptomic modifications in both coding and non‑coding RNAs. Additionally, the methods used for their detection and important associations with genetic variations in the context of CVD were summarized. Current knowledge on cardiac epitranscriptomics, albeit limited still, indicates that the impact of epitranscriptomic editing in the heart, in both physiological and pathological conditions, holds untapped potential for the development of novel targeted therapeutic approaches in a dynamic manner.

Background: Cardiovascular diseases are the leading causes of mortality worldwide. One reason behind this lethality lies in the fact that often cardiovascular illnesses develop into systemic failure due to the multiple connections to organismal metabolism. This in turn is associated with co-morbidities and multimorbidity. The prevalence of coexisting diseases and the relationship between the molecular origins adds to the complexity of the management of cardiovascular diseases and thus requires a profound knowledge of the genetic interaction of diseases. Objective: In order to develop a deeper understanding of this phenomenon, we examined the patterns of comorbidity as well as their genetic interaction of the diseases (or the lack of evidence of it) in a large set of cases diagnosed with cardiovascular conditions at the national reference hospital for cardiovascular diseases in Mexico. Methods: We performed a cross-sectional study of the National Institute of Cardiology. Socioeconomic information, principal diagnosis that led to the hospitalization and other conditions identified by an ICD-10 code were obtained for 34,099 discharged cases. With this information a cardiovascular comorbidity networks were built both for the full database and for ten 10-years age brackets. The associated cardiovascular comorbidities modules were found. Data mining was performed in the comprehensive ClinVar database with the disease names (as extracted from ICD-10 codes) to establish (when possible) connections between the genetic associations of the genetic interaction of diseases. The rationale is that some comorbidities may have a stronger genetic origin, whereas for others, the environment and other factors may be stronger. Results: We found that comorbidity networks are highly centralized in prevalent diseases, such as cardiac arrhythmias, heart failure, chronic kidney disease, hypertension, and ischemic diseases. Said comorbidity networks are actually modular on their connectivity. Modules recapitulate physiopathological commonalities, e.g., ischemic diseases clustering together. This is also the case of chronic systemic diseases, of congenital malformations and others. The genetic and environmental commonalities behind some of the relations in these modules were also found by resorting to clinical genetics databases and functional pathway enrichment studies. Conclusions: This methodology, hence may allow the clinician to look up for non-evident comorbidities whose knowledge will lead to improve therapeutically designs. By continued and consistent analysis of these types of patterns, we envisaged that it may be possible to acquire, strong clinical and basic insights that may further our advance toward a better understanding of cardiovascular diseases as a whole. Hopefully these may in turn lead to further development of better, integrated therapeutic strategies.

ABO blood groups have been associated with various disease phenotypes, particularly cardiovascular diseases. Cardiovascular diseases are the most common causes of death in developed countries and their prevalence rate is rapidly growing in developing countries. There have been substantial historical associations between non-O blood group status and an increase in some cardiovascular disorders. Recent GWASs have identified ABO as a locus for thrombosis, myocardial infarction, and multiple cardiovascular risk biomarkers, refocusing attention on mechanisms and potential for clinical advances. As we highlight in this paper, more recent work is beginning to probe the molecular basis of the disease associations observed in these observational studies. Advances in our understanding of the physiologic importance of various endothelial and platelet-derived circulating glycoproteins are elucidating the mechanisms through which the ABO blood group may determine overall cardiovascular disease risk. The role of blood group antigens in the pathogenesis of various cardiovascular disorders remains a fascinating subject with potential to lead to novel therapeutics and prognostics and to reduce the global burden of cardiovascular diseases.

In recent year, increasing evidence suggests that noncoding RNAs play important roles in the regulation of tissue homeostasis and pathophysiological conditions. Besides small noncoding RNAs (eg, microRNAs), >200-nucleotide long transcripts, namely long noncoding RNAs (lncRNAs), can interfere with gene expressions and signaling pathways at various stages. In the cardiovascular system, studies have detected and characterized the expression of lncRNAs under normal physiological condition and in disease states. Several lncRNAs are regulated during acute myocardial infarction (eg, Novlnc6) and heart failure (eg, Mhrt), whereas others control hypertrophy, mitochondrial function and apoptosis of cardiomyocytes. In the vascular system, the endothelial-expressed lncRNAs (eg, MALAT1 and Tie-1-AS) can regulate vessel growth and function, whereas the smooth-muscle-expressed lncRNA smooth muscle and endothelial cell-enriched migration/differentiation-associated long noncoding RNA was recently shown to control the contractile phenotype of smooth muscle cells. This review article summarizes the data on lncRNA expressions in mouse and human and highlights identified cardiovascular lncRNAs that might play a role in cardiovascular diseases. Although our understanding of lncRNAs is still in its infancy, these examples may provide helpful insights how lncRNAs interfere with cardiovascular diseases.

Coenzyme Q10 (CoQ10) is a ubiquitous factor present in cell membranes and mitochondria, both in its reduced (ubiquinol) and oxidized (ubiquinone) forms. Its levels are high in organs with high metabolism such as the heart, kidneys, and liver because it acts as an energy transfer molecule but could be reduced by aging, genetic factors, drugs (e.g., statins), cardiovascular (CV) diseases, degenerative muscle disorders, and neurodegenerative diseases. As CoQ10 is endowed with significant antioxidant and anti-inflammatory features, useful to prevent free radical-induced damage and inflammatory signaling pathway activation, its depletion results in exacerbation of inflammatory processes. Therefore, exogenous CoQ10 supplementation might be useful as an adjuvant in the treatment of cardiovascular diseases such as heart failure, atrial fibrillation, and myocardial infarction and in associated risk factors such as hypertension, insulin resistance, dyslipidemias, and obesity. This review aims to summarize the current evidences on the use of CoQ10 supplementation as a therapeutic approach in cardiovascular diseases through the analysis of its clinical impact on patients' health and quality of life. A substantial reduction of inflammatory and oxidative stress markers has been observed in several randomized clinical trials (RCTs) focused on several of the abovementioned diseases, even if more RCTs, involving a larger number of patients, will be necessary to strengthen these interesting findings.

Class A1 scavenger receptors (SR-A1) are membrane glycoproteins that can form homotrimers. This receptor was originally defined by its ability to mediate the accumulation of lipids in macrophages. Subsequent studies reveal that SR-A1 plays critical roles in innate immunity, cell apoptosis and proliferation. This review highlights recent advances in understanding the structure, receptor pathway and regulation of SR-A1. Although its role in atherosclerosis is disputable, recent discoveries suggest that SR-A1 function in anti-inflammatory responses by promoting an M2 macrophage phenotype in cardiovascular diseases. Therefore, SR-A1 may be a potential target for therapeutic intervention of cardiovascular diseases.

Population development is reflected by sustainable development indicators, among them are the indicators describing longevity and healthy aging. Longevity is reflected by life expectancy, and healthy aging is reflected by healthy life expectancy; high values of these indicators reflect good conditions of living for people. Life expectancy and healthy life expectancy analyses are of big interest among academics, policymakers, medical researchers, and others in order to direct the flow of funds in the most effective way possible to the population groups in most need. High life expectancy and low birth rate will lead to aging of the population, having profound implications on the school age population, politics, healthcare, labor force, social protection, social security issues, and public finances. Healthy life expectancy reflects health conditions, including the impacts of mortality and morbidity. As cardiovascular disease causes more than half of all deaths across Europe, this paper examines the influence of cardiovascular disease on longevity and healthy aging across Europe. The methodology was chosen so as to test the research hypotheses: (a) principal component analysis provided the socio-economic factors that are correlated to longevity and healthy aging; (b) regression analysis identified the relationship between healthy aging and cardiovascular disease; and (c) hierarchical cluster analysis allowed us to find common features of the groups of countries according to healthy aging and longevity.

Coenzyme Q10 (CoQ10) is an essential cofactor in oxidative phosphorylation (OXPHOS), present in mitochondria and cell membranes in reduced and oxidized forms. Acting as an energy transfer molecule, it occurs in particularly high levels in the liver, heart, and kidneys. CoQ10 is also an anti-inflammatory and antioxidant agent able to prevent the damage induced by free radicals and the activation of inflammatory signaling pathways. In this context, several studies have shown the possible inverse correlation between the blood levels of CoQ10 and some disease conditions. Interestingly, beyond cardiovascular diseases, CoQ10 is involved also in neuronal and muscular degenerative diseases, in migraine and in cancer; therefore, the supplementation with CoQ10 could represent a viable option to prevent these and in some cases might be used as an adjuvant to conventional treatments. This review is aimed to summarize the clinical applications regarding the use of CoQ10 in migraine, neurodegenerative diseases (including Parkinson and Alzheimer diseases), cancer, or degenerative muscle disorders (such as multiple sclerosis and chronic fatigue syndrome), analyzing its effect on patients' health and quality of life.

Hypertension is associated with body mass index (BMI) and cardiovascular and cerebrovascular diseases (CCDs). Whether hypertension modifies the relationship between BMI and CCDs is still unclear. We examined the association between BMI and CCDs and tested whether effect measure modification was present by hypertension. We identified a population-based sample of 3,942 participants in Shuncheng, Fushun, Liaoning, China. Hypertension was defined as any past use of antihypertensive medication or having a measured systolic/diastolic blood pressure ≥130/80 mm Hg. BMI was calculated from measured body weight and body height. Data on diagnosed CCDs were self-reported and validated in the medical records. We used logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for associations between BMI and CCDs. Higher BMI was associated with increased odds of having CCDs (OR = 1.19, 95% CI: 1.07-1.31). This association was significantly modified by hypertension (P for interaction <0.001), with positive associations observed among hypertensive individuals (OR = 1.28, 95% CI: 1.14-1.42). Age, sex, and diabetic status did not modify the relationship between BMI and CCDs (all P for interaction >0.10). Although higher BMI was associated with increased odds of CCDs, the relationship was mainly limited to hypertensive patients.

Cardiovascular diseases (CVDs) and dementia are the leading causes of disability and mortality. Genetic connections between cardiovascular risk factors and dementia have not been elucidated. We conducted a scoping review and pathway analysis to reveal the genetic associations underlying both CVDs and dementia. In the PubMed database, literature was searched using keywords associated with diabetes mellitus, hypertension, dyslipidemia, white matter hyperintensities, cerebral microbleeds, and covert infarctions. Gene lists were extracted from these publications to identify shared genes and pathways for each group. This included high penetrance genes and single nucleotide polymorphisms (SNPs) identified through genome wide association studies. Most risk SNPs to both diabetes and dementia participate in the phospholipase C enzyme system and the downstream nositol 1,4,5-trisphosphate and diacylglycerol activities. Interestingly, AP-2 (TFAP2) transcription factor family and metabolism of vitamins and cofactors were associated with genetic variants that were shared by white matter hyperintensities and dementia, and by microbleeds and dementia. Variants shared by covert infarctions and dementia were related to VEGF ligand-receptor interactions and anti-inflammatory cytokine pathways. Our review sheds light on future investigations into the causative relationships behind CVDs and dementia, and can be a paradigm of the identification of dementia treatments.

Inflammation has been recognized as a common trait in the pathogenesis of multifactorial diseases including obesity, where a low-grade inflammation has been established and may be responsible for the cardiovascular risk related to the disease. Obesity has also been associated with the increased incidence and a worse outcome of rheumatoid arthritis (RA) and osteoarthritis (OA). RA is characterized by systemic inflammation, which is thought to play a key role in accelerated atherosclerosis and in the increased incidence of cardiovascular disease, an important comorbidity in patients with RA. The inflammatory process underlying the cardiovascular risk both in obesity and RA may be mediated by adipocytokines, a heterogeneous group of soluble proteins mainly secreted by the adipocytes. Many adipocytokines are mainly produced by white adipose tissue. Adipocytokines may also be involved in the pathogenesis of OA since a positive association with obesity has been found for weight-bearing and nonweight-bearing joints, suggesting that, in addition to local overload, systemic factors may contribute to joint damage. In this review we summarize the current knowledge on experimental models and clinical studies in which adipocytokines were examined in obesity, RA, and OA and discuss the potential of adipocytokines as comorbidity biomarkers for cardiovascular risk.

Mitochondria are implicated in the pathogenesis of cardiovascular diseases (CVDs) but the reasons for this are not well understood. Maternally-inherited population variants of mitochondrial DNA (mtDNA) which affect all mtDNA molecules (homoplasmic) are associated with cardiometabolic traits and the risk of developing cardiovascular disease. However, it is not known whether mtDNA mutations only affecting a proportion of mtDNA molecules (heteroplasmic) also play a role. To address this question, we performed a high-depth (~1000-fold) mtDNA sequencing of blood DNA in 1,399 individuals with hypertension (HTN), 1,946 with ischemic heart disease (IHD), 2,146 with ischemic stroke (IS), and 723 healthy controls. We show that the per individual burden of heteroplasmic single nucleotide variants (mtSNVs) increases with age. The age-effect was stronger for low-level heteroplasmies (heteroplasmic fraction, HF, 5-10%), likely reflecting acquired somatic events based on trinucleotide mutational signatures. After correcting for age and other confounders, intermediate heteroplasmies (HF 10-95%) were more common in hypertension, particularly involving non-synonymous variants altering the amino acid sequence of essential respiratory chain proteins. These findings raise the possibility that heteroplasmic mtSNVs play a role in the pathophysiology of hypertension.

Cardiovascular diseases (CVDs) are the leading cause of morbidity and mortality worldwide and Inflammation plays a critical role in the development of CVD. Despite considerable progress in understanding the underlying mechanisms and various treatment options available, significant gaps in therapy necessitate the identification of novel therapeutic targets. Sphingolipids are a family of lipids that have gained attention in recent years as important players in CVDs and the inflammatory processes that underlie their development. As preclinical studies have shown that targeting sphingolipids can modulate inflammation and ameliorate CVDs, targeting sphingolipids has emerged as a promising therapeutic strategy. This review discusses the current understanding of sphingolipids' involvement in inflammation and cardiovascular diseases, the existing therapeutic approaches and gaps in therapy, and explores the potential of sphingolipids-based drugs as a future avenue for CVD treatment.

Cardiovascular disease (CVD) is globally considered as the leading cause of death with 80% of CVD related deaths being reported from low and middle income countries like India. The relatively early onset age of CVD in India in comparison to Western countries also implies that most productive ages of the patient's life are lost fighting the disease. Conventional cardiovascular risk is attributed to lifestyle changes and altered metabolic activity. This forms the basis of a 10-year risk prediction score inspired by the Framingham study. Since South Asians display considerable heterogeneity in risk factors as compared to developed countries, there is a need to identify risk factors which would not only help in primary prevention but also prevent their recurrence. We reviewed published data on novel risk factors and their potential to identify cardiovascular risk at an early stage, with special emphasis on the Indian population. Emerging risk factors were reviewed to identify their potential to prevent CVD progression independently as well as in association with other cardiovascular risk factors. The most commonly studied emerging cardiovascular risk factors included coronary artery calcium score, lipoprotein (a), apolipoproteins, homocysteine, thrombosis markers like fibrinogen, and plasminogen activator inhibitor 1, carotid intima-media thickness, genotypic variations, non-alcoholic fatty liver disease, C-reactive protein, platelets, and birth weight levels. Nonetheless, more studies on large sample size can ascertain the utility of these risk factors in estimation and analysis of cardiovascular risk especially in the Indian context.

Cardiovascular diseases (CVDs) remain the world's leading cause of death. Cardiomyocyte autophagy helps maintain normal metabolism and functioning of the heart. Importantly, mounting evidence has revealed that autophagy plays a dual role in CVD pathology. Under physiological conditions, moderate autophagy maintains cell metabolic balance by degrading and recycling damaged organelles and proteins, and it promotes myocardial survival, but excessive or insufficient autophagy is equally deleterious and contributes to disease progression. Noncoding RNAs (ncRNAs) are a class of RNAs transcribed from the genome, but most ncRNAs do not code for functional proteins. In recent years, increasingly, various ncRNAs have been identified, and they play important regulatory roles in the physiological and pathological processes of organisms, as well as in autophagy. Thus, determining whether ncRNA-regulated autophagy plays a protective role in CVDs or promotes their progression can help us to develop ncRNAs as therapeutic targets in autophagy-related CVDs. In this review, we briefly summarize the regulatory roles of several important ncRNAs, including microRNAs (miRNAs), long ncRNAs (lncRNAs), and circular RNAs (circRNAs), in the autophagy of various CVDs to provide a theoretical basis for the etiology and pathogenesis of CVDs and develop novel therapies to treat CVDs.

Cardiovascular diseases (CVD) are the leading cause of death in the United States. The previous literature demonstrates the importance of vitamin D for overall health, and a significant body of literature has examined the benefits of optimal serum 25-hydroxyvitamin D [25(OH)D] on cardiovascular health, but the results remain inconclusive. The objective of this study was to determine the association between reported CVD and [25(OH)D]. We utilized the 2015-2018 National Health and Nutrition Examination Survey and included adults aged 20 years and older (n = 9825). CVD was defined as having a stroke, heart attack, heart failure, or coronary heart disease. Vitamin D status was categorized as a serum 25(OH)D deficiency at <30 nmol/L; insufficiency at 30 to 49.9 nmol/L; normal/optimal at 50 to 125 nmol/L; and adequacy at >125 nmol/L. Statistical analysis was performed using Chi-square tests, t-tests were conducted to investigate the differences in participant characteristics among those with CVD and without CVD, and regression models were used to explore the association between vitamin D levels and CVD status. We found 25(OH)D deficiency associated with CVD (Adjusted Odds Ratio (AOR) = 1.48; 95% CI = 1.11-1.98; p < 0.05). [25(OH)D] insufficiency was also associated with CVD (AOR = 1.28; 95% CI = 1.06-1.54; p < 0.05). The 25(OH)D adequacy was not associated with reported CVD. For the prevention of CVD, healthcare professionals may recommend the use of vitamin D supplementation to improve cardiovascular health in adults while considering individual needs.