Circadian dysfunction and cardio-metabolic disorders in humans.

The topic of human circadian rhythms is not only attracting the attention of clinical researchers from various fields but also sparking a growing public interest. The circadian system comprises the central clock, located in the suprachiasmatic nucleus of the hypothalamus, and the peripheral clocks in various tissues that are interconnected; together they coordinate many daily activities, including sleep and wakefulness, physical activity, food intake, glucose sensitivity and cardiovascular functions. Disruption of circadian regulation seems to be associated with metabolic disorders (particularly impaired glucose tolerance) and cardiovascular disease. Previous clinical trials revealed that disturbance of the circadian system, specifically due to shift work, is associated with an increased risk of type 2 diabetes mellitus. This review is intended to provide clinicians who wish to implement knowledge of circadian disruption in diagnosis and strategies to avoid cardio-metabolic disease with a general overview of this topic.

Cardiovascular Considerations and Implications for Treatment in Psoriasis: An Updated Review.

Psoriasis, a prevalent chronic inflammatory skin disorder affecting 2-3% of the global population, has transcended its dermatological confines, revealing a profound association with cardiovascular diseases (CVD). This comprehensive review explores the intricate interplay between psoriasis and cardiovascular system, delving into genetic links, immune pathways, and adipose tissue dysfunction beyond conventional CVD risk factors. The pathophysiological connections unveil unique signatures, distinct from other inflammatory skin conditions, in particular psoriasis-specific genetic polymorphisms in IL-23 and TNF-α have consistently been linked to CVD. The review navigates the complex landscape of psoriasis treatments, addressing challenges and future directions in particular relevance to CVDs in psoriasis. Therapeutic interventions, including TNF inhibitors (TNFi), present promise in reducing cardiovascular risks, and methotrexate could constitute a favourable choice. Conversely, the relationship between IL-12/23 inhibitors and cardiovascular risk remains uncertain, while recent evidence indicates that Janus kinase inhibitors may not carry CVD risks. Emerging evidence supports the safety and efficacy of IL-17 and IL-23 inhibitors in patients with CVDs, hinting at evolving therapeutic paradigms. Lifestyle modifications, statins, and emerging therapies offer preventive strategies. Dedicated screening guidelines for CVD risk assessment in psoriasis are however lacking. Further, the impact of different disease phenotypes and treatment hierarchies in cardiovascular outcomes remains elusive, demanding ongoing research at the intersection of dermatology, rheumatology, and cardiology. In conclusion, unraveling the intricate connections between psoriasis and CVD provides a foundation for a holistic approach to patient care. Collaboration between specialties, advancements in screening methodologies, and a nuanced understanding of treatment impacts are essential for comprehensive cardiovascular risk management in individuals with psoriasis.

Psoriasis is a skin condition that not only affects the skin but is also linked to issues in the body's fat tissue, which can lead to inflammation and heart problems. The fat tissue in people with psoriasis contains various immune cells, contributing to obesity and insulin resistance. Research has found a strong connection between inflammation in fat tissues and cardiovascular problems in people with psoriasis. Specific substances released by fat tissue, like leptin, resistin, and adiponectin, can impact inflammation and cardiovascular health. Psoriasis patients often show increased levels of these substances. Treatment for psoriasis may influence cardiovascular health. Some studies suggest that certain medications, like methotrexate or TNF inhibitors, may lower the risk of heart events. However, there are also concerns about potential adverse effects, and further research is needed to fully understand how psoriasis treatments affect cardiovascular outcomes. To manage the cardiovascular risks associated with psoriasis, regular screening for heart-related issues is recommended. Lifestyle changes, such as a healthy diet, stress management, and smoking cessation, are also essential. Additionally, specific medications, like statins and metformin, may be beneficial in controlling cardiovascular risk factors in people with psoriasis. Despite advancements in understanding the relationship between psoriasis and cardiovascular health, there are still challenges. Research is ongoing to develop better screening guidelines and treatment strategies. Collaboration between dermatologists, rheumatologists, and cardiologists is crucial to address the complex nature of this condition and its impact on the heart.

Infrared thermography for normal endothelial function screening.

BACKGROUND: Endothelial dysfunction (ED) suspicion will allow to prevent accelerated atherosclerosis and premature death. OBJECTIVE: To establish the usefulness of thermography for endothelial function screening in adults with cardiovascular risk factors. MATERIAL AND METHODS: Cross-sectional, analytical diagnostic test. A brachial arterial diameter (BAD) increase < 11% at one-minute post-ischemia meant probable ED and was confirmed if BAD was ≥ 11% post-sublingual nitroglycerin. Thermographic photographs of the palmar region were obtained at one minute. Descriptive statistics, ROC curve, Mann-Whitney's U-test, chi-square test, or Fisher's exact test were used. RESULTS: Thirty-eight subjects with a median age of 50 years, and with 624 thermographic measurements were included. Nine had ED (flow-mediated vasodilation [FMV]: 2.5%). The best cutoff point for normal endothelial function in subjects with cardiovascular risk factors was ≥ 36 °C at one minute of ischemia, with 85% sensitivity, 70% specificity, positive and negative predictive values of 78 and 77%, area under the curve of 0.796, LR+ 2.82, LR- 0.22. CONCLUSION: An infrared thermography-measured temperature in the palmar region greater than or equal to 36 °C after one minute of ischemia is practical, non-invasive, and inexpensive for normal endothelial function screening in adults with cardiovascular risk factors.

ANTECEDENTES: La sospecha de disfunción endotelial (DE) permitirá prevenir la aterosclerosis acelerada y la muerte prematura. OBJETIVO: Establecer la utilidad de la termografía en el cribado de la función endotelial en adultos con factores de riesgo cardiovascular. MATERIAL Y MÉTODOS: Estudio transversal analítico de prueba diagnóstica. El incremento del diámetro de la arteria braquial < 11 % a un minuto posisquemia significó probable DE, confirmada si el diámetro fue ≥ 11 % posnitroglicerina sublingual. Se obtuvieron fotografías termográficas al minuto de la región palmar. Se aplicó estadística descriptiva, curva ROC, pruebas U de Mann-Whitney, chi cuadrada o exacta de Fisher. RESULTADOS: Se incluyeron 38 sujetos, mediana de edad de 50 años, con 624 mediciones termográficas; nueve presentaron DE (vasodilatación mediada por flujo de 2.5 %). El mejor punto de corte para la función endotelial normal en sujetos con factores de riesgo cardiovascular fue ≥ 36 °C al minuto de isquemia, con sensibilidad de 85%, especificidad de 70%, valores predictivos positivo y negativo de 78 y 77%, área bajo la curva de 0.796, razón de verisimilitud positiva de 2.82 y razón de verisimilitud negativa de 0.22. CONCLUSIÓN: La medición de la temperatura en la región palmar mediante termografía infrarroja ≥ 36 °C tras un minuto de isquemia es práctica, no invasiva y económica para el cribado de la función endotelial normal en adultos con factores de riesgo cardiovascular.

Direct and indirect effects of adiposity on markers of autonomic nervous system activity in older adults.

Several cardiovascular disease (CVD) risk factors (e.g., hypertension, poor glycemic control) can affect and be affected by autonomic nervous system (ANS) activity. Since excess adiposity can influence CVD development through its effect on hypertension and diabetes mellitus, it is important to determine how adiposity and altered ANS activity are related. The present study employed structural equation modeling to investigate the relation between adiposity and ANS activity both directly and indirectly through biological variables typically associated with glycemic impairment and cardiac stress in older adults. Utilizing the Atherosclerosis Risk in Communities (ARIC) dataset, 1,145 non-smoking adults (74±4.8 yrs, 62.8% female) free from known CVD, hypertension, and diabetes and not currently taking beta-blockers were evaluated for fasting blood glucose (FBG), insulin, and HbA1c concentrations, waist circumference (WC), blood pressure (BP), and markers of ANS activity. WC was recorded just above the iliac crest and was used to reflect central adiposity. Resting 2-minute electrocardiograph recordings, pulse wave velocity, and ankle-brachial index data were used to assess the root mean square of successive differences in RR intervals (RMSSD) and the pre-ejection period (PEP), markers of parasympathetic and sympathetic activity, respectively. FBG, insulin, and HbA1c inferred a latent variable termed glycemic impairment (GI), whereas heart rate and diastolic BP inferred a latent variable termed cardiac stress (CS). The structural equation model fit was acceptable [root mean square error of approximation = 0.050 (90% CI = .036, .066), comparative fit index = .970, Tucker Lewis Index = 0.929], with adiposity having both significant direct (ß = 0.208, p = 0.018) and indirect (ß = -.217, p = .041) effects on PEP through GI. Adiposity displayed no significant direct effect on RMSSD. CS displayed a significant pathway (ß = -0.524, p = 0.035) on RMSSD, but the indirect effect of WC on RMSSD through CS did not reach statistical significance (ß = -0.094, p = 0.137). These results suggest that adiposity's relation to ANS activity is multifaceted, as increased central adiposity had opposing direct and indirect effects on markers of sympathetic activity in this population of older adults.

Salt Sensitivity of Blood Pressure.

The year 2024 marks the centennial of the initiation of the American Heart Association. Over the past 100 years, the American Heart Association has led groundbreaking discoveries in cardiovascular disease including salt sensitivity of blood pressure, which has been studied since the mid-1900s. Salt sensitivity of blood pressure is an important risk factor for cardiovascular events, but the phenotype remains unclear because of insufficient understanding of the underlying mechanisms and lack of feasible diagnostic tools. In honor of this centennial, we commemorate the initial discovery of salt sensitivity of blood pressure and chronicle the subsequent scientific discoveries and efforts to mitigate salt-induced cardiovascular disease with American Heart Association leading the way. We also highlight determinants of the pathophysiology of salt sensitivity of blood pressure in humans and recent developments in diagnostic methods and future prospects.

Effects of temporal changes in resting heart rate on future diabetes-related outcomes.

Background and aims: Most studies have analyzed the relationship between resting heart rate (RHR) measured at only one time point and future clinical events. The current study aims to investigate the impact of long-term RHR changes on future clinical outcomes in a decade-long cohort with type 2 diabetes mellitus (T2DM). Methods: The two-staged follow-up involved 2,513 T2DM participants. The first stage (2008-2014) intended to identify levels and trends in RHR changes, while the second stage (2014-2018) attempted to collect new occurrence records of clinical results. Cox proportional hazards models were applied to predict hazard ratios (HRs), along with 95% confidence interval (CI) for the correlation between RHR changes and future events. Results: There is no significant correlation between baseline RHR levels and long-term clinical events. According to the range of RHR change, compared with the stable RHR group, the adjusted HRs for cardiovascular events and all-cause death in the large increase group were 3.40 (95% CI: 1.33-8.71, p=0.010) and 3.22 (95% CI: 1.07-9.64, p=0.037), respectively. While the adjusted HRs for all-cause death and major adverse cardiac and cerebrovascular events (MACCE) in the moderate decrease group were 0.55 (95% CI: 0.31-0.96, p=0.037) and 0.51 (95% CI: 0.26-0.98, p=0.046). According to the trend of RHR, compared with the normal-normal group, the adjusted HRs for composite endpoint events and cerebrovascular events in the normal-high group were 1.64 (95% CI: 1.00-2.68, p=0.047) and 2.82 (95% CI: 1.03-7.76, p=0.043), respectively. Conclusion: Changes in RHR had predictive value for long-term clinical events in diabetic populations. Individuals with significantly elevated RHR over a particular period of time showed an increased risk of adverse events.

Altered Arterial Stiffness, Ventricular-Arterial Coupling and Troponin Levels in Patients with Systemic Lupus Erythematosus.

Introduction: Systemic Lupus Erythematosus (SLE) is an autoimmune disease associated with an increased risk of cardiovascular diseases (CVDs), leading to elevated mortality rates among patients. We aimed to evaluate the levels of cardio-ankle vascular index (CAVI), global longitudinal strain (GLS), ventricular-arterial coupling (VAC), and high-sensitivity cardiac troponin I (hsTnI) in SLE patients and to explore their relationship with clinical parameters. Methods: This cross-sectional study enrolled 82 SLE patients without evident cardiac or kidney impairment and 41 age- and sex-matched healthy controls. We comparatively evaluated CAVI, GLS, VAC, and hsTnI between SLE patients and controls, and we assessed their association among SLE patients with disease activity based on the SELENA-SLEDAI Activity Index. Multivariate regression analysis was performed to identify independent predictors of CAVI and hsTnI within the SLE cohort. Results: In comparison to healthy controls, SLE patients presented with significantly higher CAVI, GLS, and hsTnI levels, while VAC was significantly reduced (p < 0.001). Furthermore, SLE patients with active disease (SELENA-SLEDAI ≥ 4) exhibited higher levels of CAVI and troponin than those with inactive disease (p < 0.001). SLEDAI was an independent predictor of CAVI, while VAC and SLEDAI were independent determinants of hsTnI in the SLE cohort. Conclusions: SLE patients displayed abnormal levels of CAVI, VAC, GLS, and troponin compared to healthy individuals. Our findings implicate the potential of those CV novel CVD risk factors to refine screening and therapeutic strategies for this specific population.

The Relationship between the Ewing Test, Sudoscan Cardiovascular Autonomic Neuropathy Score and Cardiovascular Risk Score Calculated with SCORE2-Diabetes.

Background and Objectives: Cardiac autonomic neuropathy (CAN) is a severe complication of diabetes mellitus (DM) strongly linked to a nearly five-fold higher risk of cardiovascular mortality. Patients with Type 2 Diabetes Mellitus (T2DM) are a significant cohort in which these assessments have particular relevance to the increased cardiovascular risk inherent in the condition. Materials and Methods: This study aimed to explore the subtle correlation between the Ewing test, Sudoscan-cardiovascular autonomic neuropathy score, and cardiovascular risk calculated using SCORE 2 Diabetes in individuals with T2DM. The methodology involved detailed assessments including Sudoscan tests to evaluate sudomotor function and various cardiovascular reflex tests (CART). The cohort consisted of 211 patients diagnosed with T2DM with overweight or obesity without established ASCVD, aged between 40 to 69 years. Results: The prevalence of CAN in our group was 67.2%. In the study group, according SCORE2-Diabetes, four patients (1.9%) were classified with moderate cardiovascular risk, thirty-five (16.6%) with high risk, and one hundred seventy-two (81.5%) with very high cardiovascular risk. Conclusions: On multiple linear regression, the SCORE2-Diabetes algorithm remained significantly associated with Sudoscan CAN-score and Sudoscan Nephro-score and Ewing test score. Testing for the diagnosis of CAN in very high-risk patients should be performed because approximately 70% of them associate CAN. Increased cardiovascular risk is associated with sudomotor damage and that Sudoscan is an effective and non-invasive measure of identifying such risk.

Body surface area is positively associated with ankle-brachial index.

BACKGROUND: Ankle-brachial index (ABI) measurement is a widely used diagnostic test for lower extremity artery disease. Previously, a larger body surface area (BSA) has been associated with lower blood pressure and lower 2-h post-load glucose concentrations in the oral glucose tolerance test. Our aim was to evaluate whether BSA has an impact on ABI and the prevalence of lower ABI values. METHODS: ABI measurements were performed on 972 subjects aged 45 to 70 years at high cardiovascular disease (CVD) risk. Subjects with previously diagnosed kidney disease, CVD, and diabetes were excluded. Their BSA was calculated by the Mosteller formula. Study subjects were divided into five BSA levels corresponding to 12.5th, 25th, 25th, 25th, and 12.5th percentiles of the total distribution. Effect modification by BSA in ABI between sexes was derived from a four-knot restricted cubic splines regression model. RESULTS: After adjustments for age, sex, pulse pressure, glucose regulation, waist circumference, alcohol intake, smoking status, leisure-time physical activity and medication, BSA level had a positive linear relationship with ABI (p for linearity <0.001). When BSA was less than 2.0 m2, there was no difference between the sexes, but when BSA was higher than 2.0 m2, men had higher ABI. CONCLUSION: BSA shows a positive linear relationship with ABI in CVD risk subjects without manifested CVD. The difference in ABI between men and women is modified by BSA and is appreciable when BSA is larger than 2.0 m2.

Muscle fibre morphometric analysis (MusMA) correlates with muscle function and cardiovascular risk prognosis.

Morphometry of striated muscle fibres is critical for monitoring muscle health and function. Here, we evaluated functional parameters of skeletal and cardiac striated muscle in two experimental models using the Morphometric Analysis of Muscle Fibre tool (MusMA). The collagen-induced arthritis model was used to evaluate the function of skeletal striated muscle and the non-alcoholic fatty liver disease model was used for cardiac striated muscle analysis. After euthanasia, we used haeamatoxylin and eosin stained sections of skeletal and cardiac muscle to perform muscle fibre segmentation and morphometric analysis. Morphometric analysis classified muscle fibres into six subpopulations: normal, regular hypertrophic, irregular hypertrophic, irregular, irregular atrophic and regular atrophic. The percentage of atrophic fibres was associated with lower walking speed (p = 0.009) and lower body weight (p = 0.026), respectively. Fibres categorized as normal were associated with maximum grip strength (p < 0.001) and higher march speed (p < 0.001). In the evaluation of cardiac striated muscle fibres, the percentage of normal cardiomyocytes negatively correlated with cardiovascular risk markers such as the presence of abdominal adipose tissue (p = .003), miR-33a expression (p = .001) and the expression of miR-126 (p = .042) Furthermore, the percentage of atrophic cardiomyocytes correlated significantly with the Castelli risk index II (p = .014). MusMA is a simple and objective tool that allows the screening of striated muscle fibre morphometry, which can complement the diagnosis of muscle diseases while providing functional and prognostic information in basic and clinical research.

Hypoxic and Autonomic Mechanisms from Sleep-Disordered Breathing Leading to Cardiopulmonary Dysfunction.

Obstructive sleep apnea (OSA) is a common sleep-related breathing disorder. Its prevalence has increased due to increasing obesity and improved screening and diagnostic strategies. OSA overlaps with cardiopulmonary diseases to promote intermittent hypoxia and autonomic dysfunction. Intermittent hypoxia increases the risk for oxidative stress and inflammation, which promotes endothelial dysfunction and predisposes to atherosclerosis and other cardiovascular complications. OSA is associated with an increased sympathetic nervous system drive resulting in autonomic dysfunction leading to worsening of cardiopulmonary diseases. Cardiovascular diseases are observed in 40% to 80% of OSA patients. Therefore, it is essential to screen and treat cardiovascular diseases.

Low ankle-brachial index is associated with higher cardiovascular mortality in individuals with nonalcoholic fatty liver disease.

BACKGROUND AND AIMS: Ankle brachial index (ABI) is a risk factor for cardiovascular mortality, but it is unclear whether ABI is associated with cardiovascular mortality in patients with nonalcoholic fatty liver disease (NAFLD). The current study aimed to evaluate the association between ABI with cardiovascular and all-cause mortality in patients with NAFLD. METHODS: We performed a cohort study using the data of the1999-2004 National Health and Nutrition Examination Survey data of adults. Mortality data were followed up to December 2015. NAFLD was defined by the hepatic steatosis index or the US fatty liver index. ABI was classified into three groups: ABI ≤ 0.9 (low value); 0.9 < ABI ≤ 1.1 (borderline value); ABI greater than 1.1 (normal value). RESULTS: We found that low ABI was associated with an increased risk of cardiovascular mortality in patients with NAFLD (HR: 2.42, 95% CI 1.10-5.33 for low value ABI vs normal value ABI, P for trend = 0.04), and the relationship was linearly and negatively correlated in the range of ABI < 1.4. However, low ABI was not associated with all-cause mortality in patients with NAFLD. Stratified by cardiovascular disease, ABI remains inversely correlated with cardiovascular mortality in NAFLD patients without cardiovascular disease. Stratified by diabetes, ABI is inversely correlated with cardiovascular mortality in NAFLD patients regardless of diabetes status. CONCLUSIONS: Low ABI is independently associated with higher cardiovascular mortality in NAFLD cases. This correlation remains significant even in the absence of pre-existing cardiovascular disease or diabetes.

Life's Essential 8 Cardiovascular Health Score and Cardiorespiratory Fitness in the Community.

BACKGROUND: The relation of cardiorespiratory fitness (CRF) to lifestyle behaviors and factors linked with cardiovascular health remains unclear. We aimed to understand how the American Heart Association's Life's Essential 8 (LE8) score (and its changes over time) relate to CRF and complementary exercise measures in community-dwelling adults. METHODS AND RESULTS: Framingham Heart Study (FHS) participants underwent maximum effort cardiopulmonary exercise testing for direct quantification of peak oxygen uptake (V̇O2). A 100-point LE8 score was constructed as the average across 8 factors: diet, physical activity, nicotine exposure, sleep, body mass index, lipids, blood glucose, and blood pressure. We related total LE8 score, score components, and change in LE8 score over 8 years with peak V̇O2 (log-transformed) and complementary CRF measures. In age- and sex-adjusted linear models (N=1838, age 54±9 years, 54% women, LE8 score 76±12), a higher LE8 score was associated favorably with peak V̇O2, ventilatory efficiency, resting heart rate, and blood pressure response to exercise (all P<0.0001). A clinically meaningful 5-point higher LE8 score was associated with a 6.0% greater peak V̇O2 (≈1.4 mL/kg per minute at sample mean). All LE8 components were significantly associated with peak V̇O2 in models adjusted for age and sex, but blood lipids, diet, and sleep health were no longer statistically significant after adjustment for all LE8 components. Over an ≈8-year interval, a 5-unit increase in LE8 score was associated with a 3.7% higher peak V̇O2 (P<0.0001). CONCLUSIONS: Higher LE8 score and improvement in LE8 over time was associated with greater CRF, highlighting the importance of the LE8 factors in maintaining CRF.

Effects on physical activity, physical fitness and well-being in a 36-months randomized controlled study, comparing a multimodal hospital-based intervention programme for primary cardiovascular prevention with usual care.

BACKGROUND: Cardiovascular disease is a major cause of mortality and morbidity worldwide, and primary prevention efforts are poorly developed in people at high cardiovascular risk. On this background, we performed the Hjerteløftet Study and demonstrated that participation over 36 months in a multimodal primary prevention programme, significantly reduced validated cardiovascular risk scores. In the current substudy we aimed to further explore several elements and effects following the intervention programme. METHODS: A random sample from the original Hjerteløftet Study was included for further examinations (n = 255, 40% women), and these patients were already randomized to an intervention group (IG) (n = 127), or a control group (CG) (n = 128). We compared changes from baseline to 36-months follow-up in physical activity, cardiorespiratory fitness, psychological well-being (WHO-5), cardiovascular medication use, smoking habits, and cardiometabolic risk factors (blood pressure, lipids, blood glucose, HbA1c, Apolipoprotein A-I, Apolipoprotein B and high-sensitive C-reactive protein). RESULTS: Self-reported physical activity increased significantly with absolute difference in mean delta Physical Activity Index score in the IG compared to the CG: 0.90, 95% CI: 0.10 to 1.70, p = 0.028 (ANCOVA). There were no corresponding differences in cardiorespiratory fitness. The participation resulted in psychological well-being improvement in both groups with a larger increase in the IG compared to the CG. The mean difference in delta WHO-5 score was 5.06, 95% CI: 0.68 to 9.45, p = 0.024, and 3.28, 95% CI: -0.69 to 5.25, p = 0.104 when controlled for baseline values (ANCOVA). The use of antihypertensive medication increased significantly more in the CG (p = 0.044). Only minor, nonsignificant changes were observed for traditional risk factors and cardiometabolic variables. CONCLUSIONS: Participation in the Hjerteløftet Study intervention programme resulted in an improved physical activity level, but without changing cardiorespiratory fitness. Participation in the programme also tended to improve psychological well-being, possibly related to increased physical activity, less smoking and less use of cardiovascular medication. Concerning the metabolic status, no major differences were observed, but minor changes may have been concealed by a larger increase in cardiovascular medication use in the control group. TRIAL REGISTRATION: ClinicalTrials.gov (NCT01741428), 04/12/2012.

Mechanical stress induced mitochondrial dysfunction in cardiovascular diseases: Novel mechanisms and therapeutic targets.

Cardiovascular diseases (CVDs) are the leading cause of mortality worldwide. Others and our studies have shown that mechanical stresses (forces) including shear stress and cyclic stretch, occur in various pathological conditions, play significant roles in the development and progression of CVDs. Mitochondria regulate the physiological processes of cardiac and vascular cells mainly through adenosine triphosphate (ATP) production, calcium flux and redox control while promote cell death through electron transport complex (ETC) related cellular stress response. Mounting evidence reveal that mechanical stress-induced mitochondrial dysfunction plays a vital role in the pathogenesis of many CVDs including heart failure and atherosclerosis. This review summarized mitochondrial functions in cardiovascular system under physiological mechanical stress and mitochondrial dysfunction under pathological mechanical stress in CVDs (graphical abstract). The study of mitochondrial dysfunction under mechanical stress can further our understanding of the underlying mechanisms, identify potential therapeutic targets, and aid the development of novel treatments of CVDs.

SIRT6 in Regulation of Mitochondrial Damage and Associated Cardiac Dysfunctions: A Possible Therapeutic Target for CVDs.

Cardiovascular diseases (CVDs) can be described as a global health emergency imploring possible prevention strategies. Although the pathogenesis of CVDs has been extensively studied, the role of mitochondrial dysfunction in CVD development has yet to be investigated. Diabetic cardiomyopathy, ischemic-reperfusion injury, and heart failure are some of the CVDs resulting from mitochondrial dysfunction Recent evidence from the research states that any dysfunction of mitochondria has an impact on metabolic alteration, eventually causes the death of a healthy cell and therefore, progressively directing to the predisposition of disease. Cardiovascular research investigating the targets that both protect and treat mitochondrial damage will help reduce the risk and increase the quality of life of patients suffering from various CVDs. One such target, i.e., nuclear sirtuin SIRT6 is strongly associated with cardiac function. However, the link between mitochondrial dysfunction and SIRT6 concerning cardiovascular pathologies remains poorly understood. Although the Role of SIRT6 in skeletal muscles and cardiomyocytes through mitochondrial regulation has been well understood, its specific role in mitochondrial maintenance in cardiomyocytes is poorly determined. The review aims to explore the domain-specific function of SIRT6 in cardiomyocytes and is an effort to know how SIRT6, mitochondria, and CVDs are related.