Evolving perspectives in reverse cardio-oncology: A review of current status, pathophysiological insights, and future directives.

Cardiovascular disease (CVD) and cancer are leading causes of mortality worldwide, traditionally linked through adverse effects of cancer therapies on cardiovascular health. However, reverse cardio-oncology, a burgeoning field, shifts this perspective to examine how cardiovascular diseases influence the onset and progression of cancer. This novel approach has revealed a higher likelihood of cancer development in patients with pre-existing cardiovascular conditions, attributed to shared risk factors such as obesity, a sedentary lifestyle, and smoking. Underlying mechanisms like chronic inflammation and clonal hematopoiesis further illuminate the connections between cardiovascular ailments and cancer. This comprehensive narrative review, spanning a broad spectrum of studies, outlines the syndromic classification of cardio-oncology, the intersection of cardiovascular risk factors and oncogenesis, and the bidirectional dynamics between CVD and cancer. Additionally, the review also discusses the pathophysiological mechanisms underpinning this interconnection, examining the roles of cardiokines, genetic factors, and the effects of cardiovascular therapies and biomarkers in cancer diagnostics. Lastly, it aims to underline future directives, emphasising the need for integrated healthcare strategies, interdisciplinary research, and comprehensive treatment protocols.

Clonal Hematopoiesis and Cardiovascular Disease in Patients With Multiple Myeloma Undergoing Hematopoietic Cell Transplant.

Importance: There is a paucity of information on the association between clonal hematopoiesis of indeterminate potential (CHIP) and cardiovascular disease (CVD) in patients with cancer, including those with multiple myeloma (MM) undergoing hematopoietic cell transplant (HCT), a population at high risk of developing CVD after HCT. Objective: To examine the association between CHIP and CVD in patients with MM and to describe modifiers of CVD risk among those with CHIP. Design, Setting, and Participants: This was a retrospective cohort study of patients with MM who underwent HCT between 2010 and 2016 at City of Hope Comprehensive Cancer Center in Duarte, California, and had pre-HCT mobilized peripheral blood stem cell (PBSC) products cryopreserved and accessible for CHIP analyses. The study team performed targeted panel DNA sequencing to detect the presence of CHIP (variant allele frequency 2% or more). Main Outcomes and Measures: The primary end point was the 5-year cumulative incidence and risk for developing de novo CVD (heart failure, coronary artery disease, or stroke) after HCT. Results: Of 1036 consecutive patients with MM (580 male [56%]; median age, 60.0 years) who underwent a first autologous HCT, 201 patients had at least 1 CHIP variant (19.4%) and 35 patients had 2 or more variants (3.4%). The 5-year incidence of CVD was significantly higher in patients with CHIP (21.1% vs 8.4%; P < .001) compared with those without CHIP; the 5-year incidence among those with 2 or more variants was 25.6%. In the multivariable model, CHIP was associated with increased risk of CVD (hazard ratio [HR], 2.72; 95% CI, 1.70-4.39), as well as of individual outcomes of interest, including heart failure (HR, 4.02; 95% CI, 2.32-6.98), coronary artery disease (HR, 2.22; 95% CI, 1.06-4.63), and stroke (HR, 3.02; 95% CI, 1.07-8.52). Patients who had both CHIP and preexisting hypertension or dyslipidemia were at nearly 7-fold and 4-fold increased risk of CVD, respectively (reference: no CHIP, no hypertension, or dyslipidemia). Conclusion and Relevance: CHIP was significantly and independently associated with risk of CVD in patients with MM undergoing HCT and may serve as a novel biologically plausible biomarker for CVD in this cohort. Patients with MM and both CHIP and cardiovascular risk factors had an exceptionally high risk of CVD. Additional studies are warranted to determine if cardiovascular preventive measures can reduce CHIP-associated CVD risk.

Fish Oil Derivatives in Hypertriglyceridemia: Mechanism and Cardiovascular Prevention: What Do Studies Say?

Hypertriglyceridemia is a type of dyslipidemia characterized by high triglyceride levels in the blood and increases the risk of cardiovascular disease. Conventional management includes antilipidemic medications such as statins, lowering LDL and triglyceride levels as well as raising HDL levels. However, the treatment may be stratified using omega-3 fatty acid supplements such as eicosatetraenoic acid (EPA) and docosahexaenoic acid (DHA), aka fish oil derivatives. Studies have shown that fish oil supplements reduce the risk of cardiovascular diseases; however, the underlying mechanism and the extent of reduction in CVD need more clarification. Our paper aims to review the clinical trials and observational studies in the current literature, investigating the use of fish oil and its benefits on the cardiovascular system as well as the proposed underlying mechanism.

Omega-3 supplementation effects on cardiovascular risk and inflammatory profile in chronic kidney disease patients in hemodialysis treatment: An intervention study.

BACKGROUND AND AIMS: Chronic Kidney Disease (CKD) is characterized by slow, progressive, and irreversible kidney function loss and the disease itself and hemodialysis treatment can predispose an inflammatory state that increased cardiovascular complications, being one of major mortality causes in kidney patients. The study purpose was to evaluate nutritional profile and impacts of w-3 fatty acid supplementation on inflammatory parameters and cardiovascular events risk in patients with CKD undergoing hemodialysis treatment. METHODS: Non-randomized clinical trial, patients with CKD were randomly grouped into a control (n = 29) and supplemented (n = 30) group. Supplemented group patients were instructed to consume two w-3 capsules a day (2g/day) for 8 weeks for further analysis of pre- and post-supplementation C-reactive protein (CRP) and other blood parameters. To nutritional status assessment, anthropometric and bioelectrical impedance data were measured, carried out close to supplementation start. RESULTS: 59 patients were evaluated, 49.1% (n = 29) were overweight and 70.7% (n = 41) had high percentage of body fat. Comparing control versus supplemented groups after supplementation serum CRP levels have reduced, no differences were observed (p = 0.716) nevertheless there was reduction in cardiovascular events risk according to C-reactive protein classification (p = 0.004). Ferritin levels have improved in all groups. Changes in the levels of other biochemical markers hemoglobin, hematocrit, urea, creatinine, and Kt/v have happened. However, group that received w-3 showed an improvement in serum albumin levels (p = 0.014), in addition to demonstrating greater adequacy classification of albumin after supplementation (p = 0.022). CONCLUSION: Omega-3 supplementation have caused an improvement in albumin plasma levels suitableness in Chronic Kidney Disease patients, however, it did not demonstrate statistical effects to reducing CRP levels, although this helped to reduce cardiovascular risk.

A Review of Healthy Dietary Choices for Cardiovascular Disease: From Individual Nutrients and Foods to Dietary Patterns.

Cardiovascular disease (CVD) remains the first cause of mortality globally. Diet plays a fundamental role in cardiovascular health and is closely linked to the development of CVD. Numerous human studies have provided evidence on the relationship between diet and CVD. By discussing the available findings on the dietary components that potentially influence CVD progression and prevention, this review attempted to provide the current state of evidence on healthy dietary choices for CVD. We focus on the effects of individual macronutrients, whole food products, and dietary patterns on the risks of CVD, and the data from population-based trials, observational studies, and meta-analyses are summarized. Unhealthy dietary habits, such as high intake of saturated fatty acids, sugar-sweetened beverages, red meat, and processed meat as well as high salt intake are associated with the increased risk of CVD. Conversely, increased consumption of plant-based components such as dietary fiber, nuts, fruits, and vegetables is shown to be effective in reducing CVD risk factors. The Mediterranean diet appears to be one of the most evidence-based dietary patterns beneficial for CVD prevention. However, there is still great debate regarding whether the supplementation of vitamins and minerals confers cardioprotective benefits. This review provides new insights into the role of dietary factors that are harmful or protective in CVD, which can be adopted for improved cardiovascular health.

The Impact of an 8-Week Supplementation with Fermented and Non-Fermented Aronia Berry Pulp on Cardiovascular Risk Factors in Individuals with Type 2 Diabetes.

Aronia berries contain antioxidants that may be health-promoting, e.g., demonstrated positive effects on hypertension and dyslipidaemia. There is a close link between cardiovascular diseases and hypertension and dyslipidaemia, and cardiovascular events are the leading cause of death among subjects with type 2 diabetes (T2D). Thus, we investigated the effect of an 8-week supplementation with fermented aronia extract (FAE), non-fermented aronia extract (AE), and placebo on cardiovascular risk factors. Snack bars were produced containing 34 g (37%) aronia extract, or 17 g (21%) wheat bran for placebo, as well as raisins and coconut oil. The study was randomized and blinded with a triple-crossover design. We examined the effects of aronia extracts on blood pressure, adiponectin, and high-sensitive C-reactive protein, and found no effects. After supplementation with placebo, there were significantly higher blood concentrations of total cholesterol, LDL-cholesterol, and HDL-cholesterol, with the placebo group showing significantly higher increases in total cholesterol and LDL-cholesterol than the AE group. Furthermore, we observed an increase in HDL-cholesterol in the FAE group and an increase in triglyceride in the AE group. Thus, we assume that the raisins may have increased the participants' cholesterol levels, with both AE and FAE having the potential to prevent this increase.

Reassessing the Effects of Dietary Fat on Cardiovascular Disease in China: A Review of the Last Three Decades.

Cardiovascular disease (CVD) is a leading cause of global mortality, and is considered one of diseases with the most rapid growth rate in China. Numerous studies have indicated a closed relationship between an increased incidence of CVD and dietary factors. Dietary fat is one of the three primary nutrients of consumption; however, high fat dietary in causing CVD has been neglected in some official dietary guidelines. Our present review has analyzed the relationship between dietary fat consumption and CVD in China over the past 30 years (from 1990 to 2019). There is a significant correlation between CVD incidence and mortality for consumption of both vegetable oils and animal fats, per capita consumption, and the relative weight of dietary fat exceeding that of other food ingredients (e.g., salt, fruit, and marine food). For fatty acid species, the proportion of ω6 fatty acid consumption increased, causing a significant increase in the ratios of ω6/ω3 fatty acids, whereas the proportion of monounsaturated fatty acid consumption decreased. Such changes have been considered a characteristic of dietary fat consumption in Chinese residents over the past 30 years, and are closely related to the incidence of CVD. Therefore, we suggest that the government should spread awareness regarding the consumption of dietary fat intake to prevent CVD and related health disorders. The public should be educated to avoid high fat diet and increase the intake of monounsaturated fatty acids and ω3 fatty acids.

Maternal-Periconceptional Vitamin B12 Deficiency in Wistar Rats Leads to Sex-Specific Programming for Cardiometabolic Disease Risk in the Next Generation.

BACKGROUND: Maternal vitamin B12 deficiency plays a vital role in fetal programming, as corroborated by previous studies on murine models and longitudinal human cohorts. OBJECTIVES: This study assessed the effects of diet-induced maternal vitamin B12 deficiency on F1 offspring in terms of cardiometabolic health and normalization of these effects by maternal-periconceptional vitamin B12 supplementation. METHODS: A diet-induced maternal vitamin B12 deficient Wistar rat model was generated in which female rats were either fed a control AIN-76A diet (with 0.01 g/kg vitamin B12) or the same diet with vitamin B12 removed. Females from the vitamin B12-deficient group were mated with males on the control diet. A subset of vitamin B12-deficient females was repleted with vitamin B12 on day 1 of conception. The offspring in the F1 generation were assessed for changes in body composition, plasma biochemistry, and molecular changes in the liver. A multiomics approach was used to obtain a mechanistic insight into the changes in the offspring liver. RESULTS: We showed that a 36% reduction in plasma vitamin B12 levels during pregnancy in F0 females can lead to continued vitamin B12 deficiency (60%-70% compared with control) in the F1 offspring and program them for cardiometabolic adversities. These adversities, such as high triglycerides and low high-density lipoprotein cholesterol, were seen only among F1 males but not females. DNA methylome analysis of the liver of F1 3-mo-old offspring highlights sexual dimorphism in the alteration of methylation status of genes critical to signaling processes. Proteomics and targeted metabolomics analysis confirm that sex-specific alterations occur through modulations in PPAR signaling and steroid hormone biosynthesis pathway. Repletion of deficient mothers with vitamin B12 at conception normalizes most of the molecular and biochemical changes. CONCLUSIONS: Maternal vitamin B12 deficiency has a programming effect on the next generation and increases the risk for cardiometabolic syndrome in a sex-specific manner. Normalization of the molecular risk markers on vitamin B12 supplementation indicates a causal role.

Coffee Consumption and Incidence of Cardiovascular and Microvascular Diseases in Never-Smoking Adults with Type 2 Diabetes Mellitus.

The relationship between coffee consumption and diabetes-related vascular complications remains unclear. To eliminate confounding by smoking, this study assessed the relationships of coffee consumption with major cardiovascular disease (CVD) and microvascular disease (MVD) in never-smokers with type 2 diabetes mellitus (T2DM). Included were 9964 never-smokers with T2DM from the UK Biobank without known CVD or cancer at baseline (7781 were free of MVD). Participants were categorized into four groups according to daily coffee consumption (0, 0.5-1, 2-4, ≥5 cups/day). CVD included coronary heart disease (CHD), myocardial infarction (MI), stroke, and heart failure (HF). MVD included retinopathy, peripheral neuropathy, and chronic kidney disease (CKD). Cox regression models were used to estimate hazard ratios (HRs) and 95% confidential intervals (CIs) of total CVD and MVD and the component outcomes associated with coffee consumption. During a median of 12.7 years of follow-up, 1860 cases of CVD and 1403 cases of MVD were identified. Coffee intake was nonlinearly and inversely associated with CVD (P-nonlinearity = 0.023) and the component outcomes. Compared with no coffee intake, HRs (95% CIs) associated with a coffee intake of 2 to 4 cups/day were 0.82 (0.73, 0.93) for CVD, 0.84 (0.73, 0.97) for CHD, 0.73 (0.57, 0.92) for MI, 0.76 (0.57, 1.02) for stroke, and 0.68 (0.55, 0.85) for HF. Higher coffee intake (≥5 cups/day) was not significantly associated with CVD outcomes. Coffee intake was linearly and inversely associated with risk of CKD (HR for ≥5 vs. 0 cups/day = 0.64; 95% CI: 0.45, 0.91; P-trend = 0.0029) but was not associated with retinopathy or peripheral neuropathy. Among never-smoking individuals with T2DM, moderate coffee consumption (2-4 cups/day) was associated with a lower risk of various CVD outcomes and CKD, with no adverse associations for higher consumption.

The Role of the Circadian Rhythm in Dyslipidaemia and Vascular Inflammation Leading to Atherosclerosis.

Cardiovascular diseases (CVD) are among the leading causes of death worldwide. Many lines of evidence suggest that the disturbances in circadian rhythm are responsible for the development of CVDs; however, circadian misalignment is not yet a treatable trait in clinical practice. The circadian rhythm is controlled by the central clock located in the suprachiasmatic nucleus and clock genes (molecular clock) located in all cells. Dyslipidaemia and vascular inflammation are two hallmarks of atherosclerosis and numerous experimental studies conclude that they are under direct influence by both central and molecular clocks. This review will summarise the results of experimental studies on lipid metabolism, vascular inflammation and circadian rhythm, and translate them into the pathophysiology of atherosclerosis and cardiovascular disease. We discuss the effect of time-respected administration of medications in cardiovascular medicine. We review the evidence on the effect of bright light and melatonin on cardiovascular health, lipid metabolism and vascular inflammation. Finally, we suggest an agenda for future research and recommend on clinical practice.

Paralysis under pressure.

Treating cardiovascular paralysis with epidural electrical neuromodulation.

Serum 25(OH)D Concentration, Vitamin D Supplementation, and Risk of Cardiovascular Disease and Mortality in Patients with Type 2 Diabetes or Prediabetes: a Systematic Review and Dose-Response Meta-Analysis.

BACKGROUND: Evidence is uncertain about the association between serum 25-hydroxyvitamin D (25(OH)D) concentration and health outcomes in people with type 2 diabetes. OBJECTIVES: We aimed to assess the association between vitamin D status and all-cause mortality and cardiovascular disease in people with type 2 diabetes. METHODS: We did a systematic search in PubMed, Scopus, CENTRAL, and Web of Science until May 2022. We selected 1) cohort studies investigating the association between serum 25(OH)D concentration and mortality or cardiovascular disease in people with type 2 diabetes or prediabetes and 2) randomized trials of vitamin D supplementation in these patients. We used random-effects pairwise meta-analyses to calculate summary relative risks (RRs) and 95% confidence intervals (CI). RESULTS: 21 cohort studies and 6 randomized trials were included. Compared with sufficient vitamin D status (≥50 nmol/L), the RR of all-cause mortality was 1.36 (95% CI: 1.23, 1.49; n = 11 studies, GRADE = moderate) for vitamin D insufficiency (25 to <50 nmol/L), and 1.58 (1.33, 1.83; n = 16, GRADE = moderate) for deficiency (<25 nmol/L). Similar findings were observed for cardiovascular mortality and morbidity but not for cancer mortality. The certainty of evidence ranged from very low to moderate. Dose-response meta-analyses indicated nonlinear associations, with the lowest risk at 25(OH)D ∼60 nmol/L for all-cause and cardiovascular mortality. Supplementation with vitamin D did not reduce the risk of all-cause mortality (RR: 0.96, 95% CI: 0.79, 1.16; risk difference per 1000 patients: 3 fewer, 95% CI: 16 fewer, 12 more; n = 6 trials with 7316 participants; GRADE = low) or the risk of cardiovascular mortality and morbidity (very low- to low-certainty evidence). CONCLUSIONS: Vitamin D deficiency and insufficiency are associated with a higher risk of all-cause and cardiovascular mortality in patients with type 2 diabetes or prediabetes. Vitamin D deficiency should be corrected in patients with type 2 diabetes to reach normal serum 25(OH)D concentrations, preferably 60 nmol/L. SYSTEMATIC REVIEW REGISTRATION: This systemic review was registered at PROSPERO as CRD42022326429 (=https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=326429).

Milk-Fat-Globule-Membrane-Enriched Dairy Milk Compared with a Soy-Lecithin-Enriched Beverage Did Not Adversely Affect Endotoxemia or Biomarkers of Gut Barrier Function and Cardiometabolic Risk in Adults with Metabolic Syndrome: A Randomized Controlled Crossover Trial.

Full-fat dairy milk may protect against cardiometabolic disorders, due to the milk fat globule membrane (MFGM), through anti-inflammatory and gut-health-promoting activities. We hypothesized that a MFGM-enriched milk beverage (MEB) would alleviate metabolic endotoxemia in metabolic syndrome (MetS) persons by improving gut barrier function and glucose tolerance. In a randomized crossover trial, MetS persons consumed for two-week period a controlled diet with MEB (2.3 g/d milk phospholipids) or a comparator beverage (COMP) formulated with soy phospholipid and palm/coconut oil. They then provided fasting blood and completed a high-fat/high-carbohydrate test meal challenge for evaluating postprandial metabolism and intestinal permeability. Participants had no adverse effects and achieved high compliance, and there were no between-trial differences in dietary intakes. Compared with COMP, fasting endotoxin, glucose, incretins, and triglyceride were unaffected by MEB. The meal challenge increased postprandial endotoxin, triglyceride, and incretins, but were unaffected by MEB. Insulin sensitivity; fecal calprotectin, myeloperoxidase, and short-chain fatty acids; and small intestinal and colonic permeability were also unaffected by MEB. This short-term study demonstrates that controlled administration of MEB in MetS persons does not affect gut barrier function, glucose tolerance, and other cardiometabolic health biomarkers, which contradicts observational evidence that full-fat milk heightens cardiometabolic risk. Registered at ClinicalTrials.gov (NCT03860584).

Dietary Intake and Arterial Stiffness in Children and Adolescents: A Systematic Review.

Arterial stiffness is a risk factor for cardiovascular disease that is affected by diet. However, research understanding how these dietary risk factors are related to arterial stiffness during childhood is limited. The purpose of this review was to determine whether various dietary factors were associated with arterial stiffness in the pediatric population. Five databases were systematically searched. Intervention studies, cross-sectional and cohort studies were included that investigated nutrient or food intake and outcomes of arterial stiffness, primarily measured by pulse wave velocity (PWV) and augmentation index (AIx), in the pediatric population (aged 0-18 years). A final 19 studies (six intervention and 13 observational) were included. Only two intervention studies, including a vitamin D and omega-3 supplementation trial, found protective effects on PWV and AIx in adolescents. Findings from observational studies were overall inconsistent and varied. There was limited evidence to indicate a protective effect of a healthy dietary pattern on arterial stiffness and an adverse effect of total fat intake, sodium intake and fast-food consumption. Overall, results indicated that some dietary factors may be associated with arterial stiffness in pediatric populations; however, inconsistencies were observed across all study designs. Further longitudinal and intervention studies are warranted to confirm the potential associations found in this review.

Plasma fatty acid composition and some markers of dietary habits are associated with cardiovascular disease risk determined by an atherogenic plasma index in postmenopausal women.

It is hypothesized that plasma proportion of selected fatty acids (FAs) and dietary habits are linked with the risk of cardiovascular disease (CVD) in postmenopausal women. Therefore, this study was designed to determine the association of plasma FA composition and markers of dietary habits with an atherogenic index of plasma (AIP), a predictor of CVD risk in postmenopausal women. In total, 87 postmenopausal women with an average age of 57 ± 7 years were recruited and their dietary intake, anthropometric and biochemical parameters, and FA status in total plasma lipid proportions were determined, showing that 65.5% of the participants had a high risk of CVD according to their AIP value. After adjusting for some confounders (age, body mass index, and physical activity level), the risk of CVD was only positively associated with the frequency of consumption of animal fat spreads (butter and lard) of terrestrial origin. Regarding the FA profile, CVD risk was positively associated with the percentages of vaccenic acid, dihomo-γ-linolenic acid, and monounsaturated fatty acids (MUFA; mainly n-7) in total FA, as well as the MUFA/SFA ratio in total plasma and stearoyl-CoA desaturase-16 activity (16:1/16:0 ratio). In contrast, the risk of CVD was negatively associated with percentages of α-linolenic acid, total polyunsaturated fatty acids (PUFA), and PUFA/MUFA ratio in total plasma lipid, and the estimated activity of Δ5-desaturase (20:4/20:3 n-6 ratio). These results support the current recommendations to decrease the frequency of animal fat spread intake because it is associated with a reduced CVD risk based on AIP in postmenopausal women. In accordance with these plasma percentages of ALA, vaccenic acid, dihomo-γ-linolenic acid, PUFA, PUFA/MUFA ratio, and 16:1/16:0 ratio may be important parameters in CVD risk assessment.

[Influence of chronic pain in osteoarthritis on the risk of cardiovascular diseases and modern methods of drug prevention]. / Vliyanie khronicheskoi boli pri osteoartrite na risk razvitiya serdechno-sosudistykh zabolevanii i sovremennye sposoby ikh lekarstvennoi profilaktiki.

The purpose of the review of scientific medical literature was to evaluate the data of the epidemiology of osteoarthritis (OA) and cardiovascular diseases (CVD) with the analysis of risk factors, pathophysiological and pathobiochemical mechanisms of the relationship between OA and the risk of developing CVD in the presence of chronic pain, modern strategies for screening and management of this cohort of patients, the mechanism of action and pharmacological effects of chondroitin sulfate (CS). Conclusions were drawn about the need for additional clinical and observational studies of the efficacy and safety of the parenteral form of CS (Chondroguard) in patients with chronic pain in OA and CVD, improvement of clinical recommendations for the treatment of chronic pain in patients with OA and cardiovascular risk, with special attention to interventions that eliminate mobility restrictions in patients and the inclusion of basic and adjuvant therapy with DMOADs to achieve the goals of multipurpose monotherapy in patients with contraindications to standard therapy drugs.

Coconut oil: an overview of cardiometabolic effects and the public health burden of misinformation.

Recent data from meta-analyses of randomized clinical trials (RCTs) suggest that dietary intake of coconut oil, rich in saturated fatty acids, does not result in cardiometabolic benefits, nor in improvements in anthropometric, lipid, glycemic, and subclinical inflammation parameters. Nevertheless, its consumption has surged in recent years all over the world, a phenomenon which can possibly be explained by an increasing belief among health professionals that this oil is as healthy as, or perhaps even healthier than, other oils, in addition to social network misinformation spread. The objective of this review is to present nutritional and epidemiological aspects related to coconut oil, its relationship with metabolic and cardiovascular health, as well as possible hypotheses to explain its high rate of consumption, in spite of the most recent data regarding its actual effects.

Does the Combination of Finnish Sauna Bathing and Other Lifestyle Factors Confer Additional Health Benefits? A Review of the Evidence.

Sauna bathing, a tradition deeply rooted in the Finnish culture, has been used for thousands of years for leisure, relaxation, and wellness. Sauna bathing is linked with substantial health benefits beyond its use for leisure and relaxation. Several observational and interventional studies suggest that regular or frequent sauna bathing reduces the incidence of vascular and nonvascular diseases, such as hypertension, cardiovascular disease, dementia, and respiratory conditions; may improve the severity of conditions such as musculoskeletal disorders, COVID-19, headache, and influenza; and increases the life span. The beneficial effects of sauna bathing on adverse outcomes have been linked to its blood pressure-reducing, anti-inflammatory, antioxidant, cytoprotective, and stress-reducing properties and its synergistic effect on neuroendocrine, circulatory, cardiovascular, and immune function. Evidence suggests that frequent sauna bathing is an emerging protective risk factor that may augment the beneficial effects of other protective risk or lifestyle factors, such as physical activity and cardiorespiratory fitness, or attenuate or offset the adverse effects of other risk factors, such as high blood pressure, systemic inflammation, and low socioeconomic status. This review summarizes the available epidemiologic and interventional evidence linking the combined effects of Finnish sauna bathing and other risk factors on vascular outcomes including cardiovascular disease and intermediate cardiovascular phenotypes, nonvascular outcomes, and mortality. We also discuss the mechanistic pathways underlying the joint contributions of Finnish sauna bathing and other risk factors on health outcomes, the public health and clinical implications of the findings, gaps in the existing evidence base, and future directions.