Pharmacotherapy and revascularization strategies of peripheral artery disease.

The global epidemiological transition of atherosclerotic vascular diseases is witnessing a rapid redistribution of its burden, shifting from high-income to low- and middle-income countries. With a wide clinical spectrum, spanning from intermittent claudication to more complex critical limb threatening ischemia, nonhealing ulcers, gangrene as well as acute limb ischemia, peripheral artery disease is often faced with the challenges of under-diagnosis and under-treatment despite its high prevalence. The management of peripheral arterial disease in patients with multiple comorbidities presents a formidable challenge and remains a pressing global health concern. In this review, we aim to provide an in-depth overview of the pathophysiology of peripheral artery disease and explore evidence-based management strategies encompassing pharmacological, lifestyle, interventional, and surgical approaches. By addressing these challenges, the review contributes to a better understanding of the evolving landscape of peripheral artery disease, offering insights into effective and holistic management strategies.

The Effect of Yoga on Cardiovascular Disease Risk Factors: A Meta-Analysis.

Yoga has been increasingly popular yet has shown inconsistent benefits on cardiovascular disease (CVD) risk factors. We aimed to systematically analyze the effect of yoga on modifiable CVD risk factors. We systematically searched Ovid MEDLINE, Ovid Embase, Ovid Cochrane Database of Systematic Reviews, Scopus, and Web of Science from database inception in 1966 through June 2022 for studies evaluating the association between yoga and blood pressure, lipid profile, HbA1c and body mass index (BMI). Two investigators independently reviewed data. Conflicts were resolved through consensus. Random-effects meta-analyses were used. 64 RCTs including a total of 16,797 participants were eligible for inclusion in the meta-analysis. Yoga therapy improved both systolic as well as diastolic blood pressure (weight mean difference [WMD] (95% Confidence interval [CI]) of -4.56 [-6.37, -2.75] mm Hg, WMD [95% CI] - 3.39 [-5.01, -1.76] mm Hg respectively). There was also an improvement in BMI as well as hemoglobin A1c (HbA1c) (WMD [95% CI] of -0.57 [-1.05, -0.10] kg/m2, WMD [95% CI] of -0.14 [-0.24, -0.030] mmol/L respectively) . In addition, all parameters of the lipid profile, including low-density lipoprotein cholesterol (LDL-C) showed a significant improvement with yoga therapy (WMD [95% CI] -7.59 [-12.23, -2.95] mg/dL for LDL-C). Yoga has a modest yet positive effect on blood pressure, BMI, lipid profile and HbA1c and, therefore, may play an ancillary role in primary prevention of CVD.

Update on Omega-3 Polyunsaturated Fatty Acids on Cardiovascular Health.

Twenty percent of deaths in the United States are secondary to cardiovascular diseases (CVD). In patients with hyperlipidemia and hypertriglyceridemia, studies have shown high atherosclerotic CVD (ASCVD) event rates despite the use of statins. Given the association of high triglyceride (TG) levels with elevated cholesterol and low levels of high-density lipoprotein cholesterol, the American Heart Association (AHA)/American College of Cardiology (ACC) cholesterol guidelines recommend using elevated TGs as a "risk-enhancing factor" for ASCVD and using omega 3 fatty acids (Ω3FAs) for patients with persistently elevated severe hypertriglyceridemia. Ω3FA, or fish oils (FOs), have been shown to reduce very high TG levels, hospitalizations, and CVD mortality in randomized controlled trials (RCTs). We have published the largest meta-analysis to date demonstrating significant effects on several CVD outcomes, especially fatal myocardial infarctions (MIs) and total MIs. Despite the most intensive research on Ω3FAs on CVD, their benefits have been demonstrated to cluster across multiple systems and pathologies, including autoimmune diseases, infectious diseases, chronic kidney disease, central nervous system diseases, and, most recently, the COVID-19 pandemic. A review and summary of the controversies surrounding Ω3FAs, some of the latest evidence-based findings, and the current and most updated recommendations on Ω3FAs are presented in this paper.

Comparing eligibility for statin therapy for primary prevention under 2022 USPSTF recommendations and the 2018 AHA/ACC/ multi-society guideline recommendations: From National Health and Nutrition Examination Survey.

INTRODUCTION: The United States Preventive Services Taskforce (USPSTF) recently released recommendations for statin therapy eligibility for the primary prevention of cardiovascular disease (CVD). We report the proportion and the absolute number of US adults who would be eligible for statin therapy under these recommendations and compare them with the previously published 2018 American Heart Association (AHA)/ American College of Cardiology (ACC)/ Multisociety (MS) Cholesterol guidelines. METHODS: We used data from the National Health and Nutrition Examination Survey (NHANES) 2017-2020 of adults aged 40-75 years without prevalent self-reported atherosclerotic CVD (ASCVD) and low-density lipoprotein-cholesterol <190 mg/dL. The 2022 USPSTF recommends statin therapy for primary prevention in those with a 10-year ASCVD risk of ≥10% and ≥ 1 CVD risk factor (diabetes mellitus, dyslipidemia, hypertension, or smoking). The 2018 AHA/ ACC/ MS Cholesterol guideline recommends considering statin therapy for primary prevention for those with diabetes mellitus, or 10-year ASCVD risk ≥20% or 10-year ASCVD risk 7.5 to <20% after accounting for risk-enhancers and shared decision making. Survey recommended weights were used to project these proportions to national estimates. RESULTS: Among 1799 participants eligible for this study, the weighted mean age was 56.0 ± 0.5 years, with 53.0% women (95% confidence interval [CI] 49.7, 56.3), and 10.6% self-reported NH Black individuals (95% CI 7.7, 14.3). The weighted mean 10-year ASCVD risk was 9.6 ± 0.3%. The 2022 USPSTF recommendations and the 2018 AHA/ ACC/ MS Cholesterol guidelines indicated eligibility for statin therapy in 31.8% (95% CI 28.6, 35.1) and 46.8% (95% CI 43.0, 50.5) adults, respectively. These represent 33.7 million (95% CI 30.4, 37.2) and 49.7 million (95% CI 45.7, 53.7) adults, respectively. For those with diabetes mellitus, 2022 USPSTF recommended statin therapy in 63.0% (95% CI 52.1, 72.7) adults as compared with all adults with diabetes aged 40-75 years under the 2018 AHA/ ACC/ MS Cholesterol guidelines. CONCLUSION: In this analysis of the nationally representative US population from 2017 to 2020, approximately 15% (~16.0 million) fewer adults were eligible for statin therapy for primary prevention under the 2022 USPSTF recommendations as compared to the 2018 AHA/ ACC/ MS Cholesterol guideline.

Association Between Cinnamon Consumption and Risk of Cardiovascular Health: A Systematic Review and Meta-Analysis.

BACKGROUND: Cinnamon has been used as a traditional herbal medication for decades. Several studies have investigated cinnamon consumption and cardiovascular risk. So far, the evidence remains inconclusive. Thus, we aim to systematically review the currently available literature and quantify the evidence, if possible. METHODS: We systematically searched Ovid MEDLINE, Ovid Embase, Ovid Cochrane Database of Systematic Reviews, Scopus, and Web of Science from database inception in 1966 through December 2020. The exposure of interest was cinnamon consumption, the outcome was cardiovascular risk defined as hemoglobin A1C, low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c). Two investigators independently reviewed the data. Conflicts were resolved through consensus. Random-effects meta-analyses were used. RESULTS: Of 23 studies (1070 subjects), the included studies were heterogeneous, generally of very poor quality. We found no difference in LDL-c levels in patients who consumed cinnamon vs those who did not, with a weighted mean difference (WMD) of 0.38 (confidence interval [CI], -6.07-6.83). We also found no difference in HDL-c between the 2 groups with WMD 0.40 (CI, -1.14-1.94). In addition, we found no statistical differences in hemoglobin A1C between the 2 groups with WMD of 0.0 (CI, -0.44-0.45). CONCLUSIONS: Our meta-analysis suggests that there is no association between cinnamon consumption and differences in LDL-c, HDL-c, and hemoglobin A1C levels. Further randomized control trials studies using a robust design with long-term cinnamon consumption are needed to further investigate any potential effect.

The COVID-19 pandemic and physical activity during intermittent fasting, is it safe? A call for action.

Intermittent fasting (IF) has recently gained popularity, and has been used for centuries in many religious practices. The Ramadan fasting is a mandatory form of IF practiced by millions of healthy adult Muslims globally for a whole lunar month every year. In Islam, the "Sunna" also encourages Muslims to practice IF all along the year (e.g.; two days a week). The 2019-Coronavirus disease (COVID-19) pandemic in the context of Ramadan has raised the question whether fasting is safe practice during the COVID-19 pandemic health crisis, and what would be the healthy lifestyle behaviors while fasting that would minimize the risk of infection. As COVID-19 lacks a specific therapy, IF and physical activity could help promote human immunity and be part of holistic preventive strategy against COVID-19. In this commentary, the authors focus on this dilemma and provide recommendations to the fasting communities for safely practicing physical activity in time of COVID-19 pandemic.

Prevention and Treatment of Atrial Fibrillation via Risk Factor Modification.

Atrial fibrillation (AF) is the most common clinically significant arrhythmia, and it increases stroke risk. A preventive approach to AF is needed because virtually all treatments such as cardioversion, antiarrhythmic drugs, ablation, and anticoagulation are associated with high cost and carry significant risk. A systematic review was performed to identify effective lifestyle-based strategies for reducing primary and secondary AF. A PubMed search was performed using articles up to March 1, 2021. Search terms included atrial fibrillation, atrial flutter, exercise, diet, metabolic syndrome, type 2 diabetes mellitus, obesity, hypertension, stress, tobacco smoking, alcohol, Mediterranean diet, sodium, and omega-3 fatty acids. Additional articles were identified from the bibliographies of retrieved articles. The control of hypertension, ideally with a renin-angiotensin-aldosterone system inhibitor, is effective for preventing primary AF and recurrence. Obstructive sleep apnea is a common cause of AF, and treating it effectively reduces AF episodes. Alcohol increases the risk of AF in a dose-dependent manner, and abstinence reduces risk of recurrence. Sedentary behavior and chronic high-intensity endurance exercise are both risk factors for AF; however, moderate physical activity is associated with lower risk of AF. Recently, sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 agonists have been associated with reduced risk of AF. Among overweight/obese patients, weight loss of ≥10% is associated with reduced AF risk. Lifestyle changes and risk factor modification are highly effective for preventing AF.

Impact of nutraceuticals on markers of systemic inflammation: Potential relevance to cardiovascular diseases - A position paper from the International Lipid Expert Panel (ILEP).

Inflammation is a marker of arterial disease stemming from cholesterol-dependent to -independent molecular mechanisms. In recent years, the role of inflammation in atherogenesis has been underpinned by pharmacological approaches targeting systemic inflammation that have led to a significant reduction in cardiovascular disease (CVD) risk. Although the use of nutraceuticals to prevent CVD has largely focused on lipid-lowering (e.g, red-yeast rice and omega-3 fatty acids), there is growing interest and need, especially now in the time of coronavirus pandemic, in the use of nutraceuticals to reduce inflammatory markers, and potentially the inflammatory CVD burden, however, there is still not enough evidence to confirm this. Indeed, diet is an important lifestyle determinant of health and can influence both systemic and vascular inflammation, to varying extents, according to the individual nutraceutical constituents. Thus, the aim of this Position Paper is to provide the first attempt at recommendations on the use of nutraceuticals with effective anti-inflammatory properties.

Beyond cardioversion, ablation and pharmacotherapies: Risk factors, lifestyle change and behavioral counseling strategies in the prevention and treatment of atrial fibrillation.

IMPORTANCE: It has been suggested that atrial fibrillation (AF) is the new cardiovascular disease epidemic of the 21st century. Clinical cardiology has largely focused on AF treatment and associated stroke prevention rather than preventing AF itself. To reduce the global consequences and associated costs of AF, it is critical to now embrace prevention as a priority. Proactively addressing the risk factors for AF and the underlying unhealthy lifestyle habits that contribute to them, using research-based counseling approaches, represents a complementary and adjunctive alternative in combatting this disease burden. OBSERVATIONS: Encouraging and sustaining patient involvement to reduce AF incidence and improve outcomes begins with screening to identify risk factors, unhealthy lifestyle habits, and characteristics associated with failed attempts at favorably modifying these causalities. Modulators of and common barriers to achieving risk reduction and lifestyle change include self-efficacy, social support, age, sex, marital and socioeconomic status, education, employment, and psychosocial factors such as depression, isolation, anxiety and chronic life stress. Focused behavioral counseling approaches, including assessing the patient's readiness to change, motivational interviewing and using the 5 A's (assess, advise, agree, assist, arrange), along with employing initial downscaled goals to overcome inertia, are proven methodologies to overcome these common barriers to favorably modifying risk factors and unhealthy lifestyle habits. CONCLUSIONS AND RELEVANCE: To complement and enhance the current armamentarium for the medical management of cardiac arrhythmias, there is an urgent need to proactively address the causative factors triggering new-onset, recurrent and persistent AF. Beyond the counseling skills of highly trained professionals (eg, psychiatrists, psychologists), this narrative review highlights the need for and potential impact on lifestyle modification that non-behavioral scientists, including internal medicine, cardiology, and allied health professionals, can have on the patients they serve.

Finnish sauna and COVID-19.

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Vitamin D and cardiovascular health.

The principal source of vitamin D in humans is its biosynthesis in the skin through a chemical reaction dependent on sun exposure. In lesser amounts, the vitamin can be obtained from the diet, mostly from fatty fish, fish liver oil and mushrooms. Individuals with vitamin D deficiency, defined as a serum level of 25 hydroxyvitamin D < 20 ng/dl, should be supplemented. Vitamin D deficiency is a prevalent global problem caused mainly by low exposure to sunlight. The main role of 1,25 dihydroxyvitamin D is the maintenance of calcium and phosphorus homeostasis. However, vitamin D receptors are found in most human cells and tissues, indicating many extra-skeletal effects of the vitamin, particularly in the immune and cardiovascular (CV) systems. Vitamin D regulates blood pressure by acting on endothelial cells and smooth muscle cells. Its deficiency has been associated with various CV risk factors and appears to be linked to a higher mortality and incidence of CV disease (CVD). Several mechanisms have been proposed relating vitamin D deficiency to CV risk factors such as renin-angiotensin-aldosterone system activation, abnormal nitric oxide regulation, oxidative stress or altered inflammatory pathways. However, in the latest randomized controlled trials no benefits of vitamin D supplementation for CVD have been confirmed. Although more work is needed to establish the protective role of vitamin D in this setting, according to current evidences vitamin D supplements should not be recommended for CVD prevention.

An Update on Omega-3 Polyunsaturated Fatty Acids and Cardiovascular Health.

Interest in the potential cardiovascular (CV) benefits of omega-3 polyunsaturated fatty acids (Ω-3) began in the 1940s and was amplified by a subsequent landmark trial showing reduced CV disease (CVD) risk following acute myocardial infarction. Since that time, however, much controversy has circulated due to discordant results among several studies and even meta-analyses. Then, in 2018, three more large, randomized trials were released-these too with discordant findings regarding the overall benefits of Ω-3 therapy. Interestingly, the trial that used a higher dose (4 g/day highly purified eicosapentaenoic acid (EPA)) found a remarkable, statistically significant reduction in CVD events. It was proposed that insufficient Ω-3 dosing (<1 g/day EPA and docosahexaenoic acid (DHA)), as well as patients aggressively treated with multiple other effective medical therapies, may explain the conflicting results of Ω-3 therapy in controlled trials. We have thus reviewed the current evidence regarding Ω-3 and CV health, put forth potential reasoning for discrepant results in the literature, highlighted critical concepts such as measuring blood levels of Ω-3 with a dedicated Ω-3 index and addressed current recommendations as suggested by health care professional societies and recent significant scientific data.

Effect of Omega-3 Dosage on Cardiovascular Outcomes: An Updated Meta-Analysis and Meta-Regression of Interventional Trials.

OBJECTIVES: To quantify the effect of eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids on cardiovascular disease (CVD) prevention and the effect of dosage. METHODS: This study is designed as a random effects meta-analysis and meta-regression of randomized control trials with EPA/DHA supplementation. This is an update and expanded analysis of a previously published meta-analysis which covers all randomized control trials with EPA/DHA interventions and cardiovascular outcomes published before August 2019. The outcomes included are myocardial infarction (MI), coronary heart disease (CHD) events, CVD events (a composite of MI, angina, stroke, heart failure, peripheral arterial disease, sudden death, and non-scheduled cardiovascular surgical interventions), CHD mortality and fatal MI. The strength of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation framework. RESULTS: A total of 40 studies with a combined 135,267 participants were included. Supplementation was associated with reduced risk of MI (relative risk [RR], 0.87; 95% CI, 0.80 to 0.96), high certainty number needed to treat (NNT) of 272; CHD events (RR, 0.90; 95% CI, 0.84 to 0.97), high certainty NNT of 192; fatal MI (RR, 0.65; 95% CI, 0.46 to 0.91]), moderate certainty NNT = 128; and CHD mortality (RR, 0.91; 95% CI, 0.85 to 0.98), low certainty NNT = 431, but not CVD events (RR, 0.95; 95% CI, 0.90 to 1.00). The effect is dose dependent for CVD events and MI. CONCLUSION: Cardiovascular disease remains the leading cause of death worldwide. Supplementation with EPA and DHA is an effective lifestyle strategy for CVD prevention, and the protective effect probably increases with dosage.

Cardiovascular Effects of ADHD Therapies: JACC Review Topic of the Week.

Although the prevalence of attention-deficit/hyperactivity disorder (ADHD) has been stable over the past 3 decades, prescriptions of sympathomimetic stimulants have steadily increased in the United States. This study consisted of a systematic review of PubMed articles screened for ADHD medications and potential cardiovascular toxicity as well as nondrug strategies for managing ADHD. The cumulative body of data showed that ADHD medications cause modest elevations in resting heart rate and blood pressure. Other adverse effects reported with ADHD stimulants included arrhythmia, nonischemic cardiomyopathy, Takotsubo cardiomyopathy, and sudden death. However, such reports did not imply causation, and there was a paucity of randomized trial evidence addressing long-term safety of ADHD medications, particularly among adults. Further studies are essential to clarify the risks and benefits of ADHD stimulant medications and to explore nonpharmacological options, including regular exercise and omega-3 fatty acids, which could be helpful for improving ADHD symptoms.

Do Antioxidant Vitamins Prevent Exercise-Induced Muscle Damage? A Systematic Review.

Free radicals produced during exercise play a role in modulating cell signaling pathways. High doses of antioxidants may hamper adaptations to exercise training. However, their benefits are unclear. This review aims to examine whether vitamin C (VitC) and/or vitamin E (VitE) supplementation (SUP) prevents exercise-induced muscle damage. The PubMed, Web of Science, Medline, CINAHL, and SPORTDiscus databases were searched, and 21 articles were included. Four studies examined the effects of acute VitC SUP given pre-exercise: in one study, lower CK levels post-exercise was observed; in three, no difference was recorded. In one study, acute VitE SUP reduced CK activity 1 h post-exercise in conditions of hypoxia. In three studies, chronic VitE SUP did not reduce CK activity after an exercise session. Chronic VitE SUP did not reduce creatine kinase (CK) concentrations after three strength training sessions, but it was effective after 6 days of endurance training in another study. Chronic SUP with VitC + E reduced CK activity post-exercise in two studies, but there was no such effect in four studies. Finally, three studies described the effects of chronic VitC + E SUP and long-term exercise, reporting dissimilar results. To conclude, although there is some evidence of a protective effect of VitC and/or VitE against exercise-induced muscle damage, the available data are not conclusive.