Cardiovascular Effects of Stimulators of Soluble Guanylate Cyclase Administration: A Meta-analysis of Randomized Controlled Trials.

PURPOSE OF REVIEW: Heart failure (HF) is one of the main causes of cardiovascular mortality in the western world. Despite great advances in treatment, recurrence and mortality rates remain high. Soluble guanylate cyclase is an enzyme which, by producing cGMP, is responsible for the effects of vasodilation, reduction of cardiac pre- and after-load and, therefore, the improvement of myocardial performance. Thus, a new therapeutic strategy is represented by the stimulators of soluble guanylate cyclase (sGCs). The aim of this meta-analysis was to analyze the effects deriving from the administration of sGCs, in subjects affected by HF. A systematic literature search of Medline, SCOPUS, and Google Scholar was conducted up to December 2022 to identify RCTs assessing the cardiovascular effects, as NT-pro-BNP values and ejection fraction (EF), and all-cause mortality, of the sGCs. Quantitative data synthesis was performed using a random-effects model, with weighted mean difference (WMD) and 95% confidence interval (CI) as summary statistics. RECENT FINDINGS: The results obtained documented a statistically significant improvement in NT-proBNP values (SMD: - 0.258; 95% CI: - 0.398, - 0.118; p < 0.001) and EF (WMD: 0.948; 95% CI: 0.485, 1.411; p < 0.001) in subjects treated with sGCs; however, no significant change was found in the all-cause mortality rate (RR 0.96; 95% CI 0.868 to 1.072; I2, p = 0). The sGCs represent a valid therapeutic option in subjects suffering from HF, leading to an improvement in cardiac performance.

Gender Differences in Epidemiology, Pathophysiology, and Treatment of Hypertension.

PURPOSE OF REVIEW: This review aims to examine gender differences in both the epidemiology and pathophysiology of hypertension and to explore gender peculiarities on the effects of antihypertensive agents in decreasing BP and CV events. RECENT FINDINGS: Men and women differ in prevalence, awareness, and control rate of hypertension in an age-dependent manner. Studies suggest that sex hormones changes play a pivotal role in the pathophysiology of hypertension in postmenopausal women. Estrogens influence the vascular system inducing vasodilatation, inhibiting vascular remodeling processes, and modulating the renin-angiotensin aldosterone system and the sympathetic system. This leads to a protective effect on arterial stiffness during reproductive age that is dramatically reversed after menopause. Data on the efficacy of antihypertensive therapy between genders are conflicting, and the underrepresentation of aged women in large clinical trials could influence the results. Therefore, further clinical research is needed to uncover potential gender differences in hypertension to promote the development of a gender-oriented approach to antihypertensive treatment.

Gender differences in cardiovascular prophylaxis: Focus on antiplatelet treatment.

Cardiovascular disease (CVD) represents the leading cause of death worldwide, and equally affects both sexes although women develop disease at an older age than men. A number of clinical evidence has identified the female sex as an independent factor for poor prognosis, with the rate of mortality and disability following an acute cardiovascular (CV) event being higher in women than men. It has been argued that the different level of platelet reactivity between sexes may account for a different responsiveness to anti-platelet therapy, with consequent important implications on clinical outcomes. However, conclusive evidence supporting the concept of a gender-dependent effectiveness of platelet inhibitors are lacking. On the contrary, sex-related dissimilarities have been evidenced in cardiovascular patients in terms of age of presentation, comorbidities such as obesity, diabetes and renal disease, and a different pharmacological approach to and effectiveness in controlling classical cardiovascular risk factors such as hypertension, glucose profile and lipid dysmetabolism. All these factors could place women at an increased level of cardiovascular risk compared to men, and may concur to an enhanced pro-thrombogenic profile. The purpose of this manuscript is to provide an overview of gender-related differences in cardiovascular treatment, in order to highlight the need to improve the pharmacological prophylaxis adopted in women through a more accurate evaluation of the overall cardiovascular risk profile with consequent establishment of a more effective and targeted anti-thrombotic strategy which is not limited to the use of anti-platelet agents.

Impact of statin therapy on plasma resistin and visfatin concentrations: A systematic review and meta-analysis of controlled clinical trials.

The beneficial effects of statin therapy in reducing cardiovascular morbidity and mortality is not merely explained by the lipid-modulating effects. Although adipokines levels have been associated with cardiometabolic disorders, a few studies have explored the effect of statin on resistin and visfatin. We aimed to evaluate the impact of statin therapy on levels of resistin and visfatin through a meta-analysis of published studies. A systematic literature search in Medline and SCOPUS databases was conducted up to January 2015 to identify controlled trials assessing changes in plasma concentrations of visfatin and resistin during treatment with statins. Quantitative data synthesis was performed using a random-effects model, with weighed mean difference (WMD) and 95% confidence interval (CI) as summary statistics. 12 eligible studies with 14 treatment arms were included. Overall, 844 participants were studied. No significant change in plasma resistin concentrations was observed following statin therapy (WMD: -0.11ng/mL, CI: -1.94,1.73, p=0.909). This effect was robust and not affected by statin type, treatment duration and LDL-cholesterol concentrations. With respect to visfatin concentrations, there was a marginally significant reduction following statin therapy (WMD: -2.40ng/mL, CI: -4.79,-0.002, p=0.050). However, this effect size was weak and sensitive to three of the trials included in the analysis. This meta-analysis did not suggest any effect of statin therapy on plasma resistin levels, while a slight reduction in visfatin levels was found. The effect of statins on visfatin levels may represent a novel pleiotropic characteristic of these drugs.

Gender-related differences in pulmonary arterial hypertension targeted drugs administration.

During the last 15 years, a real "paradigm-shift" occurred, due to the development of PAH-targeted drugs, leading to crucial improvements in symptoms, exercise capacity, hemodynamics and outcome of PAH patients. In order to describe differences regarding epidemiology and therapy in PAH according to gender, we performed a review of the available literature in "PubMed" and "Web of Science" databases. In order to find relevant articles, we combined each of the following the keywords "pulmonary arterial hypertension", "gender", "sex", "men", "woman", "male", "female", "phosphodiesterase inhibitors", "endothelin receptor antagonists", "prostanoids". While there is a substantial agreement among epidemiological studies in reporting an increased prevalence of pulmonary arterial hypertension (PAH) among women, male PAH patients are affected by a higher impairment of the right ventricular function and consequently experience poorer outcomes. With regards to PAH-targeted drug administration, endothelin receptor antagonists (ERAs) and prostacyclin analogues (PC) show better treatment results in female PAH patients, while phosphodiesterase-5 inhibitors (PD5-I) seem to exert a more beneficial effect on male patients. However, to date no clear consensus could be formed by the available literature, which is constituted mainly by retrospective studies. Females with PAH are more prone to develop PAH, while males experience poorer outcomes. Females PAH might benefit more from ERAs and PC, while males seem to have more beneficial effects from PD5-I administration. However, more research is warranted in order to assess the most effective treatment for PAH patients according to gender.

Effect of monoclonal antibodies to PCSK9 on high-sensitivity C-reactive protein levels: a meta-analysis of 16 randomized controlled treatment arms.

AIMS: Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are an emerging class of low-density lipoprotein cholesterol (LDL-C)-lowering agents. In spite of their known effects on lipids, the impact of these drugs on systemic inflammation is less known. We aimed to investigate the effect of PCSK9 inhibitors on high-sensitivity C-reactive protein (hs-CRP) levels through a meta-analysis of randomized controlled trials (RCTs). METHODS: A systematic literature search of Medline, SCOPUS and Google Scholar was conducted up to December 2015 to identify RCTs assessing changes in hs-CRP concentrations during treatment with PCSK9 inhibitors. Quantitative data synthesis was performed using a random-effects model, with weighed mean difference (WMD) and 95% confidence interval (CI) as summary statistics. RESULTS: Sixteen treatment arms, with a total of 2546 participants, were included. Random-effects meta-analysis did not show any significant effect of PCSK9 inhibitors on hs-CRP levels (WMD: 0.002 mg l(-1) , CI: -0.017, 0.021; P = 0.807; I(2) = 37.26%). This effect size was robust, not sensitive to any single study, and not affected by the type of PCSK9 inhibitor (evolocumab: WMD: 0.002 mg l(-1) , CI: -0.02, 0.02; P = 0.855; alirocumab WMD: 0.15 mg l(-1) , CI: -0.11, 0.40; P = 0.259; I(2) = 0%), or dosing frequency (biweekly: WMD: 0.13 mg l(-1) , CI: -0.20, 0.46; P = 0.433; I(2) = 55.19%; monthly: WMD: 0.003 mg l(-1) , CI: -0.01, 0.01; P = 0.59; I(2) = 0%). Random-effects meta-regression did not suggest any association of changes in hs-CRP levels with changes in plasma LDL-C concentrations (P = 0.697) or cumulative dosage of the drug (P = 0.980). CONCLUSIONS: This meta-analysis of RCTs did not suggest an effect of PCSK9 inhibitors on hs-CRP concentrations.

The role of nutrition in inflammaging.

BACKGROUND: Old age is characterized by a peculiar low-grade, chronic, and "sterile" inflammatory state, which has been termed "inflammaging." This is believed to substantially contribute to the pathogenesis of many age-related diseases and to the progression of the ageing process. An adequate nutritional status is of great importance for maintaining proper immune system functionality and preventing frailty in the elderly. METHODS: The purpose of this narrative review is to synthesize what is known about the interaction between inflammaging and nutrition, focusing on the role of the Mediterranean diet, gut microbiota and calorie restriction (CR) in reducing systemic inflammation and improving clinical outcomes. CONCLUSIONS: Dietary components may affect inflammation directly, counteracting the low grade age-related inflammation. In this regard, healthy diets, including the Mediterranean diet, are associated with lower concentrations of inflammatory mediators, like C-reactive protein (CRP) and Tumor Necrosis Factor-α (TNF-α), that are hallmarks of inflammaging. Among the components of a healthy diet, a higher intake of whole grains, vegetables and fruits, nuts and fish are all associated with lower inflammation. One area of promising research is the microbiome-ageing interaction. Indeed, dysbiosis plays a role in sub-optimal metabolism, immune function and brain function and contributes to the poor health and impaired well-being associated with ageing. Modulation of the gut microbiota has shown promising results in some disorders. Additionally, the discovery of several molecular pathways associated with ageing, and the characterization of the beneficial effects of calorie restriction (CR) in modulating metabolic pathways and preventing inflammation, should encourage research on CR mimetics, drugs able to promote lifespan and extend healthspan.

Mitochondrial Dysfunction and Cardiovascular Disease: Pathophysiology and Emerging Therapies.

Mitochondria ensure the supply of cellular energy through the production of ATP via oxidative phosphorylation. The alteration of this process, called mitochondrial dysfunction, leads to a reduction in ATP and an increase in the production of reactive oxygen species (ROS). Mitochondrial dysfunction can be caused by mitochondrial/nuclear DNA mutations, or it can be secondary to pathological conditions such as cardiovascular disease, aging, and environmental stress. The use of therapies aimed at the prevention/correction of mitochondrial dysfunction, in the context of the specific treatment of cardiovascular diseases, is a topic of growing interest. In this context, the data are conflicting since preclinical studies are numerous, but there are no large randomized studies.

Celiac Trunk Mycotic Aneurysm: Diagnosis and Treatment of a Post-infective Endocarditis Complication.

Pseudoaneurysms could be the dynamic evolution of an infectious break in the arterial wall; in the post-antibiotic era they are uncommon complication following infective endocarditis (IE) and are associated with high rates of morbidity and mortality especially for patients in whom a prompt diagnosis and therapeutic strategy are not performed. In this report, we describe a case of pseudoaneurysm of the celiac trunk developed as a complication of IE. Endovascular treatment is our first-line approach.

Anderson-Fabry Disease: From Endothelial Dysfunction to Emerging Therapies.

The Anderson-Fabry disease is a rare, X-linked, multisystemic, progressive lysosomal storage disease caused by α-galactosidase A total or partial deficiency. The resulting syndrome is mainly characterized by early-onset autonomic neuropathy and life-threatening multiorgan involvement, including renal insufficiency, heart disease, and early stroke. The enzyme deficiency leads to tissue accumulation of the glycosphingolipid globotriaosylceramide and its analogues, but the mechanisms linking such accumulation to organ damage are only partially understood. In contrast, enzyme replacement and chaperone therapies are already fully available to patients and allow substantial amelioration of quality and quantity of life. Substrate reduction, messenger ribonucleic acid (mRNA)-based, and gene therapies are also on the horizon. In this review, the clinical scenario and molecular aspects of Anderson-Fabry disease are described, along with updates on disease mechanisms and emerging therapies.

Statin therapy and sex hormones.

Current guidelines recommend statin therapy for all adult patients with coronary artery disease irrespective of sex. Over recent years, some concerns have been raised concerning the effects of statins on endogenous steroid hormones synthesis. The aim of this review was to summarize the effects of statins on endogenous sex hormones in order to clarify their role and safety in different clinical settings. Results suggest that HMG-CoA inhibitors may slightly impair adrenal and/or gonadal steroid hormone production. In men, statins do not cause any clinically-relevant harmful effects on erectile function and spermatogenesis and, in women, statins have beneficial effects in treatment of polycystic ovary syndrome (PCOS). Additional research is needed to provide specific clinical recommendations concerning this topic.

Pathophysiological mechanisms of statin-associated myopathies: possible role of the ubiquitin-proteasome system.

BACKGROUND: Statins are the cornerstone of pharmacotherapy for atherosclerotic cardiovascular disease. While these drugs are generally safe, treatment adherence is not optimal in a considerable proportion of patients because of the adverse effects on skeletal muscles in the forms of myopathy, myalgia, muscular pain, nocturnal muscle cramping, weakness, and rare rhabdomyolysis. METHODS: For the purpose of this narrative review, we searched for the literature suggesting the involvement of the ubiquitin-proteasome system in the development of statin-induced myopathy. RESULTS: Statins have been shown to up-regulate the expression of the muscle-specific ubiquitin-proteasome system as the major non-lysosomal intracellular protein degradation system. It has been postulated that statins may provoke instability in the myocyte cell membrane when subjected to eccentric exercise stress, triggering activation of intracellular proteolytic cascades and changes in protein degradation machinery. This is accompanied by the up-regulation of a series of genes implicated in protein catabolism, in addition to those of the ubiquitin-proteasome system. CONCLUSIONS: Based on the available literature, it seems that the involvement of ubiquitin-proteasome system is potentially implicated in the pathophysiology of statin-induced myopathy.

Climate Changes and Human Health: A Review of the Effect of Environmental Stressors on Cardiovascular Diseases Across Epidemiology and Biological Mechanisms.

BACKGROUND: Climate change is rapidly affecting all the regions of our planet. The most relevant example is global warming, which impacts on the earth's ecosystems, threatening human health. Other effects include extreme variations in temperature and increases in air pollution. These events may negatively impact mortality and morbidity for cardiovascular diseases. METHODS: In this review, we discuss the main effects of climate changes on cardiovascular diseases, reporting the epidemiological evidences and the biological mechanisms linking climate change consequences to hypertension, diabetes, ischemic heart diseases, heart failure and stroke. RESULTS: Up to now, findings suggest that humans acclimate under different weather conditions, even though extreme temperatures and higher levels of air pollution can influence health-related outcomes. In these cases, climate change adversely affects cardiovascular system and the high-risk subjects for cardiovascular diseases are those more exposed. CONCLUSION: Finally, we examine climate change implications on publich health and suggest adaptation strategies to monitor the high-risk population, and reduce the amount of hospital admissions associated to these events. Such interventions may minimize the costs of public health and reduce the mortality for cardiovascular diseases.

Comparison of Clinical Outcomes Between Genders Following Antihypertensive Therapy: A Meta-Analysis.

BACKGROUND: Numerous studies have reported sex and gender differences in the prevalence and treatment of cardiovascular diseases. However, sex differences in the therapy of hypertension have not been completely examined. OBJECTIVE: To estimate the gender-specific dissimilarity in outcomes among patients following antihypertensive treatment, using a meta-analysis of available studies. METHODS: A systematic literature search in Medline and SCOPUS databases was performed from January 1990 to January 2015 to find studies assessing clinical outcomes in male and female subjects after hypertension treatment, separately. Quantitative data synthesis was performed using a random-effects model, with weighed mean difference (WMD) and 95% confidence interval (CI) as summary statistics. RESULTS: the analysis included 10 studies with 16 treatment arms. Outcomes were found to be significantly more frequent in men then in women (odds ratio [OR]: 1.25, 95% confidence interval [CI]: 1.17, 1.33, p < 0.001; I2:40.17%), and this result was robust and independent. Random-effects meta-regression showed no association of outcomes with treatment duration and baseline levels. CONCLUSION: The present meta-analysis demonstrates that clinical outcomes are more frequent in men compared with women after the same treatment of hypertension. Numerous reasons, including disparities in compliance, age, and intrinsic higher risk in male, contribute to justify these findings.

The role of inflammatory biomarkers in developing targeted cardiovascular therapies: lessons from the cardiovascular inflammation reduction trials.

Anti-inflammatory add-on therapy to conventional cardiovascular prophylaxis has been proposed as a novel therapeutic approach to potentially reduce residual cardiovascular risk. This hypothesis has been challenged by a series of unsuccessful Phase III studies testing the impact on clinical outcomes of novel agents with immunomodulatory actions. Specifically, the apparent ability of phospholipase A2 (PLA2) inhibitors and of antioxidants to ameliorate inflammation and to reduce coronary disease in Phase II trials did not translate into improved secondary cardiovascular prevention in larger population-based studies. Other anti-inflammatory agents are still under scrutiny. However, studies to date have lacked information on the inflammatory profile of the participants, both at baseline and at follow-up, thereby limiting the possibility of identifying subgroups of patients in whom 'residual inflammation' can be detected despite optimal conventional therapy, and who could therefore benefit from a cardiovascular prevention strategy specifically targeting inflammation. This has also rendered it difficult to interpret the results as a conclusive demonstration of inefficacy of the tested anti-inflammatory strategies in the treatment of atherosclerosis. We here discuss the importance of better patient characterization to minimize heterogeneity of the study population, so that effectiveness of different anti-inflammatory strategies can be evaluated in targeted subgroups of patients. We also illustrate how specific inflammatory biomarkers could assist in this process, with particular emphasis on the roles of high-sensitivity C-reactive protein and circulating monocyte phenotype.

Anti-platelet drugs attenuate the expansion of circulating CD14highCD16+ monocytes under pro-inflammatory conditions.

AIMS: Levels of circulating CD14(high)CD16(+) monocytes increase in atherosclerotic patients and are predictive of future cardiovascular events. Platelet activation has been identified as a crucial determinant in the acquisition of a CD16(+) phenotype by classical CD14(high)CD16(-) cells. We tested the hypothesis that anti-platelet drugs modulate the phenotype of circulating monocytes. METHODS AND RESULTS: Sixty healthy subjects undergoing influenza immunization were randomly assigned to either no treatment or anti-platelet therapy, namely aspirin 300 mg or 75 mg daily, or clopidogrel (300 mg loading dose followed by 75 mg), for 48 h post-immunization (n = 15/group). Monocyte subsets, high-sensitivity C-reactive protein, pro-inflammatory cytokines, and P-selectin were measured at baseline and post-immunization. The CD14(high)CD16(+) monocyte cell count rose by 67.3% [interquartile range (IQR): 35.7/169.2; P = 0.0002 vs. baseline] in untreated participants. All anti-platelet regimes counteracted expansion of this monocytic subpopulation. Although no statistical differences were noted among the three treatments, aspirin 300 mg was the most efficacious compared with the untreated group (-12.5% change from baseline; IQR: -28.7/18.31; P = 0.001 vs. untreated). Similarly, the rise in P-selectin (17%; IQR: -5.0/39.7; P = 0.03 vs. baseline) observed in untreated participants was abolished by all treatments, with aspirin 300 mg exerting the strongest effect (-30.7%; IQR: -58.4/-0.03; P = 0.007 vs. untreated). Changes in P-selectin levels directly correlated with changes in CD14(high)CD16(+) cell count (r = 0.5; P = 0.0002). There was a similar increase among groups in high-sensitivity C-reactive protein (P < 0.03 vs. baseline levels). CONCLUSIONS: Anti-platelet drugs exert an immunomodulatory action by counteracting CD14(high)CD16(+) monocyte increase under pro-inflammatory conditions, with this effect being dependent on the amplitude of P-selectin reduction.

Air Pollution Exposure and Blood Pressure: An Updated Review of the Literature.

Both high arterial blood pressure (BP) and elevated levels of fine particulate matter (PM2.5) air pollution have been associated with an increased risk for several cardiovascular (CV) diseases, including stroke, heart failure, and myocardial infarction. Given that PM2.5 and high BP are each independently leading risk factors for premature mortality worldwide, a potential relationship between these factors would have tremendous public health repercussions. Therefore, the aim of this review is to summarize recent evidence linking air pollution and BP. Epidemiological findings demonstrate that particulate pollutants cause significant increases in BP parameters in relation to both short and long-term exposures, with robust evidence for exposures to PM2.5. Moreover, recent epidemiological studies suggest a positive association between residence within regions with higher levels of ambient PM and an increased incidence and prevalence of overt hypertension. Studies provide consistent results that elevated concentrations of pollutants increase hospital admissions and/or emergency visits for hypertensive disorders and also support that PM levels increases BP in vulnerable subsets of individuals (pregnant women, high CV risk individuals). In this context, PM-mediated BP elevations may be an important pathway which acts as a potential triggering factor for acute CV events. Mechanistic evidence illustrates plausible pathways by which acute and chronic exposures to air pollutants might disrupt hemodynamic balance favoring vasoconstriction, including autonomic imbalance and augmented release of various pro-oxidative, inflammatory and/or hemodynamically-active mediators. Together these responses may underlie PM-induced BP elevations; however, full details regarding the responsible mechanisms require further studies. As a consequence of the ubiquity of air pollution, even a small effect on raising BP and/or the prevalence of hypertension, i.e. the major risk factor for mortality and morbidity worldwide, would have enormous global public health implications.

Cocoa consumption dose-dependently improves flow-mediated dilation and arterial stiffness decreasing blood pressure in healthy individuals.

BACKGROUND: Cocoa flavonoids exert beneficial vascular effects and reduce the risk of cardiovascular morbidity and mortality. Nevertheless, the involved mechanisms have not been clarified and no study has yet focused on the dose-response effects. OBJECTIVES: We aimed to investigate the effects of different doses of cocoa flavonoids on flow-mediated dilation (FMD), endothelin-1 (ET-1), pulse wave velocity (PWV), and SBP and DBP. DESIGN: According to a randomized, double-blind, controlled, cross-over design, 20 healthy volunteers (1.5% improvement in FMD in 20 individuals: 0.99 at alpha = 0.05) were assigned to receive either five treatments with daily intake of 10 g cocoa (0, 80, 200, 500 and 800 mg cocoa flavonoids/day) in five periods lasting 1 week each. RESULTS: Cocoa dose-dependently increased FMD from 6.2% (control) to 7.3, 7.6, 8.1 and 8.2% after the different flavonoid doses, respectively (P < 0.0001). Compared with the control, even 80  mg cocoa flavonoids per day increased FMD (P < 0.0001). Cocoa dose-dependently decreased PWV (P < 0.0001). Cocoa intake decreased office blood pressure (BP) (SBP: -4.8 ±â€Š1.03  mmHg, P < 0.0001; DBP: -3.03 ±â€Š1.07 mmHg, P = 0.0011). With respect to control, cocoa ingestion decreased 24-h (P = 0.05) and daytime (P = 0.038) SBP, and 24-h (P = 0.0064), daytime (P = 0.0088) and night-time (P = 0.0352) pulse pressure. Compared with the control, cocoa dose-dependently decreased ET-1 levels [from 17.1 (control) to 15.2, 14.5, 14.2 and 14.1 pg/ml, after the different flavonoid doses, respectively (P for treatment <0.05)]. Compared with the control, significant changes were observed for all doses of flavonoids (ET-1; P < 0.05). CONCLUSION: Our study showed for the first time that cocoa dose-dependently improved FMD and decreased PWV and ET-1 also by ameliorating office and monitored BP. Our findings are clinically relevant, suggesting cocoa, with very low calorie intake, might be reasonably incorporated into a dietary approach, representing a consistent tool in cardiovascular prevention.

Cocoa, blood pressure, and cardiovascular health.

High blood pressure is an important risk factor for cardiovascular disease and cardiovascular events worldwide. Clinical and epidemiological studies suggest that cocoa-rich products reduce the risk of cardiovascular disease. According to this, cocoa has a high content in polyphenols, especially flavanols. Flavanols have been described to exert favorable effects on endothelium-derived vasodilation via the stimulation of nitric oxide-synthase, the increased availability of l-arginine, and the decreased degradation of NO. Cocoa may also have a beneficial effect by protecting against oxidative stress alterations and via decreased platelet aggregation, decreased lipid oxidation, and insulin resistance. These effects are associated with a decrease of blood pressure and a favorable trend toward a reduction in cardiovascular events and strokes. Previous meta-analyses have shown that cocoa-rich foods may reduce blood pressure. Long-term trials investigating the effect of cocoa products are needed to determine whether or not blood pressure is reduced on a chronic basis by daily ingestion of cocoa. Furthermore, long-term trials investigating the effect of cocoa on clinical outcomes are also needed to assess whether cocoa has an effect on cardiovascular events. A 3 mmHg systolic blood pressure reduction has been estimated to decrease the risk of cardiovascular and all-cause mortality. This paper summarizes new findings concerning cocoa effects on blood pressure and cardiovascular health, focusing on putative mechanisms of action and "nutraceutical " viewpoints.