Background: Metabolic syndrome (MetS) is characterized by the simultaneous presence of obesity, hypertension, dyslipidemia and hyperglycemia in an individual, leading to increased cardiovascular disease (CVD) risk. It affects almost 35% of the US adult population, while its prevalence increases with age. Elevated blood pressure is the most frequent component of the syndrome; however, until now, the optimal antihypertensive regiment has not been defined. Objective: The purpose of this review is to present the proposed definitions for the metabolic syndrome, as well as the prevalence of hypertension in this condition. Moreover, evidence regarding the metabolic properties of the different antihypertensive drug classes and their effect on MetS will be displayed. Method: A comprehensive review of the literature was performed to identify data from clinical studies for the prevalence, pathophysiology and treatment of hypertension in the metabolic syndrome. Results: Hypertension is present in almost 80% of patients with metabolic syndrome. The use of thiazide diuretics and b-blockers has been discouraged in this population; however, new evidence suggests their use under specific conditions. Calcium channel blockers seem to exert a neutral effect on MetS, while renin-angiotensin system inhibitors are believed to be of the most benefit, although differences exist between the different agents of this category. Conclusion: Controversy still exists regarding the optimal antihypertensive treatment for hypertension in MetS. Due to the high prevalence of hypertension in this population, more data from clinical trials are needed in the future.

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease (30% of the general population) and up to 40% of cases advance to the more severe form of the disease: non-alcoholic steatohepatitis (NASH), which is causally related to cirrhosis and cardiovascular disease (CVD). There is no generally accepted effective treatment for NAFLD/NASH. The joint guidelines of the European Association for the Study of the Liver (EASL), the European Association for the Study of Diabetes (EASD) and the European Association for the Study of Obesity (EASO) suggest the “off label” use of pioglitazone in patients without type 2 diabetes mellitus (T2DM) and pioglitazone in subjects with T2DM or vitamin E or their combination for the treatment of NASH; however pioglitazone has considerable limitations: weight gain, bone fractures in women, and heart failure. The aim of this narrative review is to assess the existing evidence supporting statin use for the treatment of NASH and the reduction of the high CVD risk of these patients. Animal data suggest that there is some benefit from statin use in liver histology in models of NASH. In humans, 3 post hoc analyses of randomised controlled trials (n=1,600, n=1,123, n=8,864) suggest that the use of atorvastatin (even in 80 mg/day) has a beneficial effect on NAFLD/NASH, in terms of liver enzyme reduction and ultrasonographic amelioration. Moreover, and most importantly, statin treatment halved CVD morbidity and mortality in statin-treated NAFLD/NASH patients compared with statin-treated participants with normal liver structure and function and reduced by 2/3rds CVD events in comparison with NAFLD/NASH patients that were not on a statin (90% of this population is not on statins because of the unjustified fear for liver damage). Three biopsy studies (n=20, n=107 and n=356) showed that statin treatment had a protective effect on steatosis, steatohepatitis and fibrosis. Data suggest that statin treatment in humans substantially improve or cure NAFLD/NASH, but above all substantially reduce CVD morbidity and mortality. Administration of potent statins appears safe and effective in saving lives in NAFLD/NASH patients.

Background: Sexual dysfunction affects millions of people with an increasing prevalence, worldwide. The pathophysiology of the disease shares several similarities with cardiovascular disease (CVD), including atherosclerosis, endothelial dysfunction, structural vascular damage and subclinical inflammation. Erectile dysfunction (ED) and female sexual dysfunction are common among patients with CVD and risk factors such as hypertension, diabetes, obesity and metabolic syndrome. Given the common pathogenesis of the diseases, ED is an independent prognostic factor of future ED events. Patients with overt ED or risk factors are usually treated with several drugs for the management of these conditions. Several of these drugs have been evaluated for their effect on sexual activity. Results and Conclusion: Among the antihypertensive drugs, diuretics and beta-blockers seem to exert a detrimental impact on sexual function, with nebivolol being the only beta-blocker with favorable properties through an increase in nitric oxide bioavailability. In contrast, renin-angiotensin system inhibitors and calcium-channel blockers have a neutral effect on sexual activity. Hypoglycemic drugs have been less evaluated in the ED setting, with metformin, pioglitazone and liraglutide presenting favorable results. Statins on the other hand have not provided consistent results with observational studies suggesting a detrimental role in sexual activity and a few randomized studies indicating a neutral or even beneficial effect on erectile function.

Background: Non-alcoholic fatty liver disease (NAFLD) and its advanced form non-alcoholic steatohepatitis (NASH) are the most common causes of elevated liver enzymes in the general population. NASH, and to a lesser extent NAFLD have been associated with increased liver-related, cardiovascular disease (CVD), and allcause mortality. No effective treatment is widely acceptable. Objective: The purpose of this review is to summarize available data on the impact of statins on NAFLD and NASH. Method: A comprehensive review of the literature was performed to identify studies assessing the effect of statin use in NAFLD/NASH. Results: Recent reports have shown that the use of statins in patients with elevated plasma aminotransferases may be beneficial. Post hoc data from three large prospective randomized clinical trials (n>11, 000) suggest that specific statins (mainly atorvastatin) ameliorate NAFLD/NASH and reduce CVD events twice as much as in those with normal liver function. Several biopsy studies have found that rosuvastatin use is related with significant histological ameliorating effects in the setting of NASH. Statin treatment may also protect from hepatocellular carcinoma (HCC) related to NAFLD/NASH. Conclusion: Since NAFLD/NASH patients have high CVD risk, they will probably require a statin. Thus, why not select a specific statins (atorvastatin or rosuvastatin, both generic now) that offer a substantial liver- and CVDrelated adverse event reduction? The administration of statins in these patients is as safe as in the general population.

Diabetes mellitus is a major risk factor for cardiovascular morbidity and mortality. Current therapeutic strategies have not provided constant beneficial cardiovascular-related results. Sodium–glucose co-transporters 2 (SGLT-2) inhibitors have emerged as a novel antidiabetic class of drugs that exert favourable results in a variety of other cardiovascular risk factors too, such as increased blood pressure and body weight. The Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes (EMPA-REG OUTCOME) study was the first trial that evaluated cardiovascular outcomes in patients with diabetes with the use of empagliflozin, a member of this new class of drugs. Empagliflozin was associated with remarkable reduction of cardiovascular morbidity and mortality and all-cause death. On the contrary, stroke incidence was slightly increased, although the result did not reach statistical significance. It could be assumed that a drug providing such beneficial effects on cardiovascular outcomes, would have also the same impact in stroke risk. This finding could theoretically be attributed to ‘play of chance’. However, an increase of haematocrit was observed in EMPA-REG and other SGLT-2 inhibitors studies. Accumulating evidence suggests a direct association between increased haematocrit and stroke risk. Could this ‘stroke paradox’ be a result of the increased haematocrit levels noted with SGLT-2 inhibitors? The aim of this review is to critically assess both possibilities, given that increased stroke rates (if indeed true) should not be neglected and unattended.