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Aims: Despite the established link between familial hypercholesterolemia (FH) and increased risk of coronary heart disease (CHD), its association with other common atherosclerotic and metabolic diseases has not been extensively studied. The aim of this study was to report the prevalence of peripheral arterial disease (PAD) [i.e., common carotid artery disease (CCAD) and lower extremity arterial disease (LEAD)], aortic valve stenosis, chronic kidney disease (CKD) and non-alcoholic fatty liver disease (NAFLD) in patients with FH., Materials & Methods: This was a cross-sectional study retrieving data from the Hellenic Familial Hypercholesterolemia Registry (HELLAS-FH)., Results: A total of 1,633 adult patients (850 males) with heterozygous FH (HeFH) were included (mean age 51.3±14.6 years at registration and 44.3±15.9 years at diagnosis). Any common carotid artery stenosis (CCAS) was diagnosed in 124 out of 569 patients with available related data (21.8%), while the prevalence of CCAD (defined as a CCAS ≥50%) was 4.2%. The median (interquartile range - IQR) CCAS was 30% (20-40), whereas the median (IQR) carotid intima-media thickness (CIMT) was 0.7 (0.1-1.4) mm. LEAD was reported in 44 patients (prevalence 2.7%). The prevalence of aortic valve stenosis and CKD was 2.0% and 6.4%, respectively. NAFLD was present in 24% of study participants., Conclusion: HeFH is associated with a relatively high prevalence of any CCAS and CCAD. The prevalence of LEAD, CKD and aortic valve stenosis was relatively low, whereas the prevalence of NAFLD was similar to that of the general population., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Renovascular hypertension (RVH) remains among the most prevalent and important, but also potentially reversible, causes of secondary hypertension. The predominant causes of renal artery stenosis (RAS) are atherosclerotic renovascular arterial stenosis (ARAS) and renal fibromuscular dysplasia. This condition can lead to progressive renal injury, cardiovascular complications and 'flash pulmonary edema'. Duplex Doppler ultrasonography, computed tomographic angiography and magnetic resonance angiography are the most commonly used diagnostic methods. There are three therapeutic options available: medical therapy including renin-angiotensin-aldosterone system antagonists, lipid-lowering agents, and antiplatelet therapy, percutaneous angioplasty with or without stent placement and surgical revascularization. Three large trials failed to demonstrate the superiority of renal artery revascularization over pharmaceutical therapy in controlling blood pressure and preserving renal function. For this reason, today revascularization is only recommended for patients with progressive worsening of renal function, recurrent 'flash pulmonary edema' and rapid increase in antihypertensive requirement in patients with previously well-controlled hypertension. However, more properly designed trials are needed in order to identify which patient populations would probably benefit from renal revascularization., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

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: nonalcoholic 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., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Objective: Arterial Stiffness (AS) and Non-Alcoholic Fatty Liver Diseases (NAFLD) are 2 related, prevalent, risk predictors of Cardiovascular Disease (CVD). We assessed the effect of low dose (5 mg/day) vs. high dose (20-40 mg/day) rosuvastatin on aortic elasticity and central haemodynamics as well as on NAFLD in patients with Arterial Hypertension (AH)., Methods: Forty patients with optimally controlled AH were randomised to 2 rosuvastatin doses and followed for 6 months. 24h AS was assessed by Mobil-O-Graph, which calculates (adjusted for age and gender) Pulse Wave Velocity (PWV), adjusted for Heart Rate (HR) augmentation index (AIx75%) and central haemodynamics. The diagnosis of NAFLD was based on >5% liver steatosis on ultrasound and moderately elevated serum levels of liver enzymes., Results: Both doses of rosuvastatin reduced Central Pulse Pressure (cPP), PWV and AIx75% (adjusted for HR) to normal values (p = NS adjusted for age, gender and HR). Liver enzymes were reduced in those with NAFLD to normal, but steatosis was reduced more by the 20-40 mg/day rosuvastatin dose (p=0.01) compared with the 5 mg/day dose., Conclusion: Both doses of rosuvastatin had a beneficial effect on AS; the high dose was more efficient in reducing PWVs and central haemodynamics, and also the high dose was more effective in ameliorating NAFLD. Given that AH control was optimal and lipid values attained targets, 4 other CVD predictors were also addressed. Larger and longer term studies are needed to demonstrate the clinical benefit of such treatment preference., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Background: Statin treatment exhibits a beneficial effect on non-alcoholic fatty liver disease (NAFLD) and on cardiovascular disease (CVD) in patients with NAFLD., Objective: The aim of this review is to summarize the role of proprotein convertase subtilisin kexin type- 9(PCSK9) in the pathogenesis of NAFLD and discuss the effects of the new hypolipidaemic drugs PCSK9 inhibitors on NAFLD., Results: Data indicates that high intrahepatic or circulating PCSK9 levels increase muscle and liver lipid storage, adipose energy storage and hepatic fatty acids, as well as triglycerides storage and secretion, thus contributing to the pathogenesis of NAFLD. The findings of animal and human studies, aiming to reduce PCSK9 with inhibitors (human IGG antibodies, antisense particles against PCSK9 mRNA, and small anti PCSK9 antibodies) point towards liver protection from NAFLD through inhibition of PCSK9 expression in the induction of degradation of hepatic HNF1a protein, insulin resistance (IR), and other mechanisms., Conclusions: The use of PCSK9 inhibitors ameliorates NAFLD, aside from beneficial effects on CVD and independently of low density lipoprotein cholesterol level reduction., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The implications and prognosis of nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH) are substantially different. The aim of the present review is to describe and compare the pathological and clinical implications of these two conditions. Patients with NASH have a higher risk of progressing to cirrhosis than patients with NAFL but without steatohepatitis, who tend to have a non-progressive disease and only a minority progresses to NASH. Patients with NASH also are at greater risk to develop hepatocellular cancer (HCC) and NASH is the third commonest cause of HCC. In contrast, only few cases of HCC have been reported in patients with isolated NAFL. Given that nonalcoholic fatty liver disease is the hepatic manifestation of metabolic syndrome, it is also strongly related to cardiovascular disease (CVD). Again, it appears that patients with NASH have higher cardiovascular risk than patients with NAFL. Finally, all-cause mortality is also higher in patients with NASH than in patients with NAFL; mortality rates in the latter patients do not differ from the general population. In conclusion, NAFL and NASH have different prognosis and therefore it is imperative to develop accurate, noninvasive methods that will identify the presence of steatohepatitis in this population., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Introduction: Resistant hypertension (HT) is a common clinical entity with debilitating cardiovascular consequences. The highly heterogeneous nature of resistant HT requires a meticulous workup to exclude 'pseudo-resistance' and secondary forms of arterial HT. Resistant HT has recently gained wide scientific interest due to the introduction of interventional methods (renal sympathetic denervation and carotid baroreceptor stimulation) for blood pressure (BP) reduction in this patient population. Despite however the recent advances in understanding the pathophysiology and the clinical characteristics of the disease, the appropriate management of resistant HT remains elusive. The marked heterogeneity of BP response to interventional therapy underlines the need for careful patient selection and the identification of ideal candidates for interventional therapy., Conclusion: The renin-angiotensin-aldosterone system seems to play a cardinal role in the pathophysiology of resistant HT and requires appropriate management. Furthermore, primary aldosteronism is considered the most common form of secondary HT, with increased prevalence in patients with resistant HT. This review aims to provide a simplified work-up for patients with resistant HT, summarize the rationale for the determination of renin and aldosterone levels, and critically discuss available evidence on when and how to measure renin/aldosterone in resistant HT., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Backgound: Current drug therapy for the management of arterial hypertension and heart failure has provided substantial benefits but has also some limitations. LCZ696, a dual inhibitor of angiotensin receptor blockers and neprilysin, and finerenone, a non-steroidal mineralocorticoid receptor antagonist, are two recently developed novel agents for the management of these conditions., Methods: This review aims to present the pathophysiological basis for the use of these two novel drugs, critically discuss available clinical data, and provide future perspectives., Results: LCZ696 seems a very promising antihypertensive agent, that additionally generates clinically meaningful benefits in patients with heart failure with reduced injection fraction and raises expectations for the management of patients with heart failure with preserved ejection fraction. Finerenone aims to be safer than current aldosterone antagonists and has been so far tested in patients with heart failure and in patients with albuminuria. First available data are very promising for the efficacy of the drug, while it provides a better safety profile than current mineralocorticoid antagonists., Conclusion: LCZ696 and finerenone are two novel drugs for the management of arterial hypertension and heart failure. First available data point toward important clinical benefits from their use. Future large trials further investigating the cardiovascular profile of these agents will establish the use of these drugs., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Background: Diabetes mellitus is a major cardiovascular risk factor. Despite the vast pharmaceutical armamentarium, current therapeutic options for the treatment of type 2 diabetes mellitus were unable to provide consistent cardiovascular benefits, apart for metformin. The newest antidiabetic class of drugs, the SGLT-2 inhibitors, seem to provide significant survival benefits. The aim of this review is to present available data that will clarify whether SGLT-2 inhibitors could precipitate in reducing cardiovascular risk in diabetes mellitus., Methods: A comprehensive literature search was performed to identify available data from clinical and experimental studies evaluating the impact of SGLT-2 inhibitors in cardiovascular risk factors and outcomes., Results: Along with a mild antihyperglycemic effect, SGLT-2 inhibitors seem to possess multi-dimensional properties, affecting positively several recognized cardiovascular risk factors such as increased blood pressure, arterial stiffness, body weight and dyslipidemia. Furthermore, preliminary data point towards additional benefits, including reduction of albuminuria in diabetic nephropathy, and reduction of oxidative markers and fatty liver disease in experimental models. The efficacy and safety profile of empagliflozin, an SGLT-2 inhibitor, was evaluated in the EMPA-REG outcome study, and the results were quite impressive. Further credence comes from the analysis of pooled data of SGLT-2 inhibitors trials that have shown similar results., Conclusion: SGLT-2 Inhibitors seem to be related with ameliorating effects on multiple cardiovascular risk factors. The first data from the EMPA-REG outcome study are indeed very promising. Several ongoing cardiovascular studies with this novel class of drugs will shed light and enforce or question current enthusiasm., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)