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The primary and secondary prevention strategies of atherosclerotic cardiovascular disease (ASCVD) largely rely on the management of arterial hypertension and hypercholesterolemia, two major risk factors possibly linked in pathophysiological terms by the renin-angiotensin system activation and that often coexist in the same patient synergistically increasing cardiovascular risk. The classic pharmacologic armamentarium to reduce hypercholesterolemia has been based in the last two decades on statins, ezetimibe, and bile acid sequestrants. More recently numerous novel, additive resources targeting different pathways in LDL cholesterol metabolism have emerged. They include drugs targeting the proprotein convertase subtilisin/kexin type 9 (PCSK9) (inhibitory antibodies; small-interfering RNAs), the angiopoietin-like protein 3 (inhibitory antibodies), and the ATP-citrate lyase (the inhibitory oral prodrug, bempedoic acid), with PCSK9 inhibitors and bempedoic acid already approved for clinical use. With the potential of at least halving LDL cholesterol levels faster and more effectively with the addition of ezetimibe than with high-intensity statin alone, and even more with the addition of the novel available drugs, this document endorsed by the Italian Society of Hypertension proposes a novel paradigm for the treatment of the hypertensive patient with hypercholesterolemia at high and very high ASCVD risk. Our proposal is based on the use as a first-line of a preferably fixed combination of lipid-lowering drugs, under the motto "Our goal: achieve control. No setback: combine and check".

Hypertension is a major contributor to fatal/nonfatal cardiovascular diseases, and timely identification and appropriate management of factors affecting hypertension and its control are mandatory public health issues. By inducing neurohormonal alterations and metabolic impairment, sleep disorders have an impact on a variety of cardiovascular risk factors, including hypertension, and ultimately increase the risk of cardiovascular events. There is evidence that qualitative and quantitative sleep disorders are associated with resistant hypertension and with impaired circadian blood pressure variations. However, sleep disturbances are often unrecognized, or heterogeneity exists in their management by non-specialists in the field. This document by the Italian Society of Hypertension summarizes the updated evidence linking sleep disorders to hypertension and cardiovascular diseases, the major underlying mechanisms, and the possible management strategies. A simplified, evidence-based diagnostic and therapeutic algorithm for comorbid hypertension and common sleep disorders, namely obstructive sleep apnoea and insomnia, is proposed.

Introduction: Hypertesion is the leading cause of morbidity and mortality, worldwide, and its prevalence has been increasing in several countries, including Italy. Aims: To assess hypertension prevalence, awareness, treatment, and control in a real-world sample of adults with self-reported diabetes compared with nondiabetic individuals. Methods: Following the 2018 World Hypertension Day, a nationwide, cross-sectional epidemiological survey on cardiovascular risk factors (“Abbasso la Pressione!”) in 3956 Italian pharmacies enrolled 47217 self-presenting volunteers (≥18 years). Participants underwent standardized blood pressure (BP) measurements and answered a questionnaire on cardiovascular risk factors and lifestyle habits. Questions included if they had an established diagnosis of diabetes, hypertension or were on a BP medication. Hypertension prevalence was defined as systolic BP ≥140 and/or diastolic BP ≥90 mmHg. A double definition for hypertension control based on the recent European and US guidelines on hypertension was applied. Results: Diabetic individuals (N=5695, 12%) had higher rates of hypertension prevalence (80% vs. 54.7%, p < 0.001), awareness (85.6% vs 77.3%, p < 0.001) and treatment (85.8% vs. 76.7%, p < 0.001), but lower hypertension control rates (36.1% vs. 39.6% according to the 2018 European guidelines, p < 0.001; 25.4% vs 30.8% according to the 2017 US guidelines, p < 0.001) than nondiabetics. Diabetic participants tended to be older, sedentary, overweight/obese, dyslipidemic men, with higher 10-years cardiovascular risk than nondiabetics (p < 0.001). Uncontrolled hypertension was associated with male gender, diabetes, body mass index, unhealthy lifestyle habits, and older age. Conclusions: Elevated hypertension awareness and treatment rates in diabetic adults do not translate into adequate BP control in the real world. Concomitant unfavorable metabolic features and unhealthy lifestyle habits might contribute to this observation.

Extra virgin olive oil (EVOO) intake is associated with reduced cardiovascular risk, and its phenolic compound oleocanthal (OC) has anti-oxidant and anti-inflammatory properties. The cardiometabolic effects of EVOO with a high OC concentration have not been fully elucidated. We administered EVOO with a high OC concentration daily to 23 subjects with the metabolic syndrome (MetS) and hepatic steatosis (15 men and 8 women, age: 60 &plusmn, 11 years) for 2 months. Anthropometric data, metabolic parameters, hepatic steatosis (by fatty liver index, FLI), abdominal fat distribution (by ultrasound), and pro- and anti-inflammatory cytokines were assessed before and after the intervention. EVOO supplementation was associated with a reduction in body weight, waist circumference, body mass index (BMI), alanine transaminase and FLI, as well as interleukin (IL)-6, IL-17A, tumor necrosis factor-&alpha, and IL-1B, while IL-10 increased. Maximum subcutaneous fat thickness (SFT max) also increased, with a concomitant decrease in the ratio of visceral fat layer thickness/SFT max. Correlation analysis revealed positive associations between changes in body weight and BMI and those in SFT max, along with an inverse association between changes in IL-6 and those in SFT max. In conclusion, ingestion of EVOO with a high OC concentration had beneficial effects on metabolic parameters, inflammatory cytokines and abdominal fat distribution in MetS subjects with hepatic steatosis, a category of patients at high cardiometabolic risk.

Background Bempedoic acid is a first-in-class lipid-lowering drug recommended by guidelines for the treatment of hypercholesterolemia. Our objective was to estimate its average effect on plasma lipids in humans and its safety profile. Methods and findings We carried out a systematic review and meta-analysis of phase II and III randomized controlled trials on bempedoic acid (PROSPERO: CRD42019129687). PubMed (Medline), Scopus, Google Scholar, and Web of Science databases were searched, with no language restriction, from inception to 5 August 2019. We included 10 RCTs (n = 3,788) comprising 26 arms (active arm [n = 2,460]; control arm [n = 1,328]). Effect sizes for changes in lipids and high-sensitivity C-reactive protein (hsCRP) serum concentration were expressed as mean differences (MDs) and 95% confidence intervals (CIs). For safety analyses, odds ratios (ORs) and 95% CIs were calculated using the Mantel–Haenszel method. Bempedoic acid significantly reduced total cholesterol (MD −14.94%; 95% CI −17.31%, −12.57%; p < 0.001), non-high-density lipoprotein cholesterol (MD −18.17%; 95% CI −21.14%, −15.19%; p < 0.001), low-density lipoprotein cholesterol (MD −22.94%; 95% CI −26.63%, −19.25%; p < 0.001), low-density lipoprotein particle number (MD −20.67%; 95% CI −23.84%, −17.48%; p < 0.001), apolipoprotein B (MD −15.18%; 95% CI −17.41%, −12.95%; p < 0.001), high-density lipoprotein cholesterol (MD −5.83%; 95% CI −6.14%, −5.52%; p < 0.001), high-density lipoprotein particle number (MD −3.21%; 95% CI −6.40%, −0.02%; p = 0.049), and hsCRP (MD −27.03%; 95% CI −31.42%, −22.64%; p < 0.001). Bempedoic acid did not significantly modify triglyceride level (MD −1.51%; 95% CI −3.75%, 0.74%; p = 0.189), very-low-density lipoprotein particle number (MD 3.79%; 95% CI −9.81%, 17.39%; p = 0.585), and apolipoprotein A-1 (MD −1.83%; 95% CI −5.23%, 1.56%; p = 0.290). Treatment with bempedoic acid was positively associated with an increased risk of discontinuation of treatment (OR 1.37; 95% CI 1.06, 1.76; p = 0.015), elevated serum uric acid (OR 3.55; 95% CI 1.03, 12.27; p = 0.045), elevated liver enzymes (OR 4.28; 95% CI 1.34, 13.71; p = 0.014), and elevated creatine kinase (OR 3.79; 95% CI 1.06, 13.51; p = 0.04), though it was strongly associated with a decreased risk of new onset or worsening diabetes (OR 0.59; 95% CI 0.39, 0.90; p = 0.01). The main limitation of this meta-analysis is related to the relatively small number of individuals involved in the studies, which were often short or middle term in length. Conclusions Our results show that bempedoic acid has favorable effects on lipid profile and hsCRP levels and an acceptable safety profile. Further well-designed studies are needed to explore its longer-term safety., Maciej Banach and colleagues discuss the efficacy and safety of bempedoic acid, a drug that designed to lower LDL-C levels., Author summary Why was this study done? Lowering low-density lipoprotein cholesterol (LDL-C) is effective for reducing cardiovascular events over time. A number of phase II and phase III randomized controlled trials (RCTs) are already available showing encouraging results of bempedoic acid treatment on LDL-C. We aimed to perform a systematic review and meta-analysis on the clinical evidence available to date to better define the efficacy and tolerability profile of treatment with bempedoic acid. What did the researchers do and find? In this analysis of bempedoic acid that included 10 randomized clinical trials (n = 3,788 patients) comprising 26 arms (active arm [n = 2,460]; control arm [n = 1,328]), we confirmed that bempedoic acid significantly reduced total cholesterol (by 15%), non-high-density lipoprotein cholesterol (by 18.2%), LDL-C (by 22.9%), low-density lipoprotein particle number (by 20.7%), apolipoprotein B (by 15.2%), and high-sensitivity C-reactive protein (hsCRP) (by 27%), while negatively affecting serum levels of high-density lipoprotein cholesterol (−5.8%) and high-density lipoprotein particle number (−3.2%). Our results also confirmed that the therapy is overall safe and well tolerated, with no significant increase of serious adverse effects. What do these findings mean? The current meta-analysis demonstrates the multiple positive effects of bempedoic acid on lipid profile and hsCRP serum levels, as well as acceptable safety profile. This could be relevant in a setting where statin intolerance is very frequent and the LDL-C target suggested by international guidelines for dyslipidemia management is hard to achieve with standard therapies. An ongoing long-term cardiovascular outcomes trial will answer questions on the effect of bempedoic acid on cardiovascular events and mortality as well as on the drug’s safety issues.

Serum uric acid (SUA) levels discriminating across the different strata of cardiovascular risk is still unknown. By utilizing a large population-based database, we assessed the threshold of SUA that increases the risk of total mortality and cardiovascular mortality (CVM). The URRAH study (Uric Acid Right for Heart Health) is a multicentre retrospective, observational study, which collected data from several large population-based longitudinal studies in Italy and subjects recruited in the hypertension clinics of the Italian Society of Hypertension. Total mortality was defined as mortality for any cause, CVM as death due to fatal myocardial infarction, stroke, sudden cardiac death, or heart failure. A total of 22 714 subjects were included in the analysis. Multivariate Cox regression analyses identified an independent association between SUA and total mortality (hazard ratio, 1.53 [95% CI, 1.21–1.93]) or CVM (hazard ratio, 2.08 [95% CI, 1.146–2.97]; P P

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Effect of a nutraceutical containing Ortosiphon stamineus leaf extract on blood pressure and metabolic syndrome components in hypertensive dyslipidaemic patients treated with calcium-channel blockers, or angiotensin converting enzyme inhibitors: a randomized clinical trial.

The aim of this study was to evaluate the effect of an oral glucose tolerance test (OGTT) on the level of endothelial dysfunction and vascular inflammation markers in healthy subjects (H) and diabetic overweight patients (D). We enrolled 256 healthy subjects and 274 type 2 diabetic patients. We evaluated blood glucose (BG), soluble intercellular adhesion molecule-1 (sICAM-1), interleukin-6 (IL-6), high-sensitivity C reactive protein (hsCRP), soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble E-selectin (sE-selectin), and tumor necrosis factor-alpha (TNF-alpha) at baseline and after OGTT. We observed that BG, sICAM-1, IL-6, hs-CRP, sVCAM-1, sE-selectin, and TNF-alpha values were higher in D group than in H group. In a large sample of adult healthy subjects and type 2 diabetics we observed that both answer to an OGTT with a significant increase in biomarkers of systemic low-grade inflammation and endothelial dysfunction such as hsCRP, IL-6, TNF-alpha, sICAM-1, sVCAM-1, and sE-selectin. Type 2 diabetics experienced, however, a more significant increase in TNF-alpha, and sE-selectin.

Serum uric acid is representative for xanthine-oxidase, the key enzyme involved in the production of uric acid, which is up-regulated in the failing heart, and may play an important role in the pathophysiologic process that leads to heart failure. In our study, we investigated the relation between stroke volume, cardiac output and serum uric acid in a large sample of overall healthy pharmacologically untreated subjects. The Brisighella Heart Study included 2,939 men and women between the ages of 14-84 without prior coronary heart disease or cerebrovascular disease who were not taking antihypertensive therapy at baseline. For this study, we selected 734 adult subjects enrolled in the last Brisighella population survey not taking antihypertensive, antidiabetic, lipid-lowering and uric acid-lowering drugs, and who were also not affected by chronic heart failure or by gout. The main predictors of cardiac functionality parameters were mean arterial pressure (MAP), HR, SUA and age (all p < 0.001), while gender, BMI, LDL-cholesterol, HDL-cholesterol, triglycerides, fasting plasma glucose, creatinine, estimated glomerular filtration rate, physical activity and smoking habit were not significantly associated (all p > 0.05). In particular, there is a strong relation between estimated cardiac output and serum uric acid (B = -0.219, p < 0.001) and between stroke volume and serum uric acid (B = -3.684, p < 0.001). These observations might have an impact on future considerations about serum uric acid as an early inexpensive marker of heart function decline in the general population

The association of chronic kidney disease (CKD) and hearing disorders is well known, and was first reported more than 80 years ago by Alport, who described a case of familial kidney disease associated with hearing loss. Subsequently, a number of rare conditions or syndromes were described as occurring with a close link between hearing impairment and CKD (see Table 1). Moreover, some observational, cross-sectional, population-based studies concerning patients with CKD, or on dialysis therapy, confirmed this association suggesting the possibility that the linkage between the ear and the kidney is more than casual. In particular, Vilayur et al. report several physiological, ultrastructural and antigenic similarities between the kidney and the cochlea that strongly support the link between the hearing impairment and CKD [1]. The inner ear and the kidney share a series of basic processes for water and ion regulation as well as some specific cellular water channels known as aquaporins, which are known to have a crucial role in the functional activity of both organs. Moreover, the presence of a kidney-specific ion transport system has recently been demonstrated in the rat and human endolymphatic sac that, to date, represents the only known localization outside the kidney [2]. Once again this underlines a strict correspondence between the kidney and the inner ear, with both organs involved in highly energy-requiring processes linked to the strict necessity of maintaining the balance of ions and a stable pH. In particular, a derangement in the mechanisms regulating fluid and electrolyte homeostasis has been hypothesized both in the cochlear striavascularis, and in the kidney, to explain the possible association of inner ear and kidney diseases. A further contribution in order to clarify the importance of the analogies between kidney and inner ear comes from the progress in genetic research, revealing a possible common ground of dysfunction [3]. Finally, some cardiovascular risk factors such as age, diabetes, hypertension, electrolyte disorders and hemodialysis can affect both the ear and the kidney, and separately contribute to the development and the progression of organ-specific diseases [1]. Nevertheless, these reported connections and analogies between the ear and the kidney deserve to be considered according to a more comprehensive hypothesis. In particular, we speculate that a baseline condition of hemodynamic imbalance leading to a different extent of transient ischemia and hypoxia may elicit similar mechanisms of disease in both organs. Over the last decade, we have provided several observations supporting the hypothesis that some inner ear disorders of undetermined origin may depend on a large decrease in blood pressure values associated with an abnormal peripheral vasoconstriction [4]. This mechanism can be activated either in subjects without major cardiovascular risk factors (other than a generic sympathetic hyperreactivity), or in patients treated for hypertension or chronic congestive heart failure. In ‘‘healthy’’ subjects, the proposed model can provide a theoretical explanation for the cases of inner ear diseases usually labeled as ‘‘idiopathic’’, as well as for the different inner ear disturbances including the largely unexplained Meniere’s disease [5]. In patients with cardiovascular diseases, the symptoms of A. Pirodda Department of Specialist Surgical and Anesthesiological Sciences, S. Orsola-Malpighi University Hospital, Via Massarenti 9, 40138 Bologna, Italy

Berberine is an alkaloid that is highly concentrated in the roots, rhizomes, and stem bark of various plants. It affects glucose metabolism, increasing insulin secretion, stimulating glycolysis, suppressing adipogenesis, inhibiting mitochondrial function, activating the 5' adenosine monophosphate-activated protein kinase (AMPK) pathway, and increasing glycokinase activity. Berberine also increases glucose transporter-4 (GLUT-4) and glucagon-like peptide-1 (GLP-1) levels. On GLP-1 receptor activation, adenylyl cyclase is activated, and cyclic adenosine monophosphate is generated, leading to activation of second messenger pathways and closure of adenosine triphosphate-dependent potassium channels. Increased intracellular potassium causes depolarization, and calcium influx through the voltage-dependent calcium channels occurs. This intracellular calcium increase stimulates the migration and exocytosis of the insulin granules. In glucose-consuming tissues, such as adipose, or liver or muscle cells, berberine affects both GLUT-4 and retinol-binding protein-4 in favor of glucose uptake into cells; stimulates glycolysis by AMPK activation; and has effects on the peroxisome proliferator-activated receptor γ molecular targets and on the phosphorylation of insulin receptor substrate-1, finally resulting in decreased insulin resistance. Moreover, recent studies suggest that berberine could have a direct action on carbohydrate metabolism in the intestine. The antidiabetic and insulin-sensitizing effect of berberine has also been confirmed in a few relatively small, short-term clinical trials. The tolerability is high for low dosages, with some gastrointestinal complaints appearing to be associated with use of high dosages.

We evaluated the association of the sex hormone pattern and the serum level of the main adipokines to metabolic syndrome (MS) and its components in 199 pharmacologically untreated subjects. Men and women included in the age-class subgroups were matched for body mass index, waist circumference, blood pressure, heart rate, fasting plasma glucose, and plasma lipids. Men without MS had significantly lower leptin/adiponectin ratio than men with MS. Women without MS had lower leptin and leptin/adiponectin ratio than women with MS but had significantly higher adiponectin, estrone, and dehydroepiandrosterone levels. In men, the leptin/adiponectin ratio is the main factor associated to MS diagnosis (OR: 3.36, 95% CI 1.40–8.08), while in women adiponectin alone appears to be a protective factor (OR: 0.87, 95% CI 0.79–0.95). In conclusion, in a sample of pharmacologically untreated subjects, leptin/adiponectin ratio seems to be the factor more strongly associated to MS and its components.

BACKGROUND: Incretin-based therapies have provided additional options for the treatment of type 2 diabetes mellitus. The aim of our study was to evaluate the effects of exenatide compared to glibenclamide on body weight, glycemic control, beta-cell function, insulin resistance, and inflammatory state in patients with diabetes. METHODS: One hundred twenty-eight patients with uncontrolled type 2 diabetes mellitus receiving therapy with metformin were randomized to take exenatide 5 microg twice a day or glibenclamide 2.5 mg three times a day and titrated to exenatide 10 microg twice a day or glibenclamide 5 mg three times a day. We evaluated body weight, body mass index (BMI), glycated hemoglobin (HbA(1c)), fasting plasma glucose (FPG), postprandial plasma glucose (PPG), fasting plasma insulin (FPI), homeostasis model assessment insulin resistance (HOMA-IR) index, homeostasis model assessment beta-cell function (HOMA-beta) index, plasma proinsulin (PPr), PPr/FPI ratio, resistin, retinol binding protein-4 (RBP-4), and high-sensitivity C-reactive protein (Hs-CRP) at baseline and after 3, 6, 9, and 12 months. RESULTS: Body weight and BMI decreased with exenatide and increased with glibenclamide. A similar improvement of HbA(1c), FPG, and PPG was obtained in both groups, whereas FPI decreased with exenatide and increased with glibenclamide. The HOMA-IR index decreased and the HOMA-beta index increased with exenatide but not with glibenclamide. A decrease of PPr was reported in both groups, but only glibenclamide decreased the PPr/FPI ratio. Resistin and RBP-4 decreased with exenatide and increased with glibenclamide. A decrease of Hs-CRP was obtained with exenatide, whereas no variations were observed with glibenclamide. CONCLUSIONS: Both exenatide and glibenclamide gave a similar improvement of glycemic control, but only exenatide gave improvements of insulin resistance and beta-cell function, giving also a decrease of body weight and of inflammatory state.

We evaluated the effect of an oral glucose tolerance test (OGTT) on the level of biomarkers of vascular remodelling. We enrolled 256 Caucasian overweight healthy subjects (H) and 274 overweight type 2 diabetic patients (D). All patients underwent basal measurements of blood glucose (BG), nitrites/nitrates, adiponectin (ADP), matrix metalloproteinase-2 (MMP-2), and matrix metalloproteinase-9 (MMP-9) before and after OGTT. Nitrites/nitrates decrease was present after 60, 90, 120, and 180 min in both groups. Nitrite/nitrate levels were decreased at baseline, after 30 and 60 min in D group compared to H group. ADP decrease was present after 90, 120, and 180 min, in both groups. ADP levels were lower in D group than in H group during OGTT. MMP-2 increase was present after 60, 90, and 120 min in H group, while MMP-2 increase was observed after 90, 120, and 180 min in D group. MMP-2 levels were higher in D group than in H group during OGTT. MMP-9 increase was present in H group after 60, 90, 120, and 180 min, while MMP-9 increase was observed after 90, 120, and 180 min in D group. MMP-9 levels were higher in D group than in H group during OGTT. Postprandial glycemia induces an acute increase in biomarkers of vascular remodelling.

Background: Metabolic syndrome is a highly prevalent condition in the Italian population. This study assesses the feasibility and efficacy of a multifactorial approach for primary prevention of cardiovascular disease risk assessment in patients with metabolic syndrome in the daily clinical practice setting. Methods: 726 patients were enrolled (males : females = 7 : 3), their ages ranging from 26 to 70 years, with metabolic syndrome and cardiovascular death risk ≥5%, computed by means of the European Systematic COronary Risk Evaluation (SCORE) algorithm. The first phase (3 months) consisted of an improvement in lifestyle and, if necessary, the initial administration of an antihypertensive therapy (valsartan 160 mg/day for patients with blood pressure ≥140/90 mmHg and ≥130/80 mmHg for diabetic patients). During phase 2 (6 months), patients with systolic blood pressure (SBP) ≥140 mmHg and/or diastolic blood pressure (DBP) ≥90 mmHg (≥130/80 mmHg for diabetic patients) were administered valsartan 160 mg/day + hydrochlorothiazide 12.5 mg/day combined; those with total cholesterol levels ≥190 mg/dL (≥175 mg/dL for diabetic patients) started treatment with fluvastatin 80 mg prolonged release (XL), as prescribed in the guidelines. A control group was approached with another conventional treatment. Results: After 9 months of monitoring, the SBP dropped by 27 mmHg in the valsartan-treated patients and by 11 mmHg in the control group, while the DBP dropped by 12 mmHg in the former group and 2 mmHg in the latter. Total cholesterolaemia was reduced by 47 mg/dL in patients undergoing fluvastatin and valsartan therapy, by 19 mg/dL in those treated with valsartan only and by 33 mg/dL in those administered another conventional treatment. Relative risk reduction observed after 9 months, compared with the beginning of the study, was almost 48% in the valsartan/valsartan + fluvastatin group, versus 28% observed with the other conventional treatment. The reduction of risk at 60 years of age was an average of 39% at 3 months and 48% at 9 months, compared with the beginning of the study. Therapeutic success was accomplished with 78% of the patients treated with valsartan/valsartan + fluvastatin, compared with 47% of patients in the conventional therapy group. Conclusion: The present study demonstrated that the normalization of the main cardiovascular risk factors in patients with metabolic syndrome may be easily achieved in standard clinical practice settings, by leading an adequate lifestyle and, if necessary, the administration of antihypertensive and/or lipid-lowering monotherapy at the usual doses.

OBJECTIVE: To evaluate the effect on coagulation and fibrinolysis parameters and on non-conventional cardiovascular risk factors of metformin plus nateglinide or glibenclamide in naïve type 2 diabetes patients. PATIENTS AND METHODS: A total of 248 type 2 diabetic patients were enrolled and randomly assigned to receive nateglinide or glibenclamide, and metformin for 12 months. We assessed body mass index (BMI), glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), postprandial plasma glucose (PPG), fasting plasma insulin (FPI), postprandial plasma insulin (PPI), homeostasis model assessment index (HOMA index), lipid profile with lipoprotein (a) [Lp(a)], fibrinogen (Fg), plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator (t-PA), homocysteine (Hcy), systolic blood pressure (SBP), diastolic blood pressure (DBP). RESULTS: After 9 months of treatment, both tested drug combinations were similarly associated with a significant reduction in FPG (nateglinide, -17.2%; glibenclamide, -16.9%, both p

It is well known that hypertension is a strong independent risk factor for coronary and cerebrovascular diseases, as well as for heart failure, atrial fibrillation and chronic renal failure, in both industrialised and developing countries,1 thus substantially contributing to the global burden of disease. Moreover, it is well known that reducing blood pressure (BP) in hypertensive patients is associated with a significant reduction in the rate of cardiovascular complications and decline in renal function.2,3 The association between blood pressure and cardiovascular risk is continuous, without apparent lower threshold, up to the value of 70mmHg, which epidemiologically supports the assumption that the lower the blood pressure, the better the cardiovascular prognosis.2 Today, a remarkable number of antihypertensive drug classes with robust scientific evidence of long-term efficacy and safety are available on the market. The therapeutic arsenal includes many different compounds, such as diuretics, beta-adrenergic receptor blockers, alpha-adrenergic receptor blockers, angiotensinogen-converting enzyme inhibitors, angiotensin receptor blockers and calcium antagonists.2,4 Other drug

Background: Albuminuria is the best and most readily available marker for glomerular damage and progressive renal function loss in patients with diabetic nephropathy. Recently, administration of the oral glycosaminoglycan sulodexide (a mixture of 80% fast-moving heparin and 20% dermatan sulphate) was shown to effectively decrease albumin excretion rate in diabetics with nephropathy. Aims: To evaluate whether the hypoalbuminuric effect of sulodexide is associated with improvement of the renal vascular or tubule function. Methods: Forty-five type 1 diabetic patients, affected by diabetic nephropathy with albuminuria for at least 5 years, were randomly allocated to sulodexide or untreated. Those allocated to sulodexide were given 100 mg of sulodexide daily for 120 days. Renal vascular function (DIR) and N-acetyl-β-D-glucosaminidase (NAG) excretion were estimated before and at the end of the study, the former in thesulodexide group only. DIR was measured as two Crcl lasting 120 min (before and during 2 µg/kg b.w. i.v. dopamine). Results: The analysis of trends during the study demonstrated a marked reduction of albuminuria in the sulodexide group (from 126.1 ± 15.41 to 93.6 ± 13.7 mg/day). DIR rose from 13.2 ± 2.1% to 15.44 ± 1.9% (relative increase: +16.9%), and NAG excretion showed a decreasing trend decreased in the sulodexide group only (from 5.1 ± 0.62 to 4.7 ± 0.40 U/gcreat). Conclusion: The findings presented in this study indicate for the first time that orally available sulodexide may favorably affect the renal vascular function in type 1 diabetic patients with nephropathy and microalbuminuria. The effect of sulodexide on NAG is strongly influenced by the baseline NAG values, with a significant NAG reduction in the patients with the highest baseline NAG values.