In vitro characterization of mitochondrial function and structure in rat and human cells with a deficiency of the NADH: ubiquinone oxidoreductase Ndufc2 subunit.

Ndufc2, a subunit of the NADH: ubiquinone oxidoreductase, plays a key role in the assembly and activity of complex I within the mitochondrial OXPHOS chain. Its deficiency has been shown to be involved in diabetes, cancer and stroke. To improve our knowledge on the mechanisms underlying the increased disease risk due to Ndufc2 reduction, we performed the present in vitro study aimed at the fine characterization of the derangements in mitochondrial structure and function consequent to Ndufc2 deficiency. We found that both fibroblasts obtained from skin of heterozygous Ndufc2 knock-out rat model showed marked mitochondrial dysfunction and PBMC obtained from subjects homozygous for the TT genotype of the rs11237379/NDUFC2 variant, previously shown to associate with reduced gene expression, demonstrated increased generation of reactive oxygen species and mitochondrial damage. The latter was associated with increased oxidative stress and significant ultrastructural impairment of mitochondrial morphology with a loss of internal cristae. In both models the exposure to stress stimuli, such as high-NaCl concentration or LPS, exacerbated the mitochondrial damage and dysfunction. Resveratrol significantly counteracted the ROS generation. These findings provide additional insights on the role of an altered pattern of mitochondrial structure-function as a cause of human diseases. In particular, they contribute to underscore a potential genetic risk factor for cardiovascular diseases, including stroke.

Legacy Effect in the Treatment of Hypertension: Persistent Cardiovascular Protection after Conclusion of Randomized Clinical Trials in Hypertension.

RECENT FINDINGS: Essential hypertension is the main determinant of cardiovascular morbidity and mortality worldwide. During the last decades, several antihypertensive drug therapies have been introduced and tested in clinical trials, both as monotherapies and combination therapies. The current recommended therapeutic approaches effectively reduce the lifetime risk of experiencing major cardiovascular outcomes and disabling comorbidities, such as myocardial infarction, stroke, and congestive heart failure. On the basis of multiple proofs, antihypertensive therapy is currently recommended for improving event-free survival rate and quality of life in different clinical settings and conditions. At the same time, other cardiovascular drugs, including novel lipid-lowering, anti-platelet, and anti-coagulation agents, have been made available and also contribute to reduce the incidence of atherothrombotic diseases. PURPOSE OF REVIEW: Beyond the beneficial aspects obtained by pharmacological treatment of major cardiovascular risk factors and comorbidities, including hypertension, several aspects remain to be defined. One major limitation linked to randomized, controlled clinical trials is represented by the relatively short duration of the studies, which usually ranges between 1 and 5 years. Whether antihypertensive therapy should be maintained for a longer time (after 5 years) and whether this is supported by sufficient evidence of a persisting benefit is supported by limited post-trial observations but mostly by findings derived from large clinical registries. The so-called legacy effect in the treatment of hypertension, in which patients who are treated with a given antihypertensive therapy may derive a long-term benefit after discontinuation of therapy, has been recently proposed on the basis of accumulating evidence and, in particular, on the availability of long-term post-trial observations in randomized controlled clinical trials. In this review, we discuss the evidence witnessing a legacy effect of antihypertensive therapy and whether this supports sufficiently lifetime drug treatment of hypertension.

Polypharmacy in heart failure patients.

In heart failure (HF), the progressive use of multiple drugs and a complex therapeutic regimen is common and is recommended by international guidelines. With HF being a common disease in the elderly, patients often have numerous comorbidities that require additional specific treatment, thus producing a heavy pill burden. Polypharmacy, defined as the chronic use of five or more medications, is an underestimated problem in the management of HF patients. However, polypharmacy has an important impact on HF treatment, as it often leads to inappropriate drug prescription, poor adherence to pharmacological therapies, drug-drug interactions, and adverse effects. The growing complexity of HF patients, whose mean age increases progressively and who present multiple comorbidities, suggests the need for newer models of primary care to improve the management of HF patients. Self-care, telemonitoring, and natriuretic peptide-guided therapy represent promising new HF care models to face the complexity of the disease and its therapeutic regimen.

Pathogenesis of chronic cardiorenal syndrome: is there a role for oxidative stress?

Cardiorenal syndrome is a frequently encountered clinical condition when the dysfunction of either the heart or kidneys amplifies the failure progression of the other organ. Complex biochemical, hormonal and hemodynamic mechanisms underlie the development of cardiorenal syndrome. Both in vitro and experimental studies have identified several dysregulated pathways in heart failure and in chronic kidney disease that lead to increased oxidative stress. A decrease in mitochondrial oxidative metabolism has been reported in cardiomyocytes during heart failure. This is balanced by a compensatory increase in glucose uptake and glycolysis with consequent decrease in myocardial ATP content. In the kidneys, both NADPH oxidase and mitochondrial metabolism are important sources of TGF-ß1-induced cellular ROS. NOX-dependent oxidative activation of transcription factors such as NF-kB and c-jun leads to increased expression of renal target genes (phospholipaseA2, MCP-1 and CSF-1, COX-2), thus contributing to renal interstitial fibrosis and inflammation. In the present article, we postulate that, besides contributing to both cardiac and renal dysfunction, increased oxidative stress may also play a crucial role in cardiorenal syndrome development and progression. In particular, an imbalance between the renin-angiotensin-aldosterone system, the sympathetic nervous system, and inflammation may favour cardiorenal syndrome through an excessive oxidative stress production. This article also discusses novel therapeutic strategies for their potential use in the treatment of patients affected by cardiorenal syndrome.

Left ventricular mass increase is associated with cognitive decline and dementia in the elderly independently of blood pressure.

AIMS: Left ventricular (LV) mass increase is considered part of composite target organ damage in hypertension and an independent risk factor for cardiovascular (CV) events. This study was designed to explore whether left ventricular mass index (LVMI) is associated with cognitive decline and dementia in elderly subjects, independently of blood pressure (BP) levels. METHODS AND RESULTS: Four hundred subjects (mean age 79 +/- 6 years) were studied. Left ventricular mass was measured echocardiographically in accordance with American Society of Echocardiography and normalized for body height to the 2.7 (LVMI). Global cognitive function was evaluated with the mini-mental state examination (MMSE) (maximum score 30). Dementia was defined as an MMSE score <21. Arterial stiffness was evaluated as carotid-femoral pulse wave velocity by Complior. Prevalence of hypertension was 70% and diabetes mellitus was diagnosed in 25%. No significant differences in traditional CV risk factors were observed across LVMI quartiles. Mini-mental state examination showed an inverse trend across LVMI quartiles (the higher the LVMI, the lower the MMSE, P for trend <0.05); systolic and diastolic BP levels were not different across LVMI quartiles. In multivariable logistic regression models, including age, sex, BP levels, and use of antihypertensive drugs as covariates, the highest LVMI was found to be independently associated with a two-fold higher likelihood of having dementia. The association persisted significant even after adjustment for arterial stiffness. CONCLUSION: In elderly subjects, LVMI is associated with a progressive cognitive decline. This association is independent of BP levels and/or large artery stiffness.

Antihypertensive drugs and the risk of cancer: a critical review of available evidence and perspective.

: The issue of a potential danger of antihypertensive drugs related to cancer susceptibility is currently generating a major debate in the scientific community, concerns in the public and emphasized interest from the media. The present article is a thorough review of what is known on the various classes of antihypertensive drugs concerning the risk of developing different neoplasms and about the suggested pathophysiological mechanisms, whenever available. The main limitations of evidence derived from studies currently available in this setting are also discussed, high-lightening the need for newly developed approaches to generate more accurate recommendations and informed advice for physicians.

Immigration Emergency in Italy: The Impact of Socioeconomic Status on Blood Pressure Levels and Control.

INTRODUCTION: Nowadays there are more than 5 millions of immigrants (8.3% of general adult population) in Italy. AIM: To evaluate the potential impact of immigration and the possession of a permanent residence on blood pressure (BP) levels and control in a low income population of immigrants from different countries. METHODS: We evaluated clinical characteristics and social status of adult individuals with known diagnosis of hypertension afferent to the Poliambulatorio della Caritas Diocesana in Rome, Italy, between 2010-2016. Subjects were stratified according to their macro-areas of origin (Europe, Asia, Africa, South-America), housing (with or without house), and immigration status (presence or absence of residence permit). BP levels were measured in three consecutive visits according to recommendations from current European Guidelines. RESULTS: From an overall population sample of 9827 adult individuals, we initially identified 994 patients with a diagnosis of hypertension (10.1%), among whom 536 (5.4%) had valid BP data. Among these, 50.6% came from Europe, 21.6% from Africa, 24.1% from Asia, and 3.7% from South-America. They were predominantly male (54.7%), middle aged (42.8 ± 12.1 years at arrival and 51.6 ± 10.6 years at first visit) and untreated (72.8%) individuals with baseline systolic/diastolic BP levels of 156.9 ± 22.2/97.3 ± 12.4 mmHg). BP levels remained higher in homeless than in housed people at both visit 2 (150.0 ± 21.8/92.6 ± 12.9 mmHg vs. 142.9 ± 19.3/89.9 ± 11.6 mmHg; P < 0.001) and visit 3 (147.9 ± 22.2/91.7 ± 12.5 mmHg vs. 141.8 ± 19.4/89.2 ± 12.0 mmHg; P = 0.013). We also observed reductions of both systolic and diastolic BP levels compared to baseline values in immigrants stratified according to residence permit, although without relevant differences among groups. CONCLUSIONS: Beyond conventional risk factors, socio-economic issues, including lack of residence permit or habitation, may affect BP levels and control in frail populations of immigrants, which have been marginally considered before.

Achievement of low density lipoprotein (LDL) cholesterol targets in primary and secondary prevention: Analysis of a large real practice database in Italy.

BACKGROUND AND AIMS: Target and intensity of low-density lipoprotein cholesterol (LDL-C) lowering therapy should be tailored according to the individual global cardiovascular (CV) risk. We aimed at retrospectively evaluating real-life LDL-C goal attainment and predictive factors for predefined LDL-C therapeutic goals both in primary and secondary prevention. METHODS: We collected data from a large cohort of outpatients aged 40-65 years, followed by general practitioners, cardiologists and diabetologists in Italy. All data were centrally analysed for global CV risk assessment and rates of control of major CV risk factors, including LDL-C. Study population was stratified according to the presence or absence of previous CV events, including coronary artery disease (CAD), peripheral artery disease (PAD) or stroke/TIA. CV risk profile characterization was based on the European SCORE. Predefined therapeutic goals were set according to the European guidelines on dyslipidaemia: LDL-C levels <70 mg/dl for very high CV risk patients in primary prevention and for those in secondary prevention; <100 mg/dl LDL-C levels for high CV risk patients in primary prevention. Logistic regression analysis with clinical covariates was used to identify predictive factors for achieving these goals; lipid lowering therapy entered in the analysis as continuous (model 1) or categorical variable (model 2). RESULTS: We included 4,142 outpatients (43,7% female, age 58.0 ±â€¯5.2 years, BMI 28.5 ±â€¯5.0 kg/m2) among whom 2,964 (71.6%) in primary and 1,178 (28.4%) in secondary prevention. In primary prevention, none of the patients at very high CV risk had LDL-C <70 mg/dl and 8.9% of patients at high CV risk showed LDL-C <100 mg/dl. Only 5.8% of patients in secondary prevention had LDL-C levels <70 mg/dl, specifically 6.5% of patients with CAD, 2.6% of patients with PAD and 4.7% of patients with CVD (p < 0.001). Beyond diabetes and lipid lowering therapy, high risk SCORE estimation resulted a strong and independent predictor for the lack of achieving all predefined therapeutic targets, including LDL-C <100 mg/dl [OR: 0.806 (0.751-0.865)); p < 0.001], and LDL-C <70 mg/dl [OR: 0.712 (0-576-0.880); p = 0.002], in primary prevention. CONCLUSIONS: Despite high or very high SCORE risk and use of lipid lowering therapies, we observed poor achievement of LDL-C targets in this large cohort of outpatients followed in a setting of real practice in Italy.

Reclassification of Hypertensive Outpatients According to New US Guidelines on High Blood Pressure.

BACKGROUND: US guidelines on high blood pressure (BP) have recently proposed a new BP stratification. OBJECTIVE: To evaluate the redistribution of adult outpatients according to 2003 and 2017 US hypertension guidelines. METHODS: We extracted data referred to individuals aged between 40 and 70 years with valid BP assessment from a national, cross-sectional database. The following systolic/diastolic BP strata were considered: (i) 2003 guidelines: 0 = normal (<120/180 mm Hg), 1 = prehypertension (≥120 and ≤139/≥80 and ≤89 mm Hg), 2 = stage 1 (≥140 and ≤159/≥90 and ≤99 mm Hg), 3 = stage 2 (≥160/≥100 mm Hg) and (ii) 2017 American College of Cardiology/American Heart Association guidelines: 0 = normal (<120/80 mm Hg), 1 = elevated (≥120 and ≤129/<80 mm Hg); 2 = stage 1 (≥130 and ≤139/≥80 and ≤89 mm Hg), 3 = stage 2 (≥140/≥90 mm Hg). Cardiovascular (CV) risk profile characterization was based on Framingham, 10-year risk of a first atherosclerotic cardiovascular disease and European score equations. RESULTS: From an overall population sample of 10,012 individuals, we selected 8,911 (89.0%) with valid clinic BP data (44.4% female, age = 60.7 ± 6.6 years, body mass index = 28.2 ± 4.9 kg/m2, clinic BP = 136.8 ± 14.5/82.1 ± 8.3 mm Hg), among whom 339 (3.8%) were in the normal BP range. According to 2003 guidelines, 3,919 (44.0%) patients had prehypertension, 3,698 (41.5%) had stage-1 and 955 (10.7%) had stage-2 hypertension. According to 2017 guidelines, 635 (3.8%) patients had elevated BP, 3,284 (36.9%) had stage-1 and 4,653 (52.2%) had stage-2 hypertension. New BP classification moved 37% individuals from "pre-hypertension" to "stage 1" and 41% from "stage 1" to "stage 2" hypertension, respectively. CONCLUSIONS: Redistribution of hypertensive patients according to 2017 US hypertension guidelines compared with previous ones may help to better identify uncontrolled hypertensive patients with high CV risk profile.

24-Hour ambulatory blood pressure levels and control in a large cohort of adult outpatients with different classes of obesity.

Effective and sustained blood pressure (BP) control in hypertensive patients with moderate-to-severe obesity is often difficult to achieve. We evaluated clinic, 24h, day-time and night-time systolic/diastolic BP levels and control in a large cohort of adult outpatients with different classes of obesity. A single center, prospective, cohort study was conducted at Hypertension Unit, Division of Cardiology, Sant'Andrea Hospital, Rome Italy. All BP measurements were performed and BP thresholds were set according to guidelines. Study population was stratified according to BMI. We included 4,766 individuals (women 48.6%, age 60.3 ± 11.6 years, clinic BP 143.8 ± 18.2/90.9 ± 12.3 mmHg, 24h BP 130.2 ± 13.3/79.1 ± 9.5 mmHg), among whom 36.0% had normal weight, 43.5% were overweight, 15.7% had class I, and 4.8% class II/III obesity. Obese outpatients had higher prevalence of risk factors, and were treated more frequently and with more antihypertensive drugs than those with normal body weight. Obese outpatients showed higher systolic BP levels at all BP measurements, mostly 24h and night-time periods, than those observed in normal weight outpatients. BMI resulted significantly related with clinic (r = 0.053; P < 0.001), 24h (r = 0.098; P < 0.001) and night-time systolic BP (r = 0.126; P < 0.001), and left ventricular mass indexed by height^2.7 (r = 0.311; P < 0.001). BMI was also negatively and independently associated with predefined BP goals at all types of BP measurements. Obesity was associated with higher systolic BP levels during the entire 24h period and increased left ventricular mass. These effects were independently observed, even after correction for major cardiovascular risk factors and comorbidities, as well as the number and type of antihypertensive drug classes.

Role of oxidative stress in the process of vascular remodeling following coronary revascularization.

Percutaneous coronary interventions (PCI), including balloon angioplasty and implantation of both bare metal and drug eluting coronary stents, are associated with risk of restenosis and in-stent thrombosis. A better understanding of signals that regulate cellular proliferation, neointimal formation and vessel wall thickening following PCI may contribute to identify novel preventive and therapeutic strategies aimed to reduce the atherosclerosis progression and the consequent vascular sequelae. Among the possible mechanisms, an increased level of reactive oxygen species (ROS) is associated with endothelial dysfunction and vascular smooth muscle cells (VSMCs) proliferation and migration involved in the post-procedural remodeling process. This review article provides an overview of the current knowledge on the contribution of increased oxidative stress to the post-procedural pathological vascular changes. We discuss the role of nicotinamide adenine dinucleotide phosphate oxidase, nitric oxide synthase, and of proteins regulating the mitochondrial function and dynamics. We will also highlight new knowledge on the atypical Fat1 cadherin that appears to play a key role in VSMCs proliferation. In fact, its induction after vascular injury serves as a physiological regulator of VSMCs growth. Specific molecular mechanisms, including Pin1- and H2S-mediated pathways, have been identified in the vascular complications of type 2 diabetic patients. The identification of novel key players may expand our perspectives and promote the development of new tools for future preventive and therapeutic strategies in order to reduce the adverse vascular remodeling following PCI. The latter represents one of the major goals in the development of innovative technologies with relevance for clinical practice.

Therapeutic Approach to Hypertension Urgencies and Emergencies During Acute Coronary Syndrome.

Uncontrolled hypertension is one of the most common determinant for the persistently high burden of cardiovascular (CV) disease, mostly including coronary artery disease (CAD) and hospital admissions due to acute coronary events. Markedly high blood pressure (BP) levels are also frequently observed during the acute phase of coronary syndromes (both ST-segment and non-ST-segment elevation myocardial infarction and unstable angina). In particular, a sustained raise of BP levels above 180/110 mmHg associated with acute cardiac organ damage, i.e. myocardial ischemia, represents a condition of hypertension emergency and requires rapid hospital admission, prompt pharmacological therapies and non-pharmacological interventions, aimed at restoring coronary flow and preserve vital myocardium. Diagnosis of CAD in hypertensive patients may often be complicated by the concomitant presence of electrocardiographic abnormalities, such as ST-segment depression (at rest or during exercise), which may occur even in the absence of coronary atherosclerosis. Thus, proper identification of CAD may result difficult to perform in the setting of clinical practice, mostly in the presence of left ventricular hypertrophy. In this review, we will briefly discuss diagnostic protocols and pharmacological strategies that can be applied in a setting of hypertension emergency with acute cardiac organ damage in the light of the currently available evidence and recommendations from recent guidelines on hypertension management and control.

Chronic heart failure is characterized by altered mitochondrial function and structure in circulating leucocytes.

Oxidative stress is currently viewed as a key factor in the genesis and progression of Heart Failure (HF). The aim of this study was to characterize the mitochondrial changes linked to oxidative stress generation in circulating peripheral blood mononuclear cells isolated from chronic HF patients (HF_PBMCs) in order to highlight the involvement of mitochondrial dysfunction in the pathophysiology of HF. To assess the production of reactive oxygen species (ROS), mitochondrial function and ultrastructure and the mitophagic flux in circulating PBMCs we enrolled 15 patients with HF and a control group of ten healthy subjects. The HF_PBMCs showed a mitochondrial population consisting of damaged and less functional organelles responsible of higher superoxide anion production both at baseline and under in vitro stress conditions, with evidence of cellular apoptosis. Although the mitophagic flux at baseline was enhanced in HF_PBMCs at level similar to those that could be achieved in control PBMCs only under inflammatory stress conditions, the activation of mitophagy was unable to preserve a proper mitochondrial dynamics upon stress stimuli in HF. In summary, circulating HF_PBMCs show structural and functional derangements of mitochondria with overproduction of reactive oxidant species. This mitochondrial failure sustains a leucocyte dysfunctional status in the blood that may contribute to development and persistence of stress conditions within the cardiovascular system in HF.

Nocturnal blood pressure patterns and cardiovascular outcomes in patients with masked hypertension.

Masked hypertension (MHT) is characterized by normal clinic and above normal 24-hour ambulatory blood pressure (BP) levels. We evaluated clinical characteristics and CV outcomes of different nocturnal patterns of MHT. We analyzed data derived from a large cohort of adult individuals, who consecutively underwent home, clinic, and ambulatory BP monitoring at our Hypertension Unit between January 2007 and December 2016. MHT was defined as clinic BP <140/90 mm Hg and 24-hour BP ≥ 130/80 mm Hg, and stratified into three groups according to dipping status: (a) dippers, (b) nondippers, and (c) reverse dippers. From an overall sample of 6695 individuals, we selected 2628 (46.2%) adult untreated individuals, among whom 153 (5.0%) had MHT. In this group, 67 (43.8%) were nondippers, 65 (42.5%) dippers, and 21 (13.7%) reverse dippers. No significant differences were found among groups regarding demographics, clinical characteristics, and prevalence of risk factors, excluding older age in reverse dippers compared to other groups (P < 0.001). Systolic BP levels were significantly higher in reverse dippers than in other groups at both 24-hour (135.6 ± 8.5 vs 130.4 ± 6.0 vs 128.2 ± 6.8 mm Hg, respectively; P < 0.001) and nighttime periods (138.2 ± 9.1 vs 125.0 ± 6.3 vs 114.5 ± 7.7 mm Hg; P < 0.001). Reverse dipping was associated with a significantly higher risk of stroke, even after correction for age, gender, BMI, dyslipidemia, and diabetes (OR 18.660; 95% IC [1.056-33.813]; P = 0.046). MHT with reverse dipping status was associated with higher burden of BP and relatively high risk of stroke compared to both dipping and nondipping profiles, although a limited number of CV outcomes have been recorded during the follow-up.

Ferrari Corporate Wellness Program: Results of a Pilot Analysis and the "Drag" Impact in the Workplace.

INTRODUCTION: Preventive strategies based on advice and interventions on lifestyle habits represent the most powerful resource available to reduce the burden of cardiovascular (CV) diseases. Workplace represents an unmissable context for lifestyle changes at population level. AIM: To evaluate the mid-term efficacy of a corporate wellness program in a cohort of healthy and physically active employees of the Ferrari car manufacturer. METHODS: A corporate wellness program, named "Ferrari Formula Benessere", was proposed to adult individuals working in a Ferrari car company at Maranello, Modena (Italy). Employees who voluntarily agreed to the program received healthy nutritional advice and were trained three times a week (60 min per session), and periodically re-evaluated during a 4-year follow-up period. RESULTS: Among the 719 Ferrari employees that joined the program, 168 (23%) subjects (88.5% males, age 30.8 ± 5.9 years) were considered the most active participants, based on a self-administered standardized questionnaire, and included in the study. A relevant improvement of several CV risk factors (body mass index, total and LDL cholesterol, triglycerides, blood pressure) and cardio-respiratory fitness parameters (estimated VO2max, Wattpeak, METs) was observed compared to baseline values. Furthermore, it was recorded a clear "drag effect" towards non-participating and sedentary peers, resulting in a 90% adherence increase over the years. CONCLUSIONS: The "Ferrari Formula Benessere" corporate wellness project proved to be effective in improving CV risk profile and cardio-respiratory fitness in a population of already physically active employees.

Prevalence and clinical outcomes of white-coat and masked hypertension: Analysis of a large ambulatory blood pressure database.

The aim of this study was to analyze prevalence and clinical outcomes of the following clinical conditions: normotension (NT; clinic BP < 140/90 mm Hg; 24-hour BP < 130/80 mm Hg), white-coat hypertension (WCHT; clinic BP ≥ 140 and/or ≥90 mm Hg; 24-hour BP < 130/80 mm Hg), masked hypertension (MHT; clinic BP < 140/90 mm Hg; 24-hour BP ≥ 130 and/or ≥80 mm Hg), and sustained hypertension (SHT; clinic BP ≥ 140 and/or ≥90 mm Hg; 24-hour BP ≥ 130 and/or ≥80 mm Hg) in a large cohort of adult untreated individuals. Systematic research throughout the medical database of Regione Lazio (Italy) was performed to estimate incidence of myocardial infarction (MI), stroke, and hospitalizations for HT and heart failure (HF). Among a total study sample of 2209 outpatients, 377 (17.1%) had NT, 351 (15.9%) had WCHT, 149 (6.7%) had MHT, and 1332 had (60.3%) SHT. During an average follow-up of 120.1 ± 73.9 months, WCHT was associated with increased risk of hospitalization for HT (OR 95% CI: 1.927 [1.233-3.013]; P = .04) and HF (OR 95% CI: 3.449 [1.321-9.007]; P = .011). MHT was associated with an increased risk of MI (OR 95% CI: 5.062 [2.218-11.550]; P < .001), hospitalization for HT (OR 95% CI: 2.553 [1.446-4.508]; P = .001), and for HF (OR 95% CI: 4.214 [1.449-12.249]; P = .008). These effects remained statistically significant event after corrections for confounding factors including age, BMI, gender, smoking, dyslipidaemia, diabetes, and presence of antihypertensive therapies.

Achievement of multiple therapeutic targets for cardiovascular disease prevention: Retrospective analysis of real practice in Italy.

BACKGROUND: Pharmacological therapy in patients at high cardiovascular (CV) risk should be tailored to achieve recommended therapeutic targets. HYPOTHESIS: To evaluate individual global CV risk profile and to estimate the control rates of multiple therapeutic targets for in adult outpatients followed in real practice in Italy. METHODS: Data extracted from a cross-sectional, national medical database of adult outpatients in real practice in Italy were analyzed for global CV risk assessment and rates of control of major CV risk factors, including hypertension, dyslipidemia, diabetes, and obesity. CV risk characterization was based on the European SCORE equation and the study population stratified into 3 groups: low risk (<2%), intermediate risk (≥2%-<5%), and high to very high risk (≥5%). RESULTS: We analyzed data from 7158 adult outpatients (mean age, 57.7 ±5.3 years; BMI, 28.3 ±5.0 kg/m2 , BP, 136.0 ±14.3/82.2 ±8.3 mm Hg; total cholesterol, 212.7 ±40.7 mg/dL), among whom 2029 (45.2%) had low, 1730 (24.2%) intermediate, and 731 (16.3%) high to very high risk. Increased SCORE risk was an independent predictor of poor achievement of diastolic BP <90 mm Hg (OR: 0.852, 95% CI: 0.822-0.882), LDL-C < 130 mg/dL (OR: 0.892, 95% CI: 0.861-0.924), HDL-C > 40 (males)/>50 (females) mg/dL (OR: 0.926, 95% CI: 0.895-0.958), triglycerides <160 mg/dL (OR: 0.925, 95% CI: 0.895-0.957), and BMI <25 kg/m2 (OR: 0.888, 95% CI: 0.851-0.926), even after correction for diabetes, renal function, pharmacological therapy, and referring physicians (P < 0.001). CONCLUSIONS: Despite low prevalence and optimal medical therapy, individuals with high to very high SCORE risk did not achieve recommended therapeutic targets in a real-world practice.

Effects of different statin types and dosages on systolic/diastolic blood pressure: Retrospective analysis of 24-hour ambulatory blood pressure database.

We previously demonstrated lower diastolic blood pressure (BP) levels under statin therapy in adult individuals who consecutively underwent 24-hour ambulatory BP monitoring and compared their levels to untreated outpatients. Here we evaluated systolic/diastolic BP levels according to different statin types and dosages. 987 patients (47.5% female, age 66.0 ± 10.1 years, BMI 27.7 ± 4.6 kg/m2 , clinic BP 146.9 ± 19.4/86.1 ± 12.1 mm Hg, 24-hour BP 129.2 ± 14.4/74.9 ± 9.2 mm Hg) were stratified into 4 groups: 291 (29.5%) on simvastatin 10-80 mg/d, 341 (34.5%) on atorvastatin 10-80 mg/d, 187 (18.9%) on rosuvastatin 5-40 mg/d, and 168 (17.0%) on other statins. There were no significant BP differences among patients treated by various statin types and dosages, except in lower clinic (P = .007) and daytime (P = .013) diastolic BP in patients treated with simvastatin and atorvastatin compared to other statins. Favorable effects of statins on systolic/diastolic BP levels seem to be independent of types or dosages, thus suggesting a potential class effect of these drugs.

Triple Combination Therapies Based on Olmesartan: A Personalized Therapeutic Approach to Improve Blood Pressure Control.

Recent epidemiological surveys have demonstrated that effective and sustained blood pressure (BP) control is achieved in a relatively small proportion of treated hypertensive patients. Indeed, treatment of hypertension represents a key strategy for preventing coronary artery disease, stroke, congestive heart failure and cardiovascular death. Several interventions have been proposed by international guidelines for ameliorating hypertension management and control, mostly including integrated and multi-dimensional pharmacological and non-pharmacological strategies. In particular, numerous evidence demonstrated that a more extensive use of combination therapy may represent a valid therapeutic option for treating hypertensive patients at different risk profile. This strategy has been definitely strengthened by the availability of single pill fixed-dose combinations. Among potential combination therapies, those based on the association of renin-angiotensin system antagonists, thiazide diuretics and calcium channel blockers are very effective in lowering BP levels and well tolerated. We will provide here an overview of clinical evidence supporting the use of triple combination therapy, with a focus on that based on olmesartan medoxomil, a thiazide diuretic (hydrochlorothiazide) and a calcium channel blocker (amlodipine besylate), which is available in multiple dosages. Finally, in view of the recognised importance of single-pill combination therapy for treating hypertension, we will examine the potential benefits of dual (fixed) combination therapy based on olmesartan medoxomil with either thiazide diuretic hydrochlorothiazide or calcium channel blocker amlodipine in terms of efficacy, safety and tolerability profile.

Monotherapy and Dual Combination Therapies Based on Olmesartan: A Comprehensive Strategy to Improve Blood Pressure Control.

Olmesartan medoxomil is an antihypertensive drug of the class of angiotensin II type 1 (AT1) receptor antagonists (or blockers), characterized by tight and prolonged binding to AT1 receptor compared to other molecules within the same class. These characteristics produce effective and sustained blood pressure reductions in hypertensive patients at different cardiovascular risk profile with a good tolerability profile. After a brief description of the pharmacological characteristics of olmesartan, we will provide a thorough overview of the clinical studies that investigated its efficacy and safety in the clinical management of hypertensive patients both in monotherapy and in dual combination therapies with either thiazide diuretics or calcium channel blockers. These studies demonstrated that olmesartan-based antihypertensive strategy may indeed provide sustained BP control over the 24-h period in a wide proportion of hypertensive patients, thus contributing to a substantial progress in hypertension management. Finally, since growing evidence suggest that olmesartan may also exert potential favourable effects at vascular level, thereby antagonizing the vascular inflammatory process involved in the development and progression of atherosclerosis, the main clinical studies addressing this issue will be also discussed.