Lipoprotein(a) as a Risk Factor for Venous Thromboembolism: A Systematic Review and Meta-analysis of the Literature.

Elevated plasma levels of lipoprotein(a) (Lp(a)) are associated with increased cardiovascular risk in several clinical studies. However, there is a lack of data supporting a positive association between elevated Lp(a) levels and venous thromboembolism (VTE). Thus, we conducted a systematic review of the literature to better clarify its role as a risk factor for VTE. Medline and the Embase (up to May 2015) electronic databases were used to identify potentially eligible studies. Studies measuring Lp(a) values in adult patients with deep vein thrombosis and/or pulmonary embolism and in a population of patients without a VTE were selected. Studies on patients with major venous thromboembolic events occurring at other unusual site, case reports, and case series were excluded. The odds ratios (ORs) of the association between high values of Lp(a) and VTE and the weighted mean difference (WMD) in Lp(a) levels in cases and in controls were calculated using a random-effect model. Results were presented with 95% confidence interval (CI). Fourteen studies for a total of more than 14,000 patients were finally included in our analysis. Lp(a) was slightly but significantly associated with an increased risk of VTE (OR: 1.56, 95% CI: 1.36, 1.79; 10 studies, 13,541 patients). VTE patients had significantly higher Lp(a) values compared with controls (WMD: 14.46 mg/L, 95% CI: 12.14, 16.78; 4 studies, 470 patients). Lp(a) appeared to be significantly associated with increased risk of VTE. However, Lp(a) levels were only slightly increased in VTE patients compared with controls.

Relationship between regulatory T cells subsets and lipid profile in dyslipidemic patients: a longitudinal study during atorvastatin treatment.

BACKGROUND: The CD4+ T-lymphocytes and their subtype CD4 + CD25(high)FoxP3+ regulatory T cells are receiving growing interest as major regulators of atherogenesis. We sought to investigate 1) whether the CD4 + cell subsets were expressed differently in dyslipidemic patients (Pts) and healthy subjects (HS) and 2) whether atorvastatin treatment could be associated in-vivo and in-vitro with cell changes in expression and functional response. METHODS: CD4+ subsets frequency (CD4 + CD25(high)FoxP3+, CD4 + CD25-FoxP3+) and mRNA expression for FoxP3, IL-10 and TGF-ß were evaluated in 30 consecutive Pts at baseline and after a 3-month atorvastatin therapy, and in 17 HS. RESULTS: The % of CD4 + cells did not differ between HS and Pts. The % of CD4 + CD25(high)FoxP3+ was higher in Pts than HS and did not change during treatment. The CD4 + CD25-FoxP3+ cells were similar between the two groups and were lower in Pts at visit 2. Cytokine expression and FoxP3 did not differ in HS and Pts and no substantial change was observed during treatment. At visit 1, CD4 + CD25(high)FoxP3+ cells were significantly correlated with both total-cholesterol (r = 0.570, P = 0.0002), LDL-cholesterol (r = 0.715, P = 0.0001), Apolipoprotein B (r = 0.590, P = 0.0001). In-vitro atorvastatin (up to 5 µM) failed to induce any significant modulation of cell functions. CONCLUSION: CD4 + CD25(high)FoxP3+ regulatory cells seem to be over-stimulated in the early pre-clinical phase of atherosclerosis and a relationship exists between their frequency and circulating lipids. A potential immuno-modulation by statin treatment is not achieved through a normalization in peripheral CD4 + cell subsets.

Gender Difference in Efficacy and Safety of Nonvitamin K Antagonist Oral Anticoagulants in Patients with Nonvalvular Atrial Fibrillation or Venous Thromboembolism: A Systematic Review and a Meta-Analysis of the Literature.

INTRODUCTION: Limited information exists on gender-related differences in the safety and efficacy of non-vitamin K antagonist oral anticoagulants (NOACs). AIM OF THE STUDY: To assess the safety and efficacy of direct oral anticoagulants (DOACs)/NOACs in men and women pooling data from randomized controlled trials on the prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation (AF) and on the acute and extended treatment of venous thromboembolism (VTE). METHODS: MEDLINE and EMBASE databases were searched up to June 2014. The efficacy outcome was defined as the prevention of stroke and systemic embolism (AF studies), or as the prevention of recurrent VTE or VTE-related death (VTE studies). The safety outcome was defined as the occurrence of major and/or clinically relevant non-major bleeding. Differences in the efficacy and safety outcomes were expressed as risk ratio (RR) with pertinent 95% confidence intervals (95% CI). RESULTS: A total of 13 studies (> 100,000 patients) were included. DOACs appeared to have a similar efficacy and safety compared with vitamin K antagonists in female and male patients treated for nonvalvular AF and acute VTE. In the extended treatment of VTE NOACs had a RR of bleeding of 4.97 (95% CI 1.06, 23.41) in males and 1.33 (95% CI 0.63, 2.83) in females compared with placebo (subgroup difference chi-square test: 2.25, p = 0.13). CONCLUSIONS: No gender-related difference in the efficacy and safety of NOACs in patients with AF or acute VTE was found. A trend toward an increased risk of bleeding in male patients as compared with female patients was detected in the extended treatment of VTE.

Association between statin-induced creatine kinase elevation and genetic polymorphisms in SLCO1B1, ABCB1 and ABCG2.

PURPOSE: Treatment with statins requires close monitoring of serum creatine kinase (CK) levels to prevent myopathy, a common and potentially serious dose-dependent adverse effect of these drugs. We have investigated the correlation between elevated CK levels and polymorphisms in the genes encoding transporters involved in statin disposition. METHODS: Patients with and without statin-induced elevated serum CK levels were genotyped for polymorphisms in SLCO1B1 (SLCO1B1 A388G and SLCO1B1 T521C), ABCB1 (ABCB1 C1236T and ABCB1 C3435T) and ABCG2 (ABCG2 C421A). RESULTS: Patients carrying SLCO1B1 T521C or ABCB1 C1236T single nucleotide polymorphisms (SNPs) had an odds ratio (OR) for statin-induced elevated serum CK levels of 8.86 (p<0.01) and 4.67 (p<0.05), respectively, while patients carrying the SLCO1B1 A388G SNP had an OR of 0.24 (p<0.05). An arbitrary score based on genotype combination discriminated patients with and without CK elevation at a specificity of 97 % and a sensitivity of 39 %. CONCLUSION: Genotyping of the SLCO1B1, ABCB1 and ABCG2 genes deserves consideration as a clinical approach to improve statin safety while concomitantly reducing the burden of blood tests for CK measurements.

Simvastatin down-regulates the production of interleukin-8 by neutrophil leukocytes from dyslipidemic patients.

BACKGROUND: Neutrophil (PMN) leukocytes participate to the initial phases of atherosclerosis through the release of Interleukin 8 (CxCL8; IL-8) that contribute to amplification of inflammation. Aim of the study is to investigate the production of IL-8 by PMN leukocytes from dyslipidemic patients treated with simvastatin. METHODS: In 15 dyslipidemic subjects with moderately increased cardiovascular risk, assessed by Framingham Risk Score, blood samples were obtain to investigate PMNs IL-8 production [at baseline and after N-formyl-Met-Leu-Phe (fMLP) stimulation] before and after long-term (1-year) simvastatin treatment. RESULTS: The resting release of IL-8 was higher in dyslipidemic patients at baseline when compared with control subjects (p < 0.05). One year of treatment was significantly associated with reduced IL-8 production (p < 0.01). Moreover, the fMLP-induced IL-8 production in dyslipidemic untreated patients was higher than that of controls (p < 0.05) and was reduced after simvastatin treatment (p < 0.01). IL-8 release after 1 year of treatment was reduced to levels which were lower than those observed in control subjects both for resting and stimulated cytokine production (p < 0.01). CONCLUSIONS: Prolonged treatment with simvastatin is associated with a reduction of IL-8 production, suggesting the possibility of statin to modulate the pro-inflammatory response in PMNs of patients with moderately increased cardiovascular risk.

Angiotensin II type 1 and type 2 receptor expression in circulating monocytes of diabetic and hypercholesterolemic patients over 3-month rosuvastatin treatment.

BACKGROUND: In diabetes, a variety of pro-inflammatory cellular changes has been found in various cell types, including monocytes which are known to be involved in all the phases of atherogenesis. Angiotensin II (Ang II) type 1 receptor (AT1R) mediates the pro-atherogenic effects of Ang II whereas the type 2 receptor (AT2R) seems associated with atheroprotection. We sought to investigate the potential changes of AT1R-AT2R expression in human monocytes of type 2 diabetic- hypercholesterolemic patients and in hypercholesterolemic subjects, upon clinical treatment with rosuvastatin. METHODS: The AT1R membrane protein and mRNA AT1R and AT2R expression in monocytes were investigated in 10 type 2 diabetic-hypercholesterolemic patients and in 10 hypercholesterolemic subjects, before and after 3-month rosuvastatin treatment. Moreover, the serum cytokine levels of interferon-γ (IFN-γ) and interleukin-4 (IL-4) were detected. RESULTS: As expected, rosuvastatin was associated with a change in the lipid profile in the two groups. Both the membrane protein (P = 0.008) and the AT1R mRNA expression (P = 0.038) were significantly reduced during treatment in the absence of AT2R expression change in diabetic-hypercholesterolemic patients whereas no significant difference was observed in hypercholesterolemic subjects. The serum IL-4 levels were increased during treatment whereas no change was observed in IFN-γ in diabetic-hypercholesterolemic patients. No cytokine change was observed in hypercholesterolemic subjects. CONCLUSIONS: Our study on monocytes of diabetic-hypercholesterolemic patients, showing a reduced AT1R but not AT2R expression during rosuvastatin treatment, suggests that statin therapy may modulate favorably the AT1-AT2 receptor balance in subjects with coexistent type 2 diabetes.

JAK2V617F mutation for the early diagnosis of Ph- myeloproliferative neoplasms in patients with venous thromboembolism: a meta-analysis.

Recent studies suggested that JAK2V617F mutation is frequent in patients with splanchnic vein thrombosis (SVT) but not in patients with other venous thromboembolic events (VTE). However, whether screening for the JAK2V617F mutation in VTE patients is justified remains unclear. Therefore, we performed a systematic review to assess the frequency of JAK2 mutation in VTE patients and the role of JAK2V617F mutation in the diagnosis of myeloproliferative neoplasms. MEDLINE and EMBASE databases were searched. Two reviewers independently performed study selection and extracted study characteristics. Pooled odds ratios of case-control studies and weighted mean proportion of the prevalence of JAK2V617F mutation of uncontrolled series were calculated. Twenty-four studies involving 3123 patients were included. Mean prevalence of JAK2 mutation was 32.7% (95% confidence interval, 25.5%-35.9%) in SVT patients. JAK2 mutation was associated with increased risk of SVT (odds ratio, 53.98; 95% confidence interval, 13.10-222.45). Mean prevalence of JAK2 mutation in other VTE patients was low (range, 0.88%-2.57%). Presence of JAK2V617F mutation in SVT patients was associated with a subsequent diagnosis of myeloproliferative neoplasm in many patients. JAK2 mutation is strongly associated with SVT, and routine screening of JAK2 mutation appears to be indicated in these patients.

Self-reported weight and height: implications for left ventricular hypertrophy detection. An Italian multi-center study.

We examined the difference between self-reported and measured body size values and their impact on detection of left ventricular hypertrophy (LVH) by echocardiographic LV mass indexation. A total of 1963 subjects referred by their practitioners for routine echocardiographic examination to nine outpatient echocardiographic laboratories across Italy were included in the study. Left ventricular hypertrophy was defined according to two gender- specific criteria as: A) Left ventricular mass (LVM) index ≥49 g/h(2.7) in men and ≥45 g/h(2.7) in women; B) LVM index ≥125 g/m(2) in men and ≥110 g/m(2) in women. Prevalence of LVH was calculated by indexing LVM to both self-reported and measured anthropometric values. In the whole population, LVH tended to be underestimated by self-reported values by 5.4% according to criterion A (48.5% vs. 53.9%, p < 0.001) and by 1.2% according to criterion B (29.6% vs. 30.8%, p < 0.01); similar findings were observed in the hypertensive subgroup encompassing one-half of the sample. Underestimation of LVH was more pronounced in older patients than in younger patients: 8.6% vs. 3.2% (p < 0.001) by criterion A, 3.1% vs. 0.1% (p < 0.001) by criterion B, in women than in men (8.6% vs. 3.3% (p < 0.001) by criterion A and 1.8% vs. 0.5% (p < 0.01) by criterion B. In a sample of outpatients attending echocardiographic laboratories, LVH is misclassified when left ventricular mass is normalized to self-reported weight and height. The error is related to the clinical characteristics of patients and is more pronounced when LVM is normalized to height(2.7).

TMAO as a biomarker of cardiovascular events: a systematic review and meta-analysis.

BACKGROUND: Unmasking the residual cardiovascular risk is a major research challenge in the attempt to reduce cardiovascular disease (CVD) morbidity and mortality. Mounting evidence suggests that a high circulating level of trimethylamine N-oxide is a new potential CVD risk factor. We performed a systematic review of the published studies to clarify the association between circulating high levels of TMAO and cardiovascular events. METHODS: Studies evaluating the association between TMAO and CVD events were searched by electronic databases up to December 2018. Pooled results were expressed as risk ratio (RR) with 95% pertinent confidence interval (CI). RESULTS: Three studies for a total of 923 patients at high/very high CVD risk were included in our analysis. Overall, a high TMAO level was associated with both major adverse cardiovascular events (RR = 2.05; 95% CI 1.61-2.61) and all-cause mortality (RR = 3.42; 95% CI 2.27-5.15). CONCLUSIONS: Our findings support a role of high TMAO levels in predicting CVD events. High levels of TMAO may be a new CVD risk factor, potentially useful to better plan personalized CVD prevention strategies.

Right ventricular remodelling in mild hypertensive patients: role of left ventricular morpho-functional parameters.

Previous studies suggested that hypertensive patients with left ventricular (LV) hypertrophy display right ventricular (RV) remodelling. Few data are available about RV remodelling in naive hypertensives without severe cardiac organ damage. Our aim was to evaluate the relationship between RV and LV morpho-functional parameters in never-treated patients with grade 1 hypertension and whether central blood pressure (CBP), inflammatory and metabolic parameters are potentially associated with RV remodelling. 150 never-treated subjects without evidence of diabetes or other cardiovascular diseases were enrolled in our study. We recruited 100 patients with mild hypertension (twenty-four hours blood pressure (24 h BP) ≥ 130/80 mmHg) and 50 normotensive subjects matched for gender, age and body mass index. To estimate the LV/RV parameters, we performed echography as well as arterial tonometry to assess pulse wave analysis/velocity (PWA/PWV). We found 24 h BP, CBP and PWV were higher in hypertensive patients than in normotensives. In addition, LV mass index was higher in hypertensives, and greater RV free wall thickness was observed (5.3 ± 1.4 vs 4.6 ± 1.2 mm, P = 0.02). RV thickness correlated with interventricular septum (IVS), systolic CBP and RV E' (r = 0.50, P = 0.0001, r = 0.30, P = 0.003, r = -0.24, P = 0.015); linear regression analysis showed a correlation with only IVS (ß = 0.39, P = 0.001). RV E' was correlated with IVS, LV E' and systolic CBP (r = -0.35, P = 0.0001, r = 0.25, P = 0.012, r = -0.24, P = 0.019); the correlation with IVS and LV E' (ß = -0.310, P = 0.001; ß = 0.27, P = 0.004) was confirmed by linear regression analysis. Our study shows RV remodelling is mostly correlated with IVS thickness, supporting the ventricular interdependence hypothesis.

Perioperative Safety and Efficacy of Different Anticoagulation Strategies With Direct Oral Anticoagulants in Pulmonary Vein Isolation: A Meta-Analysis.

OBJECTIVES: The purpose of this study was to evaluate the safety and efficacy of uninterrupted and interrupted direct oral anticoagulant (DOAC) administration in patients undergoing pulmonary vein isolation (PVI). BACKGROUND: The optimal periprocedural management of DOACs in patients undergoing PVI is not well defined, and different strategies are used. METHODS: A systematic search of PubMed/MEDLINE, Ovid/MEDLINE, and EMBASE was performed. Three strategies for periprocedural DOAC administration were considered: uninterrupted, mildly interrupted (<12 h), and interrupted (≥12 h). Primary endpoints were major bleeding (MB) and thromboembolic (TE) complications; pooled weighted mean incidence (WMI) was calculated using a random-effects model. A secondary endpoint was the WMI of overall bleeding (OB). RESULTS: The analysis included 43 studies for a total of 8,362 patients. DOACs showed similar safety and efficacy in the 3 subgroups. The WMI of MB was 1.02%, 1.49%, and 1.17% for the uninterrupted, mildly interrupted, and interrupted strategy, respectively; the WMI of TE complications was 0.16%, 0.46%, and 0.49% for the uninterrupted, mildly interrupted, and interrupted strategy, respectively, with no heterogeneity. OB appeared to be higher in uninterrupted (6.33%) and mildly interrupted (8.62%) groups compared with the interrupted (3.53%), with substantial heterogeneity among studies. No interaction was found between the incidence of MB and TE complications and different DOACs. CONCLUSIONS: In patients undergoing PVI, these 3 anticoagulation strategies may have similar safety and efficacy in terms of MB and TE complications. OB appears to be higher in uninterrupted and mildly interrupted strategies compared with the interrupted strategy. No substantial differences were observed among DOACs regarding the incidence of MB and TE complications.

Impact of neutrophils to lymphocytes ratio on major clinical outcomes in patients with acute coronary syndromes: A systematic review and meta-analysis of the literature.

BACKGROUND: Inflammatory markers are significantly associated with cardiovascular disease. The ratio between neutrophils and lymphocytes (NLR) is a potential new biomarker, which can single out individuals at risk for future cardiovascular events. Among total white blood cell count (WBC) and its subtypes, NLR seems to have the greatest predictive value for death and major adverse cardiovascular events (MACE) in patients with acute coronary syndrome (ACS). We conducted a meta-analysis of the literature to assess the relation between NLR and cardiovascular outcomes in STEMI/NSTEMI patients. METHODS: MEDLINE and EMBASE databases were searched. Two reviewers selected studies and extracted data. Pooled results were reported as odds ratios (ORs) and were presented with the corresponding 95% confidence intervals (CI). RESULTS: Twenty-three studies for a total of >16,000 patients were included. Compared to those with low NLR, high NLR on-admission was associated with a higher overall mortality both in patients with STEMI (OR: 4.60, 95% CI: 2.84-7.45; P < 0.00001) and in patients with NSTEMI (OR: 6.41, 95% CI: 2.65-15.50; P < 0.00001). An increased MACE risk was found in STEMI patients with high NLR (OR: 3.71, 95% CI: 2.67-5.17; P < 0.00001). Post-PCI mortality risk was significantly increased in patients with high NLR (OR: 3.76, 95% CI: 2.64-5.34; P < 0.00001). CONCLUSIONS: In this large meta-analysis on prognostic significance of NLR in ACS we found that on-admission high NLR in patients with STEMI/NSTEMI appeared to affect clinically important outcomes including both in-hospital and long-term mortality and MACE.

Prognostic role of neutrophils to lymphocytes ratio in patients with acute pulmonary embolism: a systematic review and meta-analysis of the literature.

The prognostic assessment of patients with acute pulmonary embolism (PE) is essential to drive its management. The search for new prognostic factors is a central issue for a more accurate estimate of short-term adverse events. Circulating neutrophils/lymphocytes ratio (NLR) has been suggested as prognostic biomarker for different cardiovascular diseases. Given the central role of inflammation, and in particular of neutrophils in the pathogenesis of VTE and its clinical history, NLR might represent a prognostic tool also in this setting. We performed a systematic review and meta-analysis of the literature to assess the prognostic role of NLR in patients with acute PE. MEDLINE and EMBASE were searched up to 2017, week 21. A bivariate random-effects regression approach was used to obtain summary estimate of accuracy of the high NLR adjusting for inter-study variability. Six studies for a total of 1424 patient are included. High NLR has a weighted mean sensitivity of 77% (95% CI 68-83) and a weighted mean specificity of 74% (95% CI 68-79). High NLR positive and negative predictive values are 24.4% (95% CI 20.4-28.3) and 96.7% (95% CI 95.6-97.8), respectively. The relevant impact of NLR on short-term mortality after an acute PE makes it a promising biomarker to better stratify patient prognosis.

Masked hypertension in type 2 diabetes mellitus. Relationship with left-ventricular structure and function.

BACKGROUND: To evaluate in type 2 diabetes mellitus the relationship between masked hypertension (MH) and left ventricular (LV) morpho-functional characteristics. METHODS: Using 24-hour BP monitoring and echocardiography, we evaluated 71 type 2 diabetic patients, without overt cardiac disease and never treated with antihypertensive drugs: 45 normotensive subjects with clinic BP <130/85 mmHg and 26 sustained hypertensives (SH)(clinic BP > or = 140 and/or 90 mmHg and 24-hour BP > or =125 and/or 80 mmHg), matched for age, gender, BMI and duration of diabetes with clinically normotensive patients. MH was diagnosed with clinic BP <130/85 mmHg and 24-hour BP > or =125 and/or 80 mmHg. RESULTS: Among clinically normotensive patients, 21 (47%) had MH and 24 were true normotensive (NT, 24-hour BP <125/80 mmHg). LV mass increased from NT to MH to SH (p < 0.001); the parameters of LV diastolic function were similar between MH and SH and significantly lower than in NT. CONCLUSION: In type 2 diabetic patients with clinic BP <130/85 mmHg, MH is frequent and is associated with LV remodelling characterized by increased myocardial mass and preclinical impairment of LV diastolic function; the remodelling is qualitatively and for some aspects also quantitatively similar to that found in sustained hypertensive patients. Therefore it would be useful to look for MH in diabetic subjects with clinic BP <130/85 mmHg, who, following the guidelines, are not entitled to antihypertensive treatment: the finding of MH could identify a subgroup of patients at higher cardiovascular risk and therefore needing a prompt antihypertensive treatment.

Imatinib discontinuation in chronic myeloid leukaemia patients with undetectable BCR-ABL transcript level: A systematic review and a meta-analysis.

PURPOSE: Tyrosine kinase inhibitors (TKIs) are the cornerstones of treatment for patients with chronic myeloid leukaemia (CML). In recent years, several studies were conducted to evaluate the safety of TKIs discontinuation. We performed a systematic review of the literature to determine the incidence of CML relapse, to identify possible factors relapse rates and to evaluate the long-term safety in CML patients with stable undetectable BCR-ABL transcript level who discontinued TKIs. DESIGN: Studies evaluating TKIs discontinuation in CML patients with undetectable BCR-ABL transcript level were identified by electronic search of MEDLINE and EMBASE database until May 2015. Weighted mean proportion and 95% confidence intervals (CIs) of CML relapse was calculated using a fixed-effects and a random-effects model. Statistical heterogeneity was evaluated using the I2 statistic. RESULTS: Fifteen cohort studies, for a total of 509 patients, were included. Nine studies were at low-risk of bias. All 15 studies included only patients on imatinib. Overall weighted mean molecular relapse rate of CML was 51% (95% CI 44-58%; I2 = 55). Weighted mean molecular relapse rate at 6-month follow-up was 41% (95% CI 32-51%; I2 = 78). Eighty percent of molecular relapses occurred in the first 6 months. All 509 patients were alive at 2-year follow-up and only one patient (0.8%, 95% CI 0.2-1.8%; I2 = 0) has progressed to a blastic crisis. CONCLUSIONS: Our findings suggest that imatinib discontinuation is feasible for the majority of CML patients with stable undetectable BCR-ABL transcript level. Approximately 50% of patients remain therapy-free after imatinib discontinuation. Restarting TKIs therapy was followed by a very high rate of molecular response, with no deaths 2 years after discontinuation.

PCSK9 inhibitors for treating dyslipidemia in patients at different cardiovascular risk: a systematic review and a meta-analysis.

Statin-induced lowering of low-density lipoprotein cholesterol (LDL-C) reduces cardiovascular morbidity and mortality, but many patients do not adequately reduce their LDL-C levels. Monoclonal antibodies targeting PCKS9 are currently in the advanced phase of development. We aimed to investigate the efficacy and safety of PCSK9 inhibitors in patients at different cardiovascular risk in a systematic review. Studies were searched on MEDLINE and EMBASE until January 2016. Differences in the outcomes among groups were expressed as mean differences, or pooled odds ratio (OR) and corresponding 95% confidence interval (CI), which were calculated using a fixed-effects and a random-effects model. Statistical heterogeneity was evaluated using the I 2 statistic. 22 RCTs and 8833 patients were included. Six studies were performed in patients affected by homozygous or heterozygous familial hypercholesterolemia, or with increased cardiovascular risk, two in patients with statin intolerance, three in statin-naïve patients, and 10 in patients unable to achieve LDL-C target with statin therapy. PCSK9 inhibitors were associated with a statistically significant reduction of LDL-C (mean = -48.8%; 95% CI -54.1, -43.4; I 2 = 94%) compared to control groups, and with a statistically significant reduction in death for any cause (OR = 0.34; 95% CI 0.17, 0.69; I 2 = 0) and a favorable trend for cardiovascular events (OR = 0.79; 95% CI 0.61, 1.02; I 2 = 0%). PCSK9 inhibitors reduce LDL-C concentration in every group explored. A significant reduction in death by all cause was observed in the PCSK9 inhibitors groups, compared with control groups, even in the short time frame studied.

Longitudinal study on hypertension control in primary care: the Insubria study.

BACKGROUND: Hypertension control is still unsatisfactory. The study was aimed to evaluate blood pressure (BP) control rate and the impact of training general practitioners (GPs) about hypertension 1999 World Health Organization/International Society of Hypertension guidelines. METHODS: After a training session on the hypertension guidelines, 588 GPs consecutively enrolled 5524 known hypertensive patients. During the first and follow-up visits (after 3, 6, and 9 months) GPs recorded BP, lifestyle habits, and drug therapy. RESULTS: The BP was controlled in 33.4%, with systolic BP less controlled than diastolic BP. The BP control rate decreased (P < .001) from low to very high cardiovascular risk group and from lean to overweight and obese subjects. At the first visit 97.3% of the patients were already on drug treatment: 40.3% with 1 drug, 38.9% with 2 drugs, 17.2% with 3 drugs and 3.6% with 4 or 5 drugs. The adherence to correct dietary and lifestyle habits was low. The drugs most often used were the angiotensin-converting enzyme inhibitors (3009 patients, 56%). During follow-up body weight and BP decreased; 1 or more drugs were added in 17.8% and the adherence to healthier lifestyle habits significantly increased. At the end of the survey BP control rate was significantly improved (52.7%). CONCLUSIONS: In primary care the hypertension control rate was still unsatisfactory, and our data suggest that it may be due to a not aggressive enough drug treatment and a low adherence to recommended lifestyle and dietary habits. Increasing the knowledge of GPs about guidelines was associated with an improvement of hypertension control rate.

Antihypertensive therapy: role of aldosterone antagonists.

The interest for the therapeutic potential of aldosterone antagonists in essential hypertension comes from the recently discovered nonclassical pathways of aldosterone actions, above all the presence of extra-adrenal aldosterone production and the discovery of aldosterone's proinflammatory and profibrotic actions. The review begins with the discussion of experimental studies on animals, demonstrating the role of aldosterone in cardiovascular remodeling and the effects of aldosterone blockade on hypertensive target organ damage. Then recent clinical studies are presented, that confirm in humans the deleterious role of aldosterone, in particular in the development of myocardial hypertrophy, cardiovascular fibrosis and arterial stiffness. After a brief description of the new selective aldosterone antagonist, eplerenone, compared to the well-known non-selective aldosterone antagonist, spironolactone, the results of studies on essential hypertensive patients are discussed, evaluating the efficacy of aldosterone antagonists in lowering blood pressure, but, more important, in protecting against target organ damage.

Treatment of hypertension and adherence to treatment guidelines in clinical practice: an Italian study.

Despite the results from clinical trials in patients with hypertension and the development of a long list of guidelines for the management of hypertension, many physicians and other healthcare professionals still manage hypertension using approaches that clearly diverge at least partially from the recommendations of these guidelines. Whatever the underlying reasons for physicians' failure to adhere to these guidelines, it is one of the main causes of the high percentage of treated patients with uncontrolled hypertension. This article is a report of the outcomes of a project designed to identify specific discrepancies between hypertension guidelines and clinical practice in Italy then guide the physicians to reach a consensus on hypertension management through discussions with their peers. A total of 1120 internists from all 20 regions in Italy were recruited to participate in workshops conducted between June 2002 and July 2004. They were divided into 57 groups to discuss at least 7 key topics, including the blood pressure level at which to start drug therapy, target-organ damage, isolated systolic hypertension, pulse pressure, clinical trials, generic drugs, and fixed combination drug therapy. The project findings confirmed that the vast majority of internists agree with the guidelines but do not adhere to them completely in clinical practice. Through open discussions that allowed them to identify common viewpoints, the participants may have developed a better awareness of and insight into the guidelines for hypertension management. Hopefully this strategy for group participation will lead to improvements in the management of hypertension throughout Italy.