Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

INVESTIGATION OF THE CYP3A4 AND PON1 GENE VARIANTS IN TURKISH PATIENTS WITH FAMILIAL CORONARY ARTERY DISEASE

Ozbayer, Cansu/0000-0002-1120-1874;WOS: 000440358702255Objective: Coronary artery disease (CAD), a complex multifactorial disorder, has been suggested to be associated by the interaction of both environmental and genetic risk factors

Haplotype analyses of CYP2C19*2 and CYP2C19*17 genetic polymorphisms in clopidogrel non-responsiveness after percutaneous coronary intervention with stent implantation

50th European-Society-of-Human-Genetics (ESHG) Conference -- MAY 27-30, 2017 -- Copenhagen, DENMARKWOS: 000489312606105[No abstract available]European Soc Human Gene

An observational study to evaluate factors responsible and actions taken for hypertensive patients who are not at blood pressure goal: I-target Goal Study

PubMed ID: 22318207To evaluate the percentage of hypertensive patients who could achieve target blood pressure (TBP) according to the guidelines in the context of recommended measures and the factors responsible for failure. A total of 589 hypertensive patients (59.0% female; mean age: 57.7±10.4 years) were assessed twice for TBP achievement based on 2007 ESH/ESC guidelines and the investigators' view, in addition to the recommended measures and possible causes of failure in hypertension management in this national multi-center (n=99), non-interventional observational study. Only 29.5% of the patients at the first visit and 46.8% at the second visit achieved the TBP levels specified by the guidelines. However, the investigators' evaluation indicated a higher achievement rate at the first (43.5%) as well as the second (69.1%) visit when compared with the guideline-based assessments (P<0.001). The primary reasons identified by the investigators for the failure to reach TBP were non-compliance with dietary recommendations (61.6%) at the first visit and non-compliance with treatment (63.92%) at the second visit. Recommendations for lifestyle were the most commonly identified treatment plan by the investigators at both visits (62.9% and 66.1%, respectively). Although more patients achieved the TBP levels specified by the guidelines for the second visit compared with the first, effective blood pressure control was achieved only in 29.5% of our patients. Interestingly, the investigators had a more optimistic view about their patients' control of hypertension, which may have contributed to a poor achievement of TBP. © 2012 The Japanese Society of Hypertension All rights reserved

Association of paraoxonase 1 (PON1) gene polymorphisms and concentration with essential hypertension

Human serum paraoxonase 1 (PON1) is carried by high-density lipoprotein in blood circulation and is shown to be effective in preventing oxidized phospholipids carried by low-density lipoprotein particles, thus it acts as an antioxidant. Polymorphism in this gene has been investigated for many metabolic diseases, but it is not thought to be a genetic risk factor for essential hypertension. The aim of this study was to determine whether there was an association between PON1 gene polymorphisms and concentration with essential hypertension. The study population was comprised of 100 patients with essential hypertension and 100 healthy controls. One promoter region [C(-108)T] and two coding region (Q192R and L55M) polymorphisms in the PON1 gene were genotyped in individuals by using the TaqMan assay. Plasma PON1 concentration in all volunteers was also measured spectrophotometrically by the enzyme-linked immunosorbent assay method. The genotype and allele frequencies of the PON1 C(-108)T polymorphism showed significant differences between the essential hypertensive and control groups (CT vs. CC: p<0.001; T allele vs. C allele: p<0.001). There was no significant difference for the PON1 L55M polymorphism between the groups, while the heterozygote genotype of the PON1 Q192R polymorphism showed significant difference (p = 0.03). The PON1 concentration was also found to be significantly lower in hypertensive patients (p < 0.001). Decline in the level of PON1 gene may be one of the main factors in the development of essential hypertension, and the PON1 C(-108)T polymorphism may have a prognostic value in the patients with essential hypertension

Efficacy of sublingual immunotherapy for house dust mite allergic rhinitis

In the present study, we investigated the outcomes of sublingual immunotherapy (SLIT) in house dust mite-induced allergic rhinitis (HDM-AR) patients. In this prospective, multicentric study, 186 patients with AR who had positive skin prick test results for HDMs were included. The patients were administered SLIT using Staloral 300 for 1 year. Evaluation of the patients regarding symptom scores, clinical findings and Rhinitis Quality of Life Questionnaire (RQLQ) scores was performed at baseline, and then at 6 and 12 months of therapy. Our results showed that, for all of the evaluated items (symptom scores, clinical findings and RQLQ scores), 12-month values were significantly lower than those at 6 months and baseline. Similarly, 6-month values were significantly lower than those at baseline. There were no complications in any of our patients. SLIT for HDM-AR is a treatment modality that can be used safely. We obtained better results than expected, and the treatment showed a positive psychological effect; the patients believed that SLIT was the final step of treatment and, which made them feel better