Phenome-wide association analysis of LDL-cholesterol lowering genetic variants in PCSK9.

BACKGROUND: We characterised the phenotypic consequence of genetic variation at the PCSK9 locus and compared findings with recent trials of pharmacological inhibitors of PCSK9. METHODS: Published and individual participant level data (300,000+ participants) were combined to construct a weighted PCSK9 gene-centric score (GS). Seventeen randomized placebo controlled PCSK9 inhibitor trials were included, providing data on 79,578 participants. Results were scaled to a one mmol/L lower LDL-C concentration. RESULTS: The PCSK9 GS (comprising 4 SNPs) associations with plasma lipid and apolipoprotein levels were consistent in direction with treatment effects. The GS odds ratio (OR) for myocardial infarction (MI) was 0.53 (95% CI 0.42; 0.68), compared to a PCSK9 inhibitor effect of 0.90 (95% CI 0.86; 0.93). For ischemic stroke ORs were 0.84 (95% CI 0.57; 1.22) for the GS, compared to 0.85 (95% CI 0.78; 0.93) in the drug trials. ORs with type 2 diabetes mellitus (T2DM) were 1.29 (95% CI 1.11; 1.50) for the GS, as compared to 1.00 (95% CI 0.96; 1.04) for incident T2DM in PCSK9 inhibitor trials. No genetic associations were observed for cancer, heart failure, atrial fibrillation, chronic obstructive pulmonary disease, or Alzheimer's disease - outcomes for which large-scale trial data were unavailable. CONCLUSIONS: Genetic variation at the PCSK9 locus recapitulates the effects of therapeutic inhibition of PCSK9 on major blood lipid fractions and MI. While indicating an increased risk of T2DM, no other possible safety concerns were shown; although precision was moderate.

Smoking prevalence and associated risk factors among healthcare professionals in Nicosia general hospital, Cyprus: a cross-sectional study.

BACKGROUND: In recent years, a significant progress has been achieved globally in reduction of smoking among physicians and nurses, however, in some countries the smoking prevalence of health professionals is maintained at very high levels, without significant difference from the general population. This study aims to investigate the prevalence of smoking among physicians and nurses working at Nicosia General Hospital, as well as their knowledge and attitudes towards smoking cessation strategies. METHODS: This is a cross-sectional questionnaire-based study. The study consisted of 119 doctors and 392 nurses currently working at Nicosia General Hospital in Cyprus. Study participants were recruited from all hospital wards between May and June 2008. Both physicians and nurses were asked to answer an anonymous questionnaire, which included questions regarding their smoking habits, knowledge and attitudes about smoking and smoking cessation strategies. RESULTS: Overall smoking prevalence among healthcare professionals was 28.2 % (28.6 % among physicians and 28.1 % among nurses). Multivariate analysis revealed that being male, younger than 34 years old, unmarried and with a family history of smoking were associated with increased likelihood of being a current smoker. An impressive 72 % of current smokers reported that they wished to quit smoking, however, only 5.6 % of physicians and 6.9 % of nurses, reported ever using any smoking cessation aids. Never- smokers counseled their patients to quit smoking more often (96.4 %) compared to former (84.6 %) and current smokers (72.7 %), (p < 0.001). In addition, those who felt more confident about their knowledge regarding smoking cessation, reported counseling their patients to quit smoking more often compared to those who did not (92 % vs 60 %, p < 0.001). CONCLUSIONS: Smoking prevalence among physicians and nurses working at Nicosia General Hospital was similar to that of the general Cypriot population. Further training of healthcare professionals towards smoking cessation strategies is needed in order to improve their knowledge and consequently their efforts on counseling and support to their patients who wish to quit smoking.

Association between presence of the metabolic syndrome and its components with carotid intima-media thickness and carotid and femoral plaque area: a population study.

BACKGROUND: We aimed to explore the association between presence and number of components of the Metabolic Syndrome (MetS) and subclinical atherosclerosis outcomes (common carotid intima media thickness, plaque presence and sum of plaque area) in both the carotid and femoral bifurcations. METHODS: Cross-sectional analysis of 771 volunteers from the ongoing epidemiological Cyprus Study (46% male; mean age = 60.1 ± 9.8). (a) Carotid intima-media thickness (IMTcc), (b) sum of plaque area in the carotid bifurcations (sum of the largest plaques in each carotid bifurcation-SPAcar), (c) sum of plaque area in the femoral bifurcations (sum of the largest plaques in each femoral bifurcation-SPAfem) and (d) sum of plaque area in both carotid and femoral bifurcations (sum of the areas of the largest plaques present in each of the four bifurcations-SPA) were measured at baseline using ultrasound. Presence and number of components of the MetS was ascertained using the National Cholesterol Education Program ATPIII definition and their association tested using multivariable regression models. RESULTS: MetS was present in 259 (33.6%) individuals and was associated with a 0.02 mm increase in IMTcc (95% CI: 0.00 to 0.04, p = 0.047) after adjustment for age, sex, family history of CVD, alcohol consumption (BU/week) and smoking (pack-years). Each additional component of the MetS was associated with a 16% higher SPA (95% CI: 6.8% to 25.2%, pfor trend = 0.001), a 10% higher SPAcar (95% CI: 5% to 24%, pfor trend = 0.003) and a 14% higher SPAfem in the adjusted model. CONCLUSIONS: We confirm an association between the MetS and IMTcc as well as report for the first time an association between the MetS and its components and femoral plaque area, in a general population over 40 years of age. Having any risk factors for the MetS increases the risk for subclinical atherosclerosis, with the risk increasing with each additional component. Using the dichotomous definition of the MetS may be overlooking the risk for subclinical atherosclerosis -and by inference future cardiovascular events- associated with having less than 3 risk factors.