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.

• MeSH
• anticholesteremika škodlivé účinky   terapeutické užití   MeSH
• biologické markery krev   MeSH
• celogenomová asociační studie MeSH
• cévní mozková příhoda epidemiologie   prevence a kontrola   MeSH
• down regulace MeSH
• dyslipidemie krev   farmakoterapie   epidemiologie   genetika   MeSH
• hodnocení rizik MeSH
• infarkt myokardu epidemiologie   prevence a kontrola   MeSH
• inhibitory serinových proteinas škodlivé účinky   terapeutické užití   MeSH
• ischemie mozku epidemiologie   prevence a kontrola   MeSH
• jednonukleotidový polymorfismus * MeSH
• LDL-cholesterol krev   MeSH
• lidé MeSH
• PCSK9 inhibitory MeSH
• proproteinkonvertasa subtilisin/kexin typu 9 genetika   MeSH
• randomizované kontrolované studie jako téma MeSH
• rizikové faktory MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH

BACKGROUND: In the late 1980s, Czechia was among the countries which had the highest cardiovascular mortality in the world. In spite of enormous improvements since that time, there are still large opportunities in further improving cardiovascular health. METHODS: Based on the Czech Health, Alcohol and Psychosocial Factors in Eastern Europe sample (n=8449 at baseline, 12 years of follow-up, 494 cardiovascular disease (CVD) deaths up to 2015-events), the impact of selected covariates such as education, smoking habits, high blood pressure, blood cholesterol level, diabetes, obesity, physical activity and binge drinking and their multifactorial effects on cardiovascular mortality was evaluated by Cox regression. In addition, population attributable fractions (PAFs) were used to quantify the impact of these factors on CVD mortality in the population. RESULTS: Education was found as the strongest determinant of CVD mortality (primary vs university, HR 2.77, P<0.001; PAF=50.5%). CVD risk was two times higher for persons with diabetes compared with those without (HR 2.02, P<0.001, PAF=23.2%). Furthermore, significant factors found were smoking (smoker vs non-smoker, HR 1.91, P<0.001; PAF=26.5%), high blood pressure (HR 1.73, P<0.001; PAF=35.3%) and physical inactivity (none vs sufficient, HR 1.60, P<0.001; PAF=22.9%). Conversely, the effect of obesity was low (HR 1.29, P value =0.020), and binge drinking and high blood cholesterol level were not significant at all. CONCLUSIONS: Education had the largest impact on cardiovascular mortality among the Czech population. More than 50% of CVD death would be prevented if the whole population had the same risk values as the highest educated population. Reducing disparities in health related to education should benefit from attention to cardiovascular health literacy.

• MeSH
• cholesterol MeSH
• diabetes mellitus epidemiologie   MeSH
• dospělí MeSH
• hypertenze epidemiologie   MeSH
• kardiovaskulární nemoci epidemiologie   mortalita   MeSH
• komorbidita MeSH
• kouření MeSH
• lidé středního věku MeSH
• lidé MeSH
• nárazové pití alkoholu MeSH
• následné studie MeSH
• pití alkoholu epidemiologie   MeSH
• senioři MeSH
• socioekonomické faktory MeSH
• stupeň vzdělání MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH

OBJECTIVE: To test the association between coffee consumption and risk of all-cause, CVD and cancer death in a European cohort. DESIGN: Prospective cohort study. Cox proportional hazards models with adjustment for potential confounders to estimate multivariable hazard ratios (HR) and 95 % CI were used. SETTING: Czech Republic, Russia and Poland. SUBJECTS: A total of 28561 individuals followed for 6·1 years. RESULTS: A total of 2121 deaths (43·1 % CVD and 35·7 % cancer mortality) occurred during the follow-up. Consumption of 3-4 cups coffee/d was associated with lower mortality risk in men (HR=0·83; 95 % CI 0·71, 0·99) and women (HR=0·63; 95 % CI 0·47, 0·84), while further intake showed non-significant reduced risk estimates (HR=0·71; 95 % CI 0·49, 1·04 and HR=0·51; 95 % CI 0·24, 1·10 in men and women, respectively). Decreased risk of CVD mortality was also found in men (HR=0·71; 95 % CI 0·54, 0·93) for consumption of 3-4 cups coffee/d. Stratified analysis revealed that consumption of a similar amount of coffee was associated with decreased risk of all-cause (HR=0·61; 95 % CI 0·43, 0·87) and cancer mortality (HR=0·59; 95 % CI 0·35, 0·99) in non-smoking women and decreased risk of all-cause mortality for >4 cups coffee/d in men with no/moderate alcohol intake. CONCLUSIONS: Coffee consumption was associated with decreased risk of mortality. The protective effect was even stronger when stratification by smoking status and alcohol intake was performed.

• MeSH
• hodnocení stavu výživy MeSH
• kardiovaskulární nemoci mortalita   prevence a kontrola   MeSH
• káva * MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory mortalita   prevence a kontrola   MeSH
• následné studie MeSH
• pití alkoholu škodlivé účinky   MeSH
• proporcionální rizikové modely MeSH
• prospektivní studie MeSH
• průzkumy a dotazníky MeSH
• rizikové faktory MeSH
• senioři MeSH
• životní styl MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Geografické názvy
• Česká republika MeSH
• Polsko MeSH
• Rusko MeSH

BACKGROUND: The aim was to examine the association of objective measures of physical functioning (PF) with education and material circumstances and the decline in PF with age by socioeconomic position (SEP). METHODS: In 3,205 subjects (60-75 years) from the Czech Republic, we assessed relationship between PF, SEP, and age. Linear regression was used to assess PF measures and SEP measures. RESULTS: Cross-sectional decline in PF by age was similar in all individuals. Differences between SEP groups were similar across age groups, except for the difference in walk speed by material circumstances in men-bigger at older ages (p = .004). Men and women with the highest education were about 2 s faster at the chair rise test than those with the lowest education. DISCUSSION: Findings suggest strong educational gradient in PF, an inconsistent role of self-assessed material circumstances, and virtually no interaction of SEP with the cross-sectional decline in PF by age.

• MeSH
• chůze fyziologie   psychologie   MeSH
• cvičení fyziologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• postura těla fyziologie   MeSH
• průřezové studie MeSH
• senioři MeSH
• síla ruky fyziologie   MeSH
• sociální facilitace * MeSH
• socioekonomické faktory MeSH
• stárnutí fyziologie   psychologie   MeSH
• tělesná výkonnost fyziologie   psychologie   MeSH
• zrychlení MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• srovnávací studie MeSH
• Geografické názvy
• Česká republika MeSH

AIMS: The Systematic COronary Risk Evaluation (SCORE) scale assesses 10 year risk of fatal atherosclerotic cardiovascular disease (CVD), based on conventional risk factors. The high-risk SCORE version is recommended for Central and Eastern Europe and former Soviet Union (CEE/FSU), but its performance has never been systematically assessed in the region. We evaluated SCORE performance in two sets of population-based CEE/FSU cohorts. METHODS AND RESULTS: The cohorts based on the World Health Organization MONitoring of trends and determinants in CArdiovascular disease (MONICA) surveys in the Czech Republic, Poland (Warsaw and Tarnobrzeg), Lithuania (Kaunas), and Russia (Novosibirsk) were followed from the mid-1980s. The Health, Alcohol, and Psychosocial factors in Eastern Europe (HAPIEE) study follows Czech, Polish (Krakow), and Russian (Novosibirsk) cohorts from 2002-05. In Cox regression analyses, the high-risk SCORE ≥5% at baseline significantly predicted CVD mortality in both MONICA [n = 15 027; hazard ratios (HR), 1.7-6.3] and HAPIEE (n = 20 517; HR, 2.6-10.5) samples. While SCORE calibration was good in most MONICA samples (predicted and observed mortality were close), the risk was underestimated in Russia. In HAPIEE, the high-risk SCORE overpredicted the estimated 10 year mortality for Czech and Polish samples and adequately predicted it for Russia. SCORE discrimination was satisfactory in both MONICA and HAPIEE. CONCLUSION: The high-risk SCORE underestimated the fatal CVD risk in Russian MONICA but performed well in most MONICA samples and Russian HAPIEE. This SCORE version might overestimate the risk in contemporary Czech and Polish populations.

• MeSH
• ateroskleróza mortalita   MeSH
• dospělí MeSH
• hodnocení rizik MeSH
• kohortové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• mortalita trendy   MeSH
• prognóza MeSH
• rozložení podle pohlaví MeSH
• senioři MeSH
• věkové rozložení MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Geografické názvy
• Česká republika MeSH
• Litva MeSH
• Polsko MeSH
• Rusko MeSH

OBJECTIVES: Previous research shows only limited evidence on the contextual (neighbourhood-based) socioeconomic influences on mental health and depression. We investigated the association between individual and neighbourhood socioeconomic characteristics and depressive symptoms in the Czech Republic. METHODS: Dichotomized CESD score of depressive symptoms was used as the outcome in a random sample of 3534 men and 4082 women aged 45-69 years in the Czech HAPIEE Study. 220 small areas were characterized by the proportion of university educated persons and the proportion of unemployed from the economically active population in the 2001 Census. Multilevel logistic regression was used for the analysis. RESULTS: After controlling for individual-level variables, the effects of area-based characteristics were largely eliminated. The strongest area-based effect was that of the proportion of university educated persons; the ORs for 2(nd), 3(rd) and 4(th) quartile, compared with the 1(st) quartile, were 1.02, 0.93, and 0.82, respectively (p-value for trend 0.06). There were no cross-level interactions between socioeconomic variables. CONCLUSIONS: The effects of neighbourhood characteristics in this study were largely explained by individual socioeconomic variables.

• MeSH
• charakteristiky bydlení * MeSH
• chudoba * MeSH
• deprese ekonomika   epidemiologie   psychologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• logistické modely MeSH
• nezaměstnanost MeSH
• senioři MeSH
• stupeň vzdělání MeSH
• surveillance populace MeSH
• zdravotnické přehledy MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Geografické názvy
• Česká republika MeSH

BACKGROUND: Depression and depressive symptoms have been repeatedly linked to elevated levels of C-reactive protein (CRP) but questions remain as to the statistical robustness of the association and particularly whether the association between depression and CRP reflects the presence of a chronic disease. METHODS: A random sample of 6,126 men and women aged 45-69 years was examined in a cross-sectional study in seven towns in the Czech Republic. Depressive symptoms were assessed by the Center for Epidemiologic Studies Depression (CESD) scale. RESULTS: Center for Epidemiologic Studies Depression score was significantly related to increased levels of CRP in a linear fashion. After controlling for a range of potential confounders, subjects with depressive symptoms (CESD score >or= 16) had CRP concentrations 0.43 mg/l (95% CI 0.16-0.72) higher than those without symptoms. The association remained significant when study sample was restricted to healthy subjects; among individuals who did not report any chronic disease, the difference between those with and without depressive symptoms was 0.44 mg/l (95% CI 0.14-0.74), and among persons who did not visit a doctor in the last 12 months the difference was 1.20 mg/l (95% CI 0.52-1.87). CONCLUSIONS: These results confirm that there is a statistically robust association between depressive symptoms and increased levels of CRP. We did not find evidence that the association is due presence of a chronic condition.

• MeSH
• C-reaktivní protein analýza   MeSH
• chronická nemoc MeSH
• deprese krev   diagnóza   patofyziologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• průřezové studie MeSH
• průzkumy a dotazníky MeSH
• senioři MeSH
• úzkostné poruchy MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Geografické názvy
• Česká republika MeSH