"MR/R024227/1"
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AIMS: The Southern European Atlantic diet (SEAD) is the traditional dietary pattern of northwestern Spain and northern Portugal, but it may resemble that of central, eastern, and western European countries. The SEAD has been found associated with lower risk of myocardial infarction and mortality in older adults, but it is uncertain whether this association also exists in other European populations and if it is similar as that found in its countries of origin. METHODS AND RESULTS: We conducted a prospective analysis of four cohorts with 35 917 subjects aged 18-96 years: ENRICA (Spain), HAPIEE (Czechia and Poland), and Whitehall II (United Kingdom). The SEAD comprised fresh fish, cod, red meat and pork products, dairy, legumes and vegetables, vegetable soup, potatoes, whole-grain bread, and moderate wine consumption. Associations were adjusted for sociodemographic variables, energy intake, lifestyle, and morbidity. After a median follow-up of 13.6 years (range = 0-15), we recorded 4 973 all-cause, 1 581 cardiovascular, and 1 814 cancer deaths. Higher adherence to the SEAD was associated with lower mortality in the pooled sample. Fully adjusted hazard ratios and 95% confidence interval per 1-standard deviation increment in the SEAD were 0.92 (0.89, 0.95), 0.91 (0.86, 0.96), and 0.94 (0.89, 0.99) for all-cause, cardiovascular, and cancer mortality, respectively. The association of the SEAD with all-cause mortality was not significantly different between countries [Spain = 0.93 (0.88, 0.99), Czechia = 0.94 (0.89,0.99), Poland = 0.89 (0.85, 0.93), United Kingdom = 0.98 (0.89, 1.07); P for interaction = 0.16]. CONCLUSION: The SEAD was associated with lower all-cause, cardiovascular, and cancer mortality in southern, central, eastern, and western European populations. Associations were of similar magnitude as those found for existing healthy dietary patterns.
OBJECTIVE: Higher resting heart rate (rHR) and lower heart rate variability (HRV) are associated with increased risk of cardiovascular disease (CVD) and all-cause mortality in people with and without diabetes. It is unknown whether temporal changes in rHR and HRV may contribute to this risk. We investigated associations between 5-year changes in rHR and HRV and risk of future CVD and death, taking into account participants' baseline glycemic state. RESEARCH DESIGN AND METHODS: In this prospective, population-based cohort study we investigated 4,611 CVD-free civil servants (mean [SD] age, 60 [5.9] years; 70% men). We measured rHR and/or six indices of HRV. Associations of 5-year change in 5-min rHR and HRV with fatal and nonfatal CVD and all-cause mortality or the composite of the two were assessed, with adjustments made for relevant confounders. Effect modification by glycemic state was tested. RESULTS: At baseline, 63% of participants were normoglycemic, 29% had prediabetes, and 8% had diabetes. During a median (interquartile range) follow-up of 11.9 (11.4; 12.3) years, 298 participants (6.5%) experienced a CVD event and 279 (6.1%) died of non-CVD-related causes. We found no association between 5-year changes in rHR and HRV and future events. Only baseline rHR was associated with all-cause mortality. A 10 bpm-higher baseline HR level was associated with an 11.4% higher rate of all-cause mortality (95% CI 1.0-22.9%; P = 0.032). Glycemic state did not modify associations. CONCLUSIONS: Changes in rHR and HRV and possibly also baseline values of these measures are not associated with future CVD or death in people with or without dysglycemia.
- MeSH
- diabetes mellitus * MeSH
- kardiovaskulární nemoci * MeSH
- kohortové studie MeSH
- lidé středního věku MeSH
- lidé MeSH
- prospektivní studie MeSH
- rizikové faktory MeSH
- srdeční frekvence MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
AIMS: Cardiovascular disease (CVD) risk prediction models are used in Western European countries, but less so in Eastern European countries where rates of CVD can be two to four times higher. We recalibrated the SCORE prediction model for three Eastern European countries and evaluated the impact of adding seven behavioural and psychosocial risk factors to the model. METHODS AND RESULTS: We developed and validated models using data from the prospective HAPIEE cohort study with 14 598 participants from Russia, Poland, and the Czech Republic (derivation cohort, median follow-up 7.2 years, 338 fatal CVD cases) and Estonian Biobank data with 4632 participants (validation cohort, median follow-up 8.3 years, 91 fatal CVD cases). The first model (recalibrated SCORE) used the same risk factors as in the SCORE model. The second model (HAPIEE SCORE) added education, employment, marital status, depression, body mass index, physical inactivity, and antihypertensive use. Discrimination of the original SCORE model (C-statistic 0.78 in the derivation and 0.83 in the validation cohorts) was improved in recalibrated SCORE (0.82 and 0.85) and HAPIEE SCORE (0.84 and 0.87) models. After dichotomizing risk at the clinically meaningful threshold of 5%, and when comparing the final HAPIEE SCORE model against the original SCORE model, the net reclassification improvement was 0.07 [95% confidence interval (CI) 0.02-0.11] in the derivation cohort and 0.14 (95% CI 0.04-0.25) in the validation cohort. CONCLUSION: Our recalibrated SCORE may be more appropriate than the conventional SCORE for some Eastern European populations. The addition of seven quick, non-invasive, and cheap predictors further improved prediction accuracy.
- MeSH
- hodnocení rizik MeSH
- kardiovaskulární nemoci * epidemiologie MeSH
- kohortové studie MeSH
- lidé MeSH
- prospektivní studie MeSH
- rizikové faktory kardiovaskulárních chorob MeSH
- rizikové faktory MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
- Geografické názvy
- Česká republika MeSH
- Polsko MeSH
- Rusko MeSH
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 Increased vagal modulation is a mechanism that may partially explain the protective effect of healthy lifestyles. However, it is unclear how healthy lifestyles relate to vagal regulation longitudinally. We prospectively examined associations between a comprehensive measure of 4 important lifestyle factors and vagal modulation, indexed by heart rate variability (HRV) over 10 years. Methods and Results The fifth (1997-1999), seventh (2002-2004), and ninth (2007-2009) phases of the UK Whitehall II cohort were analyzed. Analytical samples ranged from 2059 to 3333 (mean age: 55.7 years). A healthy lifestyle score was derived by giving participants 1 point for each healthy factor: physically active, not smoking, moderate alcohol consumption, and healthy body mass index. Two vagally mediated HRV measures were used: high-frequency HRV and root mean square of successive differences of normal-to-normal R-R intervals. Cross-sectionally, a positively graded association was observed between the healthy lifestyle score and HRV at baseline (Poverall≤0.001). Differences in HRV according to the healthy lifestyle score remained relatively stable over time. Compared with participants who hardly ever adhered to healthy lifestyles, those with consistent healthy lifestyles displayed higher high-frequency HRV (β=0.23; 95% CI, 0.10-0.35; P=0.001) and higher root mean square of successive differences of normal-to-normal R-R intervals (β=0.15; 95% CI, 0.07-0.22; P≤0.001) at follow-up after covariate adjustment. These differences in high-frequency HRV and root mean square of successive differences of normal-to-normal R-R intervals are equivalent to ≈6 to 20 years differences in chronological age. Compared with participants who reduced their healthy lifestyle scores, those with stable scores displayed higher subsequent high-frequency HRV (β=0.24; 95% CI, 0.01-0.48; P=0.046) and higher root mean square of successive differences of normal-to-normal R-R intervals (β=0.15; 95% CI, 0.01-0.29; P=0.042). Conclusions Maintaining healthy lifestyles is positively associated with cardiac vagal functioning, and these beneficial adaptations may be lost if not sustained.
- MeSH
- časové faktory MeSH
- chování snižující riziko * MeSH
- cvičení MeSH
- dospělí MeSH
- hodnocení rizik MeSH
- index tělesné hmotnosti MeSH
- kardiovaskulární nemoci epidemiologie patofyziologie prevence a kontrola MeSH
- lidé středního věku MeSH
- lidé MeSH
- nekuřáci MeSH
- nervus vagus patofyziologie MeSH
- ochranné faktory MeSH
- pití alkoholu epidemiologie MeSH
- prospektivní studie MeSH
- rizikové faktory MeSH
- senioři MeSH
- srdce inervace MeSH
- srdeční frekvence * MeSH
- zdravotní stav MeSH
- zdravý životní styl * MeSH
- zvyky 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
- Research Support, N.I.H., Extramural MeSH
- Geografické názvy
- Londýn MeSH