| 1. |
- Wormser, David, et al.
(författare)
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Adult height and the risk of cause-specific death and vascular morbidity in 1 million people : individual participant meta-analysis
- 2012
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Ingår i: International Journal of Epidemiology. - : Oxford University Press (OUP). - 0300-5771 .- 1464-3685. ; 41:5, s. 1419-1433
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe extent to which adult height, a biomarker of the interplay of genetic endowment and early-life experiences, is related to risk of chronic diseases in adulthood is uncertain.MethodsWe calculated hazard ratios (HRs) for height, assessed in increments of 6.5 cm, using individual-participant data on 174 374 deaths or major non-fatal vascular outcomes recorded among 1 085 949 people in 121 prospective studies.ResultsFor people born between 1900 and 1960, mean adult height increased 0.5-1 cm with each successive decade of birth. After adjustment for age, sex, smoking and year of birth, HRs per 6.5 cm greater height were 0.97 (95% confidence interval: 0.96-0.99) for death from any cause, 0.94 (0.93-0.96) for death from vascular causes, 1.04 (1.03-1.06) for death from cancer and 0.92 (0.90-0.94) for death from other causes. Height was negatively associated with death from coronary disease, stroke subtypes, heart failure, stomach and oral cancers, chronic obstructive pulmonary disease, mental disorders, liver disease and external causes. In contrast, height was positively associated with death from ruptured aortic aneurysm, pulmonary embolism, melanoma and cancers of the pancreas, endocrine and nervous systems, ovary, breast, prostate, colorectum, blood and lung. HRs per 6.5 cm greater height ranged from 1.26 (1.12-1.42) for risk of melanoma death to 0.84 (0.80-0.89) for risk of death from chronic obstructive pulmonary disease. HRs were not appreciably altered after further adjustment for adiposity, blood pressure, lipids, inflammation biomarkers, diabetes mellitus, alcohol consumption or socio-economic indicators.ConclusionAdult height has directionally opposing relationships with risk of death from several different major causes of chronic diseases.
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| 2. |
- Di Angelantonio, Emanuele, et al.
(författare)
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Association of Cardiometabolic Multimorbidity With Mortality : The Emerging Risk Factors Collaboration
- 2015
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Ingår i: Journal of the American Medical Association (JAMA). - : American Medical Association (AMA). - 0098-7484 .- 1538-3598. ; 314:1, s. 52-60
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE The prevalence of cardiometabolic multimorbidity is increasing.OBJECTIVE To estimate reductions in life expectancy associated with cardiometabolic multimorbidity.DESIGN, SETTING, AND PARTICIPANTS Age-and sex-adjusted mortality rates and hazard ratios (HRs) were calculated using individual participant data from the Emerging Risk Factors Collaboration (689 300 participants; 91 cohorts; years of baseline surveys: 1960-2007; latest mortality follow-up: April 2013; 128 843 deaths). The HRs from the Emerging Risk Factors Collaboration were compared with those from the UK Biobank (499 808 participants; years of baseline surveys: 2006-2010; latest mortality follow-up: November 2013; 7995 deaths). Cumulative survival was estimated by applying calculated age-specific HRs for mortality to contemporary US age-specific death rates. EXPOSURES A history of 2 or more of the following: diabetes mellitus, stroke, myocardial infarction (MI).MAIN OUTCOMES AND MEASURES All-cause mortality and estimated reductions in life expectancy.RESULTS In participants in the Emerging Risk Factors Collaboration without a history of diabetes, stroke, or MI at baseline (reference group), the all-cause mortality rate adjusted to the age of 60 years was 6.8 per 1000 person-years. Mortality rates per 1000 person-years were 15.6 in participants with a history of diabetes, 16.1 in those with stroke, 16.8 in those with MI, 32.0 in those with both diabetes and MI, 32.5 in those with both diabetes and stroke, 32.8 in those with both stroke and MI, and 59.5 in those with diabetes, stroke, and MI. Compared with the reference group, the HRs for all-cause mortality were 1.9 (95% CI, 1.8-2.0) in participants with a history of diabetes, 2.1 (95% CI, 2.0-2.2) in those with stroke, 2.0 (95% CI, 1.9-2.2) in those with MI, 3.7 (95% CI, 3.3-4.1) in those with both diabetes and MI, 3.8 (95% CI, 3.5-4.2) in those with both diabetes and stroke, 3.5 (95% CI, 3.1-4.0) in those with both stroke and MI, and 6.9 (95% CI, 5.7-8.3) in those with diabetes, stroke, and MI. The HRs from the Emerging Risk Factors Collaboration were similar to those from the more recently recruited UK Biobank. The HRs were little changed after further adjustment for markers of established intermediate pathways (eg, levels of lipids and blood pressure) and lifestyle factors (eg, smoking, diet). At the age of 60 years, a history of any 2 of these conditions was associated with 12 years of reduced life expectancy and a history of all 3 of these conditions was associated with 15 years of reduced life expectancy.CONCLUSIONS AND RELEVANCE Mortality associated with a history of diabetes, stroke, or MI was similar for each condition. Because any combination of these conditions was associated with multiplicative mortality risk, life expectancy was substantially lower in people with multimorbidity.
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| 3. |
- Pennells, Lisa, et al.
(författare)
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Equalization of four cardiovascular risk algorithms after systematic recalibration : individual-participant meta-analysis of 86 prospective studies
- 2019
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 40:7, s. 621-
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Tidskriftsartikel (refereegranskat)abstract
- Aims: There is debate about the optimum algorithm for cardiovascular disease (CVD) risk estimation. We conducted head-to-head comparisons of four algorithms recommended by primary prevention guidelines, before and after ‘recalibration’, a method that adapts risk algorithms to take account of differences in the risk characteristics of the populations being studied.Methods and results: Using individual-participant data on 360 737 participants without CVD at baseline in 86 prospective studies from 22 countries, we compared the Framingham risk score (FRS), Systematic COronary Risk Evaluation (SCORE), pooled cohort equations (PCE), and Reynolds risk score (RRS). We calculated measures of risk discrimination and calibration, and modelled clinical implications of initiating statin therapy in people judged to be at ‘high’ 10 year CVD risk. Original risk algorithms were recalibrated using the risk factor profile and CVD incidence of target populations. The four algorithms had similar risk discrimination. Before recalibration, FRS, SCORE, and PCE over-predicted CVD risk on average by 10%, 52%, and 41%, respectively, whereas RRS under-predicted by 10%. Original versions of algorithms classified 29–39% of individuals aged ≥40 years as high risk. By contrast, recalibration reduced this proportion to 22–24% for every algorithm. We estimated that to prevent one CVD event, it would be necessary to initiate statin therapy in 44–51 such individuals using original algorithms, in contrast to 37–39 individuals with recalibrated algorithms.Conclusion: Before recalibration, the clinical performance of four widely used CVD risk algorithms varied substantially. By contrast, simple recalibration nearly equalized their performance and improved modelled targeting of preventive action to clinical need.
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| 4. |
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| 5. |
- Vasan, Ramachandran S, et al.
(författare)
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Relative importance of borderline and elevated levels of coronary heart disease risk factors.
- 2005
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Ingår i: Ann Intern Med. - 1539-3704. ; 142:6, s. 393-402
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Clinical trials indicate that a sizable proportion of adults have multiple borderline coronary risk factors and may benefit from treatment. OBJECTIVE: To estimate the relative and absolute contributions of borderline and elevated risk factors to the population burden of coronary heart disease (CHD) events. DESIGN: A prospective cohort study and a national cross-sectional survey. SETTING: The Framingham Study and the Third National Health and Nutrition Examination Survey (NHANES III). PARTICIPANTS: White non-Hispanic persons in the Framingham Study and in NHANES III who were between 35 to 74 years of age and had no CHD. MEASUREMENTS: Occurrence of first CHD events according to 5 major CHD risk factors: blood pressure, low-density lipoprotein and high-density lipoprotein cholesterol levels, glucose intolerance, and smoking. Three categories-optimal, borderline, and elevated-were defined for each risk factor per national guidelines. Sex-specific 10-year CHD event rates from the Framingham Study were applied to numbers of at-risk individuals estimated from NHANES III and the 2000 U.S. Census. RESULTS: Twenty-six percent of men and 41% of women had at least 1 borderline risk factor in NHANES III. According to estimates, more than 90% of CHD events will occur in individuals with at least 1 elevated risk factor, and approximately 8% will occur in people with only borderline levels of multiple risk factors. Absolute 10-year CHD risk exceeded 10% in men older than age 45 years who had 1 elevated risk factor and 4 or more borderline risk factors and in those who had at least 2 elevated risk factors. In women, absolute CHD risk exceeded 10% only in those older than age 55 years who had at least 3 elevated risk factors. LIMITATIONS: The generalizability of the findings to persons of other ethnic backgrounds is unknown. CONCLUSIONS: Borderline CHD risk factors alone account for a small proportion of CHD events.
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| 8. |
- Kathiresan, Sekar, et al.
(författare)
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A genome-wide association study for blood lipid phenotypes in the Framingham Heart Study
- 2007
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Ingår i: BMC Medical Genetics. - 1471-2350. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Background: Blood lipid levels including low-density lipoprotein cholesterol ( LDL-C), high-density lipoprotein cholesterol ( HDL-C), and triglycerides ( TG) are highly heritable. Genome-wide association is a promising approach to map genetic loci related to these heritable phenotypes. Methods: In 1087 Framingham Heart Study Offspring cohort participants ( mean age 47 years, 52% women), we conducted genome-wide analyses ( Affymetrix 100K GeneChip) for fasting blood lipid traits. Total cholesterol, HDL-C, and TG were measured by standard enzymatic methods and LDL-C was calculated using the Friedewald formula. The long-term averages of up to seven measurements of LDL-C, HDL-C, and TG over a similar to 30 year span were the primary phenotypes. We used generalized estimating equations ( GEE), family-based association tests ( FBAT) and variance components linkage to investigate the relationships between SNPs ( on autosomes, with minor allele frequency >= 10%, genotypic call rate >= 80%, and Hardy-Weinberg equilibrium p >= 0.001) and multivariable-adjusted residuals. We pursued a three-stage replication strategy of the GEE association results with 287 SNPs ( P < 0.001 in Stage I) tested in Stage II ( n similar to 1450 individuals) and 40 SNPs ( P < 0.001 in joint analysis of Stages I and II) tested in Stage III ( n similar to 6650 individuals). Results: Long-term averages of LDL-C, HDL-C, and TG were highly heritable ( h(2) = 0.66, 0.69, 0.58, respectively; each P < 0.0001). Of 70,987 tests for each of the phenotypes, two SNPs had p < 10(-5) in GEE results for LDL-C, four for HDL-C, and one for TG. For each multivariable-adjusted phenotype, the number of SNPs with association p < 10(-4) ranged from 13 to 18 and with p < 10(-3), from 94 to 149. Some results confirmed previously reported associations with candidate genes including variation in the lipoprotein lipase gene ( LPL) and HDL-C and TG ( rs7007797; P = 0.0005 for HDL-C and 0.002 for TG). The full set of GEE, FBAT and linkage results are posted at the database of Genotype and Phenotype (dbGaP). After three stages of replication, there was no convincing statistical evidence for association ( i.e., combined P < 10(-5) across all three stages) between any of the tested SNPs and lipid phenotypes. Conclusion: Using a 100K genome-wide scan, we have generated a set of putative associations for common sequence variants and lipid phenotypes. Validation of selected hypotheses in additional samples did not identify any new loci underlying variability in blood lipids. Lack of replication may be due to inadequate statistical power to detect modest quantitative trait locus effects ( i.e., < 1% of trait variance explained) or reduced genomic coverage of the 100K array. GWAS in FHS using a denser genome-wide genotyping platform and a better-powered replication strategy may identify novel loci underlying blood lipids.
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| 9. |
- Sundström, Johan, et al.
(författare)
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Plasma homocysteine, hypertension incidence, and blood pressure tracking : the Framingham Heart Study.
- 2003
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Ingår i: Hypertension. - 1524-4563. ; 42:6, s. 1100-5
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Tidskriftsartikel (refereegranskat)abstract
- Plasma homocysteine is cross-sectionally associated with blood pressure in large, community-based studies. It is unknown whether elevated plasma homocysteine predicts hypertension incidence. We investigated the relations of baseline plasma total homocysteine levels to hypertension incidence and blood pressure tracking in 2104 Framingham Heart Study participants (mean age, 57 years; 58% women), who were free of hypertension, myocardial infarction, heart failure, atrial fibrillation, or renal failure at baseline. Baseline mean+/-SD plasma homocysteine was 10.1+/-3.7 micromol/L. On follow-up 4 years from baseline, 360 persons (17.1%) had developed hypertension, and 878 persons (41.7%) had progressed to a higher blood pressure stage. In unadjusted analyses, a 1-SD higher log homocysteine value was associated with increased odds of developing hypertension (odds ratio [OR], 1.18; 95% confidence interval [CI], 1.05 to 1.32) and increased odds of blood pressure progression (OR, 1.17; 95% CI, 1.07 to 1.27). The relations of plasma homocysteine to the incidence of hypertension or blood pressure progression were statistically nonsignificant in age- and sex-adjusted logistic regression models (OR, 0.98; 95% CI, 0.87 to 1.11 and OR, 1.05; 95% CI, 0.96 to 1.16, respectively) and in multivariable models adjusted for age, sex, body mass index, diabetes, interim weight change, smoking, serum creatinine, baseline blood pressure, and blood pressure category (OR, 0.92; 95% CI, 0.81 to 1.06 and OR, 1.07; 95% CI, 0.97 to 1.18, respectively). In conclusion, we found no major relation of baseline plasma homocysteine levels to hypertension incidence or longitudinal blood pressure progression in a large, community-based cohort of nonhypertensive individuals after adjustment for age, sex, and other important covariates.
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| 10. |
- Sundström, Johan, et al.
(författare)
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Relations of plasma homocysteine to left ventricular structure and function : the Framingham Heart Study.
- 2004
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Ingår i: Eur Heart J. - 0195-668X. ; 25:6, s. 523-30
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: Hyperhomocysteinaemia is a risk factor for congestive heart failure, especially in women. We investigated if homocysteine promotes left ventricular (LV) remodelling. METHODS AND RESULTS: We examined cross-sectional relations of plasma total homocysteine to echocardiographic LV structure and function in 2697 Framingham Heart Study participants (mean age 58 years, 58% women) free of heart failure and previous myocardial infarction. Adjusting for age and height, plasma homocysteine was positively related to LV mass, wall thickness, and relative wall thickness in women (p=0.0004-0.04), but not in men (p=0.28-0.68). Adjusting additionally for other clinical covariates, the relations of plasma homocysteine to LV mass and wall thickness in women remained statistically significant, but the relation to relative wall thickness became of borderline significance (1.92 g, 0.01 cm, and 0.29% increase, respectively, for a 1-SD increase in ln[homocysteine], p=0.01-0.08). LV mass and wall thickness were higher in the fourth quartile of plasma homocysteine compared to the lower three in all models in women (p=0.0003-0.02), but not in men (p=0.25-0.78). Plasma homocysteine was not related to left atrial size or LV fractional shortening in either sex. CONCLUSION: In our community-based sample, plasma homocysteine was directly related to LV mass and wall thickness in women but not in men.
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| 11. |
- Ärnlöv, Johan, et al.
(författare)
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Endogenous sex hormones and cardiovascular disease incidence in men
- 2006
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Ingår i: Annals of Internal Medicine. - 0003-4819 .- 1539-3704. ; 145:3, s. 176-184
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Tidskriftsartikel (refereegranskat)abstract
- Background: Data suggest that endogenous sex hormones (testosterone, dehydroepiandrosterone sulfate [DHEA-S], and estradiol) influence cardiovascular disease (CVD) risk factors and vascular function. Yet, prospective studies relating sex hormones to CVD incidence in men have yielded inconsistent results. Objective: To examine the association of circulating sex hormone levels and CVD risk in men. Design: Prospective cohort study. Setting: Community-based study in Framingham, Massachusetts. Participants: 2084 middle-aged white men without CVD at baseline. Measurements: The authors used multivariable Cox regression to relate baseline levels of testosterone, DHEA-S, and estradiol to the incidence of CVD (coronary, cerebrovascular, or peripheral vascular disease or heart failure) during 10 years of follow-up. Results: During follow-up, 386 men (18.5%) experienced a first CVD event. After adjustment for baseline standard CVD risk factors, higher estradiol level was associated with lower risk for CVD (hazard ratio per SD increment in log estradiol, 0.90 [95% Cl, 0.82 to 0.99]; P = 0.035). The authors observed effect modification by age: Higher estradiol levels were associated with lower CVD risk in older (median age > 56 years) men (hazard ratio per SD increment, 0.86 [Cl, 0.78 to 0.96]; P = 0.005) but not in younger (median age <= 56 years) men (hazard ratio per SD increment, 1.11 [Cl, 0.89 to 1.38]; P = 0.36). The association of higher estradiol level with lower CVD incidence remained robust in time-dependent Cox models (updating standard CVD risk factors during follow-up). Serum testosterone and DHEA-S levels were not statistically significantly associated with incident CVD. Limitations: Sex hormone levels were measured only at baseline, and the findings may not be generalizable to women and nonwhite people. Conclusions: In the community-based sample, a higher serum estradiol level was associated with lower risk for CVD events in older men. The findings are consistent with the hypothesis that endogenous estrogen has vasculoprotective influences in men.
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