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- Ingelsson, Erik, et al.
(författare)
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Diurnal blood pressure pattern and risk of congestive heart failure
- 2006
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Ingår i: Journal of the American Medical Association (JAMA). - 0098-7484 .- 1538-3598. ; 295:24, s. 2859-2866
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: High blood pressure is the most important risk factor for congestive heart failure (CHF) at a population level, but the relationship of an altered diurnal blood pressure pattern to risk of subsequent CHF is unknown. OBJECTIVES: To explore 24-hour ambulatory blood pressure characteristics as predictors of CHF incidence and to investigate whether altered diurnal blood pressure patterns confer any additional risk information beyond that provided by conventional office blood pressure measurements. DESIGN, SETTING, AND PARTICIPANTS: Prospective, community-based, observational cohort in Uppsala, Sweden, including 951 elderly men free of CHF, valvular disease, and left ventricular hypertrophy at baseline between 1990 and 1995, followed up until the end of 2002. Twenty-four-hour ambulatory blood pressure monitoring was performed at baseline, and the blood pressure variables were analyzed as predictors of subsequent CHF. MAIN OUTCOME MEASURE: First hospitalization for CHF. RESULTS: Seventy men developed heart failure during follow-up, with an incidence rate of 8.6 per 1000 person-years at risk. In multivariable Cox proportional hazards models adjusted for antihypertensive treatment and established risk factors for CHF (myocardial infarction, diabetes, smoking, body mass index, and serum cholesterol level), a 1-SD (9-mm Hg) increase in nighttime ambulatory diastolic blood pressure (hazard ratio [HR], 1.26; 95% confidence interval [CI], 1.02-1.55) and the presence of "nondipping" blood pressure (night-day ambulatory blood pressure ratio > or =1; HR, 2.29; 95% CI, 1.16-4.52) were associated with an increased risk of CHF. After adjusting for office-measured systolic and diastolic blood pressures, nondipping blood pressure remained a significant predictor of CHF (HR, 2.21; 95% CI, 1.12-4.36 vs normal night-day pattern). Nighttime ambulatory diastolic blood pressure and nondipping blood pressure were also significant predictors of CHF after exclusion of all participants who had an acute myocardial infarction before baseline or during follow-up. CONCLUSIONS: Nighttime blood pressure appears to convey additional risk information about CHF beyond office-measured blood pressure and other established risk factors for CHF. The clinical value of this association remains to be established in future studies.
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- Ingelsson, Erik, et al.
(författare)
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Insulin resistance and risk of congestive heart failure
- 2005
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Ingår i: Journal of the American Medical Association (JAMA). - 0098-7484 .- 1538-3598. ; 294:3, s. 334-41
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: Diabetes and obesity are established risk factors for congestive heart failure (CHF) and are both associated with insulin resistance. OBJECTIVE: To explore if insulin resistance may predict CHF and may provide the link between obesity and CHF. DESIGN, SETTING, AND PARTICIPANTS: The Uppsala Longitudinal Study of Adult Men, a prospective, community-based, observational cohort in Uppsala, Sweden. We investigated 1187 elderly (>or=70 years) men free from CHF and valvular disease at baseline between 1990 and 1995, with follow-up until the end of 2002. Variables reflecting insulin sensitivity (including euglycemic insulin clamp glucose disposal rate) and obesity were analyzed together with established risk factors (prior myocardial infarction, hypertension, diabetes, electrocardiographic left ventricular hypertrophy, smoking, and serum cholesterol level) as predictors of subsequent incidence of CHF, using Cox proportional hazards analyses. MAIN OUTCOME MEASURE: First hospitalization for heart failure. RESULTS: One hundred four men developed CHF during a median follow-up of 8.9 (range, 0.01-11.4) years. In multivariable Cox proportional hazards models adjusted for established risk factors for CHF, increased risk of CHF was associated with a 1-SD increase in the 2-hour glucose value of an oral glucose tolerance test (hazard ratio [HR], 1.44; 95% confidence interval [CI], 1.08-1.93), fasting serum proinsulin level (HR, 1.29; 95% CI, 1.02-1.64), body mass index (HR, 1.35; 95% CI, 1.11-1.65), and waist circumference (HR, 1.36; 95% CI, 1.10-1.69), whereas a 1-SD increase in clamp glucose disposal rate decreased the risk (HR, 0.66; 95% CI, 0.51-0.86). When adding clamp glucose disposal rate to these models as a covariate, the obesity variables were no longer significant predictors of subsequent CHF. CONCLUSIONS: Insulin resistance predicted CHF incidence independently of established risk factors including diabetes in our large community-based sample of elderly men. The previously described association between obesity and subsequent CHF may be mediated largely by insulin resistance.
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- Jobs, Elisabeth, et al.
(författare)
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Association between serum cathepsin S and mortality in older adults
- 2011
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Ingår i: Journal of the American Medical Association (JAMA). - Chicago : American Medical Association. - 0098-7484 .- 1538-3598. ; 306:10, s. 1113-1121
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Tidskriftsartikel (refereegranskat)abstract
- Context: Experimental data suggest that cathepsin S, a cysteine protease, is involved in the complex pathways leading to cardiovascular disease and cancer. However, prospective data concerning a potential association between circulating cathepsin S levels and mortality are lacking. Objective To investigate associations between circulating cathepsin S levels and mortality in 2 independent cohorts of elderly men and women.Design, Setting, and Participants: Prospective study using 2 community-based cohorts, the Uppsala Longitudinal Study of Adult Men (ULSAM; n = 1009; mean age: 71 years; baseline period: 1991-1995; median follow-up: 12.6 years; end of follow-up: 2006) and the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS; n = 987; 50% women; mean age: 70 years; baseline period: 2001-2004; median follow-up: 7.9 years; end of follow-up: 2010). Serum samples were used to measure cathepsin S.Main Outcome Measure Total mortality.Results: During follow-up, 413 participants died in the ULSAM cohort (incidence rate: 3.59/100 person-years at risk) and 100 participants died in the PIVUS cohort (incidence rate: 1.32/100 person-years at risk). In multivariable Cox regression models adjusted for age, systolic blood pressure, diabetes, smoking status, body mass index, total cholesterol, high-density lipoprotein cholesterol, antihypertensive treatment, lipid-lowering treatment, and history of cardiovascular disease, higher serum cathepsin S was associated with an increased risk for mortality (ULSAM cohort: hazard ratio [HR] for 1-unit increase of cathepsin S, 1.04 [95% CI, 1.01-1.06], P = .009; PIVUS cohort: HR for 1-unit increase of cathepsin S, 1.03 [95% CI, 1.00-1.07], P = .04). In the ULSAM cohort, serum cathepsin S also was associated with cardiovascular mortality (131 deaths; HR for quintile 5 vs quintiles 1-4, 1.62 [95% CI, 1.11-2.37]; P = .01) and cancer mortality (148 deaths; HR for 1-unit increase of cathepsin S, 1.05 [95% CI, 1.01-1.10]; P = .01).Conclusions Among elderly individuals in 2 independent cohorts, higher serum cathepsin S levels were associated with increased mortality risk. Additional research is needed to delineate the role of cathepsin S and whether its measurement might have clinical utility.
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- Vasan, Ramachandran S, et al.
(författare)
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Genetic variants associated with cardiac structure and function : a meta-analysis and replication of genome-wide association data
- 2009
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Ingår i: Journal of the American Medical Association (JAMA). - : American Medical Association (AMA). - 0098-7484 .- 1538-3598. ; 302:2, s. 168-178
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: Echocardiographic measures of left ventricular (LV) structure and function are heritable phenotypes of cardiovascular disease. OBJECTIVE: To identify common genetic variants associated with cardiac structure and function by conducting a meta-analysis of genome-wide association data in 5 population-based cohort studies (stage 1) with replication (stage 2) in 2 other community-based samples. DESIGN, SETTING, AND PARTICIPANTS: Within each of 5 community-based cohorts comprising the EchoGen consortium (stage 1; n = 12 612 individuals of European ancestry; 55% women, aged 26-95 years; examinations between 1978-2008), we estimated the association between approximately 2.5 million single-nucleotide polymorphisms (SNPs; imputed to the HapMap CEU panel) and echocardiographic traits. In stage 2, SNPs significantly associated with traits in stage 1 were tested for association in 2 other cohorts (n = 4094 people of European ancestry). Using a prespecified P value threshold of 5 x 10(-7) to indicate genome-wide significance, we performed an inverse variance-weighted fixed-effects meta-analysis of genome-wide association data from each cohort. MAIN OUTCOME MEASURES: Echocardiographic traits: LV mass, internal dimensions, wall thickness, systolic dysfunction, aortic root, and left atrial size. RESULTS: In stage 1, 16 genetic loci were associated with 5 echocardiographic traits: 1 each with LV internal dimensions and systolic dysfunction, 3 each with LV mass and wall thickness, and 8 with aortic root size. In stage 2, 5 loci replicated (6q22 locus associated with LV diastolic dimensions, explaining <1% of trait variance; 5q23, 12p12, 12q14, and 17p13 associated with aortic root size, explaining 1%-3% of trait variance). CONCLUSIONS: We identified 5 genetic loci harboring common variants that were associated with variation in LV diastolic dimensions and aortic root size, but such findings explained a very small proportion of variance. Further studies are required to replicate these findings, identify the causal variants at or near these loci, characterize their functional significance, and determine whether they are related to overt cardiovascular disease.
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