| 1. |
- Gregson, J., et al.
(författare)
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Cardiovascular Risk Factors Associated With Venous Thromboembolism
- 2019
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Ingår i: JAMA Cardiology. - : American Medical Association (AMA). - 0965-2590 .- 2380-6583 .- 2380-6591. ; 4:2, s. 163-173
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE It is uncertain to what extent established cardiovascular risk factors are associated with venous thromboembolism (VTE). OBJECTIVE To estimate the associations of major cardiovascular risk factors with VTE, ie, deep vein thrombosis and pulmonary embolism. DESIGN, SETTING, AND PARTICIPANTS This study included individual participant data mostly from essentially population-based cohort studies from the Emerging Risk Factors Collaboration (ERFC; 731728 participants; 75 cohorts; years of baseline surveys, February 1960 to June 2008; latest date of follow-up, December 2015) and the UK Biobank (421537 participants; years of baseline surveys, March 2006 to September 2010; latest date of follow-up, February 2016). Participants without cardiovascular disease at baseline were included. Data were analyzed from June 2017 to September 2018. MAIN OUTCOMES AND MEASURES Hazard ratios (HRs) per 1-SD higher usual risk factor levels (or presence/absence). Incident fatal outcomes in ERFC (VTE, 1041; coronary heart disease [CND], 25131) and incident fatal/nonfatal outcomes in UK Biobank (VTE, 2321; CHD, 3385). Hazard ratios were adjusted for age, sex, smoking status, diabetes, and body mass index (BMI). RESULTS Of the 731728 participants from the ERFC. 403 396 (55.1%) were female, and the mean (SD) age at the time of the survey was 51.9 (9.0) years; of the 421537 participants from the UK Biobank, 233 699 (55.4%) were female, and the mean (SD) age at the time of the survey was 56.4 (8.1) years. Risk factors for VTE included older age (ERFC: HR per decade, 2.67; 95% CI, 2.45-2.91; UK Biobank: HR, 1.81; 95% CI, 1.71-1.92), current smoking (ERFC: HR, 1.38; 95% CI, 1.20-1.58; UK Biobank: HR, 1.23; 95% CI, 1.08-1.40), and BMI (ERFC: HR per 1-SD higher BMI, 1.43; 95% CI, 1.35-1.50; UK Biobank: HR, 1.37; 95% CI, 1.32-1.41). For these factors, there were similar HRs for pulmonary embolism and deep vein thrombosis in UK Biobank (except adiposity was more strongly associated with pulmonary embolism) and similar HRs for unprovoked vs provoked VTE. Apart from adiposity, these risk factors were less strongly associated with VTE than CHD. There were inconsistent associations of VTEs with diabetes and blood pressure across ERFC and UK Biobank, and there was limited ability to study lipid and inflammation markers. CONCLUSIONS AND RELEVANCE Older age, smoking, and adiposity were consistently associated with higher VTE risk.
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| 2. |
- 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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| 3. |
- Robbe, P, et al.
(författare)
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Whole-genome sequencing of chronic lymphocytic leukemia identifies subgroups with distinct biological and clinical features
- 2022
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 54:11, s. 1675-
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Tidskriftsartikel (refereegranskat)abstract
- The value of genome-wide over targeted driver analyses for predicting clinical outcomes of cancer patients is debated. Here, we report the whole-genome sequencing of 485 chronic lymphocytic leukemia patients enrolled in clinical trials as part of the United Kingdom’s 100,000 Genomes Project. We identify an extended catalog of recurrent coding and noncoding genetic mutations that represents a source for future studies and provide the most complete high-resolution map of structural variants, copy number changes and global genome features including telomere length, mutational signatures and genomic complexity. We demonstrate the relationship of these features with clinical outcome and show that integration of 186 distinct recurrent genomic alterations defines five genomic subgroups that associate with response to therapy, refining conventional outcome prediction. While requiring independent validation, our findings highlight the potential of whole-genome sequencing to inform future risk stratification in chronic lymphocytic leukemia.
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| 4. |
- Weir, M. R., et al.
(författare)
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Renal outcomes in hypertensive Black patients at high cardiovascular risk
- 2012
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Ingår i: Kidney international. - : Elsevier BV. - 1523-1755 .- 0085-2538. ; 81:6, s. 568-76
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Tidskriftsartikel (refereegranskat)abstract
- The ACCOMPLISH trial (Avoiding Cardiovascular events through Combination therapy in Patients Living with Systolic Hypertension) was a 3-year multicenter, event-driven trial involving patients with high cardiovascular risk who were randomized in a double-blinded manner to benazepril plus either hydrochlorothiazide or amlodipine and titrated in parallel to reach recommended blood pressure goals. Of the 8125 participants in the United States, 1414 were of self-described Black ethnicity. The composite kidney disease end point, defined as a doubling in serum creatinine, end-stage renal disease, or death was not different between Black and non-Black patients, although the Blacks were significantly more likely to develop a greater than 50% increase in serum creatinine to a level above 2.6 mg/dl. We found important early differences in the estimated glomerular filtration rate (eGFR) due to acute hemodynamic effects, indicating that benazepril plus amlodipine was more effective in stabilizing eGFR compared to benazepril plus hydrochlorothiazide in non-Blacks. There was no difference in the mean eGFR loss in Blacks between therapies. Thus, benazepril coupled to amlodipine was a more effective antihypertensive treatment than when coupled to hydrochlorothiazide in non-Black patients to reduced kidney disease progression. Blacks have a modestly higher increased risk for more advanced increases in serum creatinine than non-Blacks.
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| 5. |
- Olsen, M. H., et al.
(författare)
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N-terminal brain natriuretic peptide predicted cardiovascular events stronger than high-sensitivity C-reactive protein in hypertension: a LIFE substudy
- 2006
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Ingår i: J Hypertens. - 0263-6352. ; 24:8, s. 1531-9
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: N-terminal pro-brain natriuretic peptide (Nt-proBNP) and high-sensitivity C-reactive protein (hsCRP) are cardiovascular risk markers in various populations, but are not well examined in hypertension. Therefore, we wanted to investigate whether high Nt-proBNP or hsCRP predicted the composite endpoint of cardiovascular death, non-fatal stroke or non-fatal myocardial infarction independently of traditional cardiovascular risk factors and the urine albumin: creatinine ratio (UACR), which is a well established cardiovascular risk factor in hypertension. METHODS: In 945 hypertensive patients from the LIFE study with electrocardiographic left ventricular (LV) hypertrophy, we measured traditional cardiovascular risk factors including electrocardiography, morning UACR, hsCRP by immunoturbidimetry assay and Nt-proBNP by immunoassay after 2 weeks of placebo treatment. During 55 months' follow-up 80 patients suffered a composite endpoint. RESULTS: HsCRP as well as Nt-proBNP above the median values of 3.0 mg/l and 170 pg/ml, respectively, was associated with a higher incidence of composite endpoint (13.1 versus 3.8%, P < 0.01, and 11.5 versus 5.4%, P < 0.01). In Cox regression analyses, standardized log(hsCRP)/SD predicted a composite endpoint [hazard ratio (HR) 1.3 per SD = 0.47 log(mg/l), P < 0.05] after adjustment for traditional cardiovascular risk factors, but not after further adjustment for UACR. Standardized log(Nt-proBNP)/SD predicted a composite endpoint after adjustment for traditional cardiovascular risk factors [HR 1.9 per SD = 0.49 log(pg/ml), P < 0.05] as well as after further adjustment for UACR [HR 1.5 per SD = 0.49 log(pg/ml), P < 0.01]. Log(Nt-proBNP) added significantly to the Cox regression models using traditional cardiovascular risk factors with and without UACR (both P < 0.001). CONCLUSION: Nt-proBNP predicted a composite endpoint after adjustment for traditional risk factors, UACR and a history of diabetes or cardiovascular disease and added significantly to the prediction of composite endpoint, whereas hsCRP did not.
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| 6. |
- Carr, A. A., et al.
(författare)
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Hospitalizations for new heart failure among subjects with diabetes mellitus in the RENAAL and LIFE studies
- 2005
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Ingår i: Am J Cardiol. - : Elsevier BV. - 0002-9149. ; 96:11, s. 1530-6
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Tidskriftsartikel (refereegranskat)abstract
- We sought to study the risk factors for heart failure (HF) and the relation between antihypertensive treatment with losartan and the first hospitalization for HF in patients with diabetes mellitus in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) and Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) studies. We evaluated 1,195 patients with hypertension, left ventricular hypertrophy, and diabetes from the LIFE study and 1,513 patients with type 2 diabetes and nephropathy from the RENAAL study. The comparative treatments were atenolol in the LIFE study and placebo in the RENAAL study. Patients with a history of HF were excluded from this analysis. Losartan significantly reduced the incidence of first hospitalizations for HF versus placebo in the RENAAL study (hazard ratio 0.74, p=0.037) and versus atenolol in the LIFE study (hazard ratio 0.57, p=0.019). Patients enrolled in the RENAAL study were at a higher risk of developing HF (hazard ratio for RENAAL vs LIFE diabetics 3.0, p<0.0001). The significant, independent baseline risk factors for the development of HF in the RENAAL study were urinary albumin/creatinine ratio, age, peripheral vascular disease, the Cornell product, body mass index, and previous angina; in the LIFE study they were the Cornell product, previous myocardial infarction, peripheral vascular disease, baseline atrial fibrillation, alcohol use (inverse relation), and urinary albumin/creatinine ratio. The beneficial effect of losartan on the reduction of risk for hospitalization for new HF was demonstrated in patients who were at high renal and/or high cardiovascular risk.
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| 7. |
- Chinali, M., et al.
(författare)
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Mitral E wave deceleration time to peak E velocity ratio and cardiovascular outcome in hypertensive patients during antihypertensive treatment (from the LIFE echo-substudy)
- 2009
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Ingår i: The American Journal of Cardiology. - : Elsevier BV. - 1879-1913 .- 0002-9149. ; 104:8, s. 1098-104
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Tidskriftsartikel (refereegranskat)abstract
- The early mitral flow deceleration time (DTE) is a prognostically validated marker of left ventricular diastolic dysfunction. It has been reported that the DTE is influenced by the loading conditions, which can vary during antihypertensive treatment. We hypothesized that normalization of the DTE for mitral peak E-velocity (mitral deceleration index [MDI]) might better predict incident cardiovascular (CV) events in hypertensive patients during treatment compared to DTE alone or other traditional indexes of diastolic function, such as the mitral E/A ratio. We evaluated 770 hypertensive patients with electrocardiogram findings of left ventricular hypertrophy (age 66 +/- 7 years; 42% women) enrolled in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) echocardiographic substudy. Echocardiographic examinations were performed annually for 5 years during intensive antihypertensive treatment. We examined the utility of the MDI at baseline and as a time-varying predictor of incident CV events. Of the 770 patients, 70 (9%) had CV events. The baseline MDI was positively associated with age and relative wall thickness and negatively associated with gender and heart rate (all p <0.01). Unadjusted Cox regression analysis showed a positive association between the baseline MDI and CV events (hazard ratio 1.21, 95% confidence interval 1.07 to 1.37, p = 0.002). In the time-varied Cox models, a greater in-treatment MDI was associated with a greater rate of CV events (hazard ratio 1.43, 95% confidence interval 1.05 to 1.93, p = 0.022), independently of the covariates. No significant association was found for in-treatment DTE or any of the prognostically validated indexes of diastolic function. In conclusion, in our population of patients with treated hypertension with electrocardiographic findings of left ventricular hypertrophy, the MDI independently predicted future CV events. Normalization of DTE for E velocity might be preferred to other traditional diastolic function indexes in evaluating diastolic function during antihypertensive treatment.
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| 8. |
- Fossum, E., et al.
(författare)
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The effect of baseline physical activity on cardiovascular outcomes and new-onset diabetes in patients treated for hypertension and left ventricular hypertrophy: the LIFE study
- 2007
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Ingår i: J Intern Med. - : Wiley. - 0954-6820. ; 262:4, s. 439-48
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Physical activity (PA) is a preventive strategy for cardiovascular disease and for managing cardiovascular risk factors. There is little information on the effectiveness of PA for the prevention of cardiovascular outcomes once cardiovascular disease is present. Thus, we studied the relationship between PA at baseline and cardiovascular events in a high-risk population. DESIGN: A prespecified analyses of observational data in a prospective, randomized hypertension study. SETTING: Losartan Intervention For Endpoint reduction in hypertension (LIFE) study. SUBJECTS: Hypertension and left ventricular hypertrophy (LVH) (n = 9,193). INTERVENTIONS: Losartan versus atenolol. MAIN OUTCOME MEASURES: Reported level of PA: never exercise, exercise 30 min twice per week at baseline and after a mean of 4.8 years of treatment with losartan- versus atenolol-based therapy. Risk reductions were calculated by level of PA for the primary composite end-point and its components cardiovascular death, stroke and myocardial infarction, and also all-cause mortality and new-onset diabetes. RESULTS: A modest level of PA (>30 min twice per week) was associated with significant reductions in risk for the primary composite end-point [adjusted hazard ratio (aHR) 0.70, P < 0.001) and its components, all-cause mortality (aHR 0.65, P < 0.001), and new-onset diabetes (aHR 0.66, P < 0.001). CONCLUSION: A modest level of self-reported PA (>30 min twice per week) in patients with hypertension and LVH in the LIFE study was associated with significant reductions in risk for the primary composite end-point and its components of cardiovascular death, stroke, and myocardial infarction, all-cause mortality, and new-onset diabetes.
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| 9. |
- Kizer, J. R., et al.
(författare)
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Stroke reduction in hypertensive adults with cardiac hypertrophy randomized to losartan versus atenolol: the Losartan Intervention For Endpoint reduction in hypertension study
- 2005
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Ingår i: Hypertension. - 1524-4563. ; 45:1, s. 46-52
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Tidskriftsartikel (refereegranskat)abstract
- The Losartan Intervention For Endpoint reduction in hypertension (LIFE) study showed that treatment with the angiotensin II type-1 receptor antagonist losartan reduces overall stroke risk compared with conventional therapy with the beta-blocker atenolol. We conducted secondary analyses in LIFE to determine the extent to which the cerebrovascular benefits of losartan apply to different clinical subgroups and stroke subtypes and to assess the dependence of these benefits on baseline and time-varying covariates. Among 9193 hypertensive patients with electrocardiographic evidence of left ventricular hypertrophy, random allocation to losartan-based treatment lowered the risk of fatal (hazard ratio [HR], 0.65; 95% confidence interval [CI], 0.43 to 0.96; P=0.032) and atherothrombotic stroke (HR, 0.72; 95% CI, 0.59 to 0.88; P=0.001) compared with atenolol-based therapy. Although comparable risk reductions occurred for hemorrhagic and embolic stroke, these were not statistically significant. The number of neurological deficits per stroke was similar, but there were fewer strokes in the losartan group for nearly every level of stroke severity. Effects were consistent in all clinical subgroups except for those defined by age and ethnicity. The benefits of losartan on all strokes were independent of baseline and time-varying risk factors, including blood pressure. The number needed to treat for 5 years to prevent 1 stroke was 54 for the average participant, declining to 25, 24, and 9 for patients with cerebrovascular disease, isolated systolic hypertension, and atrial fibrillation, respectively. In conclusion, substantial cerebrovascular benefit could be realized with the institution of losartan-based therapy over conventional therapy among hypertensive patients with left ventricular hypertrophy across the spectrum of cardiovascular risk.
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| 10. |
- Kjeldsen, S. E., et al.
(författare)
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The effects of losartan compared to atenolol on stroke in patients with isolated systolic hypertension and left ventricular hypertrophy. The LIFE study
- 2005
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Ingår i: J Clin Hypertens (Greenwich). - 1524-6175. ; 7:3, s. 152-8
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Tidskriftsartikel (refereegranskat)abstract
- The Losartan Intervention For Endpoint reduction in hypertension (LIFE) study reported that a losartan-based antihypertensive regimen reduced cardiovascular morbidity and mortality (composite of cardiovascular death, stroke, and myocardial infarction) more than therapy based on atenolol in patients with left ventricular hypertrophy and isolated systolic hypertension (ISH). Patients aged 55-80 years with blood pressures 160-200/<90 mm Hg were followed for a mean of 4.7 years. Blood pressure was similarly reduced in the losartan (n=660) and atenolol (n=666) ISH groups. There were 88 (6.6%) patients who experienced a stroke, 18 of which were fatal. Of patients experiencing strokes, 72.7% had an ischemic stroke. ISH patients in LIFE compared to the non-ISH group had a higher incidence of any stroke and embolic stroke, and similar incidences of fatal, atherosclerotic, and hemorrhagic/other strokes. The incidence of any stroke (40% risk reduction [RR], p=0.02), fatal stroke (70% RR, p=0.035), and atherothrombotic stroke (45% RR, p=0.022) was significantly lower in losartan-treated compared to the atenolol-treated patients. The 36% RR for embolic strokes in the losartan group was not statistically significantly (p=0.33) different from the atenolol group. These data suggest that losartan-based treatment is more effective than an atenolol-based treatment for patients with ISH and a high risk for stroke.
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