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- Kjeldsen, Sverre E, et al.
(författare)
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Predictors of cardiovascular events in patients with hypertension and left ventricular hypertrophy : the losartan inventervention for endpoint reduction in hypertension study
- 2009
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Ingår i: Blood Pressure. - 0803-7051 .- 1651-1999. ; 18:6, s. 348-361
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Tidskriftsartikel (refereegranskat)abstract
- Objective. We assessed readily available patient characteristics, including albuminuria (not included in traditional cardiovascular risk scores), as predictors of cardiovascular events in hypertension with left ventricular hypertrophy (LVH) and developed risk algorithms/scores for outcomes. Methods. The Losartan Intervention For Endpoint reduction in hypertension (LIFE) study compared effects of losartan-based versus atenolol-based therapy on cardiovascular events in 9193 patients with hypertension and LVH. Univariate and multivariate analyses identified baseline variables with significant impact on development of the primary composite endpoint (cardiovascular death, stroke and myocardial infarction) and its components. Multivariate analysis used a Cox regression model with stepwise selection process. Risk scores were developed from coefficients of risk factors from the multivariate analysis, validated internally using naïve and jack-knife procedures, checked for discrimination and calibration, and compared with Framingham coronary heart disease and other risk scores. Results. LIFE risk scores showed increasing endpoint rates with increasing quintile (first to fifth quintile, composite endpoint 2.8–26.7%, cardiovascular death 0.5–14.4%, stroke 1.2–11.3%, myocardial infarction 1.4–8.1%) and were confirmed with a jack-knife approach that adjusts for potentially optimistic bias. The Framingham coronary heart disease and other risk scores overestimated risk in lower risk patients and underestimated risk in higher risk patients, except for myocardial infarction. Conclusion. A number of patient characteristics predicted cardiovascular events in patients with hypertension and LVH. Risk scores developed from these patient characteristics, including albuminuria, strongly predicted outcomes and may improve risk assessment of patients with hypertension and LVH and planning of clinical trials.
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- Olsen, Michael Hecht, et al.
(författare)
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Effects of losartan compared with atenolol on lipids in patients with hypertension and left ventricular hypertrophy : the losartan intervention for endpoint reduction in hypertension (LIFE) study
- 2009
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Ingår i: Journal of Hypertension. - 0263-6352 .- 1473-5598. ; 27:3, s. 567-574
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Beta-blockers and angiotensin II receptor blockers have different effects on lipids. Methods: We examined lipid levels in the Losartan Intervention For Endpoint reduction in hypertension study and their impact on the primary composite endpoint of cardiovascular death, myocardial infarction, or stroke. We measured total and high-density lipoprotein cholesterol at baseline and annually during 4.8 years of losartan-based compared with atenolol-based treatment in 8611 patients with hypertension and left ventricular hypertrophy. Results: Patients randomized to losartan-based or atenolol-based treatment had similar baseline total (6.04 ± 1.12 vs. 6.05 ± 1.13 mmol/l, NS) and high-density lipoprotein (HDL) cholesterol (1.50 ± 0.44 vs. 1.49 ± 0.44 mmol/l, NS). Total cholesterol decreased significantly but equally (-0.37 ± 1.05 vs. -0.34 ± 1.09 mmol/l, NS), whereas HDL cholesterol decreased less during the first 2 years in patients randomized to losartan compared with atenolol (-0.13 ± 0.24 vs. -0.19 ± 0.25 mmol/l) and remained higher each year (1.38, 1.37, 1.42, 1.47, and 1.48 mmol/l vs. 1.32, 1.30, 1.36, 1.40, and 1.42 mmol/l, all P < 0.001) independent of hydrochlorothiazide or statin treatment. In Cox regression analysis, baseline total cholesterol [hazard ratio (HR) = 1.08 (1.02–1.14) per mmol/l, P < 0.01], HDL cholesterol [HR = 0.56 (0.48–0.66) per mmol/l, P < 0.001], and treatment allocation [HR = 0.86 (0.76–0.98), P < 0.05] predicted composite endpoint independently. Using time-varying analyses, the predictive strength of HDL cholesterol was increased [HR = 0.36 (0.30–0.44) per mmol/l, P < 0.001], whereas that of total cholesterol [HR = 1.03 (0.97–1.09) per mmol/l, NS] and treatment allocation [HR = 0.91 (0.80–1.03), NS] were reduced. Conclusion: Losartan blunted the decrease in HDL cholesterol during antihypertensive treatment in the LIFE study. Higher intreatment HDL cholesterol was associated with fewer composite endpoints and may partly explain the better outcome of losartan-based treatment.
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- Teo, Koon K., et al.
(författare)
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Effects of telmisartan, irbesartan, valsartan, candesartan, and losartan on cancers in 15 trials enrolling 138 769 individuals The ARB Trialists Collaboration
- 2011
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Ingår i: Journal of Hypertension. - 0263-6352 .- 1473-5598. ; 29:4, s. 623-635
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Forskningsöversikt (refereegranskat)abstract
- Background Angiotensin-converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARBs) reduce cardiovascular disease (CVD) events, but a recent meta-analysis of selected studies suggested that ARBs may increase cancer risks.Objective Candesartan, irbesartan, telmisartan, valsartan, and losartan were assessed for incident cancers in 15 large parallel long-term multicenter double-blind clinical trials of these agents involving 138 769 participants.Patients and methods Individuals at high CVD risk were randomized to telmisartan (three trials, n=51 878), irbesartan (three trials, n=14 859), valsartan (four trials, n=44 264), candesartan (four trials, n=18 566), and losartan (one trial, n=9193) and followed for 23-60 months. Incident cancer cases were compared in patients randomized to ARBs versus controls. In five trials (n=42 403), the ARBs were compared to ACEi and in 11 trials (n=63 313) to controls without ACEi. In addition, in seven trials (n=47 020), the effect of ARBs with ACEi was compared to ACEi alone and in two trials ARBs with ACEi versus ARB alone (n=25 712).Results Overall, there was no excess of cancer incidence with ARB therapy compared to controls in the 15 trials [ 4549 (6.16%) cases of 73 808 allocated to ARB versus 3856 (6.31%) of 61 106 assigned to non-ARB controls; odds ratio (OR) 1.00, 95% confidence interval (CI) 0.95-1.04] overall or when individual ARBs were examined. ORs comparing combination therapy with ARB along with ACEi versus ACEi was 1.01 (95% CI 0.94-1.10), combination versus ARB alone 1.02 (95% CI 0.91-1.13), ARB alone versus ACEi alone 1.06 (95% CI 0.97-1.16) and ARB versus placebo/control without ACEi 0.97 (95% CI 0.91-1.04). There was no excess of lung, prostate or breast cancer, or overall cancer deaths associated with ARB treatment.Conclusion There was no significant increase in the overall or site-specific cancer risk from ARBs compared to controls.
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- Adiyaman, Ahmet, et al.
(författare)
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Determinants of the ambulatory arterial stiffness index in 7604 subjects from 6 populations
- 2008
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Ingår i: Hypertension. - 1524-4563. ; 52:6, s. 1038-44
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Tidskriftsartikel (refereegranskat)abstract
- The ambulatory arterial stiffness index (AASI) is derived from 24-hour ambulatory blood pressure recordings. We investigated whether the goodness-of-fit of the AASI regression line in individual subjects (r(2)) impacts on the association of AASI with established determinants of the relation between diastolic and systolic blood pressures. We constructed the International Database on the Ambulatory Blood Pressure in Relation to Cardiovascular Outcomes (7604 participants from 6 countries). AASI was unity minus the regression slope of diastolic on systolic blood pressure in individual 24-hour ambulatory recordings. AASI correlated positively with age and 24-hour mean arterial pressure and negatively with body height and 24-hour heart rate. The single correlation coefficients and the mutually adjusted partial regression coefficients of AASI with age, height, 24-hour mean pressure, and 24-hour heart rate increased from the lowest to the highest quartile of r(2). These findings were consistent in dippers and nondippers (night:day ratio of systolic pressure >or=0.90), women and men, and in Europeans, Asians, and South Americans. The cumulative z score for the association of AASI with these determinants of the relation between diastolic and systolic blood pressures increased curvilinearly with r(2), with most of the improvement in the association occurring above the 20th percentile of r(2) (0.36). In conclusion, a better fit of the AASI regression line enhances the statistical power of analyses involving AASI as marker of arterial stiffness. An r(2) value of 0.36 might be a threshold in sensitivity analyses to improve the stratification of cardiovascular risk.
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- Boggia, Jose, et al.
(författare)
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Ambulatory Blood Pressure Monitoring in 9357 Subjects From 11 Populations Highlights Missed Opportunities for Cardiovascular Prevention in Women
- 2011
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Ingår i: Hypertension. - 0194-911X .- 1524-4563. ; 57:3, s. 397-405
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Tidskriftsartikel (refereegranskat)abstract
- To analyze sex-specific relative and absolute risks associated with blood pressure (BP), we performed conventional and 24-hour ambulatory BP measurements in 9357 subjects (mean age, 52.8 years; 47% women) recruited from 11 populations. We computed standardized multivariable-adjusted hazard ratios for associations between outcome and systolic BP. During a course of 11.2 years (median), 1245 participants died, 472 of cardiovascular causes. The number of fatal combined with nonfatal events was 1080, 525, and 458 for cardiovascular and cardiac events and for stroke, respectively. In women and men alike, systolic BP predicted outcome, irrespective of the type of BP measurement. Women compared with men were at lower risk (hazard ratios for death and all cardiovascular events=0.66 and 0.62, respectively; P<0.001). However, the relation of all cardiovascular events with 24-hour BP (P=0.020) and the relations of total mortality (P=0.023) and all cardiovascular (P=0.0013), cerebrovascular (P=0.045), and cardiac (P=0.034) events with nighttime BP were steeper in women than in men. Consequently, per a 1-SD decrease, the proportion of potentially preventable events was higher in women than in men for all cardiovascular events (35.9% vs 24.2%) in relation to 24-hour systolic BP (1-SD, 13.4 mm Hg) and for all-cause mortality (23.1% vs 12.3%) and cardiovascular (35.1% vs 19.4%), cerebrovascular (38.3% vs 25.9%), and cardiac (31.0% vs 16.0%) events in relation to systolic nighttime BP (1-SD, 14.1 mm Hg). In conclusion, although absolute risks associated with systolic BP were lower in women than men, our results reveal a vast and largely unused potential for cardiovascular prevention by BP-lowering treatment in women.
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