| 111. |
- Palmieri, V., et al.
(författare)
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Usefulness of the assessment of the appropriateness of left ventricular mass to detect left ventricular systolic and diastolic abnormalities in absence of echocardiographic left ventricular hypertrophy: the LIFE study
- 2004
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Ingår i: J Hum Hypertens. - 0950-9240. ; 18:6, s. 423-30
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Tidskriftsartikel (refereegranskat)abstract
- Conventional definitions of left ventricular (LV) hypertrophy do not account for interindividual differences in loading conditions. We may define LV mass as inappropriately high when exceeding 128% of theoretical values predicted by gender, height(2.7), and stroke work, which explain up to 82% of the variability of LV mass in normal reference subjects. In 652 participants in the Losartan Intervention For Endpoint reduction in hypertension study without clinically overt cardiovascular disease or diabetes, we investigated whether inappropriately high LV mass is associated with relevant LV abnormalities independent of traditional definition of LV hypertrophy (ie, LV mass index >116 g/m(2) in men and >104 g/m(2) in women). The study sample was divided into three groups: patients with inappropriately high LV mass but without LV hypertrophy were compared to patients with LV hypertrophy and to patients with appropriate LV mass and without LV hypertrophy. Patients with inappropriately high but nonhypertrophic LV mass had higher body mass index and relative wall thickness, and lower LV myocardial systolic function, than patients with appropriate LV mass or patients with LV hypertrophy. In multivariate analyses, inappropriately high LV mass was independently associated with lower myocardial systolic function independent of LV hypertrophy and other covariates. Inappropriately high LV mass was also associated with prolonged isovolumic relaxation time and lower mitral E/A ratio independent of covariates. In conclusion, inappropriately high LV mass was associated with relevant, often preclinical, manifestations of cardiac disease in the absence of traditionally defined echocardiographic LV hypertrophy and concentric geometry.
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| 112. |
- Poulter, N. R., et al.
(författare)
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Baseline heart rate, antihypertensive treatment, and prevention of cardiovascular outcomes in ASCOT (Anglo-Scandinavian Cardiac Outcomes Trial)
- 2009
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Ingår i: Journal of the American College of Cardiology. - 1558-3597. ; 54:13, s. 1154-61
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: The aim of this study was to evaluate the effect of baseline heart rate on the efficacy of atenolol-based compared with amlodipine-based therapy in patients with hypertension uncomplicated by coronary heart disease in the ASCOT-BPLA (Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm). BACKGROUND: Heart rate is an established risk factor for cardiovascular events. Consequently, it is a widely held belief that beta-blockers should be prescribed for management of hypertension in patients with higher heart rates. METHODS: Patients with atrial fibrillation or taking rate-limiting antihypertensive drugs at baseline were excluded. Primary analyses used Cox models to investigate the potential attenuation of the treatment effect with higher baseline heart rate on total cardiovascular events and procedures (TCVP) via introduction of an interaction term. Secondary analyses assessed coronary and total stroke outcomes. RESULTS: Primary unadjusted analyses included 12,759 patients and 1,966 TCVP. At the final visit, mean heart rate reduction from baseline was 12.0 (SD 13.7) and 1.3 (SD 12.1) beats/min in atenolol- and amlodipine-based groups, respectively. There was a reduction in TCVP in those allocated amlodipine-based therapy compared with atenolol-based therapy (unadjusted hazard ratio: 0.81, p < 0.001). This benefit was unattenuated at higher heart rates (interaction p value = 0.81). Similar results were obtained for coronary and total stroke outcomes. CONCLUSIONS: There was no evidence that the superiority of amlodipine-based over atenolol-based therapy for patients with hypertension uncomplicated by coronary heart disease was attenuated with higher baseline heart rate. These data suggest that, in similar hypertensive populations without previous or current coronary artery disease, higher baseline heart rate is not an indication for preferential use of beta-blocker-based therapy.
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| 113. |
- Poulter, N. R., et al.
(författare)
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Role of blood pressure and other variables in the differential cardiovascular event rates noted in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA)
- 2005
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Ingår i: Lancet. - 1474-547X. ; 366:9489, s. 907-13
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Results of the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA) show significantly lower rates of coronary and stroke events in individuals allocated an amlodipine-based combination drug regimen than in those allocated an atenolol-based combination drug regimen (HR 0.86 and 0.77, respectively). Our aim was to assess to what extent these differences were due to significant differences in blood pressures and in other variables noted after randomisation. METHODS: We used data from ASCOT-BPLA (n=19 257) and compared differences in accumulated mean blood pressure levels at sequential times in the trial with sequential differences in coronary and stroke events. Serial mean matching for differences in systolic blood pressure was used to adjust HRs for differences in these events. We used an updated Cox-regression model to assess the effects of differences in accumulated mean levels of various measures of blood pressure, serum HDL-cholesterol, triglycerides and potassium, fasting blood glucose, heart rate, and bodyweight on differences in event rates. FINDINGS: We noted no temporal link between size of differences in blood pressure and different event rates. Serial mean matching for differences in systolic blood-pressure attenuated HRs for coronary and stroke events to a similar extent as did adjustments for systolic blood-pressure differences in Cox-regression analyses. HRs for coronary events and stroke adjusted for blood pressure rose from 0.86 (0.77-0.96) to 0.88 (0.79-0.98) and from 0.77 (0.66-0.89) to 0.83 (0.72-0.96), respectively. Multivariate adjustment gave HRs of 0.94 (0.81-1.08) for coronary events (HDL cholesterol being the largest contributor) and 0.87 (0.73-1.05) for stroke events. INTERPRETATION: Multivariate adjustment accounted for about half of the differences in coronary events and for about 40% of the differences in stroke events between the treatment regimens tested in ASCOT-BPLA, but residual differences were no longer significant. These residual differences could indicate inadequate statistical adjustment, but it remains possible that differential effects of the two treatment regimens on other variables also contributed to the different rates noted, particularly for stroke.
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| 114. |
- Prieto-Merino, D., et al.
(författare)
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ASCORE: an up-to-date cardiovascular risk score for hypertensive patients reflecting contemporary clinical practice developed using the (ASCOT-BPLA) trial data
- 2013
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Ingår i: Journal of Human Hypertension. - : Springer Science and Business Media LLC. - 0950-9240 .- 1476-5527. ; 27:8, s. 492-6
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Tidskriftsartikel (refereegranskat)abstract
- A number of risk scores already exist to predict cardiovascular (CV) events. However, scores developed with data collected some time ago might not accurately predict the CV risk of contemporary hypertensive patients that benefit from more modern treatments and management. Using data from the randomised clinical trial Anglo-Scandinavian Cardiac Outcomes Trial-BPLA, with 15 955 hypertensive patients without previous CV disease receiving contemporary preventive CV management, we developed a new risk score predicting the 5-year risk of a first CV event (CV death, myocardial infarction or stroke). Cox proportional hazard models were used to develop a risk equation from baseline predictors. The final risk model (ASCORE) included age, sex, smoking, diabetes, previous blood pressure (BP) treatment, systolic BP, total cholesterol, high-density lipoprotein-cholesterol, fasting glucose and creatinine baseline variables. A simplified model (ASCORE-S) excluding laboratory variables was also derived. Both models showed very good internal validity. User-friendly integer score tables are reported for both models. Applying the latest Framingham risk score to our data significantly overpredicted the observed 5-year risk of the composite CV outcome. We conclude that risk scores derived using older databases (such as Framingham) may overestimate the CV risk of patients receiving current BP treatments; therefore, 'updated' risk scores are needed for current patients.
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| 115. |
- Reims, H. M., et al.
(författare)
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Alcohol consumption and cardiovascular risk in hypertensives with left ventricular hypertrophy: the LIFE study
- 2004
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Ingår i: J Hum Hypertens. - : Springer Science and Business Media LLC. - 0950-9240 .- 1476-5527. ; 18:6, s. 381-9
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Tidskriftsartikel (refereegranskat)abstract
- The Losartan Intervention For End point reduction in hypertension (LIFE) study showed superiority of losartan over atenolol for reduction of composite risk of cardiovascular death, stroke, and myocardial infarction in hypertensives with left ventricular hypertrophy. We compared hazard ratios (HR) in 4287 and 685 participants who reported intakes of 1-7 and >8 drinks/week at baseline, respectively, with those in 4216 abstainers, adjusting for gender, age, smoking, exercise, and race. Within categories, clinical baseline characteristics, numbers randomized to losartan and atenolol, and blood pressure (BP) lowering were similar on the drug regimens. Overall BP control (<140/90 mmHg) at end of follow-up was similar in the categories. Composite end point rate was lower with 1-7 (24/1000 years; HR 0.87, P<0.05) and >8 drinks/week (26/1000 years; HR 0.80, NS) than in abstainers (27/1000 years). Myocardial infarction risk was reduced in both drinking categories (HR 0.76, P<0.05 and HR 0.29, P<0.001, respectively), while stroke risk tended to increase with >8 drinks/week (HR 1.21, NS). Composite risk was significantly reduced with losartan compared to atenolol only in abstainers (HR 0.81 95% confidence interval, CI (0.68, 0.96), P<0.05), while benefits for stroke risk reduction were similar among participants consuming 1-7 drinks/week (HR 0.73, P<0.05) and abstainers (HR 0.72, P<0.01). Despite different treatment benefits, alcohol-treatment interactions were nonsignificant. In conclusion, moderate alcohol consumption does not change the marked stroke risk reduction with losartan compared to atenolol in high-risk hypertensives. Alcohol reduces the risk of myocardial infarction, while the risk of stroke tends to increase with high intake.
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| 116. |
- Reims, H. M., et al.
(författare)
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Losartan benefits over atenolol in non-smoking hypertensive patients with left ventricular hypertrophy: the LIFE study
- 2004
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Ingår i: Blood Press. - : Informa UK Limited. - 0803-7051 .- 1651-1999. ; 13:6, s. 376-84
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Tidskriftsartikel (refereegranskat)abstract
- We studied the impact of smoking in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study, which showed superiority of losartan over atenolol for reduction of composite risk of cardiovascular death, stroke and myocardial infarction in hypertensives with left ventricular hypertrophy. We compared hazard ratios in 4656 never-smokers, and 3033 previous and 1499 current smokers, adjusting for gender, age, alcohol intake, exercise and race. Composite endpoint rate was higher in previous (28/1000 years), as well as current (39/1000 years) smokers than in never-smokers (21/1000 years). Composite (hazard ratio 0.78, 95% CI 0.65-0.94, p < 0.01) and stroke (hazard ratio 0.61, 95% CI 0.47-0.80], p < 0.001) risks were lower with losartan than atenolol in never-smokers, but not significantly in previous smokers. Drug regimens did not differ in current smokers (composite hazard ratio 0.99, stroke hazard ratio 0.94). Smoking-treatment interactions were non-significant, but a borderline significant trend (p = 0.05) suggested decreasing benefit of losartan vs atenolol for stroke prevention from never- to previous to current smoking status. Smoking increased cardiovascular risk markedly in the LIFE study. The benefit of losartan vs atenolol is consistent with the overall conclusion of the LIFE study, although the treatment effect appeared largest in non-smokers.
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| 117. |
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| 118. |
- Rothwell, P. M., et al.
(författare)
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Effects of beta blockers and calcium-channel blockers on within-individual variability in blood pressure and risk of stroke
- 2010
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Ingår i: The Lancet Neurology. - 1474-4422. ; 9:5, s. 469-480
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Analyses of some randomised trials show that calcium-channel blockers reduce the risk of stroke more than expected on the basis of mean blood pressure alone and that beta blockers are less effective than expected. We aimed to investigate whether the effects of these drugs on variability in blood pressure might explain these disparities in effect on stroke risk. METHODS: The Anglo-Scandinavian Cardiac Outcomes Trial Blood Pressure Lowering Arm (ASCOT-BPLA) compared amlodipine-based regimens with atenolol-based regimens in 19 257 patients with hypertension and other vascular risk factors and the Medical Research Council (MRC) trial compared atenolol-based and diuretic-based regimens versus placebo in 4396 hypertensive patients aged 65-74 years. We expressed visit-to-visit variability of blood pressure during follow-up in the two trials as standard deviation (SD) and as transformations uncorrelated with mean blood pressure. For ASCOT-BPLA, we also studied within-visit variability and variability on 24 h ambulatory blood-pressure monitoring (ABPM). RESULTS: In ASCOT-BPLA, group systolic blood pressure (SBP) SD was lower in the amlodipine group than in the atenolol group at all follow-up visits (p<0.0001), mainly because of lower within-individual visit-to-visit variability. Within-visit and ABPM variability in SBP were also lower in the amlodipine group than in the atenolol group (all p<0.0001). Analysis of changes from baseline showed that variability decreased over time in the amlodipine group and increased in the atenolol group. The lower risk of stroke in the amlodipine group (hazard ratio 0.78, 95% CI 0.67-0.90) was partly attenuated by adjusting for mean SBP during follow-up (0.84, 0.72-0.98), but was abolished by also adjusting for within-individual SD of clinic SBP (0.99, 0.85-1.16). Findings were similar for coronary events. In the ABPM substudy, reduced variability in daytime SBP in the amlodipine group (p<0.0001) partly accounted for the reduced risk of vascular events, but reduced visit-to-visit variability in clinic SBP had a greater effect. In the MRC trial, group SD SBP and all measures of within-individual visit-to-visit variability in SBP were increased in the atenolol group compared with both the placebo group and the diuretic group during initial follow-up (all p<0.0001). Subsequent temporal trends in variability in blood pressure during follow-up in the atenolol group correlated with trends in stroke risk. INTERPRETATION: The opposite effects of calcium-channel blockers and beta blockers on variability of blood pressure account for the disparity in observed effects on risk of stroke and expected effects based on mean blood pressure. To prevent stroke most effectively, blood-pressure-lowering drugs should reduce mean blood pressure without increasing variability; ideally they should reduce both. FUNDING: None.
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| 119. |
- Rothwell, P. M., et al.
(författare)
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Prognostic significance of visit-to-visit variability, maximum systolic blood pressure, and episodic hypertension
- 2010
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Ingår i: The Lancet. - 0140-6736. ; 375:9718, s. 895-905
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The mechanisms by which hypertension causes vascular events are unclear. Guidelines for diagnosis and treatment focus only on underlying mean blood pressure. We aimed to reliably establish the prognostic significance of visit-to-visit variability in blood pressure, maximum blood pressure reached, untreated episodic hypertension, and residual variability in treated patients. METHODS: We determined the risk of stroke in relation to visit-to-visit variability in blood pressure (expressed as standard deviation [SD] and parameters independent of mean blood pressure) and maximum blood pressure in patients with previous transient ischaemic attack (TIA; UK-TIA trial and three validation cohorts) and in patients with treated hypertension (Anglo-Scandinavian Cardiac Outcomes Trial Blood Pressure Lowering Arm [ASCOT-BPLA]). In ASCOT-BPLA, 24-h ambulatory blood-pressure monitoring (ABPM) was also studied. FINDINGS: In each TIA cohort, visit-to-visit variability in systolic blood pressure (SBP) was a strong predictor of subsequent stroke (eg, top-decile hazard ratio [HR] for SD SBP over seven visits in UK-TIA trial: 6.22, 95% CI 4.16-9.29, p<0.0001), independent of mean SBP, but dependent on precision of measurement (top-decile HR over ten visits: 12.08, 7.40-19.72, p<0.0001). Maximum SBP reached was also a strong predictor of stroke (HR for top-decile over seven visits: 15.01, 6.56-34.38, p<0.0001, after adjustment for mean SBP). In ASCOT-BPLA, residual visit-to-visit variability in SBP on treatment was also a strong predictor of stroke and coronary events (eg, top-decile HR for stroke: 3.25, 2.32-4.54, p<0.0001), independent of mean SBP in clinic or on ABPM. Variability on ABPM was a weaker predictor, but all measures of variability were most predictive in younger patients and at lower (
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| 120. |
- Sacco, R. L., et al.
(författare)
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Aspirin and extended-release dipyridamole versus clopidogrel for recurrent stroke
- 2008
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Ingår i: New England Journal of Medicine. - Boston : Massachusetts medical society. - 1533-4406 .- 0028-4793. ; 359:12, s. 1238-51
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Recurrent stroke is a frequent, disabling event after ischemic stroke. This study compared the efficacy and safety of two antiplatelet regimens--aspirin plus extended-release dipyridamole (ASA-ERDP) versus clopidogrel. METHODS: In this double-blind, 2-by-2 factorial trial, we randomly assigned patients to receive 25 mg of aspirin plus 200 mg of extended-release dipyridamole twice daily or to receive 75 mg of clopidogrel daily. The primary outcome was first recurrence of stroke. The secondary outcome was a composite of stroke, myocardial infarction, or death from vascular causes. Sequential statistical testing of noninferiority (margin of 1.075), followed by superiority testing, was planned. RESULTS: A total of 20,332 patients were followed for a mean of 2.5 years. Recurrent stroke occurred in 916 patients (9.0%) receiving ASA-ERDP and in 898 patients (8.8%) receiving clopidogrel (hazard ratio, 1.01; 95% confidence interval [CI], 0.92 to 1.11). The secondary outcome occurred in 1333 patients (13.1%) in each group (hazard ratio for ASA-ERDP, 0.99; 95% CI, 0.92 to 1.07). There were more major hemorrhagic events among ASA-ERDP recipients (419 [4.1%]) than among clopidogrel recipients (365 [3.6%]) (hazard ratio, 1.15; 95% CI, 1.00 to 1.32), including intracranial hemorrhage (hazard ratio, 1.42; 95% CI, 1.11 to 1.83). The net risk of recurrent stroke or major hemorrhagic event was similar in the two groups (1194 ASA-ERDP recipients [11.7%], vs. 1156 clopidogrel recipients [11.4%]; hazard ratio, 1.03; 95% CI, 0.95 to 1.11). CONCLUSIONS: The trial did not meet the predefined criteria for noninferiority but showed similar rates of recurrent stroke with ASA-ERDP and with clopidogrel. There is no evidence that either of the two treatments was superior to the other in the prevention of recurrent stroke. (ClinicalTrials.gov number, NCT00153062.)
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