Summary Background Raised blood pressure is common after acute stroke and is associated with an adverse prognosis. We sought to assess the feasibility, safety, and effects of two regimens for ...lowering blood pressure in patients who have had a stroke. Methods Patients who had cerebral infarction or cerebral haemorrhage and were hypertensive (systolic blood pressure SBP >160 mm Hg) were randomly assigned by secure internet central randomisation to receive oral labetalol, lisinopril, or placebo if they were non-dysphagic, or intravenous labetalol, sublingual lisinopril, or placebo if they had dysphagia, within 36 h of symptom onset in this double-blind pilot trial. The doses were titrated up if target blood pressure was not reached. Analysis was by intention to treat. This trial is registered with the National Research Register, number N0484128008. Findings 179 patients (mean age 74 SD 11 years; SBP 181 SD 16 mm Hg; diastolic blood pressure DBP 95 SD 13 mm Hg; median National Institutes of Health stroke scale NIHSS score 9 IQR 5–16 points) were randomly assigned to receive labetolol (n=58), lisinopril (n=58), or placebo (n=63) between January, 2005, and December, 2007. The primary outcome—death or dependency at 2 weeks—occurred in 61% (69) of the active and 59% (35) of the placebo group (relative risk RR 1·03, 95% CI 0·80–1·33; p=0·82). There was no evidence of early neurological deterioration with active treatment (RR 1·22, 0·33–4·54; p=0·76) despite the significantly greater fall in SBP within the first 24 h in this group compared with placebo (21 17–25 mm Hg vs 11 5–17 mm Hg; p=0·004). No increase in serious adverse events was reported with active treatment (RR 0·91, 0·69–1·12; p=0·50) but 3-month mortality was halved (9·7% vs 20·3%, hazard ratio HR 0·40, 95% CI 0·2–1·0; p=0·05). Interpretation Labetalol and lisinopril are effective antihypertensive drugs in acute stroke that do not increase serious adverse events. Early lowering of blood pressure with lisinopril and labetalol after acute stroke seems to be a promising approach to reduce mortality and potential disability. However, in view of the small sample size, care must be taken when these results are interpreted and further evaluation in larger trials is needed. Funding UK National Health Service Research and Development Health Technology Assessment Programme.
Summary Background Up to 50% of patients with acute stroke are taking antihypertensive drugs on hospital admission. However, whether such treatment should be continued during the immediate ...post-stroke period is unclear. We therefore aimed to assess the efficacy and safety of continuing or stopping pre-existing antihypertensive drugs in patients who had recently had a stroke. Methods The Continue Or Stop post-Stroke Antihypertensives Collaborative Study (COSSACS) was a UK multicentre, prospective, randomised, open, blinded-endpoint trial. Patients were recruited at 49 UK National Institute for Health Research Stroke Research Network centres from January 1, 2003, to March 31, 2009. Patients aged over 18 years who were taking antihypertensive drugs were enrolled within 48 h of stroke and the last dose of antihypertensive drug. Patients were randomly assigned (1:1) by secure internet central randomisation to either continue or stop pre-existing antihypertensive drugs for 2 weeks. Patients and clinicians who randomly assigned patients were unmasked to group allocation. Clinicians who assessed 2-week outcomes and 6-month outcomes were masked to group allocation. The primary endpoint was death or dependency at 2 weeks, with dependency defined as a modified Rankin scale score greater than 3 points. Analysis was by intention to treat. This trial is registered with the International Standard Randomised Controlled Trial Register , number ISRCTN89712435. Findings 763 patients were assigned to continue (n=379) or stop (n=384) pre-existing antihypertensive drugs. 72 of 379 patients in the continue group and 82 of 384 patients in the stop group reached the primary endpoint (relative risk 0·86, 95% CI 0·65–1·14; p=0·3). The difference in systolic blood pressure at 2 weeks between the continue group and the stop group was 13 mm Hg (95% CI 10–17) and the difference in diastolic blood pressure was 8 mm Hg (6–10; difference between groups p<0·0001). No substantial differences were observed between groups in rates of serious adverse events, 6-month mortality, or major cardiovascular events. Interpretation Continuation of antihypertensive drugs did not reduce 2-week death or dependency, cardiovascular event rate, or mortality at 6 months. Lower blood pressure levels in those who continued antihypertensive treatment after acute mild stroke were not associated with an increase in adverse events. These neutral results might be because COSSACS was underpowered owing to early termination of the trial, and support the continuation of ongoing research trials. Funding The Health Foundation and The Stroke Association.
Objectives To test whether health-related quality of life (HRQL) based on societal standards differs between very low birth weight/very preterm (VLBW/VP) and full-term (FT) adolescents using self and ...parent proxy reports. Also, to examine whether self and parent reported HRQL is explained by indicators of objective functioning in childhood. Study design This prospective cohort study followed 260 VLBW/VP adolescents, 12 VLBW/VP adolescents with disability, and 282 FT adolescents. Objective functioning was assessed at 8.5 years; HRQL was assessed at 13 years with the Health Utilities Index Mark 3 (HUI3). Results Adolescents reported more functional impairment than their parents especially in the psychological aspects of health. The mean difference in HUI3 multi-attribute utility scores between FT and VLBW/VP adolescents was small (parents: 0.91 95% CI, 0.90, 0.92 vs 0.88 95% CI, 0.86, 0.90; adolescents: 0.87 95% CI, 0.85, 0.89 vs 0.84 95% CI, 0.82, 0.86), but high for VLBW/VP adolescents with disabilities (0.18, 95% CI, −0.04, 0.40). Objective function did not predict HRQL in FT adolescents but contributed to prediction of HRQL in VLBW/VP adolescents without disabilities. Different indicators of objective functioning were important for adolescent vs parent reports. More variation in HUI3 scores was explained by objective function in VLBW/VP parent reports compared with adolescent reports (25% vs 18%). Conclusions VLBW/VP adolescents reported poorer HRQL than their FT peers in early adolescence. Improvement in HRQL as VLBW/VP children grow up is, at least partly, explained by exclusion of the most disabled in self reports by VLBW/VP adolescents and the use of different reference points by adolescents compared with parents.
Leptin and Coronary Heart Disease Sattar, Naveed, FRCPath; Wannamethee, Goya, PhD; Sarwar, Nadeem, MRPharmS, MPhil ...
Journal of the American College of Cardiology,
2009, Letnik:
53, Številka:
2
Journal Article
Recenzirano
Odprti dostop
Objectives This study sought to better determine the link between leptin and coronary heart disease (CHD). Background Circulating leptin is considered a risk factor for CHD but larger studies are ...needed. Methods Leptin levels were measured in 550 men with fatal CHD or nonfatal myocardial infarction and in 1,184 controls nested within a prospective study of 5,661 British men and set in context with a meta-analysis. Results Baseline leptin correlated with body mass index (BMI), blood pressure, total cholesterol, triglyceride, and inflammatory markers; correlations persisted after BMI adjustment. The within-person consistency of leptin values over 4 years (correlation coefficient: 0.79; 95% confidence interval CI: 0.73 to 0.83) was higher than those of some established cardiovascular risk factors. In a comparison of individuals in the top third with those in the bottom third of baseline leptin, the age- and town-adjusted odds ratio for CHD was 1.25 (95% CI: 0.96 to 1.62), decreasing to 0.98 (95% CI: 0.72 to 1.34) after adjustment for BMI. A systematic review identified 7 prospective reports with heterogeneous findings (I2 = 60%, 13% to 82%). The combined adjusted risk ratio across all studies was 1.44 (95% CI: 0.95 to 2.16) in a comparison of extreme thirds of leptin levels. The inconsistency between studies was partially explained by sample size, with combined estimates from studies involving >100 CHD cases (1.28, 95% CI: 0.80 to 2.04) being somewhat weaker than those from smaller studies (1.81, 95% CI: 0.76 to 4.31). Conclusions Previous studies appear to have overestimated associations of leptin and CHD risk. Our results suggest a moderate association that is largely dependent on BMI.
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