Left ventricular hypertrophy and incident cognitive decline in older adults with hypertension.

The association between raised blood pressure and increased risk of subsequent cognitive decline is well known. Left ventricular hypertrophy (LVH), as a marker of hypertensive target organ damage, may help identify those at risk of cognitive decline. We assessed whether LVH was associated with subsequent cognitive decline or dementia in hypertensive participants aged ≥80 years in the randomized, placebo-controlled Hypertension in the Very Elderly Trial. LVH was assessed using 12-lead electrocardiography (ECG) based on the Cornell Product (CP-LVH), Sokolow-Lyon (SL-LVH), and Cornell Voltage (CV-LVH) criteria. The Mini-Mental State Examination (MMSE) was used to assess cognitive function at baseline and annually. A fall in MMSE to <24 or an annual fall of >3 points were defined as cognitive decline and triggered dementia screening (Diagnostic Statistical Manual IV). Death was defined as a competing event. Fine-Gray regression models were used to examine the relationship between baseline LVH and cognitive outcomes. There were 2645 in the analytical sample, including 201 (7.6%) with CP-LVH, 225 (8.5%) SL-LVH and 251 (9.5%) CV-LVH. CP-LVH was associated with increased risk of cognitive decline, subdistribution hazard ratio (sHR)1.3 (95% confidence interval (CI) 1.01-1.67) in multivariate analyses. SL-LVH and CV-LVH were not associated with cognitive decline (sHR1.06 (95% CI 0.82-1.37) and sHR1.13 (95% CI 0.89-1.43), respectively). LVH was not associated with dementia. LVH may be related to subsequent cognitive decline, but evidence was inconsistent depending on ECG criterion and there were no associations with incident dementia. Additional work is needed to understand the relationships between blood pressure, LVH assessment and cognition.

Blood pressure lowering and prevention of dementia: an individual patient data meta-analysis.

AIMS: Observational studies indicate U-shaped associations of blood pressure (BP) and incident dementia in older age, but randomized controlled trials of BP-lowering treatment show mixed results on this outcome in hypertensive patients. A pooled individual participant data analysis of five seminal randomized double-blind placebo-controlled trials was undertaken to better define the effects of BP-lowering treatment for the prevention of dementia. METHODS AND RESULTS: Multilevel logistic regression was used to evaluate the treatment effect on incident dementia. Effect modification was assessed for key population characteristics including age, baseline systolic BP, sex, and presence of prior stroke. Mediation analysis was used to quantify the contribution of trial medication and changes in systolic and diastolic BP on risk of dementia. The total sample included 28 008 individuals recruited from 20 countries. After a median follow-up of 4.3 years, there were 861 cases of incident dementia. Multilevel logistic regression reported an adjusted odds ratio 0.87 (95% confidence interval: 0.75, 0.99) in favour of antihypertensive treatment reducing risk of incident dementia with a mean BP lowering of 10/4 mmHg. Further multinomial regression taking account of death as a competing risk found similar results. There was no effect modification by age or sex. Mediation analysis confirmed the greater fall in BP in the actively treated group was associated with a greater reduction in dementia risk. CONCLUSION: The first single-stage individual patient data meta-analysis from randomized double-blind placebo-controlled clinical trials provides evidence to support benefits of antihypertensive treatment in late-mid and later life to lower the risk of dementia. Questions remain as to the potential for additional BP lowering in those with already well-controlled hypertension and of antihypertensive treatment commenced earlier in the life-course to reduce the long-term risk of dementia. CLASSIFICATION OF EVIDENCE: Class I evidence in favour of antihypertensive treatment reducing risk of incident dementia compared with placebo.

Atrial fibrillation and the risk of cardiovascular disease and mortality in the Hypertension in the Very Elderly Trial.

OBJECTIVE: To assess the prognostic value of electrocardiographic atrial fibrillation in older hypertensive people in the randomized, placebo-controlled Hypertension in the Very Elderly Trial. METHODS: Hypertension in the Very Elderly Trial randomized 3845 hypertensive people aged 80 years and over, 3273 with electrographic data on the presence or absence of atrial fibrillation at baseline and without established cardiovascular disease. Multivariate Cox proportional hazard models were used to estimate hazard ratios with 95% confidence intervals (CIs) for all-cause mortality, incident fatal and nonfatal major cardiovascular events, all-stroke and all-heart failure. The mean follow-up time was 2.1 years. RESULTS: Baseline prevalence of atrial fibrillation was 5.8%. Compared with people without atrial fibrillation at baseline, after adjustments the presence of atrial fibrillation was associated with increased risk of mortality (hazard ratio = 2.49, 95% CI = 1.80-3.44, P < 0.001), of nonfatal and fatal cardiovascular events (hazard ratio = 2.47, 95% CI = 1.71-3.55, P < 0.001), all-stroke (hazard ratio = 2.47, 95% CI = 1.34-4.56, P = 0.004) and all-heart failure (hazard ratio 2.33, 95% CI = 1.10-4.93, P = 0.027). CONCLUSION: Atrial fibrillation is an important risk factor to consider when assessing older hypertensive adults as it is associated with increased risk of mortality, nonfatal and fatal cardiovascular events, stroke and heart failure.

Orthostatic hypotension and symptomatic subclinical orthostatic hypotension increase risk of cognitive impairment: an integrated evidence review and analysis of a large older adult hypertensive cohort.

Aims: Systematically reviewing the literature found orthostatic hypotension (OH) to be associated with an increased risk of incident dementia but limited data were available in those at highest risk, the hypertensive oldest-old. Our aim was to analyse the relationship between OH and incident cognitive decline or dementia in this group and to synthesize the evidence base overall. Method and results: Participants aged ≥80 years, with hypertension, were from the Hypertension in the Very Elderly Trial (HYVET) cohort. Orthostatic hypotension was defined as a fall of ≥15 mmHg in systolic and or ≥7 mmHg in diastolic pressure after 2 min standing from a sitting position. Subclinical orthostatic hypotension with symptoms (SOH) was defined as a fall

Antihypertensive treatment decreases arterial stiffness at night but not during the day. Results from the Hypertension in the Very Elderly Trial.

The main Hypertension in the Very Elderly Trial (HYVET) demonstrated a very marked reduction in cardiovascular events by treating hypertensive participants 80 years or older with a low dose, sustained release prescription of indapamide (indapamide SR, 1.5 mg) to which was added a low dose of an angiotensin converting enzyme inhibitor in two-thirds of cases (perindopril 2-4 mg). This report from the ambulatory blood pressure sub-study investigates whether changes in arterial stiffness and ambulatory blood pressure (BP) could both explain the benefits observed in the main trial. A total of 139 participants were randomized to placebo [67] and to active treatment [72] and had both day and night observations of BP and arterial stiffness as determined from the Q wave Korotkoff diastolic (QKD) interval. The QKD interval was 5.6 ms longer (p = 0.017) in the actively treated group at night than in the placebo group. This was not true for the more numerous daytime readings so that 24-h results were similar in the two groups. The QKD interval remained longer at night in the actively treated group even when adjusted for systolic pressure, heart rate and height. The reduced arterial stiffness at night may partly explain the marked benefits observed in the main trial.

Left ventricular hypertrophy is a predictor of cardiovascular events in elderly hypertensive patients: Hypertension in the Very Elderly Trial.

OBJECTIVE: We assessed the prognostic value of ECG left ventricular hypertrophy (LVH) using Sokolow-Lyon (SL-LVH), Cornell voltage (CV-LVH) or Cornell product (CP-LVH) criteria in 3043 hypertensive people aged 80 years and over enrolled in the Hypertension in the Very Elderly Trial. METHODS: Multivariate Cox proportional hazard models were used to estimate hazard ratios with 95% confidence intervals (CIs) for all-cause mortality, cardiovascular diseases, stroke and heart failure in participants with and without LVH at baseline. The mean follow-up was 2.1 years. RESULTS: LVH identified by CV-LVH or CP-LVH criteria was associated with a 1.6-1.9-fold risk of cardiovascular disease and stroke. The presence of CP-LVH was associated with an increased risk of heart failure (hazard ratio 2.38, 95% CI 1.16-4.86). In sex-specific analyses, CV-LVH (hazard ratio 1.94, 95% CI 1.06-3.55) and CP-LVH (hazard ratio 2.36, 95% CI 1.25-4.45) were associated with an increased risk of stroke in women and of heart failure in men, CV-LVH (hazard ratio 6.47, 95% CI 1.41-29.79) and CP-LVH (10.63, 95% CI 3.58-31.57), respectively. There was no significant increase in the risk of any outcomes associated with Sokolow-Lyon-LVH. LVH identified by these three methods was not a significant predictor of all-cause mortality. CONCLUSION: Use of Cornell voltage and Cornell product criteria for LVH predicted the risk of cardiovascular disease and stroke. Only Cornell product was associated with an increased risk of heart failure. This was particularly the case in men. The identification of ECG LVH proved to be important in very elderly hypertensive people.

No evidence that frailty modifies the positive impact of antihypertensive treatment in very elderly people: an investigation of the impact of frailty upon treatment effect in the HYpertension in the Very Elderly Trial (HYVET) study, a double-blind, placebo-controlled study of antihypertensives in people with hypertension aged 80 and over.

BACKGROUND: Treatment for hypertension with antihypertensive medication has been shown to reduce stroke, cardiovascular events, and mortality in older adults, but there is concern that such treatment may not be appropriate in frailer older adults. To investigate whether there is an interaction between effect of treatment for hypertension and frailty in older adults, we calculated the frailty index (FI) for all available participants from the HYpertension in the Very Elderly Trial (HYVET) study, a double-blind, placebo-controlled study of antihypertensives in people with hypertension aged 80 and over, and obtained frailty adjusted estimates of the effect of treatment with antihypertensive medication on risk of stroke, cardiovascular events, and mortality. METHODS: Participants in HYVET were randomised 1:1 to active treatment with indapamide sustained release 1.5 mg ± perindopril 2 to 4 mg or to matching placebo. Data relating to blood pressure, comorbidities, cognitive function, depression, and quality of life were collected at entry into the study and at subsequent follow-up visits. The FI was calculated at entry, based on 60 potential deficits. The distribution of FI was similar to that seen in population studies of adults aged 80 years and above (median FI, 0.17; IQR, 0.11-0.24). Cox regression was used to assess the impact of FI at entry to the study on subsequent risk of stroke, total mortality, and cardiovascular events. Models were stratified by region of recruitment and adjusted for sex and age at entry. Extending these models to include a term for a possible interaction between treatment for hypertension and FI provided a formula for the treatment effect as a function of FI. For all three models, the point estimates of the hazard ratios for the treatment effect decreased as FI increased, although to varying degrees and with varying certainty. RESULTS: We found no evidence of an interaction between effect of treatment for hypertension and frailty as measured by the FI. Both the frailer and the fitter older adults with hypertension appeared to gain from treatment. CONCLUSIONS: Further work to examine whether antihypertensive treatment modifies frailty as measured by the FI should be explored. TRIAL REGISTRATION: ClinicalTrials.gov NCT00122811 (July 2005).

The clock drawing test, mortality, incident cardiovascular events and dementia.

OBJECTIVE: The purpose of this study is to examine the association of the clock drawing test (CDT) with incident dementia, cardiovascular events and mortality in very elderly hypertensive patients. METHOD: All participants were hypertensive and aged 80 years and over. The CDT was administered at baseline and annually thereafter. Data on incident cardiovascular, fatal events and dementia were collected over follow-up. RESULTS: There were 3845 participants recruited and followed up for a mean of 2.1 years. Of these, 2701 completed a CDT with 2259 available at baseline. Of this group, 6.6% had a cardiovascular event, 6.1% died, and 10% were diagnosed with dementia. There was no relationship between baseline CDT score and subsequent cardiovascular events or mortality. For incident dementia, the hazard ratio was 0.88 (95% confidence intervals 0.83-0.94) suggesting that better performance on the baseline CDT was associated with a lower risk of dementia. CONCLUSION: These results provide tentative support for the CDT alongside other cognitive screening tools in a hypertensive elderly population.

Subgroup and per-protocol analyses from the Hypertension in the Very Elderly Trial.

BACKGROUND: The results of the Hypertension in the Very Elderly Trial showed positive benefits from blood pressure-lowering treatment in those aged 80 and over. METHOD: An analysis by the pre-specified subgroups [age, sex, history of cardiovascular disease (CVD) and initial SBP] was performed. The Hypertension in the Very Elderly Trial was a randomized, double-blind, placebo-controlled trial of 3845 participants aged 80 and over with SBPs of 160-199 mmHg and diastolic pressures below 110 mmHg recruited from Europe, China, Australasia and Tunisia. Active treatment was indapamide sustained-release 1.5 mg with the addition of perindopril 2-4 mg as required to reach a target blood pressure of less than 150/80 mmHg. RESULTS: For total mortality, benefits were consistent: men [hazard ratio 0.82, 95% confidence interval (CI) 0.62-1.11], women (hazard ratio 0.77, 95% CI 0.66-0.99), those aged 80-84.9 (hazard ratio 0.76, 95% CI 0.60-0.96), those aged 85 and over (hazard ratio 0.87, 95% CI 0.64-1.20), those with a history of CVD (hazard ratio 0.76, 95% CI 0.48-1.20) and those without (hazard ratio 0.81, 95% CI 0.65-0.99), and similarly across a range of baseline SBPs. The point estimates for cardiovascular mortality, strokes, heart failure and cardiovascular events were all in favour of benefit. In the per-protocol analysis, strokes were reduced by 34% (P = 0.026), total mortality by 28% (P = 0.001), cardiovascular event by 37% (P < 0.001) and heart failure by 72% (P < 0.001). CONCLUSION: In hypertensive patients aged 80 or more, treatment based on indapamide (sustained-release) 1.5 mg showed consistent benefits across pre-specified subgroups including those without established CVD (the majority), supporting the need for treatment even at this advanced age. There were too few aged 90 or over to determine benefit from treatment at extreme age.

Treating hypertension in the very elderly-benefits, risks, and future directions, a focus on the hypertension in the very elderly trial.

Although the number of individuals reaching 80 who are considered to be healthy is increasing, the very elderly are likely to have long-term conditions, to report symptoms and/or be taking at least one regular medication. The impact of antihypertensive treatment has to be taken into account in this context. The treatment regimen in Hypertension in the Very Elderly Trial with a goal blood pressure of <150/80 mmHg has been shown to provide benefits in terms of a reduction in risk of total mortality, stroke, and cardiovascular events with potential benefits and no evidence of increased risk for fracture, dementia, depression, and quality-of-life outcomes. Questions remain as to the level of benefit that would be accrued in the frailer elderly and those at extreme age, for example, over 90.

Increased pulse pressure linked to dementia: further results from the Hypertension in the Very Elderly Trial - HYVET.

OBJECTIVES: High blood pressure (BP) has been associated with increased risk of dementia. Concerns have been raised about lowering BP too far in the very elderly and thereby increasing risk. There is some evidence to suggest a potential 'J'-shaped relationship between DBP and risk of cognitive impairment. This was investigated using data from the HYpertension in the Very Elderly Trial (HYVET). METHODS: HYVET was a double-blind, placebo-controlled trial of antihypertensives in patients aged at least 80 years with an untreated SBP of 160-199 mmHg. Active medication was indapamide sustained release 1.5 mg+/- perindopril 2-4 mg to reach goal pressure of less than 150/80 mmHg. Incident dementia was a secondary endpoint and was not significantly different between the two treatment groups. The relationship between pressure and incident dementia was assessed using Cox proportional hazards regression with BP entered as either a discrete (quartile analysis) or continuous predictor variable. Achieved BP was calculated as the mean of all pressures from the 9 month visit onwards. RESULTS: During a mean follow-up of 2.2 years 263 incident cases of dementia were diagnosed. After adjustment for various covariates, baseline DBP was inversely related to incident dementia (P=0.0064). Achieved DBP did not predict later dementia in the placebo group (P=0.43), but showed a U-shaped relationship in the active treatment group (P=0.0195). The relationship between incident dementia and DBP did however not differ significantly between the placebo and active treatment groups (P=0.38). SBP was not associated with incident dementia, at baseline (P=0.62) or during follow-up (placebo group P=0.13, active group P=0.36). Wider achieved pulse pressure (PP) was associated with increased risk of dementia in both treatment groups (placebo P=0.032, active P=0.0046). The same tendency was observed for baseline PP (P=0.095). CONCLUSION: Wider PP may possibly indicate an increased risk for dementia. Active treatment may act to change the shape of the relationship between DBP and dementia. Future studies need to focus on exploring the ideal goal pressure for this age group.

Prevalence and covariates of electrocardiographic left ventricular hypertrophy in the Hypertension in the Very Elderly Trial.

OBJECTIVE: To estimate the prevalence and covariates of electrocardiographic left ventricular hypertrophy (LVH) in the Hypertension in the Very Elderly Trial. METHODS: A total of 2993 hypertensive people aged at least 80 years with technically codable ECGs without pacing, bundle branch block, or ECG myocardial infarction were studied. LVH was assessed using Sokolow-Lyon (SL-LVH), Cornell voltage (CV-LVH), and Cornell product criterion (CP-LVH). RESULTS: The prevalence of LVH varied from 2.4 to 17.5% depending on sex, race, and ECG criterion. The highest prevalence of SL-LVH (12.0%) was in Chinese men and in white women for both CV-LVH (17.5%) and CP-LVH (12.9%). Increasing SBP was an independent covariate of the presence of LVH in Chinese women independently of the criterion used (ß = 0.052-0.069, P < 0.001), of SL-LVH in Chinese men (ß = 0.047 P = 0.006). In white women, CP-LVH was associated with increasing age (ß = 0.055, P = 0.027) and SBP (ß = 0.023, P = 0.040). Increasing BMI was associated inversely with SL-LVH; the association in white men only was not significant. In white men, a history of diabetes was directly and history of antihypertensive drug treatment inversely related to CV-LVH and CP-LVH. SL-ECG was associated inversely to serum uric acid concentration in Chinese women and to serum hemoglobin concentration in Chinese men. CONCLUSION: Prevalence and covariates of electrocardiographic LVH varied by sex, race, and ECG criterion. CP-LVH may prove to be the most useful measure of LVH in this study owing to its close relationship to SBP, at least in women, and independence from BMI.

Kidney function in the very elderly with hypertension: data from the hypertension in the very elderly (HYVET) trial.

BACKGROUND: numerous reports have linked impaired kidney function to a higher risk of cardiovascular events and mortality. There are relatively few data relating to kidney function in the very elderly. METHODS: the Hypertension in the Very Elderly Trial (HYVET) was a randomised placebo-controlled trial of indapamide slow release 1.5mg ± perindopril 2-4 mg in those aged ≥80 years with sitting systolic blood pressures of ≥160 mmHg and diastolic pressures of <110 mmHg. Kidney function was a secondary outcome. RESULTS: HYVET recruited 3,845 participants. The mean baseline estimated glomerular filtration rate (eGFR) was 61.7 ml/min/1.73 m(2). When categories of the eGFR were examined, there was a possible U-shaped relationship between eGFR, total mortality, cardiovascular mortality and events. The nadir of the U was the eGFR category ≥60 and <75 ml/min/1.73 m(2). Using this as a comparator, the U shape was clearest for cardiovascular mortality with the eGFR <45 ml/min/1.73 m(2) and ≥75 ml/min/1.73 m(2) showing hazard ratios of 1.88 (95% CI: 1.2-2.96) and 1.36 (0.94-1.98) by comparison. Proteinuria at baseline was also associated with an increased risk of later heart failure events and mortality. CONCLUSIONS: although these results should be interpreted with caution, it may be that in very elderly individuals with hypertension both low and high eGFR indicate increased risk.

Does white coat hypertension require treatment over age 80?: Results of the hypertension in the very elderly trial ambulatory blood pressure side project.

White coat hypertension is considered to be a benign condition that does not require antihypertensive treatment. Ambulatory blood pressure (ABP) was measured in 284 participants in the Hypertension in the Very Elderly Trial (HYVET), a double-blind randomized trial of indapamide sustained release 1.5 mg±perindopril 2 to 4 mg versus matching placebo in hypertensive subjects (systolic blood pressure 160-199 mm Hg) aged >80 years. ABP recordings (Diasys Integra II) were obtained in 112 participants at baseline and 186 after an average follow-up of 13 months. At baseline, clinic blood pressure (CBP) exceeded the morning ABP by 32/10 mm Hg. Fifty percent of participants fulfilled the established criteria for white coat hypertension. The highest ABP readings were in the morning (average 140/80 mm Hg), the average night-time pressure was low at 124/72 mm Hg, and the average 24-hour blood pressure was 133/77 mm Hg. During follow-up, the systolic/diastolic blood pressure placebo-active differences averaged 6/5 mm Hg for morning ABP, 8/5 mm Hg for 24-hour ABP, and 13/5 mm Hg for CBP. The lowering of blood pressure over 24 hours supports the reduction in blood pressure with indapamide sustained release±perindopril as the explanation for the reduction in total mortality and cardiovascular events observed in the main HYVET study. Because we estimate that 50% had white coat hypertension in the main study, this condition may benefit from treatment in the very elderly.

Impact of transiently elevated diastolic pressure on cause of death: 29-year follow-up from the General Practice Hypertension Study Group.

OBJECTIVES: High blood pressure is known to be associated with higher cardiovascular risk. The emphasis has shifted over time from diastolic pressure to systolic pressure and variability in blood pressure. This study examined the impact of transient and sustained diastolic hypertension on later mortality. METHODS: In the early 1970s, the General Practice Hypertension Study Group screened more than 20,000 patients and selected those with diastolic hypertension, with a transiently elevated diastolic pressure and age-matched and sex-matched normotensive controls to be flagged for long-term death certificate follow-up. After a mean follow-up of 29 years, Cox proportional hazard regression was used to examine the relationship between diastolic hypertension and cause of death. RESULTS: Overall those with diastolic hypertension and transient diastolic hypertension were at increased risk of total and cardiovascular mortality. When men and women were examined separately, however, the relationships remained significant in women only, with transient diastolic hypertension showing the strongest association with cardiovascular and total mortality: hazard ratio 1.57 [95% confidence interval (CI) 1.11-2.23] and hazard ratio 1.39 (95% CI 1.10-1.76), respectively. CONCLUSION: Transient diastolic hypertension does not seem to be benign, particularly in women and may point to those at higher cardiovascular risk when seen in a general practice population.

Impairment of kidney function and reduced quality-of-life in older people: a cross-sectional study.

OBJECTIVE: to assess the association of kidney function with quality-of-life in community-dwelling older adults aged 75 years or more in the UK. DESIGN: cross-sectional study. SETTING: primary care; 12 UK general practices participating in a cluster trial of health screening. SUBJECTS: estimated glomerular filtration rate (eGFR, ml/min/1.73 m(2)) using the four-variable modified diet in renal disease equation was derived in 1,195 men and 1,772 women with available bloods, these were 92% of 3,211 study participants who consented to interviews and 73% of those invited into the original cluster trial of health screening. MAIN OUTCOME MEASURES: interviews by trained fieldworker using the Sickness Impact Profile (home management, mobility, self-care, social interaction), and the Philadelphia Geriatric Morale Scale. Higher scores imply worse quality-of-life in a given domain. RESULTS: in age- and co-morbidity-adjusted analyses there was an association of eGFR <45 and the highest scores (defined as ≥median) of mobility (men: odds ratio (OR) 2.91, 95% confidence interval (CI) 1.56-5.41; women: OR 1.73, 95% CI 1.02-2.94), home management (men: OR 1.49, 95% CI 1.09-2.04; women: OR 3.50, 95% CI 1.18-10.35), social interaction (men: OR 3.34, 95% CI 1.73-6.45; women: 2.64, 95% CI 1.61-4.33) when compared with those with eGFR ≥60 and who reported no problems. Men with eGFR <45 had low morale (OR 2.45, 95% CI 1.02-5.87) but this was not found for women (OR 1.40, 95% CI 0.65-3.04), whereas women (but not men) with eGFR <45 reported problems with body care (women: OR 1.68; 95% CI 1.25-2.27: men: OR 0.89, 95% CI 0.55-1.46). CONCLUSIONS: an eGFR <45 is associated with poorer quality-of-life at older age. More research is needed to identify modifiable causes to improve quality-of-life in older people with such a degree of kidney function impairment.

CKD and hospitalization in the elderly: a community-based cohort study in the United Kingdom.

BACKGROUND: We previously have shown that chronic kidney disease (CKD) is associated with cardiovascular and all-cause mortality in community-dwelling people 75 years and older. The present study addresses the hypothesis that CKD is associated with a higher rate of hospital admission at an older age. STUDY DESIGN: Cohort study. SETTING & PARTICIPANTS: 15,336 participants from 53 UK general practices underwent comprehensive health assessment between 1994 and 1999. PREDICTOR: Data for estimated glomerular filtration rate (eGFR, derived from creatinine levels using the CKD Epidemiology Collaboration [CKD-EPI] study equation) and dipstick proteinuria were available for 12,371 participants. OUTCOMES: Hospital admissions collected from hospital discharge letters for 2 years after assessment. MEASUREMENTS: Age, sex, cardiovascular risk factors, possible biochemical and health consequences of kidney disease (hemoglobin, phosphate, and albumin levels; physical and mental health problems). RESULTS: 2,310 (17%) participants had 1 hospital admission, and 981 (7%) had 2 or more. After adjusting for age, sex, and cardiovascular risk factors, HRs were 1.66 (95% CI, 1.21-2.27), 1.17 (95% CI, 0.95-1.43), 1.08 (95% CI, 0.90-1.30), and 1.11 (95% CI, 0.91-1.35) for eGFRs <30, 30-44, 45-59, and ≥75 mL/min/1.73 m(2), respectively, compared with eGFRs of 60-74 mL/min/1.73 m(2) for hospitalizations during <6 months of follow-up. HRs were weaker for follow-up of 6-18 months. Dipstick-positive proteinuria was associated with an increased HR throughout follow-up (HR, 1.29 [95% CI, 1.11-1.49], adjusting for cardiovascular risk factors). Dipstick-positive proteinuria and eGFR <30 mL/min/1.73 m(2) were independently associated with 2 or more hospital admissions during the 2-year follow-up. Adjustment for other health factors and laboratory measurements attenuated the effect of eGFR, but not the effect of proteinuria. LIMITATIONS: Follow-up limited to 2 years, selection bias due to nonparticipation in study, missing data for potential covariates, and single noncalibrated measurements from multiple laboratories. CONCLUSIONS: The study indicates that community-dwelling older people who have dipstick-positive proteinuria and/or eGFR <30 mL/min/1.73 m(2) are at increased risk of hospitalization.

Effects of antihypertensive treatment after acute stroke in the Continue or Stop Post-Stroke Antihypertensives Collaborative Study (COSSACS): a prospective, randomised, open, blinded-endpoint trial.

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.