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

Left Ventricular Hypertrophy is a predictor of cardiovascular events in elderly hypertensives: hypertension in the the very elderly trial (HYVET)

Objective: We assessed the prognostic value of electrocardiographic 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 (HR) with 95% confidence intervals (CI) 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- or CP-LVH Criteria was associated with a 1.6 to 1.9-fold risk of cardiovascular disease and stroke. The presence of CP-LVH was associated with an increased risk of heart failure (HR 2.38, 95% CL 1.16-4.86). In gender specific analyses, CV-LVH (HR 1.94, 95%Cl 1.06-3.55) and CP-LVH (HR 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 (HR 6.47, 95 % Cl 1.41-29.79) and CP-LVH (10.63, 95Cl % 3.58-31.57), respectively. There was no significant increase in the risk of any outcomes associated with SL LVH. LVH identified by these three methods was not a significant predictor of all-cause mortality. Conclusions: 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 the risk of heart failure. This was particularly the case in men. The identification of electrocardiographic LVH proved to be important in very elderly hypertensive people

Fracture risk and the use of a diuretic (indapamide sr) ± perindopril: a substudy of the Hypertension in the Very Elderly Trial (HYVET)

BACKGROUND: The Hypertension in the Very Elderly Trial (HYVET) is a placebo controlled double blind trial of treating hypertension with indapamide Slow Release (SR) ± perindopril in subjects over the age of 80 years. The primary endpoints are stroke (fatal and non fatal). In view of the fact that thiazide diuretics and indapamide reduce urinary calcium and may increase bone mineral density, a fracture sub study was designed to investigate whether or not the trial anti-hypertensive treatment will reduce the fracture rate in very elderly hypertensive subjects. METHODS: In the trial considerable care is taken to ascertain any fractures and to identify risk factors for fracture, such as falls, co-morbidity, drug treatment, smoking and drinking habits, levels of activity, biochemical abnormalities, cardiac irregularities, impaired cognitive function and symptoms of orthostatic hypotension. POTENTIAL RESULTS: The trial is expected to provide 10,500 patient years of follow-up. Given a fracture rate of 40/1000 patient years and a 20% difference in fracture rate, the power of the sub study is 58% to detect this difference at the 5% level of significance. The corresponding power for a reduction of 25% is 78%. CONCLUSION: The trial is well under way, expected to complete in 2009, and on target to detect, if present, the above differences in fracture rate

Treatment of white coat HYpertension in the Very Elderly Trial (HYVET 2) - feasibility of a randomized controlled trial (study protocol)

The results of HYpertension in the Very Elderly Trial (HYVET) were crucial in providing evidence of benefit of the treatment of hypertension in those 80 years or older. Following a subsequent sub study analysis of the HYVET data there is a suggestion that 50% of patients in the main study had White Coat Hypertension (WCH), defined as clinic BP readings >140/90 mmHg and ambulatory BP readings <135/85 mmHg. Currently, definitive evidence in support of treatment for such individuals is not available. HYVET 2 has been designed in order to assess the feasibility of conducting a randomized controlled trial which might determine whether the treatment of WCH in the very elderly is clinically beneficial. One hundred participants aged ≥75 years diagnosed with WCH will be recruited from General Practices (GPs) in UK. Randomization will be 1:1 to a treatment arm (indapamide and perindopril) and control arm (no treatment) and follow up will be for 52 weeks. HYVET 2 will report on feasibility outcomes including participant recruitment, adherence and withdrawal rates, willingness of GPs to recruit and randomize patients and the frequency of a composite of cardiovascular events. Simple descriptive statistics will be presented

Type 2 Diabetes as a Risk Factor for Dementia in Women Compared With Men: A Pooled Analysis of 2.3 Million People Comprising More Than 100,000 Cases of Dementia

Objective: Type 2 diabetes confers a greater excess risk of cardiovascular disease in women than in men. Diabetes is also a risk factor for dementia, but whether the association is similar in women and men remains unknown. We performed a meta-analysis of unpublished data to estimate the sex-specific relationship between women and men with diabetes with incident dementia. Research design and methods: A systematic search identified studies published prior to November 2014 that had reported on the prospective association between diabetes and dementia. Study authors contributed unpublished sex-specific relative risks (RRs) and 95% CIs on the association between diabetes and all dementia and its subtypes. Sex-specific RRs and the women-to-men ratio of RRs (RRRs) were pooled using random-effects meta-analyses. Results: Study-level data from 14 studies, 2,310,330 individuals, and 102,174 dementia case patients were included. In multiple-adjusted analyses, diabetes was associated with a 60% increased risk of any dementia in both sexes (women: pooled RR 1.62 [95% CI 1.45-1.80]; men: pooled RR 1.58 [95% CI 1.38-1.81]). The diabetes-associated RRs for vascular dementia were 2.34 (95% CI 1.86-2.94) in women and 1.73 (95% CI 1.61-1.85) in men, and for nonvascular dementia, the RRs were 1.53 (95% CI 1.35-1.73) in women and 1.49 (95% CI 1.31-1.69) in men. Overall, women with diabetes had a 19% greater risk for the development of vascular dementia than men (multiple-adjusted RRR 1.19 [95% CI 1.08-1.30]; P \u3c 0.001). Conclusions: Individuals with type 2 diabetes are at ∼60% greater risk for the development of dementia compared with those without diabetes. For vascular dementia, but not for nonvascular dementia, the additional risk is greater in women

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

Response to HYVET ambulatory blood pressure substudy

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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 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. [Abstract copyright: © 2022. The Author(s).

[Abstract] P-33 treatment of white coat Hypertension in the Very Elderly Trial (HYVET 2) – A UK feasibility study for a randomised controlled trial

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