Dihydropyridine calcium channel blockers for antihypertensive treatment in older patients – evidence from the systolic hypertension in, Europe trial

Objective, The Syst-Eur study investigated whether active antihypertensive treatment could reduce cardiovascular complications in elderly patients with isolated systolic hypertension.Design.Randomised,place~ontrolled,doubl~blind outcome trial.Setting. Hypertension clinics or general practitioners' surgeries in 198 centres in 23 Western and Eastern European countries.Subjects. Patients aged ~ 60 years with sitting systolic blood pressure (BP) 160 - 219 mmHg and sitting diastolic BP < 95 mmHg during run-in phase.Methods and Results. Four thousand, six hundred and ninety-five patients were randomly assigned to active treatment (N = 2 398), Le. nitrendipine, with the possible addition of enalapril and hydrochlorothiazide, or to matching placebos (N = 2 297). In the intention-to-treat analysis, the between-group difference in blood pressure (BP) amounted to 10.1 /4.5 mmHg (P < 0.(01). Active treatment reduced the incidence of fatal and non-fatal stroke (primary endpoint) by 42% (P = 0.(03). On active treatment all cardiac endpoints decreased by 26% (P =0.03) and all cardiovascular endpoints by 31% (P < O.OOl). Cardiovascular mortality was slightly lower on active treatment (-27%, P = 0.07), but all-cause mortality was not influenced (-14%, P = 0.22). For total (P = 0.009) and cardiovascular mortality (P = 0.09), the benefit of antihypertensive treatment weakened with advancing age, and for total mortality it decreased with lower systolic BP at entry (P =0.05). The benefits of active treatment were not independently related to sex or to the presence of cardiovascular complications at entry. The antihypertensive regimen was more effective in patients with diabetes than in those without diabetes at entry. Further analyses also suggested benefit in patients who were taking nitrendipine as the sole therapy. The per-protocol analysis largely confirmed the intention-to-treat results. Active treatment reduced all strokes by 44% (P = 0.004), all cardiac endpoints by 26% (P = 0.05) and all cardiovascular endpoints by 32% (P < 0.(01). Total mortality was reduced by 26% (P = 0.05), but a similar reduction in cardiovascular mortality did not reach statistical significance in this analysis. Compared with placebo, active treatment also reduced the incidence of dementia by 50%.Conclusion. Stepwise antihypertensive drug treatment, starting with the dihydropiridine calcium-channel blocker nitrendipine, improves prognosis in elderly patients with isolated systolic hypertension

Dihydropyridine calciumchannel blockers for antihypertensive treatment in older patients evidence from the systolic hypertension in Europe trial

No Abstract

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

Response to HYVET ambulatory blood pressure substudy

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How well can blood pressure be controlled? Progress report on the Systolic Hypertension in Europe Follow-Up Study (Syst-Eur 2)

BACKGROUND: The randomised, double-blind, placebo-controlled Systolic Hypertension in Europe trial (Syst-Eur 1) proved that blood pressure (BP) lowering therapy starting with nitrendipine reduces the risk of cardiovascular complications in elderly patients with isolated systolic hypertension. In an attempt to confirm the safety of long-term antihypertensive therapy based on a dihydropyridine, the Syst-Eur patients remained in open follow-up after the end of Syst-Eur 1. This paper presents the second progress report of this follow-up study (Syst-Eur 2). It describes BP control and adherence to study medications. METHODS: After the end of Syst-Eur 1 all patients, treated either actively or with placebo, were invited either to continue or to start antihypertensive treatment with the same drugs as previously used in the active treatment arm. In order to reach the target BP (sitting SBP <150 mmHg), the first line agent, nitrendipine, could be associated with enalapril and/or hydrochlorothiazide. RESULTS: Of the 3787 eligible patients, 3516 (93%) entered Syst-Eur 2. At the last available visit, 72% of the patients were taking nitrendipine. SBP/DBP at entry in Syst-Eur 2 averaged 160/83 mmHg in the former placebo group and 151/80 mmHg in the former active-treatment group. At the last follow-up visit SBP/DBP in the patients previously randomised to placebo or active treatment had decreased by 16/5 mmHg and 7/5 mmHg, respectively. The target BP was reached by 74% of the patients. CONCLUSION: Substantial reductions in systolic BP may be achieved in older patients with isolated systolic hypertension with a treatment strategy starting with the dihydropyridine calcium-channel blocker, nitrendipine, with the possible addition of enalapril and/or hydrochlorothiazide

Prevalence of left ventricular diastolic dysfunction in a general population

BACKGROUND: Because the process of myocardial remodelling starts before the onset of symptoms, recent heart failure (HF) guidelines place special emphasis on the detection of subclinical left ventricular (LV) systolic and diastolic dysfunction and the timely identification of risk factors for HF. Our goal was to describe the prevalence and determinants (risk factors) of LV diastolic dysfunction in a general population and to compare the amino terminal probrain natriuretic peptide level across groups with and without diastolic dysfunction. METHODS AND RESULTS: In a randomly recruited population sample (n=539; 50.5% women; mean age, 52.5 years), we measured early and late diastolic peak velocities of mitral inflow (E and A), pulmonary vein flow by pulsed-wave Doppler, and the mitral annular velocities (Ea and Aa) at 4 sites by tissue Doppler imaging. A healthy subsample of 239 subjects (mean age, 43.7 years) provided age-specific cutoff limits for normal E/A and E/Ea ratios and the differences in duration between the mitral A and the reverse pulmonary vein flows during atrial systole (DeltaAd-ARd). The number of subjects in diastolic dysfunction groups 1 (impaired relaxation), 2 (elevated LV end-diastolic filling pressure), and 3 (elevated E/Ea and abnormally low E/A) were 53 (9.8%), 76 (14.1%), and 18 (3.4%), respectively. We used Delta(Ad<ARd+10) to confirm possible elevation of LV filling pressures in group 2. Compared with subjects with normal diastolic function (n=392, 72.7%), group 1 (209 versus 251 pmol/L; P=0.015) and group 2 (209 versus 275 pmol/L; P=0.0003) but not group 3 (209 versus 224 pmol/L; P=0.65) had a significantly higher adjusted NT-probrain natriuretic peptide. Higher age, body mass index, heart rate, systolic blood pressure, serum insulin, and creatinine were significantly associated with a higher risk of LV diastolic dysfunction. CONCLUSIONS: The overall prevalence of LV diastolic dysfunction in a random sample of a general population, as estimated from echocardiographic measurements, was as high as 27.3%

Isometric handgrip as an adjunct for blood pressure control: a primer for clinicians

Considered a global health crisis by the World Health Organization, hypertension (HTN) is the leading risk factor for death and disability. The majority of treated patients do not attain evidence-based clinical targets, which increases the risk of potentially fatal complications. HTN is the most common chronic condition seen in primary care; thus, implementing therapies that lower and maintain BP to within-target ranges is of tremendous public health importance. Isometric handgrip (IHG) training is a simple intervention endorsed by the American Heart Association as a potential adjuvant BP-lowering treatment. With larger reductions noted in HTN patients, IHG training may be especially beneficial for those who (a) have difficulties continuing or increasing drug-based treatment; (b) are unable to attain BP control despite optimal treatment; (c) have pre-HTN or low-risk stage I mild HTN; and (d) wish to avoid medications or have less pill burden. IHG training is not routinely prescribed in clinical practice. To shift this paradigm, we focus on (1) the challenges of current HTN management strategies; (2) the effect of IHG training; (3) IHG prescription; (4) characterizing the population for whom it works best; (5) clinical relevance; and (6) important next steps to foster broader implementation by clinical practitioners