Chronobiology international
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Randomized Controlled Trial
Cardiovascular risk of essential hypertension: influence of class, number, and treatment-time regimen of hypertension medications.
A number of observational studies have found that treated hypertensive patients, even those with controlled clinic blood pressure (BP), might have poorer prognosis than untreated hypertensives. Different trials have also shown that relatively low cardiovascular disease (CVD) risk cannot be achieved in high-risk hypertensive patients, leading to the belief they have a "residual CVD risk" that cannot be attenuated by conventional treatment. All these conclusions disregard the facts that the correlation between BP level and CVD risk is stronger for ambulatory than clinic BP and that the BP-lowering efficacy and effects on the 24-h BP pattern of different classes of hypertension medications exhibit statistically and clinically significant treatment-time (morning versus evening) differences. ⋯ Among patients randomized to ingest ≥1 medications at bedtime, however, ARBs were associated with significantly lower HR of CVD events than ingestion of any other class of medication also at bedtime (p < .017). We document significantly reduced CVD risk among hypertensive patients ingesting medications at bedtime, independent of the number of hypertension medications required to achieve proper ambulatory BP control. These findings challenge the current belief of "residual CVD risk," as a bedtime-treatment regimen of current hypertension medications, even in risk-high patients, can reduce such risk.
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Multicenter Study
Circadian pattern of ambulatory blood pressure in hypertensive patients with and without type 2 diabetes.
There is strong association between diabetes and increased risk of end-organ damage, stroke, and cardiovascular disease (CVD) morbidity and mortality. Non-dipping (<10% decline in the asleep relative to awake blood pressure [BP] mean), as determined by ambulatory BP monitoring (ABPM), is frequent in diabetes and consistently associated with increased CVD risk. The reported prevalence of non-dipping in diabetes is highly variable, probably due to differences in the study groups (normotensive subjects, untreated hypertensives, treated hypertensives), relatively small sample sizes, reliance only on a single, low-reproducibility, 24-h ABPM evaluation per participant, and definition of daytime and nighttime periods by arbitrary selected fixed clock-hour spans. ⋯ Most important, prevalence of the riser BP pattern, associated with highest CVD risk among all possible BP patterns, was more than twice as prevalent in diabetes. Patients with diabetes also presented significantly elevated ambulatory PP, reflecting increased arterial stiffness and enhanced CVD risk. These collective findings indicate that diabetes should be included among the clinical conditions for which ABPM is recommended for proper CVD risk assessment.
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Randomized Controlled Trial
Cardiovascular risk of resistant hypertension: dependence on treatment-time regimen of blood pressure-lowering medications.
In resistant hypertension, ingesting one or more blood pressure (BP)-lowering medications at bedtime is associated with significant reduction of sleep-time BP, a sensitive prognostic marker of cardiovascular disease (CVD) risk. This randomized trial investigated if bedtime therapy with at least one hypertension medication exerts better BP control and CVD risk reduction than conventional, morning-time therapy with all medications. We conducted a prospective, open-label, blinded-endpoint trial on 776 patients (387 men/389 women) with resistant hypertension, 61.6 ± 11.2 (mean ± SD) yrs of age. ⋯ At the last evaluation, patients treated with the bedtime versus awakening-time-treatment regimen showed significantly lower sleep-time systolic/diastolic BP mean values (121.6/65.4 vs. 113.0/61.1 mm Hg; p < .001) and higher prevalence of controlled ambulatory BP (61% vs. 46%; p < .001). The progressive decrease in the sleep-time systolic BP mean during follow-up was the most significant predictor of event-free survival (15% risk reduction per 5 mm Hg decreased asleep systolic BP mean). Among patients with resistant hypertension, ingestion of at least one hypertension medication at bedtime, compared with all medications upon waking, resulted in improved ambulatory BP control and fewer hard and soft CVD events.
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Randomized Controlled Trial
Ambulatory blood pressure monitoring: importance of sampling rate and duration--48 versus 24 hours--on the accurate assessment of cardiovascular risk.
Independent prospective studies have found that ambulatory blood pressure (BP) monitoring (ABPM) is more closely correlated with target organ damage and cardiovascular disease (CVD) risk than clinic BP measurement. This is based on studies in which BP was sampled every 15-30 min for ≤24 h, without taking into account that reproducibility of any estimated parameter from a time series to be potentially used for CVD risk assessment might depend more on monitoring duration than on sampling rate. Herein, we evaluated the influence of duration (48 vs. 24 h) and sampling rate of BP measurements (form every 20-30 min up to every 2 h) on the prognostic value of ABPM-derived parameters. ⋯ The HRs, however, were markedly overestimated for SBP and underestimated for DBP when the duration of ABPM was reduced from 48 to only 24 h. This study on subjects evaluated prospectively by 48-h ABPM documents that reproducibility in the estimates of prognostic ABPM-derived parameters depends markedly on duration of monitoring, and only to a lesser extent on sampling rate. The HR of CVD events associated with increased ambulatory BP is poorly estimated by relying on 24-h ABPM, indicating ABPM for only 24 h may be insufficient for proper diagnosis of hypertension, identification of dipping status, evaluation of treatment efficacy, and, most important, CVD risk stratification.
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Some studies based on ambulatory blood pressure (BP) monitoring (ABPM) have reported a reduction in sleep-time relative BP decline towards a more non-dipping pattern in the elderly, but rarely have past studies included a proper comparison with younger subjects, and no previous report has evaluated the potential role of hypertension treatment time on nighttime BP regulation in the elderly. Accordingly, we evaluated the influence of age and time-of-day of hypertension treatment on the circadian BP pattern assessed by 48-h ABPM. This cross-sectional study involved 6147 hypertensive patients (3108 men/3039 women), 54.0 ± 13.7 (mean ± SD) yrs of age, with 2137 (978 men/1159 women) being ≥60 yrs of age. ⋯ The prevalence of a riser BP pattern, associated with highest cardiovascular risk among all possible BP patterns, was 4 times more prevalent in patients ≥60 yrs of age than those <60 yr of age. Most important, there was an attenuated prevalence of a blunted nighttime BP decline at all ages when ≥1 hypertension medications were ingested at bedtime as compared with when all of them were ingested upon awakening. These findings indicate that older age should be included among the conditions for which ABPM is recommended for proper cardiovascular risk assessment.