Enhancing the Efficacy of Antihypertensive Treatment with Pharmacogenomics

In 2003,two newguidelines for hyperten—sive prevention andmanagement have beenprovided by AmericanJNC7 and European So-ciety of Hypertension.They advocated that thephysician should choosedrugs following individ—ualized treatment,

POST-STROKE ANTIHYPERTENSIVE TREATMENT STUDY A PRELIMINARY RESULT

Post-stroke Antihypertensive Treatment Study (PATS) was a randomized, double-blind and placebo-controlled trial, which aimed at determining whether antihypertensive treatment could reduce the risk of fatal and nonfatal stroke incidence in patients with a history of stroke or transient ischemic attack (TLA). 5 665 patients were randomized by a sealed envelope system. Systolic blood pressure (SBP) ranged from 80 to 280 mm Hg and diastolic (DBP) from 50 to 150 mmHg. The average SBP was 154 mmHg and average DBP 93 mmHg. The mean age was 60 years. Among the patients, women accounted for 28%. In 71% the latest stroke was ischemic. Average follow-up approximated to 2 years. The three-year average SBP was 149 mmHg for the placebo group and 144 mmHg for the indapamide treatment group, and the three-year DBP was 89 mmHg and 87 mmHg respectively. The three-year first incidence of fatal and nonfatal stroke was 12.3 per 100 patients placebo treatment and 9.4 per 100 with indapamide. The relative risk by proportional hazards regression analysis was 0.71 (P=0.0009). For deaths from all causes, the relative risk was 0.91. (P>0.05). The findings of this trial indicate that in patients with a history of stroke or TLA, blood pressure reduction of 5 / 2 mmHg with 2.5 mg indapamide reduced the first incidence of fatal and nonfatal stroke by 29%, with three-year absolute benefit of 29 events per 1000 participants.

Comparison of Clinic and Ambulatory Blood Pressure in Response to Antihypertensive Drugs in Chinese Patients

To compare the difference between 24-h ambulatory blood pressure （ABP） and trough clinic blood pressure （CBP） after 8 weeks of therapy. Methods The study used meta-regression analysis to summarize three randomized, double-blind, active controlled trials in order to compare the difference between the magnitude of the reduction in 24-h average ABP and CBP Patients. Chinese patients with seated diastolic blood pressure （SDBP） 95-115 mmHg and ambulatory diastolic blood pressure （ADBP）≥85 mmHg. Results The average age of 126 patients was 47.7 ＋ 8.3 years, ranging from 25 to 67 （95 males and 31 females）. All regimens reduced 24-h ABP and CBP after 8 weeks of treatment. In the 126 patients the baseline 24-h SBP and DBP values （142.7/94.4 mmHg） were markedly lower than those for clinic values （152.6/102.6 mmHg; P〈0.0001）. Similarly, the 24-h SBP and DBP values （132.7/87.7 mmHg） in week 8 were markedly lower than the clinic values （138.9/92.7 mmHg; P〈0.0001）. The differences between the treatment-induced reductions in 24-h ABP and CBP were statistically significant （the difference was 3.7/3.3 mmHg for SBP/DBP, P=O.OO69/P〈O.O001）. Conclusion All regimens significantly reduced seated CBP and ABP. The effect of antihypertensive treatment was greater on CBP than that on ABP, suggesting that assessment on effectiveness of an antihypertensive treatment using CBP readings only has to be carefully interpreted, and a more systematic application of ABP monitoring should be adopted.

Hypertension in the elderly： insights from recent research

Hypertension is a leading cause of mortality and morbidity around the world and,prevalence of hypertension is increasing with aging.Hypertension in the elderly is associated with increased occurrence rates of sodium sensitivity,isolated systolic hypertension,and ＇white coat effect＇.Arterial stiffness and endothelial dysfunction also increase with age.These factors should be considered in selecting antihypertensive therapy.The prime objective of this therapy is to prevent stroke.The fmdings of controlled trials show that there should be no cut-off age for treatment.A holistic program for controlling cardiovascular risks should be fully discussed with the patient,including evaluation to exclude underlying causes of secondary hypertension,and implementation of lifestyle measures.The choice of antihypertensive drug therapy is influenced by concomitant disease and previous medication history,but will typically include a thiazide diuretic as the first-line agent;to this will be added an angiotensin inhibitor and/or a calcium channel blocker.Beta blockers are not generally recommended,in part because they do not combat the effects of increased arterial stiffness.The hypertension-hypoten-sion syndrome requires case-specific management.Drug-resistant hypertension is important to differentiate from faulty compliance with medication.Patients resistant to the third-line drug therapy may benefit from treatment with extended-release isosorbide mononitrate.A trial of spironolactone may also be worthwhile.

Blood Pressure Targets in the Hypertensive Elderly

Objective： Hypertension is an important risk factor of cardiovascular disease and increases mortality in the elderly. However, the available medical evidences are both inconsistent and insufficient regarding establishing credible and useful blood pressure （BP） targets in the hypertensive elderly. This review summarizes the existing evidences used for establishing optimal BP targets for this patient population and points out some data inconsistencies which have added to the uncertainty. Data Sources： We conducted a search for the articles published in English in the PubMed database up to March 2017, with the keywords ＂hypertension,＂ ＂elderly,＂ ＂blood pressure,＂ and ＂antihypertensive.＂ Study Selection： Articles that related to BP targeting in the hypertensive elderly were selected for this review. Results： The selected studies indicated that antihypertensive therapy can substantially reduce the risk of cardiovascular events and mortality, for a subset of the elderly （60 years or older） with systolic BP 〉 160 mmHg. Studies regarding more strict targets yielded mixed findings. For the very old and frail patients （80 years or older）, there is a lack of evidence that optimal BP targets and intensive antihypertensives are helpful but in fact may be harmful. Conclusions： There are solid evidences that patients who are 60-80 years old and in good health have benefited from lowering their BP to below 150/90 mmHg. If well tolerated, the BP target can be further lowered to below 140/90 mmHg. However, for the very old and frail, individualized and careful assessment is crucial. Antihypertensive treatment should be cautious and the adverse effect of drugs requires close monitoring as such treatment can be counterproductive.

Account for Clinical Heterogeneity in Assessment of Catheter-based Renal Denervation among Resistant Hypertension Patients： Subgroup Meta-analysis

Background： Catheter-based renal denervation （RDN） is a novel treatment tbr resistant hypertension （RH）. A recent meta-analysis reported that RDN did not significantly reduce blood pressure （BP） based on the pooled effects with mild to severe heterogeneity. The aim of the present study was to identify and reduce clinical sources of heterogeneity and reassess the safety and efficacy of RDN within the identified homogeneous subpopulations. Methods： This was a meta-analysis of 9 randomized clinical trials （RCTs） among patients with RH up to June 2016. Sensitivity analyses and subgroup analyses were extensively conducted by baseline systolic blood pressure （SBP） level, antihypertensive medication change rates, and coronary heart disease （CHD）. Results： In all patients with RH, no statistical differences were found in mortality, severe cardiovascular events rate, and changes in 24-11 SBP and office SBP at 6 and 12 months. However, subgroup analyses showed significant differences between the RDN and control groups. In the subpopulations with baseline 24-h SBP 〉 155 mmHg （ 1 mmHg = 0.133 kPa） and the infrequently changed medication, the use of RDN resulted in a significant reduction in 24-h SBP level at 6 months （P = 0.100 and P = 0.009, respectively）. Subgrouping RCTs with a higher prevalent CHD in control showed that the control treatment was significantly better than RDN in office SBP reduction at 6 months （P 〈 0.001 ）. Conclusions： In all patients with RH, the catheter-based RDN is not more effective in lowering ambulatory or office BP than an optimized antihypertensive drug treatment at 6 and 12 months. However, among RH patients with higher baseline SBP, RDN might be more effective in reducing SBR

Ambulatory blood pressure monitoring for the management of hypertension

Ambulatory blood pressure monitoring(ABPM)has become indispensable in the current management of hypertension.ABPM is particularly useful in the accurate diagnosis of hypertension.Its diagnostic thresholds had been recently established based on hard clinical outcomes.Cross-classification of patients according to office and ambulatory blood pressure identifies white-coat,masked,and sustained hypertension.ABPM is also useful in cardiovascular(CV)risk assessment.It provides information on daytime and nighttime blood pressure and circadian rhythm,particularly nighttime blood pressure dipping.Nighttime blood pressure is predictive of CV risk independent of office and daytime blood pressure.Isolated nocturnal hypertension is a special form of masked hypertension,with normal daytime but elevated nocturnal blood pressure.It also helps in the evaluation of blood pressure fluctuation and variation,such as morning blood pressure surge and reading-to-reading blood pressure variability.ABPM may derive several other indexes,such as ambulatory blood pressure index and salt sensitivity index,which may be useful in CV evaluations.