Preventing and Controlling Hypertension in the Era of Genomic Innovation and Environmental Transformation

JAMA The Journal of the American Medical Association (Impact Factor: 35.29). 11/2012; 308(17):1745-6. DOI: 10.1001/jama.2012.28747
Source: PubMed
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    ABSTRACT: Recently, we reported that transient treatment of genetically hypertensive rats with high-dose angiotensin receptor blocker (ARB) causes regression of established hypertension. In this study, we investigated whether treatment with candesartan or nifedipine controlled-release (CR) resulted in a sustained regression of hypertension in humans. Patients aged 30 to 59 years with untreated stage 1 essential hypertension and a family history of hypertension were treated with the antihypertensive agents candesartan (n = 124) or nifedipine CR (n = 120). After 1 year of treatment (phase 1), the medications were tapered and discontinued (phase 2). During phase 2, home and office blood pressures were monitored for another year to assess posttreatment reoccurrence of stage 1 hypertension. In phase 1, after 1 year of treatment a similarly substantial BP decrease was seen in the candesartan (-24.5/16.1mm Hg) and nifedipine (-26.8/18.0mm Hg) groups. In phase 2 there was a substantial reoccurrence of hypertension; at the study end, only 1 patient was able to continue without antihypertensive medication. However, a Kaplan-Meier analysis revealed a significant delay of reoccurrence of hyper tension (P = 0.0001) in the candesartan group. One year of treatment with candesartan or nifedipine CR was not associated with marked regression of hypertension in humans at the standard doses used in this trial. However, withdrawal of candesartan was associated with a slightly longer delay before restarting medications. Further studies with larger doses of candesartan given over a longer time are required to determine whether such a regimen may induce sustainable and clinically relevant reversal of hypertension and alteration in its natural history.
    American Journal of Hypertension 12/2013; 26(12):1381-8. DOI:10.1093/ajh/hpt105 · 2.85 Impact Factor
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    ABSTRACT: Central obesity is closely linked to hypertension and type-2 diabetes (DM2) in young/middle-age. In the elderly, systolic hypertension is a reflection of aging/stiff arteries. Diastolic (┬▒systolic) hypertension in young/middle-age is accompanied by increased sympathetic nerve activity, particularly in the presence of the metabolic syndrome or DM2. High beta-receptor density (Bmax) and cyclic AMP (cAMP) levels in human lymphoctes, independent of blood pressure, are associated with a high risk of myocardial infarction (not stroke-risk, which is dependent on blood pressure). This has treatment implications in the young/middle-aged hypertensive subject. Antihypertensive agents that increase sympathetic nerve activity e.g. dihydropyridine calcium blockers, angiotensin receptor blockers, and thiazide-type diuretics, do not reduce (and may increase) the risk of myocardial infarction. Beta-1 blockade, effective in reversing and stabilising coronary atheromataous plaque, and with possible anti-tumor properties, is superior to ACE-inhibition, and is the treatment of choice in young/middle-aged hypertension with DM2.
    International Journal of Cardiology 04/2014; 174(3). DOI:10.1016/j.ijcard.2014.04.204 · 4.04 Impact Factor