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      Physiologic Tailoring of Treatment in Resistant Hypertension

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          Abstract

          Resistant hypertension is a major opportunity for prevention of cardiovascular disease. Despite widespread dissemination of consensus guidelines, most patients are uncontrolled with approaches that assume that all patients are the same.

          Causes of resistant hypertension include 1) non-compliance 2) consumption of substances that aggravate hypertension (such as salt, alcohol, nonsteroidal anti-inflammatory drugs, licorice, decongestants) and 3) secondary hypertension.

          Selecting the appropriate therapy for a patient depends on finding the cause of the hypertension. Once rare causes have been eliminated (such as pheochromocytoma, licorice, adult coarctation of the aorta), the cause will usually be found by intelligent interpretation (in the light of medications then being taken) of plasma renin and aldosterone.

          If stimulated renin is low and the aldosterone is high, the problem is primary aldosteronism, and the best treatment is usually aldosterone antagonists (spironolactone or eplerenone; high-dose amiloride for men where eplerenone is not available). If the renin is high, with secondary hyperaldosteronism, the best treatment is angiotensin receptor blockers or aliskiren. If the renin and aldosterone are both low the problem is over-activity of renal sodium channels and the treatment is amiloride. This approach is particularly important in patients of African origin, who are more likely to have low-renin hypertension.

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          Most cited references41

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          Hypertension treatment and control in five European countries, Canada, and the United States.

          Levels of hypertension treatment and control have been noted to vary between Europe and North America, although direct comparisons with similar methods have not been undertaken. In this study, we sought to estimate the relative impact of hypertension treatment strategies in Germany, Sweden, England, Spain, Italy, Canada, and the United States by using sample surveys conducted in the 1990s. Hypertension was defined as a blood pressure of 160/95 mm Hg or 140/90 mm Hg, plus persons taking antihypertensive medication. "Controlled hypertension" was defined as a blood pressure less than threshold among persons taking antihypertensive medications. Among persons 35 to 64 years, 66% of hypertensives in the United States had their blood pressure controlled at 160/95 mm Hg, compared with 49% in Canada and 23% to 38% in Europe. Similar discrepancies were apparent at the 140/90 mm Hg threshold, at which 29% of hypertensives in the United States, 17% in Canada, and
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            Hypertension in sub-Saharan African populations.

            Hypertension in sub-Saharan Africa is a widespread problem of immense economic importance because of its high prevalence in urban areas, its frequent underdiagnosis, and the severity of its complications. We searched PubMed and relevant journals for words in the title of this article. Among the major problems in making headway toward better detection and treatment are the limited resources of many African countries. Relatively recent environmental changes seem to be adverse. Mass migration from rural to periurban and urban areas probably accounts, at least in part, for the high incidence of hypertension in urban black Africans. In the remaining semirural areas, inroads in lifestyle changes associated with "civilization" may explain the apparently rising prevalence of hypertension. Overall, significant segments of the African population are still afflicted by severe poverty, famine, and civil strife, making the overall prevalence of hypertension difficult to determine. Black South Africans have a stroke rate twice as high as that of whites. Two lifestyle changes that are feasible and should help to stem the epidemic of hypertension in Africa are a decreased salt intake and decreased obesity, especially in women. Overall, differences from whites in etiology and therapeutic responses in sub-Saharan African populations are graded and overlapping rather than absolute. Further studies are needed on black Africans, who may (or may not) be genetically and environmentally different from black Americans and from each other in different parts of this vast continent.
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              A chimaeric 11 beta-hydroxylase/aldosterone synthase gene causes glucocorticoid-remediable aldosteronism and human hypertension.

              Glucocorticoid-remediable aldosteronism (GRA), an autosomal dominant disorder, is characterized by hypertension with variable hyperaldosteronism and by high levels of the abnormal adrenal steroids 18-oxocortisol and 18-hydroxycortisol, which are all under control of adrenocorticotropic hormone and suppressible by glucocorticoids. These abnormalities could result from ectopic expression of aldosterone synthase, which is normally expressed only in adrenal glomerulosa, in the adrenal fasciculata. Genes encoding aldosterone synthase and steroid 11 beta-hydroxylase (expressed in both adrenal fasciculata and glomerulosa), which are 95% identical and lie on chromosome 8q (refs 7, 10), are therefore candidate genes for GRA. Here we demonstrate complete linkage of GRA in a large kindred to a gene duplication arising from unequal crossing over, fusing the 5' regulatory region of 11 beta-hydroxylase to the coding sequences of aldosterone synthase (maximum lod score 5.23 for complete linkage, odds ratio of 170,000:1). This mutation can account for all the physiological abnormalities of GRA. Our result represents the demonstration of a mutation causing hypertension in otherwise phenotypically normal animals or humans.
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                Author and article information

                Journal
                Curr Cardiol Rev
                CCR
                Current Cardiology Reviews
                Bentham Science Publishers Ltd.
                1573-403X
                1875-6557
                May 2010
                : 6
                : 2
                : 119-123
                Affiliations
                [1]Stroke Prevention & Atherosclerosis Research Centre, 1400 Western Road, London, Ontario, Canada N6G 2V2
                Author notes
                [* ]Address correspondence to this author at the Stroke Prevention & Atherosclerosis Research Centre, 1400 Western Road, London, Ontario, Canada, N6G 2V2; Tel: 1-519-663-3113; Fax: 1-519-663-3018; E-mail: dspence@ 123456robarts.ca
                Article
                CCR-6-119
                10.2174/157340310791162695
                2892077
                21532778
                217ae15d-57bc-447b-95a3-e97ef5a3807d
                © 2010 Bentham Science Publishers Ltd.

                This is an open access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.5/), which permits unrestrictive use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 27 November 2009
                : 20 February 2010
                : 19 March 2010
                Categories
                Article

                Cardiovascular Medicine
                primary hyperaldosteronism,amiloride,renal sodium channel,resistant hypertension,stroke belt.,renin,african-american

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