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type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/advagg_css\/css__ce2QY63WIanKyr8eSq7eavr1XQRRmFD6ZSmwpyJi8lM__zXwFqpqmxrZOXXcd_TpBQpjuELbmIP9wBR5UuTDWAO4__YJWWMMdfCJuAFm5cUEp88OsodhO3ZA-2lzRfoBsSlk4.css\u0022 media=\u0022all\u0022 \/\u003E\n\u003Clink rel=\u0027stylesheet\u0027 type=\u0027text\/css\u0027 href=\u0027\/sites\/all\/modules\/contrib\/panels\/plugins\/layouts\/onecol\/onecol.css\u0027 \/\u003E\u003C\/head\u003E\u003Cbody\u003E\u003Cdiv class=\u0022panels-ajax-tab-panel panels-ajax-tab-panel-sageoa-tab-art\u0022\u003E\u003Cdiv class=\u0022panel-display panel-1col clearfix\u0022 \u003E\n  \u003Cdiv class=\u0022panel-panel panel-col\u0022\u003E\n    \u003Cdiv\u003E\u003Cdiv class=\u0022panel-pane pane-highwire-markup\u0022 \u003E\n  \n      \n  \n  \u003Cdiv class=\u0022pane-content\u0022\u003E\n    \u003Cdiv class=\u0022highwire-markup\u0022\u003E\u003Cdiv xmlns=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022 id=\u0022content-block-markup\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cdiv class=\u0022article fulltext-view \u0022\u003E\u003Cspan class=\u0022highwire-journal-article-marker-start\u0022\u003E\u003C\/span\u003E\u003Cdiv class=\u0022section abstract\u0022 id=\u0022abstract-1\u0022\u003E\u003Ch2\u003ESummary\u003C\/h2\u003E\n            \u003Cp id=\u0022p-1\u0022\u003EThis article revisits the 2003 JNC 7 guidelines, as well as newer evidence regarding the use of renin-angiotensin system (RAS) inhibitors, calcium channel blockers, and diuretics to treat patients with diabetes and hypertension. The American Diabetes Association issued new guidelines in 2012 to address some of the recent controversy concerning the use of antihypertensive agents in patients with diabetes and to provide additional recommendations concerning the use of RAS inhibitors. These recommendations were based on evidence from a number of clinical trials.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003ERenal Disease\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EDiabetes \u0026amp; Kidney Disease\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EDiabetes \u0026amp; Endocrinology Guidelines\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EDiabetes Mellitus\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EHypertensive Disease\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EHypertension \u0026amp; Kidney Disease\u003C\/li\u003E\u003C\/ul\u003E\u003Cp id=\u0022p-2\u0022\u003EWhile anticipating the new Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC) 8 guidelines, Suzanne Oparil, MD, University of Alabama, Birmingham, Alabama, USA, revisited the 2003 JNC 7 guidelines, as well as newer evidence regarding the use of renin-angiotensin system (RAS) inhibitors, calcium channel blockers (CCBs), and diuretics to treat patients with diabetes and hypertension.\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003EThe American Diabetes Association (ADA) issued new guidelines in 2012 to address some of the recent controversy concerning the use of antihypertensive agents (\u003Ca id=\u0022xref-table-wrap-1-1\u0022 class=\u0022xref-table\u0022 href=\u0022#T1\u0022\u003ETable 1\u003C\/a\u003E) in patients with diabetes and to provide additional recommendations concerning the use of RAS inhibitors. These recommendations were based on evidence from a number of clinical trials. Dr. Oparil discussed the United Kingdom Prospective Diabetes Study [UKPDS; Holman RR et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 2008] and the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial [ALLHAT; ALLHAT Collaborative Research Group. \u003Cem\u003EJAMA\u003C\/em\u003E 2003] in detail. In the UKPDS, 758 patients with type 2 diabetes were randomly assigned to the angiotensin-converting enzyme (ACE) inhibitor (captopril) or a \u03b2-blocker (atenolol). There were no differences in blood pressure (BP) control, in diabetes-related or cardiovascular disease (CVD)-related endpoints, or in renal outcomes between the two treatment groups.\u003C\/p\u003E\u003Cdiv id=\u0022T1\u0022 class=\u0022table pos-float\u0022\u003E\u003Cdiv class=\u0022table-inline\u0022\u003E\u003Cdiv class=\u0022callout\u0022\u003E\u003Cspan\u003EView this table:\u003C\/span\u003E\u003Cul class=\u0022callout-links\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022\/\u0022 class=\u0022table-expand-inline\u0022 data-table-url=\u0022\/highwire\/markup\/12761\/expansion?postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media%2Chighwire_embed\u0026amp;table-expand-inline=1\u0022 html=\u00221\u0022 fragment=\u0022#\u0022 external=\u00221\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView inline\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022\/highwire\/markup\/12761\/expansion?width=1000\u0026amp;height=500\u0026amp;iframe=true\u0026amp;postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media\u0022 class=\u0022colorbox colorbox-load table-expand-popup\u0022 rel=\u0022gallery-fragment-tables\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView popup\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/12761\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cdiv class=\u0022table-caption\u0022\u003E\u003Cspan class=\u0022table-label\u0022\u003ETable 1.\u003C\/span\u003E \n            \u003Cp id=\u0022p-4\u0022 class=\u0022first-child\u0022\u003ERAS Inhibitor Guidelines.\u003C\/p\u003E\n         \u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-6\u0022\u003EIn the ALLHAT study, 33,357 patients with hypertension, 12,063 of whom had diabetes, were randomly assigned to either a diuretic (chlorthalidone), a CCB (amlodipine), or an ACE inhibitor (lisinopril). CVD and end-stage renal disease (ESRD) events were similar in participants with and without diabetes. Compared with the diuretic arm, there was a higher risk of heart failure with amlodipine and a higher risk of stroke, heart failure, and combined CVD with lisinopril. Dr. Oparil cautioned that ALLHAT did not address patients with chronic kidney disease (CKD) or proteinuric nephropathy. To address this shortcoming, she discussed results of 2 studies that examined the effects of angiotensin II receptor blockers (ARBs) on the incidence of diabetic nephropathy. In the Irbesartan in Patients with Type 2 Diabetes and Microalbuminuria [IRMA 2; Parving HH et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 2001] study, adding an ARB (irbesartan) to conventional antihypertensive therapy significantly (p=0.001) reduced the incidence of diabetic nephropathy and decreased the amount of urinary albumin. The Reduction of Endpoints in Non-Insulin Dependent Diabetes With the Angiotensin II Antagonist Losartan [RENAAL; Brenner BM et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 2001] trial was a double-blind, placebo-controlled trial to evaluate the renal-protective effects of losartan in patients with type 2 diabetes with nephropathy. Losartan reduced proteinuria, delayed onset of the primary endpoint (doubling of serum creatinine\/ESRD\/death), slowed the rate of decline in renal function, delayed progression to ESRD, and lowered BP by an additional 3\/1 mm Hg. The results from these 2 studies led to the adoption of the Kidney Disease: Improving Global Outcomes (KDIGO) recommendations (\u003Ca id=\u0022xref-table-wrap-2-1\u0022 class=\u0022xref-table\u0022 href=\u0022#T2\u0022\u003ETable 2\u003C\/a\u003E).\u003C\/p\u003E\u003Cdiv id=\u0022T2\u0022 class=\u0022table pos-float\u0022\u003E\u003Cdiv class=\u0022table-inline\u0022\u003E\u003Cdiv class=\u0022callout\u0022\u003E\u003Cspan\u003EView this table:\u003C\/span\u003E\u003Cul class=\u0022callout-links\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022\/\u0022 class=\u0022table-expand-inline\u0022 data-table-url=\u0022\/highwire\/markup\/12762\/expansion?postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media%2Chighwire_embed\u0026amp;table-expand-inline=1\u0022 html=\u00221\u0022 fragment=\u0022#\u0022 external=\u00221\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView inline\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022\/highwire\/markup\/12762\/expansion?width=1000\u0026amp;height=500\u0026amp;iframe=true\u0026amp;postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media\u0022 class=\u0022colorbox colorbox-load table-expand-popup\u0022 rel=\u0022gallery-fragment-tables\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView popup\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/12762\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cdiv class=\u0022table-caption\u0022\u003E\u003Cspan class=\u0022table-label\u0022\u003ETable 2.\u003C\/span\u003E \n            \u003Cp id=\u0022p-7\u0022 class=\u0022first-child\u0022\u003EKDIGO Recommendations.\u003C\/p\u003E\n         \u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-9\u0022\u003EDr. Oparil had 3 key messages for physicians:\u003C\/p\u003E\u003Cul class=\u0022list-unord \u0022 id=\u0022list-1\u0022\u003E\u003Cli id=\u0022list-item-1\u0022\u003E\n            \u003Cp id=\u0022p-10\u0022\u003EEvidence for selecting any one drug class for initial treatment of patients with diabetes and hypertension is sparse except in the presence of CKD with proteinuria\u003C\/p\u003E\n         \u003C\/li\u003E\u003Cli id=\u0022list-item-2\u0022\u003E\n            \u003Cp id=\u0022p-11\u0022\u003EInitial drug therapy for patients with diabetes, hypertension, and CKD with proteinuria should be an ACE inhibitor or an ARB\u003C\/p\u003E\n         \u003C\/li\u003E\u003Cli id=\u0022list-item-3\u0022\u003E\n            \u003Cp id=\u0022p-12\u0022\u003EMost patients with diabetes and hypertension will require more than one antihypertensive drug to achieve BP goal\u003C\/p\u003E\n         \u003C\/li\u003E\u003C\/ul\u003E\u003Cp id=\u0022p-13\u0022\u003EPeter M. Nilsson, MD, Lund University, Malm\u00f6, Sweden, argued for more flexible goals to control hypertension in patients with diabetes. Randomized controlled trials and observational studies have shown either no benefit or even harm for increased coronary heart disease (CHD) risk that is associated with intensive systolic blood pressure (SBP) control \u0026lt;130 mm Hg.\u003C\/p\u003E\u003Cp id=\u0022p-14\u0022\u003EResults from major trials show that it is difficult to reduce BP below 130 mm Hg in patients with type 2 diabetes mellitus (T2DM) [Mancia G et al. \u003Cem\u003EJ Hypertens\u003C\/em\u003E 2009], and even when BP is reduced to very low levels, results suggest that, except for stroke, there is little reduction in primary cardiovascular outcomes or mortality (\u003Ca id=\u0022xref-fig-1-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F1\u0022\u003EFigure 1\u003C\/a\u003E) [Zanchetti A. \u003Cem\u003EEur Heart J\u003C\/em\u003E 2010; Cushman W et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 2010].\u003C\/p\u003E\u003Cdiv id=\u0022F1\u0022 class=\u0022fig pos-float  odd\u0022\u003E\u003Cdiv class=\u0022highwire-figure\u0022\u003E\u003Cdiv class=\u0022fig-inline-img-wrapper\u0022\u003E\u003Cdiv class=\u0022fig-inline-img\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/12\/10\/7\/F1.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022ACCORD-BP: Primary and Secondary Outcomes.\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-515057943\u0022 data-figure-caption=\u0022ACCORD-BP: Primary and Secondary Outcomes.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cimg class=\u0022fragment-image\u0022 alt=\u0022Figure 1.\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/12\/10\/7\/F1.medium.gif\u0022\/\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cul class=\u0022highwire-figure-links inline\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/12\/10\/7\/F1.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Figure 1.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload figure\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/12\/10\/7\/F1.large.jpg\u0022 class=\u0022highwire-figure-link highwire-figure-link-newtab\u0022 target=\u0022_blank\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EOpen in new tab\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/12760\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003Cdiv class=\u0022fig-caption attrib\u0022\u003E\u003Cspan class=\u0022fig-label\u0022\u003EFigure 1.\u003C\/span\u003E \n            \u003Cp id=\u0022p-15\u0022 class=\u0022first-child\u0022\u003EACCORD-BP: Primary and Secondary Outcomes.\u003C\/p\u003E\n         \u003Cq class=\u0022attrib\u0022 id=\u0022attrib-1\u0022\u003EReproduced with permission from PM Nilsson, MD.\u003C\/q\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-16\u0022\u003EIn a reappraisal of European guidelines, the European Society of Hypertension (ESH) recommends using a flexible BP goal in individuals with diabetes. In newly detected T2DM, the goal should be tighter risk factor control; in elderly patients with a long duration of diabetes and many comorbidities, a more flexible goal is recommended; patients should be treated when hypertension is \u2265140\/90 mm Hg or lower if signs of target organ damage are present. Use 24-hour ambulatory BP measurement to detect masked hypertension in normotensive T2DM patients. The European Guidelines on Cardiovascular Disease Prevention in Clinical Practice [Perk J et al. \u003Cem\u003EEur Heart J\u003C\/em\u003E 2012] recommend treating targets of \u0026lt;140\/80 mm Hg (Class I, Level A), while the 2011 ADA Standard of Medical Care in Diabetes [\u003Cem\u003EDiabetes Care\u003C\/em\u003E 2011] recommends a goal of SBP \u0026lt;130 mm Hg (Level C) and diastolic blood pressure (DBP) \u0026lt;80 mm Hg (Level B); however, the recommendations note that higher or lower SBP targets may be appropriate, based on a patient\u0027s characteristics and response to therapy (Level B) [\u003Cem\u003EDiabetes Care\u003C\/em\u003E 2012 Suppl]. Level of Evidence C is given for the SBP goal, which is considered low. The ADA\u0027s view is gradually shifting to be more in line with that of the ESH and the European Society of Cardiology.\u003C\/p\u003E\u003Cp id=\u0022p-17\u0022\u003EProf. Nilsson presented results from a recent study [Redon J et al. \u003Cem\u003EJ Am Coll Cardiol\u003C\/em\u003E 2012] that showed that the relationship between BP and overall cardiovascular risk had a similar pattern in patients with and without diabetes over a wide range of baseline and in-treatment BP values, although, for the same SBP, a higher risk was observed in patients with diabetes. Other evidence [Cederholm J et al. \u003Cem\u003EJ Hypertens\u003C\/em\u003E 2010] suggests the risks of CHD and stroke increased progressively with higher SBP, with no J-shaped curves, although the risk increase was significant only for SBP of at least 140 mm Hg, but did not compare 130 mm Hg to 139 mm Hg and 110 mm Hg to 129 mm Hg. In addition, baseline SBP of 110 mm Hg to 129 mm Hg showed increased CHD and CVD risk with further SBP reduction during follow-up, whereas baseline SBP of at least 130 mm Hg showed benefits. Thus, some patients with CHD might be at risk if SBP is reduced below 110 mm Hg.\u003C\/p\u003E\u003Cp id=\u0022p-18\u0022\u003EObservational data from a meta-analysis of 13 randomized trials [Bangalore S et al. \u003Cem\u003ECirculation\u003C\/em\u003E 2011] concluded that an SBP treatment goal of 130 mm Hg to 135 mm Hg is acceptable in patients with T2DM and impaired glucose control. With more aggressive goals (\u0026lt;130 mm Hg), although the risk of stroke continued to decrease, there was no benefit regarding the risk of other macrovascular or microvascular (cardiac, renal, and retinal) events, and the risk of serious adverse events increased.\u003C\/p\u003E\u003Cp id=\u0022p-19\u0022\u003ENewer guidelines are emerging that state the BP goal for most individuals is \u0026lt;140\/90 mm Hg (Level IA or IB) and levels \u0026lt;130\/80 mm Hg are defensible only if advanced proteinuric CKD is present or if the risk of stroke is high [Flynn C, Bakris GL. \u003Cem\u003ECurr Hypertens Rep\u003C\/em\u003E 2011].\u003C\/p\u003E\u003Cp id=\u0022p-20\u0022\u003EProf. Nilsson concluded that diabetes is associated with increased cardiovascular risk, and a multiple risk factor control approach is needed. Although drug combinations may be necessary, he suggested that physicians should beware of combining ACE inhibitors and angiotensin receptor blockers (ARB) solely for the treatment of hypertension because of the possibility of side effects. The use of a triple combination of an ACE inhibitors + ARB\/direct renin inhibitor should also be avoided, based on data from the Aliskiren Trial in Type 2 Diabetes Using Cardiovascular and Renal Disease Endpoints [ALTITUDE; \u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT00549757\u0026amp;atom=%2Fspmdc%2F12%2F10%2F7.atom\u0022\u003ENCT00549757\u003C\/a\u003E], showing no benefit and, in fact, an increase in adverse events, especially nonfatal stroke. Use loop diuretics if renal impairment is present and b-blockers if CHD is present.\u003C\/p\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2012 MD Conference Express\u00ae\u003C\/li\u003E\u003C\/ul\u003E\u003Cspan class=\u0022highwire-journal-article-marker-end\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Cspan id=\u0022related-urls\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Ca href=\u0022http:\/\/mdc.sagepub.com\/content\/12\/10\/7.abstract\u0022 class=\u0022hw-link hw-link-article-abstract\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView Summary\u003C\/a\u003E\u003C\/div\u003E  \u003C\/div\u003E\n\n  \n  \u003C\/div\u003E\n\u003C\/div\u003E\n  \u003C\/div\u003E\n\u003C\/div\u003E\n\u003C\/div\u003E\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_figures.js?nzneqp\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_openurl.js?nzneqp\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_tables.js?nzneqp\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}