{"id":1149,"date":"2016-11-07T16:17:07","date_gmt":"2016-11-07T16:17:07","guid":{"rendered":"http:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/?p=1149"},"modified":"2017-08-21T10:44:40","modified_gmt":"2017-08-21T10:44:40","slug":"primary-care-corner-with-geoffrey-modest-md-htn-goal-in-diabetics-without-cvd","status":"publish","type":"post","link":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/2016\/11\/07\/primary-care-corner-with-geoffrey-modest-md-htn-goal-in-diabetics-without-cvd\/","title":{"rendered":"Primary Care Corner with Geoffrey Modest MD: HTN Goal in Diabetics without CVD"},"content":{"rendered":"<p><strong>By Dr. Geoffrey Modest<\/strong><\/p>\n<p>A\u00a0large Swedish population study found that\u00a0in diabetics with no previous cardiovascular disease,\u00a0there were progressively\u00a0fewer cardiovascular events as the systolic blood pressure was lower\u00a0(see\u00a0doi.org\/10.1136\/bmj.i4070).<\/p>\n<p>Details:<\/p>\n<ul>\n<li>187,106 patients in the Swedish national diabetes register for at least 1 year, &lt;= 75 yo, and no known cardiovascular disease (CVD), from 2006-2012 with mean follow-up of 5.0 years. From 861 primary care units and hospital outpatient clinics<\/li>\n<li>Most of the demographics got worse as the cohort in each 10-mm group of BP increased: median age was 55 in the lowest SBP group vs 64 in the highest; duration of diabetes\u00a04.8 vs\u00a06.8 years and\u00a0the higher SBP group was\u00a0more likely to be on more aggressive diabetes management; \u00a0LDL 2.8 vs 3.0 mmol\/L but HDL 1.3 in all; more micro\/macroalbuminuria in those with the highest SBP; and the mean number of BP meds was 0.7 in the SBP 110-19 cohort vs 1.1 in the 130-139 cohort vs 1.6 in the &gt;160\u00a0mmHg cohort<\/li>\n<\/ul>\n<p>Results:<\/p>\n<ul>\n<li><strong>Comparing<\/strong><strong>SBP 110-119 mmHg\u00a0vs those with SBP 130-199<\/strong>:\n<ul>\n<li>Non-fatal MI, RR 0.76 (0.64-0.91, p=0.003), 24% risk reduction<\/li>\n<li>Total acute\u00a0MI, RR 0.85 (0.72-0.99, p=0.04),\u00a015% risk reduction<\/li>\n<li>Non-fatal CVD, RR 0.82\u00a0(0.72-0.93, p=0.04), 18% risk reduction<\/li>\n<li>Non-fatal coronary heart disease,\u00a0, RR 0.88\u00a0(0.79-0.99, p=0.04),12% risk reduction<\/li>\n<li>There was no suggestion of J-shaped relationship, except for heart failure and total mortality, and this\u00a0was\u00a0only significant for\u00a0the lowest SBP group<\/li>\n<\/ul>\n<\/li>\n<li>Figure\u00a0below shows that there was a consistent relationship between SBP and non-fatal CVD events over the course of the\u00a0study. For all of the CVD endpoints, this relationship held, even after controlling for age, sex, duration of diabetes, type of diabetes treatment, HbA1c, smoking\u00a0status,\u00a0LDL, HDL, triglycerides, micro\/macroalbuminura; as well as thiazide diuretics, loop diuretics, calcium antagonists, spironolactone, b-blockers, and drugs for heart disease. Of note, they did not control for those on vs not on antihypertensives, which may be important.<\/li>\n<\/ul>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-full wp-image-1150\" src=\"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/files\/2016\/11\/photo.png\" alt=\"photo\" width=\"440\" height=\"260\" \/><\/p>\n<p>&nbsp;<\/p>\n<p>Commentary:<\/p>\n<ul>\n<li>So, why is it so difficult to zero-in on a goal blood pressure in diabetics? This study suggests that lower blood pressure is better.\u00a0But\u00a0the various guideline groups have been increasing the\u00a0BP goal lately,\u00a0though based on no new evidence: the\u00a0ADA (Am Diabetes Assn) in\u00a02016 set the overall\u00a0BP\u00a0guidelines\u00a0at the higher level of\u00a0&lt;140\/90 (see\u00a0<a href=\"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/2016\/03\/09\/primary-care-corner-with-geoffrey-modest-md-new-diabetes-guidelines-from-ada\/\">https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/2016\/03\/09\/primary-care-corner-with-geoffrey-modest-md-new-diabetes-guidelines-from-ada\/<\/a>) and explicitly did\u00a0not recommend it\u00a0to be &lt;130\/70 in older adults,\u00a0in conformity with JNC8 (which also has a\u00a0higher goal than JNC7)<\/li>\n<li>I\u00a0think there could be various different explanations:\n<ul>\n<li>The current study\u00a0focused on a less-sick population than most of the others: a\u00a0younger cohort, who\u00a0had no known baseline CVD, and some did not have\u00a0treated hypertension\n<ul>\n<li>Is the diabetes itself\u00a0different? (perhaps longer-standing diabetes creates end-organ changes which dictate different optimal BP goals)<\/li>\n<li>Are we using diabetic\u00a0medications which make things worse, and using more of them on patients with longer-standing and more treatment-resistant diabetes? Similarly with\u00a0the antihypertensives?\n<ul>\n<li>In terms of diabetes control,\u00a0a case in point here is the ACCORD trial, one of the major studies\u00a0heralded as a reason to raise the\u00a0target A1c. Those assigned to the &#8220;intensive control wing&#8221;, achieved an\u00a0A1c of 6.4, but\u00a091% were\u00a0on a thiazolidinedione (TZD), vs an\u00a0A1c of\u00a07.5 in the less aggressively treated group but\u00a0with 58% on a TZD. But\u00a0the TZD of\u00a0choice was rosiglitazone, which has the unfortunate tendency to increase cardiovascular outcomes (and is one of the reasons that I\u00a0find it unfortunate that the FDA and most of us accept A1c as an acceptable clinical surrogate).<\/li>\n<li>And, this brings up the\u00a0issue of <strong>medication-flogging<\/strong>&#8230;. are those patients with easy-to-control diabetes or hypertension different? As in the first point, is there a fundamental difference in their pathophysiology or clinical\u00a0outcome?\u00a0A\u00a0subgroup analysis of this ACCORD study actually\u00a0found\u00a0that\u00a0<strong>those who achieved a lower A1c in fact\u00a0did better, all the way down to an A1c of 6!!<\/strong>, but\u00a0as the number of meds needed\u00a0in the attempt to lower the A1c increased, they had worse outcomes\u00a0(i.e., medication-flogging of patients to improve their A1c led to worse outcomes even at a much higher A1c). See Riddle MC. Diabetes Care; 33:983. An Italian observational\u00a0study also\u00a0found that the goal of A1c in terms of clinical outcomes was lower in those with fewer chronic medical conditions (see Greenfield S. Ann of Intern Med 2009; 151: 854).<\/li>\n<li>This last point brings up the parallel issue: should\u00a0the blood pressure goal be\u00a0different in those with fewer chronic changes from long-standing\u00a0hypertension (e.g. atherosclerosis, or changes in the local autoregulation of blood pressure at a microvascular level) vs those with perhaps newer onset hypertension with fewer of these\u00a0changes? should we have different BP goals in those who easily\u00a0achieve a blood pressure of 110-120 systolic if it can be achieved with 1-2 drugs, vs those with SBP of\u00a0140+ systolic, who would be\u00a0struggling to achieve even close to\u00a0the lower range\u00a0with 4 drugs? It was certainly the case in the Swedish study that as the SBP of the cohort\u00a0increased, there were more meds being used, distributed pretty evenly amongst the different types of meds.<\/li>\n<li>The prior observational studies have often found a J-shaped relationship between blood pressure and CVD events in diabetics, though this has been questioned by the potential bias in observational studies that patients who\u00a0had\u00a0more\u00a0bad outcomes at lower pressures did so\u00a0because they were\u00a0really sick at the start, and it was this increased morbidity\u00a0that\u00a0led to lower blood pressure.\u00a0It is notable in the above Swedish\u00a0study that the J-shaped curve did happen in those with lower blood pressure,\u00a0but\u00a0only for total mortality\u00a0and heart failure, and\u00a0not for the\u00a0specific CVD outcomes, suggesting that there may have been issues that these patients with lower SBP were indeed sicker. In fact those\u00a0who died in this Swedish\u00a0study\u00a0were likely to have had more comorbidities, since they had higher rates of smoking (32%), use of loop diuretics, spironolactone, and drugs for heart disease.<\/li>\n<li>The ACCORD-BP study of diabetic patients (N Engl J Med 2010; 362: 1575), another wing of the above ACCORD study,\u00a0found no overall benefit in 4733 patients in those achieving a systolic\u00a0BP of 119 mm\u00a0Hg vs 133.5 mm\u00a0Hg, except for the prespecified secondary outcome of stroke, where there was a 41% decrease (p=0.01), but at the expense of\u00a0an increase in serious adverse events (from 1.3% of the population to 3.3%). The absolute risk of stroke was 0.53%\/yr vs 0.32%\/yr, which translates roughly to 2.6% vs 1.6%\u00a0over the 4.7 year study. The serious adverse events were largely\u00a0hypotension\/syncope\/bradycardia or\u00a0arrhythmia\/hyperkalemia. The intensive group averaged 3.4 BP\u00a0meds and the standard group\u00a02.2.\u00a0But, as opposed to many strokes,\u00a0all of these serious adverse could be tracked and corrected, and there was\u00a0no\u00a0evidence\u00a0of\u00a0increased morbidity\/mortality from these adverse events.\u00a0Other trials, such as ONTARGET found a J-shaped curve, and the INVEST trial found no benefit if the SBP were lowered below 130, (though a subgroup analysis of ONTARGET found that it was those with a higher baseline risk who had\u00a0CVD events, rather than the degree of reduction of the BP). These are the trials cited in JNC8 and the ADA guidelines as the reason to shoot for a higher SBP target.<\/li>\n<\/ul>\n<\/li>\n<li>So, my best guess is that lower SBP\u00a0is better for those who don&#8217;t have lots of comorbidities and do have\u00a0more easily treated hypertension, with the following caveats:\n<ul>\n<li>We don&#8217;t go too low (as per other blogs, checking orthostatics to make sure the BP doesn&#8217;t drop too much; and being mindful of the possibility of cognitive impairment if the BP is too low, with that BP target therefore\u00a0varying in different individuals, and this probably reflects such issues as atherosclerotic disease of big and small vessels, endothelial function, coagulability, etc. (see\u00a0<a href=\"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/2016\/05\/20\/primary-care-corner-with-geoffrey-modest-md-orthostatic-hypotension-revisited\/\">https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/2016\/05\/20\/primary-care-corner-with-geoffrey-modest-md-orthostatic-hypotension-revisited\/<\/a><\/li>\n<li>We use diabetes\u00a0meds primarily that have some reasonably good data on improvement of clinical outcomes, especially metformin, and I\u00a0would add the GLP-a agonists (see, for example:\u00a0<a href=\"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/2016\/08\/18\/primary-care-corner-with-geoffrey-modest-md-insulin-vs-glp-1-agonists-for-patients-failing-oral-med-treatment\/\">https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/2016\/08\/18\/primary-care-corner-with-geoffrey-modest-md-insulin-vs-glp-1-agonists-for-patients-failing-oral-med-treatment\/<\/a> or\u00a0<a href=\"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/2016\/06\/22\/primary-care-corner-with-geoffrey-modest-md-liraglutide-decreases-cardiovascular-events\/\">https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/2016\/06\/22\/primary-care-corner-with-geoffrey-modest-md-liraglutide-decreases-cardiovascular-events\/<\/a>\u00a0)<\/li>\n<li>And, we shoot for\u00a0a higher SBP\u00a0goal, perhaps in the 140 range, in those patients where medication-flogging is required to attempt to achieve\u00a0the SBP\u00a0lower.<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<p>Also, <a href=\"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/2015\/03\/06\/primary-care-corner-with-geoffrey-modest-md-blood-pressure-goals-in-diabetics\/,\">https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/2015\/03\/06\/primary-care-corner-with-geoffrey-modest-md-blood-pressure-goals-in-diabetics\/,<\/a> a\u00a0recent\u00a0meta-analysis\u00a0found\u00a0benefit of\u00a0a goal SBP of\u00a0around\u00a0130 to be better overall than 140.<\/p>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Primary Care Corner with Geoffrey Modest MD: HTN Goal in Diabetics without CVD [&#8230;]<\/p>\n<p><a class=\"btn btn-secondary understrap-read-more-link\" href=\"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/2016\/11\/07\/primary-care-corner-with-geoffrey-modest-md-htn-goal-in-diabetics-without-cvd\/\">Read More&#8230;<\/a><\/p>\n","protected":false},"author":148,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_jetpack_memberships_contains_paid_content":false,"footnotes":""},"categories":[14283],"tags":[],"class_list":["post-1149","post","type-post","status-publish","format-standard","hentry","category-archive"],"jetpack_featured_media_url":"","jetpack_sharing_enabled":true,"_links":{"self":[{"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/posts\/1149","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/users\/148"}],"replies":[{"embeddable":true,"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/comments?post=1149"}],"version-history":[{"count":0,"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/posts\/1149\/revisions"}],"wp:attachment":[{"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/media?parent=1149"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/categories?post=1149"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/tags?post=1149"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}