Blood Pressure Targets for Patients with Diabetes or Kidney Disease
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- Flynn, C. & Bakris, G.L. Curr Hypertens Rep (2011) 13: 452. doi:10.1007/s11906-011-0228-5
The most recent scientific guideline statements from foundations and societies dealing with diabetes and kidney disease argue for blood pressure (BP) goals lower than 130/80 mm Hg, but whether the evidence from properly done clinical trials supports this BP level remains questionable. A review of all the evidence suggests that almost all of the data come from retrospective data analyses of randomized cardiovascular and chronic kidney disease (CKD) trials. Meta-analyses of all clinical trials to date demonstrate that reducing BP reduces risk for stroke and coronary heart disease, but none have achieved a mean BP goal of less than 130/80 mm Hg. In fact, only two prospective trials achieved a BP lower than 130/80 mm Hg in people with type 2 diabetes, as did three trials in advanced proteinuric CKD. Of these, one of the two diabetes trials showed a benefit for overall cardiovascular risk reduction, and two of the three kidney disease trials showed a benefit on slowing of advanced CKD. Of note, however, these two trials in CKD had baseline average proteinuria rates of more than 500 mg/day. No benefit of a lower BP was seen in microalbuminuric CKD. Therefore, the totality of the prospective randomized trial evidence indicates that a BP less than 130/80 mm Hg is not defensible to slow nephropathy progression unless proteinuria levels are at least 500 mg/day, and it does not reduce overall cardiovascular events in diabetes. Stroke benefit was uniformly seen at BP levels less than 130/80 mm Hg, however. Therefore, newer guidelines are emerging that state that the BP goal for most people is lower than 140/90 mm Hg with level IA or IB evidence, and that levels lower than 130/80 mm Hg are defensible only if advanced proteinuric CKD is present or stroke risk is very high (i.e., history of prior stroke or several risk factors for stroke, including hypertension, smoking, diabetes mellitus, dyslipidemia).
KeywordsKidney diseaseHypertensionOutcomesGuidelinesRenal diseaseCKDBlood pressure goalsClinical trialsNephropathyProteinuriaStroke risk
The most recent scientific statement from the American Diabetes Association and the American Heart Association for blood pressure (BP) goals in patients with diabetes recommends treating to a systolic BP of less than 130 mm Hg and a diastolic BP less than 80 mm Hg . The 2011 ADA Standards of Medical Care in Diabetes continued this recommendation, stating that a systolic BP lower than 130 mm Hg is appropriate in most patients and the diastolic BP should be treated to lower than 80 mm Hg . Is this level of reduction in BP justified based on the trial evidence?
Are Lower Blood Pressure Goals Defensible?
All guidelines in the Western world uniformly recommend two BP goals, less than 140/90 mm Hg for the general population, and less than 130/80 mm Hg for those with diabetes or chronic kidney disease (CKD) [3, 4]. The recommendations for a lower BP goal in these specific groups stem from retrospective data analyses that support a slower decline in CKD and greater cardiovascular disease (CVD) risk reduction when BP is lower than 130/80 mm Hg. However, are these more aggressive BP goals defensible on the basis of appropriately powered prospective outcome trials?
Meta-analyses of all clinical trials to date demonstrate that reducing BP reduces risk for stroke and coronary heart disease, but none have achieved a mean BP goal of less than 130/80 mm Hg . The failure to achieve lower BP goals is true even in trials of CVD outcome in diabetes. In trials such as the United Kingdom Prospective Diabetes Study (UKPDS)  and the Hypertension Optimal Treatment (HOT) trial , the achieved systolic BP was more than 10 mm Hg higher than this lower goal. Nevertheless, a CVD reduction benefit occurred.
One prospective study that achieved this lower BP goal in patients with type 2 diabetes and no overt nephropathy was the Appropriate Blood Pressure Control in Diabetes (ABCD) trial . ABCD demonstrated reduced cardiovascular events and risk, but there was no difference between the group with a mean systolic BP of 138 mm Hg and the intensive group at 132 mm Hg. In fact, the only prospective trials that achieved a mean systolic BP of 130 mm Hg were the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial [9•] and the Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE) trial . Only the ADVANCE trial showed a benefit on cardiovascular risk; ACCORD failed to meet the primary end point.
The recent ACCORD trial provides the definitive answer regarding whether lower levels of BP reduce cardiovascular risk more than conventional BP control [9•]. This prospective randomized trial clearly demonstrates a 14 mm Hg separation in levels of mean systolic BP (133 mm Hg vs 119 mm Hg). Even though this difference in BP was sustained for more than 4 years, there was no additional benefit on the primary end point of cardiovascular events. There was a benefit on stroke events, but at a cost of a higher side-effect profile from medications.
A review of all trials in patients with diabetes, including the ACCORD trial, makes it clear that although BP reduction to levels below 140/90 mm Hg is associated with fewer cardiovascular events, no data support reduction below 130/80 mm Hg [11•]. Additional findings from post hoc analysis of the Ongoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET) and the International Verapamil SR–Trandolapril Study (INVEST) also corroborate the findings of ACCORD. Post hoc analyses of these trials demonstrate that the benefit of lower levels of BP on cardiovascular risk reduction is lost when systolic BP levels fall below 130 mm Hg [12, 13]. INVEST further demonstrated an increase in cardiovascular events at systolic BPs lower than 115 mm Hg, although 100% of these patients had coronary artery disease .
Taken together, these trials indicate that once someone over age 50 with long-standing hypertension and coronary disease has a BP below 140/90 mm Hg, they gain little additional benefit by lowering systolic BP an additional 10 mm Hg. In fact, as noted in ONTARGET and INVEST, a systolic BP below 130 mm Hg may increase cardiovascular risk. An exception is a benefit on stroke reduction that is consistent throughout all the trials, whether prospectively or retrospectively evaluated [9•, 14].
Lower Blood Pressure Goal and Nephropathy Progression
Over a dozen appropriately powered, prospective outcome trials have examined the effect of various antihypertensive agents on CKD progression, but only three trials have examined whether a lower BP level slowed nephropathy progression [15•]. The Modification of Diet in Renal Disease (MDRD) trial was the first randomized trial to examine whether lowering the mean arterial pressure by 15 mm Hg would result in a slower decline in CKD and would reduce the risk for renal replacement therapy . This trial largely recruited patients without diabetes who had advanced nephropathy, with a mean baseline glomerular filtration rate (GFR) of 39 mL/min and more than 500 mg per day of proteinuria. It failed to show a benefit of the lower BP goal in slowing progression. However, after a 12-year follow-up, those with proteinuria greater than 1 g/day who were allocated to the low-BP group (i.e., mean BP of 92 mm Hg) manifested a significant decrease in proteinuria and rate of CKD progression . Note that the mean systolic BP in the low-target group was 126.2 ± 13.6 mm Hg during this follow-up period. It is also noteworthy that the benefit on CKD progression was seen after 1 year, at the end of the trial.
The second trial to examine prospectively the effects of different BP levels on nephropathy progression was the African American Study of Kidney Disease (AASK) . This trial examined over 1,000 African American patients with a GFR of 20–65 mL/min/1.73 m2 and albuminuria. It failed to show a benefit of a lower BP level (i.e., 128/77 mm Hg vs 140/82 mm Hg) on CKD progression. It did show that the 5% of patients who had 1 g/day of proteinuria had a trend toward a slower decline in kidney function. After an additional 5-year follow-up (yielding a 10-year total follow-up after randomization), no benefit on CKD progression was noted with more aggressive BP reduction [19•]. These data support the argument that a BP goal lower than 130/80 mm Hg will yield a greater benefit in slowing CKD in a subgroup of patients with advanced proteinuric nephropathy, but not in the CKD group as a whole.
The data from appropriately powered randomized trials support a strong association between a systolic BP less than 140 mm Hg and reduction of cardiovascular risk and CKD progression in patients with diabetes and no or low levels of albuminuria. The data supporting a target BP lower than 130/80 mm Hg are very weak for overall cardiovascular and CKD event reduction, however; they hold only for reduction of stroke risk among those with diabetes and for slowed CKD progression in those with a GFR less than 45 mL/min/1.73 m2 who have more than 500 mg per day of proteinuria.
No potential conflicts of interest relevant to this article were reported.