Treatment of Hypertension in Diabetes

What Is the Best Therapeutic Option?

Tonje A Aksnes; Sigrid N Skårn; Sverre E Kjeldsen

Disclosures

Expert Rev Cardiovasc Ther. 2012;10(6):727-734. 

In This Article

Hypertension Treatment Targets in Diabetic Patients

According to major hypertension guidelines, such as the European Society of Hypertension (ESH)[9] and the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure,[10] hypertension is defined as a blood pressure (BP) above 140/90 mmHg. However, the real threshold for hypertension and potential organ damage for the individual patient must be based on the total cardiovascular risk for each patient.[9] Many current antihypertensive guidelines recommend treatment goals lower in diabetic patients (aiming to achieve <130/80 mmHg) due to the higher risk of cardiovascular end points in diabetic patients.[10,11] However, the evidence in favor of initiating BP-lowering therapy in diabetic patients with high normal BP and a target of systolic BP (SBP) below 130 mmHg is scarce, and the recent reappraisal of the ESH guidelines on hypertension management reset the BP goal for diabetic patients to BP <140/90 mmHg and close to 130/80 mmHg, but not below the value.[11]

The Hypertension Optimal Treatment (HOT) trial found that, in the subgroup of diabetic patients, the risk of major cardiovascular events was halved in the group randomized to a diastolic BP (DBP) ≤80 mmHg compared with the target group with DBP <90 mmHg.[12] The UKPDS showed in the 1997 follow-up results that more tight (mean 144/82 mmHg; BP goal <150/85 mmHg) versus less tight (mean 154/87 mmHg, BP goal <180/106 mmHg) BP resulted in significant reductions in microvascular disease, stroke- and diabetes-related end points, but no significant benefits were found in terms of myocardial infarction and all-cause mortality.[13] However, the effect was not maintained over time, confirming the essentiality of maintaining good BP levels over time if the risk of complications is to be minimized.[13] The 10-year post monitoring follow-up of this study was published in 2008 and showed that a tight antihypertensive treatment strategy was not associated with a sustained significant reduction in cardiovascular outcomes.[13] However, the UKPDS BP substudy was not prespecified and was probably not powered (844 patients) to investigate a possible effect of BP treatment a decade earlier as no attempt was made to maintain previously randomized therapies.

Although the results of the ACCORD trial are disputed, the less aggressive approach in recent guidelines is based on these results. The BP arm of the ACCORD trial investigated if an SBP target of less than 120 mmHg (intensive therapy) might be preferable to a target of less than 140 mmHg (standard therapy) in patients with diabetes.[14] After a mean follow-up of 4.7 years, the use of an intensive strategy did not significantly reduce the annual rates of the primary composite end point of myocardial infarction, stroke or cardiovascular death (1.87 vs 2.09%; hazard ratio: 0.88; 95% CI: 0.73–1.06).[14] However, there was a significant reduction in stroke (37% reduction of nonfatal and 41% reduction of total stroke)[14] indicating that an achieved SBP level below 130 mmHg is beneficial for stroke prevention, but not for reduction of other cardiovascular events. Intensive therapy did increase the risk of major adverse events, including symptomatic hypotension, bradycardia, arrhythmia and hyperkalemia. However, there have been discussions about whether the study had been underpowered, and there had been interactions between the BP-lowering and glucose-lowering parts of the study. The very recently reported results on BP values related to cardiovascular events in the ONTARGET take the same direction.[15]

In a meta-analysis from Bangalore et al.,[16] intensive BP control (SBP ≤135 mmHg) was associated with a 10% reduction in all-cause mortality (odds ratio: 0.90; 95% CI: 0.83–0.98), 17% reduction in stroke and 20% increase in serious adverse events compared with standard BP control (SBP ≤140 mmHg). However, no significant difference in other macrovascular and microvascular (cardiac, renal and retinal) events was found.[16]

In the Task Force document published in 2009 by ESH, the authors recommend that the patients should try to lower SBP below 140 mmHg.[11] There is, however, evidence for reducing subclinical organ damage when reducing BP well below 140/90 mmHg. Asymptomatic alteration of the cardiovascular system and the kidneys are crucial intermediate stages in the disease continuum that links risk factors as hypertension to cardiovascular events and death.[11] If subclinical organ damage (particularly microalbuminuria or proteinuria) is present, it is important to initiate treatment in also high normal BP levels. However, it is important to measure both sitting and standing BP in diabetic patients, as autonomic neuropathy often leads to postural fall of BP.

Patients with diabetes mellitus have more isolated systolic hypertension, and due to the autonomic neuropathy, patients often have less reduction in nocturnal BP ('dipping') and higher heart rates compared with patients without diabetes.[17]

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