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Treatment of hypertension to specific blood pressure (BP) goals is controversial, and the exact goal BP for different clinical populations at high risk for cardiovascular disease (CVD) is hotly debated. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) specifically recommended a goal BP of ≤130/80 mm Hg for patients with chronic kidney disease (CKD) or diabetes mellitus (DM).1 The national kidney foundation (Kidney Disease Outcomes Quality Initiative [KDOQI]) guidelines also recommend a goal BP of ≤130/80 mm Hg in patients with CKD and DM and a goal BP of ≤125/75 mm Hg in CKD patients with proteinuria >1000 mg/d.2 More recent, the American Heart Association (AHA) and the European Society of Hypertension/European Society of Cardiology recommended a goal BP of ≤130/80 mm Hg in all patients with coronary artery disease (CAD) or CAD risk equivalents, including patients with carotid artery disease, peripheral arterial disease, abdominal aortic aneurysm, and patients with high risk for CVD with a Framingham 10-year risk score >10%.3,4 In addition, the AHA also recommended a BP ≤120/80 mm Hg in patients with CAD and left ventricular dysfunction.3

The rationale behind these recommendations in patients with CKD is that these patients are considered to be the “highest-risk” group for CVD. Although patients with CKD have a many-fold increased risk of CVD, there has not been a controlled trial demonstrating superior CVD prevention by lowering BP to the recommended ≤130/80 mm Hg goal. So where does this recommendation come from?

A recent meta-analysis was conducted to assess whether lower BP targets (≤135/85) are associated with reduction in mortality and morbidity as compared with standard BP targets of 140–160/90–100 mm Hg.5 Interestingly, no trials comparing different systolic BP (SBP) targets were found. Seven trials (22,089 patients) comparing different diastolic BP (DBP) targets were included. Primary outcomes were myocardial infarction, stroke, congestive heart failure, major cardiovascular (CV) events, and end-stage renal disease. Secondary outcomes were achieved mean SBP and DBP and withdrawals due to adverse effects. Despite a greater achieved reduction in SBP and DBP, the “lower targets” did not improve mortality, myocardial infarction, stroke, congestive heart failure, or end-stage renal disease. Specifically a sensitivity analysis in diabetic patients and in patients with CKD also did not show a reduction in any of the mortality and morbidity outcomes with lower targets as compared with standard targets. Treating patients to lower BP targets does not reduce mortality or morbidity.

The Action to Control Cardiovascular Risk in Diabetes (ACCORD) study of 4733 diabetics with hypertension echoes the findings of this meta-analysis.6 Despite a difference of 14 mm Hg in SBP, the primary end points (non-fatal myocardial infarction, nonfatal stroke, or CV death) were not improved by more aggressive BP reduction after nearly 5 years of follow-up. Stroke risk was, however, significantly lower in the intensive BP group (P=.01). Critics of this study have pointed out that although these were patients at high risk for CVD, they were extremely well managed, with approximately 60% of patients receiving treatment with both statins and antiplatelet therapy with overall good BP control even in the standard BP-lowering group. This population was probably more intensively managed for CV risk reduction and therefore may not be applicable to the general population of diabetics. Also, the risk reduction in stroke in the intensive BP-lowering group was clinically significant and cannot be ignored.

Regarding the BP goals in patients with CAD and CAD risk equivalents, there is again limited confirmatory data provided from randomized trials advocating for a BP goal of ≤130/80 mm Hg in patients with atherosclerotic CAD. The Heart Outcomes Prevention Evaluation (HOPE)7 and the European Trial on Reduction of Cardiac Events With Perindopril in Stable Coronary Artery Disease (EUROPA)8 trials do provide support for lower BP targets in this population; however, there are other placebo-controlled trials that do not support this lower BP goal (the Telmisartan Randomised Assessment Study in ACE Intolerant Subjects With Cardiovascular Disease [TRANSCEND],9 A Coronary Disease Trial Investigating Outcome With Nifedipine GITS [ACTION],10 and the Comparison of Amlodipine vs Enalapril to Limit Occurrences of Thrombosis [CAMELOT]11 trials). Recommendations are based on these trials; however, these were not true hypertension trials.

Recommendations for patients with increased risk of CVD with a Framingham risk score of >10% but without existence of CAD, DM, or CKD is even more controversial, as there are no proven benefits in this population for this lower BP goal. When a physician advocates for this lower BP goal, this should be done with caution, particularly in the elderly.

These recommendations bring up some important issues regarding clinical practice and future recommendations as we look forward to the recommendations of JNC 8. What are the correct BP goals in these groups of patients at very high risk for CVD? Most recommendations to date are based on studies that have used DBP as a primary outcome, and the recent meta-analysis does not show any clear evidence that a lower BP goal significantly reduces morbidity or mortality. The ACCORD study that focuses on SBP goals does not show a CV benefit with more intensive BP lowering; however, there is a reduction in stroke. The Systolic BP Intervention Trial (SPRINT) will compare a strategy of lowering SBP to <120 mm Hg vs <140 mm Hg in patients 55 years or older with hypertension (defined as SBP >140 mm Hg) or prehypertension and stage 3 CKD who also have ≥1 additional CVD risk factors. The primary outcome will be a composite of CV outcome and progression of kidney disease. The results of this study may help further define these recommendations. We feel that until additional evidence is available, it is still worthwhile to try to achieve BP goals in the range of ≤130/80 mm Hg, with particular caution in the elderly, while as clinicians we wait for further outcome studies and the recommendations of JNC 8.

References

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  2. References
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