Study Suggests Lower Risk of Death in Patients With Resistant Hypertension

May 23, 2012

May 22, 2012 (New York, New York) — An analysis from a large US database of patients with high blood pressure has shown that individuals with resistant hypertension have significantly elevated risks of MI, heart failure, stroke, and new-onset end-stage renal disease but actually have a lower risk of death. Overall, there appeared to be a linear relationship between systolic blood pressure and clinical outcomes except for mortality, where investigators observed a J-shaped relationship with systolic blood pressure and death.

Presenting the results of the analysis here at the American Society of Hypertension 2012 Scientific Sessions, lead investigator Dr John Sim (Kaiser Permanente Southern California, Los Angeles) urged caution in interpreting the reduction in mortality, stating that an undocumented difference in the utilization of healthcare resources among patients with resistant hypertension might see these patients treated differently, and this might affect the mortality rates.

"Just to give you an example of how we looked at this and the covariates that we adjusted for," said Sim. "Age, male gender, diabetes, preexisting disease--those were all associated with an increased risk of mortality--but still, this really stood out to us, the resistant-hypertension population had a 19% decreased risk of mortality in the study period."

Resistant hypertension was defined as uncontrolled blood pressure (>140/90 mm Hg) despite the use of three antihypertensive medications or the use of four antihypertensive medications regardless of blood-pressure levels. In this longitudinal cohort study, 58 784 patients with resistant hypertension were identified and followed for three years. Clinical outcomes of the patients with resistant hypertension were compared with 470 988 subjects with a documented blood-pressure measurement. The average blood pressure in the non–resistant-hypertensive group was 132/75 mm Hg compared with 143/74 mm Hg in the resistant-hypertension arm.

Patients with resistant hypertension had a 36% increased risk of heart failure, a 25% increased risk of MI, a 10% increased risk of stroke, and a 24% increased risk of end-stage renal disease. However, those with resistant hypertension had a 19% lower risk of death (hazard ratio 0.81; 95% CI 0.78–0.84).

"What we found was that in those with blood pressures below 120, 130, and 140 mm Hg, compared with higher values, there was actually an increased risk of mortality," said Sim. "To no surprise, as the blood pressure increased, there was also an increased risk of mortality as well. So we're demonstrating a U- or J-shaped curve. When we looked at the other outcomes, such as end-stage renal disease, stroke, and myocardial infarction, we found a pretty linear relationship with blood pressure, with rising blood pressure and rising risk."

The data, according to Sim, raise the specter of a "sweet spot" with regard to systolic blood pressure in patients with resistant hypertension, with the potential that doctors might aim for a nadir of 150 mm Hg to reduce the risk of death in these patients. Sim stressed, however, that further studies are needed to investigate and confirm their findings and that the limitations of a longitudinal cohort analysis cannot be overlooked. The group is currently delving into the data to identify any variables that might explain the lower risk of death and will be presenting data on medication adherence shortly.

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