'J Curve' Persists Despite Intensive Lipid Control


SAN FRANCISCO — Bringing blood pressure levels too far down increased the risk for cardiovascular events in a post hoc analysis of data on 10,001 patients with coronary artery disease in a trial of aggressive lipid-lowering therapy.

There has been some controversy around the idea of a “J curve” relationship between blood pressure and the risk for cardiovascular events, in which a higher rate of events is seen with very low and very high blood pressure levels. Every previous study, except one that looked for this phenomenon, found evidence of a J curve, but it's been unclear whether the J curve exists when other cardiovascular risk factors such as LDL cholesterol levels are managed aggressively, Dr. Franz H. Messerli said in a press conference at the annual meeting of the American Society of Hypertension.

Data for the current analysis came from the double-blind Treating to New Targets trial that randomized patients aged 35-75 years with LDL cholesterol levels below 130 mg/dL to daily cholesterol-lowering therapy with 10 or 80 mg of atorvastatin. That study found significantly reduced cardiovascular risk when LDL levels were reduced to 100 mg/dL.

The post hoc analysis revealed a J curve for blood pressure. Patients with blood pressures below or above 130-140 mm Hg systolic or 70-80 mm Hg diastolic were at higher risk for the primary end point, a composite of death from coronary disease, nonfatal MI, resuscitation after cardiac arrest, or fatal or nonfatal stroke.

The nadirs for safe low blood pressures were 141 mm Hg systolic and 80 mm Hg diastolic, Dr. Messerli, director of the hypertension program at St. Luke's Roosevelt Hospital, New York, said in a poster presentation. The study's lead investigator was Dr. Sripal Bangalore of Harvard Medical School, Boston.

“The good news is that it is a relatively shallow curve,” with mild increases in risk just below those blood pressure nadirs, Dr. Messerli said. But once blood pressure drops to 110 mm Hg systolic or 60 mm Hg diastolic or lower, risk for the primary cardiovascular end point tripled.

Similar J-curve relationships were found for secondary end points analyzed individually—all-cause mortality, cardiovascular mortality, nonfatal MI, or stroke.

Systolic blood pressure was a stronger predictor of all-cause mortality or cardiovascular mortality. Diastolic blood pressure was a stronger predictor of nonfatal MI. Systolic and diastolic pressures equally predicted the risk for stroke.

All patients in the study had coronary artery disease. Lower systolic pressures were better tolerated by patients aged 65 or younger, those who had undergone revascularization procedures, and those with no prior coronary artery bypass graft. The relationship between blood pressure and cardiovascular risk was not affected by gender, diabetes, heart failure, or prior MI.

Hypertensive specialists consider very low blood pressures a “relatively minor” concern, Dr. Messerli said, because most patients fail to reach blood pressure targets. However, “most of us would agree that at least with coronary artery disease and diastolic blood pressure, you have to be a bit careful” in how low to go.

Dr. William B. White of the University of Connecticut, Farmington, who moderated the press conference, said that as a hypertension specialist at a cardiology center, he sees patients who have blood pressures around 102/60 mm Hg on routine visits. “That's the message here—that this does happen in real-life practice,” he said.

If patients with these low pressures report dizziness or fatigue, he may adjust therapy to let blood pressures rise 10-12 mm Hg. “They'll probably be just as protected but have more energy and less risk of underperfusing their coronary circulation,” he said.

Dr. Messerli offered three possible explanations for the J curve. When blood pressure is too low, the coronaries are underperfused, increasing the risk of an MI. Secondly, a lower diastolic blood pressure means that pulse pressure is high, which indicates endothelial dysfunction and stiff arteries, which can lead to morbidity and mortality. Third, patients with low blood pressure may have concomitant pathology that produces higher mortality.

The study was funded by Pfizer Inc., which markets atorvastatin. Dr. Messerli has been a consultant, adviser, or speaker for companies that make antihypertensives and lipid-lowering drugs, but has no relationship with Pfizer.

'With coronary artery disease and diastolic blood pressure, you have to be a bit careful' in how low to go. DR. MESSERLI

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