More data show lower is not always better for BP in diabetes

Miriam E Tucker

May 27, 2013

Baton Rouge , LA - A new prospective cohort study adds to the evidence that there is a U-shaped curve when it comes to blood-pressure (BP) control in patients with type 2 diabetes, where rates of coronary heart disease (CHD) increase at the lower as well as higher ends.

Moreover, the association between BP and CHD risk becomes inverse among the elderly, write Dr Wenhui Zhao (Pennington Biomedical Research Center, Baton Rouge, LA) and colleagues in their paper published online last week in Diabetes Care[1].

"Since there is currently no robust evidence available for lowering the blood pressure [to less than] 130/80 mm Hg in people with diabetes, it might be advisable to maintain blood pressure between 130 and 139 and 80 and 89 mm Hg and to recommend less intense goals to elderly patients than to younger ones," the authors say.

The findings suggest that "we should pay attention not only to the harm of uncontrolled blood pressure, but [also to] aggressively controlled blood pressure," said study coauthor Dr Gang Hu (Louisiana State University [LSU] Health Sciences Center, Baton Rouge).

"My advice for individual clinicians is the idea of 'the lower, the better' should pass away . . . Patients need individualized or tailored treatment for their hypertension," added Hu.

But one expert disagrees with the authors' conclusion that aggressive blood-pressure lowering per se is what leads to adverse outcomes in all patients. In some, low BP itself could be a marker for poorer health, suggests Dr Joel Zonszein (University Hospital, Albert Einstein College of Medicine, Bronx, NY). Indeed, he pointed out, a sizable proportion of the study subjects weren't even taking antihypertensive medications.

However, he agrees that elderly patients and those with more comorbidities may be at increased risk for adverse effects from aggressive BP lowering. But he is concerned about extrapolating these findings to all type 2 diabetes patients, given that extensive data show the benefit of BP lowering in younger, healthier individuals with relatively recent diabetes onset.

And, he points out, this is still only "an observational study . . . showing the J-curve or U-curve that we see with glycemic control, [body-mass index], and many other parameters. There is no [proof of] cause and effect."

Concern about intensive BP lowering in diabetes

The whole issue of how much to lower BP by in type 2 diabetes patients is a subject of much contention. Current hypertension guidelines recommend lowering BP <130/80 mm Hg in patients with type 2 diabetes, but this is not based on evidence, and recent trials, including the Action to Control Cardiovascular Risk in Diabetes (ACCORD) and International Verapamil SR-Trandolapril (INVEST) trials, have shown worse outcomes for some parameters in those who undergo intensive BP lowering (systolic BP <120 mm Hg).

Last December, however, the American Diabetes Association issued new clinical-practice guidelines that included a recommendation for a less stringent systolic BP target of <140 rather than <130 mm Hg, on the basis of evidence that there is not a great deal of additional value but there is an increase in risk in pushing systolic BP much lower than 140 mm Hg, they said.

The new Joint National Committee (JNC) 8 hypertension guidelines, which it is hoped will also address this issue, are eagerly awaited.

The current study population included 30 154 patients with diabetes (12 618 white and 17 536 African American) aged 30 to 94 years with no history of CHD or stroke. All were primary-care patients seen between January 1999 and December 2009 at one of LSU's seven public hospitals or affiliated clinics, which serve a predominantly low-income population.

During a mean six years of follow-up, incident CHD developed in 3580 white and 3680 African American patients. After adjustment for age and sex, the hazard ratios (HRs) for the development of incident CHD for African Americans with baseline systolic BPs <110, 110-119, 120-129, 130-139, 140-159, and >160 mm Hg were 1.27, 1.1, 1.03, 1.05, and 1.12, respectively (p for trend=0.058). For whites, those HRs were 1.57, 1.14, 1.05, 1.00, 0.98, and 1.03 (p for trend<0.001).

This U-shaped association—with increased risks at both ends of the systolic BP spectrum and a "sweet spot" in between—did not change after adjustment for additional confounding variables, including smoking, income, type of insurance, body-mass index, HbA1c, LDL-cholesterol, estimated glomerular filtration rate, and use of medications including antihypertensives (p for trend<0.001 for whites; p for trend=0.057 for African Americans).

In the multivariate analysis, similar trends were seen for baseline diastolic BP for both white and African American patients. With either systolic or diastolic BP viewed as a continuous variable, the nadir of CHD risk was seen at systolic BP 130-140 mm Hg and diastolic BP 80-90 mm Hg.

For the combined BP values after multivariate analysis, CHD risk for African American patients with BPs of 110/65 and 110-119/65-69 mm Hg were 1.73 and 1.16 compared with the reference group of 130-139/80-90 mm Hg (HR=1.0;p for trend<0.001). For whites, these figures were 1.60 and 1.27 (p for trend<0.001).

Further adjustment for BP during follow-up and by use or nonuse of antihypertensive medication did not change the U-shaped association, Zhao and colleagues report.

However, there was a significant interaction by age, whereby the U-shaped relationship turned into an inverse one for patients aged 60 years and older.

No "one size fits all" for BP goals in diabetes

Hu said that hypoperfusion is a likely explanation for the findings. "Low blood pressure might increase cardiovascular risk by the underperfusion of vital organs. Elderly patients with type 2 diabetes represent a population that is highly enriched with underlying coronary artery disease and may be more prone than others to display the harm of underperfusion."

Zonszein said: "The most important message is you cannot have one size fits all, for the goal or the medications. . . . We have to go to the art of medicine, get a good history, look at the patient, assess comorbidities, and try to tailor both goals and medications to each patient. . . . The sweet spot really varies. It's a moving target among patient populations."

Hu added that his group's data are not the final word. "Further study is needed to assess the association of blood pressure with the risks of other macrovascular disease outcomes, such as heart failure, stroke, and amputation."

This work was supported by LSU's Improving Clinical Outcomes Network. The authors reported no relevant financial relationships. Zonszein is on the speaker's bureaus of Merck, Takeda, Novo Nordisk, and Janssen.


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