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

Moreover, the association between blood pressure and CHD risk becomes inverse among the elderly, write Wenhui Zhao, MD, PhD, from Pennington Biomedical Research Center, Baton Rouge, Louisiana, and colleagues in Diabetes Care, published online May 20, 2013.

"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," study coauthor Gang Hu, MD, PhD, from Louisiana State University (LSU) Health Sciences Center, Baton Rouge told Medscape Medical News.

"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 Dr. Hu.

But 1 expert disagrees with the authors' conclusion that aggressive blood-pressure lowering per se is what leads to the adverse outcomes in all patients. In some, the low blood pressure itself could be a marker for poorer health, suggests Joel Zonszein, MD, director of the clinical diabetes center at 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 Diabetics

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 to less than 130/80 mm Hg in patients with type 2 diabetes mellitus, but this is not grounded on evidence, and recent trials, including ACCORD and INVEST, have shown worse outcomes for some parameters in those who undergo intensive lowering (systolic BP <120 mm Hg).

Last December, however, the American Diabetes Association (ADA) issued new clinical practice guidelines which included a recommendation for a less stringent systolic BP target of less than 140 mm Hg rather than less 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, it said.

The new 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 of age without a history of CHD or stroke. All were primary-care patients seen between January 1999 and December 2009 at one of LSU's 7 public hospitals and affiliated clinics, which serve a predominantly low-income population.

During a mean 6-year follow-up, incident CHD developed in 3580 white and 3680 African-American patients. After adjustment for age and sex, the hazard ratios for the development of incident CHD for African Americans with baseline systolic blood pressures of less than 110, 110 to 119, 120 to 129, 130 to 139, 140 to 159, and 160 mm Hg or higher were 1.27, 1.1, 1.03, 1.05, and 1.12, respectively (P for trend = .058).

For whites, those hazard ratios were 1.57, 1.14, 1.05, 1.0, 0.98, and 1.03 (P for trend < .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, and P for trend = .057 for African Americans).

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

For the combined BP values after multivariate analysis, the CHD risks 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 (hazard ratio = 1.0; P for trend < .001). For whites, these figures were 1.60 and 1.27 (P for trend < .001).

Further adjustment for blood pressures during follow-up and by use or nonuse of antihypertensive medication did not change the U-shaped association, Dr. 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 Diabetics

Dr. Hu told Medscape Medical News 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."

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Dr. 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."

Dr. 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 outcome, such as heart failure, stroke, and amputation."

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

Diabetes Care. Published online May 20, 2013. Abstract