July 2010 Issue

Hypertension in Diabetes — Intensive Treatment May Be Risky for Some Patients
By Rita E. Carey, MS, RD, CDE
Today’s Dietitian
Vol. 12 No. 7 P. 12

Hypertension, defined as blood pressure greater than or equal to 140/90 mmHg, is the most prevalent risk factor for heart and macrovascular disease, as it is present in up to 70% of first heart attack, first stroke, and heart failure patients.1 Hypertension affects up to 60% of people with diabetes and substantially increases the risk these individuals have for coronary disease events (eg, heart attack, heart failure).2 In fact, people with both diabetes and hypertension have two to four times the risk of developing cardiovascular disease as nondiabetic people with hypertension.2

Several large clinical trials have demonstrated that lower mean blood pressure levels reduce the morbidity and mortality from cardiovascular disease in people with diabetes. The results of these studies have prompted healthcare professionals to set blood pressure targets for patients with diabetes and hypertension at levels lower (less than or equal to 130/70 vs. less than or equal to 140/80 mmHg) than those recommended for the general population.

However, recent evidence suggests that a threshold may exist where intensive efforts at lowering blood pressure may actually increase the risk of coronary heart disease events in some patients.

Earlier Research
Multiple studies have examined ways to reduce heart disease risk in populations both with and without diabetes. The UK Prospective Diabetes Study (UKPDS) was one of the first studies to find significant improvement in both macrovascular and microvascular disease risk in participants whose mean blood pressure was reduced to less than or equal to 144/82 mmHg. In the UKPDS, each 10-mmHg decrease in mean systolic blood pressure was associated with a 12% reduction in risk for all complications related to diabetes and an 11% reduction of risk of myocardial infarction.3

In the Hypertension Optimal Treatment trial, researchers found that participants with a targeted diastolic blood pressure of less than 80 mmHg achieved optimal outcomes.4 A large meta-analysis by the World Health Organization/International Society of Hypertension indicated that systolic blood pressure was the strongest predictor of reduction in the rate of stroke and coronary disease events.5

These studies provide evidence that a target blood pressure of less than or equal to 130 to 140/80 mmHg for people with diabetes reduces rates of cardiovascular disease.

How Low Is Too Low?
Historically, diastolic blood pressure has been considered the best predictor of cardiovascular disease risk in people with hypertension. But this paradigm began to change about 40 years ago when systolic blood pressure became the accepted predictor of risk. Today, some researchers believe that a combination of measurements—systolic blood pressure, diastolic blood pressure, and pulse pressure (the numerical gap between systolic blood pressure and diastolic blood pressure)—may paint a more complete picture of risk for a larger variety of patients.

In a paper published in 1997 in Circulation, Franklin et al wrote that as people age, systolic blood pressure gradually rises while diastolic blood pressure starts to decline. The decline in diastolic blood pressure is an indicator of increased arterial stiffness, whereas the increase in systolic blood pressure is an indicator of increased peripheral vascular resistance and overall cardiac output.

In a small observational study by Osher and Stern published in the February 2008 issue of Diabetes Care, researchers found that treating patients to a targeted systolic blood pressure of less than 130 mmHg resulted in a concomitant lowering of diastolic pressure to less than or equal to 70 mmHg in more than one half of participants (146/257). Patients with the lowest achieved diastolic pressure had a nearly twofold higher prevalence of preexisting ischemic heart disease. A low diastolic pressure was also associated with older age.

Osher and Stern commented that in recent trials such as the Anti Hypertensive and Lipid Lowering to Prevent Heart Attack Trial, multiple drug regimens helped a significant number of participants achieve systolic blood pressure targets of less than 130 mmHg. Mean diastolic blood pressures were reduced accordingly, with mean diastolic blood pressure shifting from the mid-80s to 74 mmHg. According to these authors, if the mean diastolic blood pressure was 74 mmHg, a considerable number of participants in this study must have fallen one or two standard deviations above and below this mean. Therefore, some participants likely reached diastolic blood pressure levels of 50 to 60 mmHg, a range that has potentially dangerous consequences.

Diastolic hypotension is a risk factor for increased coronary events, especially in older adults. Low diastolic pressure reduces perfusion, the transfer of arterial blood throughout the microvasculature to tissues of the body, which may lead to large-organ damage or failure. Excessive diastolic lowering, therefore, may be dangerous for some patients, as evidenced by data gathered in the Framingham Heart Study and International Verapamil-Trandolapril Study (INVEST). These studies found that the risk of coronary heart disease and myocardial infarction increased for patients with lower diastolic pressures. The Framingham study found that the risk of coronary events increased with lower diastolic pressure at any level of systolic pressure greater than 120 mmHg.6 INVEST researchers saw that risk of a first occurrence of nonfatal myocardial infarction was increased for patients with diastolic pressure less than 70 mmHg.7

Future Recommendations
An outcome of these findings will likely be a recommendation to individualize blood pressure treatment and goals for patients with diabetes. Older adult patients with diabetes and/or patients with diabetes and heart disease are the most likely candidates to develop low diastolic blood pressure with multiple antihypertensive medications. Considerations of age, diastolic blood pressure, pulse pressure, and preexisting heart disease may therefore prompt healthcare providers to aim for more moderate reductions in blood pressure to reduce the risk of cardiac events in these patients.

— Rita E. Carey, MS, RD, CDE, is a dietitian practicing in northern Arizona.

References
1. Lloyd-Jones D, Adams R, Carnethon M, et al. Heart disease and stroke statistics—2009 update: A report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation. 2009;119(3):480-486.

2. American Diabetes Association. Hypertension management in adults with diabetes. Diabetes Care. 2004;27(suppl 1):s65-s67.

3. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes.: UKPDS 38. UK Prospective Diabetes Study Group. BMJ. 1998;317(7160):703-713.

4. Zanchetti A, Hansson L, Menard J, et al. Risk assessment and treatment benefit in intensively treated hypertensive patients of the hypertension Optimal Treatment (HOT) study. J Hyperten. 2001;19(4):819-825.

5. Turnbull F; Blood Pressure Lowering Treatment Trialists’ Collaboration. Effects of different blood pressure lowering regimens on major cardiovascular events: Results of prospectively designed overviews of randomized trials. Lancet. 2003;362(9395):1527-1535.

6. Franklin SS, Khan SA, Wong ND, Larson MG, Levy D. Is pulse pressure useful in predicting risk for coronary heart disease? The Framingham Heart Study. Circulation. 1999;100(4):354-360.

7. Messerli FH, Mancia G, Conti CR, et al. Dogma disputed: Can aggressively lowering blood pressure in hypertensive patients with coronary artery disease be dangerous? Ann Intern Med. 2006;144(12):884-893.

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