A 55-year-old accountant has recently been diagnosed with impaired fasting glucose. Because of her obesity and the cardiometabolic syndrome (CMS), she will attempt to adhere to a formal dietary consultation, aerobic exercise, and weight loss program as she was advised. Her blood pressure (BP) was 138/84 mm Hg; on her follow-up visit 2 weeks later, it was 136/82 mm Hg. Her body mass index was 26 kg/ m2, with a waist-to-hip ratio of 1.23. She is concerned about starting antihypertensive medication because she read in a recent magazine article that BP medications can actually worsen or even cause diabetes. What is your advice?
Mortality rates for patients with type 2 diabetes remain two to four times higher than those for patients without diabetes. Worldwide, the number of diabetic patients is projected to more than double in the next three decades—from 171 million in 2000 to 366 million in 2030. In certain racial/ethnic groups in the United States, there is a higher prevalence of diabetes, often associated with elevated BP: 11.7% of African Americans and 9.6% of Mexican Americans have diabetes compared with 4.8% of non-Hispanic whites. Optimal control of BP and dyslipidemia and the use of low-dose aspirin remain extremely important, along with weight reduction and increased physical activity. Based on multiple clinical trials and guidelines from the American Diabetes Association and the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7), a target BP goal of <130/80 mm Hg is recommended for patients with diabetes, although no specific goal is listed for patients with CMS. Therefore, this patient may benefit from further BP lowering and, specifically, the use of medication despite the fact that her BP is below the level of 140/90 mm Hg, previously considered to be hypertension.
Patients who want to attempt lifestyle modification as the initial means of controlling high BP should be encouraged. Various components of nonpharmacologic care may improve BP, especially in patients who do not have BP elevations >20/10 mm Hg above their target. JNC 7 reported that a sodium reduction of <100 mmol/d correlated with a 2- to 8-mm Hg systolic BP reduction. If combined with the Dietary Approaches to Stop Hypertension (DASH) eating plan, a patient can achieve significant BP reduction. While weight loss is difficult, a successful reduction of 20 lb corresponds to a 5- to 20-mm Hg systolic BP decrease. Furthermore, as a component of a weight loss program, aerobic exercise (an increase in physical activity for at least 30 minutes most days of the week) has been demonstrated to produce a 4- to 9-mm Hg systolic BP reduction. These lifestyle changes are often difficult to maintain, but they may assist with BP control. Lifestyle modifications are definitely beneficial in terms of CMS and prevention of new-onset diabetes.
The Diabetes Prevention Program (DPP) demonstrated that multifactorial lifestyle modification reduces the risk for diabetes, hypertension, and dyslipidemia, supporting the proposition that with BP reduction, sodium reduction, and weight loss, progression of glucose intolerance may be prevented.
Surprisingly, many clinicians do not recognize the potential benefit of relieving psychosocial stress as a means of reducing elevated BP. JNC VI reported that relaxation responses and biofeedback have demonstrated statistically significant decreases in both systolic and diastolic BPs in multiple studies.
Nevertheless, it is reasonable to expect that a hypertensive patient with CMS will at some point need pharmacologic antihypertensive intervention to further decrease cardiovascular risk and obtain the benefits of modulation of the renin— angiotensin system (RAS). Lowering BP, and thus reducing cardiovascular and renal risk in patients with type 2 diabetes, can be achieved with multiple agents, including thiazide diuretics, β blockers, angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), and calcium channel blockers. In contrast, several older agents—including central α2 agonists, α1 blockers, and perhaps vasodilators—have not been demonstrated to offer outcome benefit for hypertension, especially in high-risk patients. A wide range of other medications is available and should be utilized; however, patients, especially those with CMS, may benefit from agents that prevent further progression of glucose intolerance while controlling BP. Many patients with higher levels of BP will need multiple or combination medications.
It has been shown in multiple trials that agents that block the RAS may not only lower BP, but may also prevent new-onset diabetes. For instance, in the Candesartan in Heart Failure Assessment of Reduction in Morbidity and Mortality (CHARM) trial, new-onset diabetes was a prespecified end point. In 5436 patients, there appeared to be a 22% reduction in new-onset diabetes with candesartan. Similar benefit has been suggested in other trials utilizing RAS-blocking agents, including ramipril, captopril, enalapril, and losartan. If the patient has been appropriately evaluated and microalbuminuria has been demonstrated—or if there is evidence of diabetic nephropathy, left ventricular dysfunction, or ischemic heart disease—ACEIs or ARBs may be particularly beneficial. Randomized trials have provided compelling evidence that RAS-blocking agents decrease cardiovascular and renal outcomes, specifically in patients with nephropathy and left ventricular dysfunction, but regardless of the antihypertensive agent, it is essential to achieve a BP goal of <130/80 mm Hg.
Although there is, indeed, increasing evidence that certain antihypertensive medications may decrease the risk of glucose intolerance, even the use of a thiazide-type diuretic has been shown to reduce risks and potential complications of cardiovascular disease in patients with diabetes. For instance, chlorthalidone lowered BP and reduced cardiovascular events in patients with diabetes in the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). Therefore, the use of thiazide diuretics should not always be avoided, despite the potential metabolic effects in patients with diabetes. The fact that thiazide diuretics have been shown in ALLHAT to be protective against cardiovascular events, despite the presence of diabetes or new-onset glucose intolerance, does not completely confirm that the long-term derangements associated with glucose intolerance caused by diuretics will not be problematic at some time in the course of the patient's care. Indeed, in a 12-year follow-up of the Multiple Risk Factor Intervention Trial (MRFIT) in middle-aged men, new-onset diabetes was the source of increased cardiovascular risk and mortality.
Lifestyle modification remains the bedrock of care for patients with CMS, but, while in the short term (2–4 years) new-onset diabetes does not appear to be an increased risk for cardiovascular events, long-term tight control of multiple risk factors, including antihypertensive agents to maintain BP <130/80 mm Hg, should be achieved to avoid the ravages of diabetes-related cardiovascular disease.
This patient should be encouraged to continue lifestyle modifications and be educated regarding the proven evidence-based benefits of antihypertensive medications. She should be appropriately evaluated for signs of target organ damage, which would indicate the need for agents based on compelling conditions and comorbidities, especially RAS-blocking agents. Specifically, because of the presence of CMS, she has a markedly increased risk of type 2 diabetes in the future. While guidelines have yet to be developed to address this dilemma, a prudent clinical approach would not further add to the patient's risk for glucose intolerance.