We are witnessing a global epidemic of diabetes. A recent report in 2011 by the Centers for Disease Control and Prevention (CDC) estimates the number of people with diabetes in the United States at 26 million, which is 11.3% of adults older than 20 years.1 Seven million of those are not aware that they have diabetes. More alarming is the number of people with prediabetes, which is estimated at 79 million, corresponding to more than a third of adults older than 20. According to the CDC, prediabetes raises the risk of type 2 diabetes, heart disease, and stroke.1 In 2008, the CDC estimated the number of persons with diabetes to be 23.6 million and those with prediabetes to be 57 million. This increase in such a short time underscores the urgently progressive rate of the epidemic. In fact, nearly 50% of adults older than 20 have some form of dysglycemia, which increases their risk for complications, including microvascular and macrovascular disease (in particular kidney disease), retinopathy, blindness, amputation, and cardiovascular disease (CVD).1,2 Half of all Americans 65 years and older have prediabetes, and nearly 27% have diabetes.1 Diabetes is the seventh leading cause of death in the United States and costs $174 billion annually.1
The majority of persons with diabetes and the metabolic syndrome have hypertension that is associated with obesity, insulin resistance (IR), and dyslipidemia.3 Approximately 75% to 76% of people with diabetes, prediabetes, and the metabolic syndrome have hypertension.4–6 Patients with diabetes are 2 to 4 times more likely to develop CVD compared with patients without diabetes.7 However, patients with diabetes and hypertension have a further increased risk of developing macrovascular and microvascular disease and kidney disease, including end-stage kidney disease.2,6,8 Hypertension often precedes type 2 diabetes; alternatively, diabetes may precede hypertension.2,6 The etiologic factors linking diabetes and hypertension are not fully clear. Genetic factors, IR, inflammation, the renin-angiotensin-aldosterone system (RAAS), sodium retention, and hyperglycemia are implicated.9–12 The activation of the RAAS system and IR may trigger production of reactive oxygen species and increased oxidative stress, which may lead to endothelial dysfunction and atherogenesis.9–11 Intensive treatment of hypertension as part of the management of diabetes will result in reduced risk of microvascular and macrovascular diseases such as myocardial infarction, congestive heart failure, blindness, and chronic kidney disease.2,13
The goal recommended by the American Diabetes Association (ADA) and the American Association of Clinical Endocrinologists (AACE) for treating hypertension in diabetes is a blood pressure (BP) goal of <130/80 mm Hg.14,15 This goal has been under attack recently based on recent published results from studies such as the Action to Control Cardiovascular Risk in Diabetes (ACCORD) hypertension trial and the Investigational Vertebroplasty Efficacy and Safety Trial (INVEST).16,17 Results from the Veterans Affairs Diabetes Trial (VADT) point out increased rates of CVD when systolic BP is >140 mm Hg and diastolic BP is <70 mm Hg, perhaps underscoring the importance of pulse pressure, although this study also emphasizes the need for prompt treatment.18
The mainstay of treating hypertension and diabetes is lifestyle modification and, in particular, implementation of the Dietary Approaches to Stop Hypertension (DASH) diet.1,19 The comprehensive approach to managing diabetes and preventing complication is one that addresses all risk factors. A good example of this was performed in the Multifactorial Intervention and CVD Events in Type 2 Diabetes (Steno-2) trial. This investigation reported that during 7.8 years, there was a significant (P=.007) reduction of 53% in the composite end point of nonfatal myocardial infarction, cardiovascular death, coronary artery bypass graft surgery, percutaneous transluminal coronary angioplasty, nonfatal stroke, cardiovascular death, amputation, peripheral vascular surgery, and a 13-year reduction in mortality comparing intense (50%) vs conventional (30%) care (P=.02).20,21
The recommended initial treatment of hypertension in diabetes is an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB),14,15 but what should be the second and third drug has become controversial, particularly as drugs such as amlodipine are challenging the traditional thiazides. An interesting result from the ACCORD trial was that treating hypertension in diabetes was beneficial in reducing kidney disease but not retinopathy,16 and in persons with prediabetes, the ARB valsartan reduced development of new-onset diabetes but had no effect on reducing microvascular or macrovascular disease.22
Understanding the need to address hypertension management in diabetes and recognizing its important role in morbidity and mortality, I am appreciative of the invitation I received from The Journal of Clinical Hypertension and its Editor in Chief, Dr Michael Weber, to serve as the guest editor of this focus issue of the Journal. We decided to add key issues in the clinical management of hypertension in diabetes, prediabetes, dyslipidemia, and its comorbidities. Knowing that there are areas of uncertainty, conflicting data, and controversies, we invited globally recognized and established leaders in their respective fields of diabetes. We asked them to write expert review articles, commentaries, and even to join in debate, thus allowing them to complement the available information with their own opinions and scientific expertise.
The issue starts with pathophysiology. Drs Willa A. Hsueh and Kathleen Wyne examine the role of the RAAS system in the development of both hypertension and diabetes and its potential effect on CVD. Dr Gerald Reaven, one of the first scientists to recognize the background of what came to be known as the metabolic syndrome, examines the relationships among IR, diabetes, hypertension, and CVD, providing critically needed background to this complex clinical constellation. Drs Samuel Dagogo-Jack and Amanda Long discuss the comorbidities of hypertension and diabetes and propose how understanding their mechanisms helps provide an approach to target organ protection.
One of the direct complications of diabetes aggravated by hypertension is chronic kidney disease. Drs Ele Ferrannini and Anna Solini discuss the pathophysiology, diagnosis, and management of this critical condition that accounts for the majority of patients who require hemodialysis in this country. The recommended BP goal in treating hypertension of 130/80 mm Hg in patients with diabetes proposed by the major societies (ADA, AACE, National Kidney Foundation) has been questioned lately. Drs David Kendall (pro) and George Bakris (con) are debating the appropriate goal. This is a difficult area and these experts provide valuable insights in setting appropriate targets.
A most important population—probably the largest—is comprised of people with prediabetes, often with other features of the (cardio)metabolic syndrome. This population does not have established management guidelines, although there have been statements by the AACE. Dr Alan Garber addresses this condition and its complications, providing guidance on its diagnosis and management designed to slow the development of diabetes and CVD. Another group of patients with special issues are women with diabetes and hypertension in pregnancy. Drs Shanon Sullivan, Jason Umans, and Robert Ratner evaluate the consequence of these two conditions on the mother and the fetus during pregnancy, discussing management to prevent complications. In recent years, we are also paying attention to the pharmaceutical management of hypertension in diabetes. Where do drugs such as ACE inhibitors, ARBs, and diuretics fit in? Are β-blockers contraindicated? Or is the only priority BP control and which drug should be used is a less important question? Dr Eberhard Ritz takes the side of ACE inhibitors, Drs Joseph Izzo and Adrienne Zion highlight the value of ARBs, and Drs Gary Sander and Thomas Giles address the pros and cons of diuretics and β-blockers, recognizing that not all β-blockers or diuretics are the same. Dr Domenic Sica evaluates the importance of BP control as compared with the pleitropic effects of specific drugs.
Drs RA Ajjan and Peter Grant discuss the role of antiplatelet therapy in the prevention of CVD in patients with hypertension and diabetes, highlighting safety issues and addressing specific drug effects in management and prevention. We complete this focus issue of the journal with a comprehensive clinical approach to the treatment of hypertension in diabetes by Drs Mariela Glandt and Zachary Bloomgarden.
I hope that you will find this issue of the journal to be informative, scientifically stimulating, and most importantly, clinically relevant to the care we provide to our high-risk patients with diabetes, hypertension, dyslipidemias, and CVD.