Raymond V. Oliva

Blood pressure effects of sodium–glucose co-transport 2 (SGLT2) inhibitors

Management of hypertension in diabetes is critical for reduction of cardiovascular mortality and morbidity. While blood pressure (BP) control has improved over the past two decades, the control rate is still well below 50% in the general population of patients with type 2 diabetes mellitus (T2DM). A new class of oral glucose-lowering agents has recently been approved; the sodium-glucose co-transporter 2 (SGLT2) inhibitors, which act by eliminating large amounts of glucose in the urine. Two agents, dapagliflozin and canagliflozin, are currently approved in the United States and Europe, and empagliflozin and ipragliflozin have reported Phase 3 trials. In addition to glucose lowering, SGLT2 inhibitors are associated with weight loss and act as osmotic diuretics, resulting in a lowering of BP. While not approved for BP-lowering, they may potentially aid BP goal achievement in people within 7-10 mm Hg of goal. It should be noted that the currently approved agents have side effects that include an increased incidence of genital infections, predominantly in women. The approved SGLT2 inhibitors have limited use based on kidney function and should be used only in those with an estimated glomerular filtration rate (eGFR) > 60 mL/min/1.73 m2 for dapagliflozin and ≥45 mL/min/1.73 m2 for canagliflozin. Cardiovascular outcome trials are ongoing with these agents and will be completed within the next 4-5 years.

Pheochromocytoma in Pregnancy. A Case Series and Review

Hypertensive disorders in pregnancy remain among the most understudied areas despite the recent advancement in medical care and management.1 Although most of this is ascribed to a pregnancy-specific disorder, preeclampsia, there is a paucity of data and few recommendations about another potentially disastrous hypertensive disorder, pheochromocytoma, a catecholamine producing tumor, with a reported incidence of <0.2 per 10 000 pregnancies.2 Despite its rarity, untreated pheochromocytomas carry a risk of mortality for both mother and fetus, as high as 58%.3 This may be attributed to several factors, such as the failure to detect the condition because of its extreme rarity, the tendency of these tumors to have varied presentations, and the fact that pregnancy may preclude certain imaging modalities and radioisotope testing.2,4,5 The enlarging uterus may also trigger tumor activity, in addition to the tendency for gravidas to undergo operative procedures on short notice.6 Thus, it is imperative that physicians who manage patients with pheochromocytoma familiarize themselves with special considerations in relation to pheochromocytoma during pregnancy. Focus should be directed toward understanding the indications of when women with chronic or de novo hypertension during gestation should undergo the special tests used to diagnose pheochromocytoma and how to manage the disease once diagnosed. This report surveys 6 pheochromocytomas managed at our institution, reviews the literature of pheochromocytomas, and presents recommendations on how to better suspect, detect, and manage these disorders in pregnant populations. We reviewed 6 cases of pheochromocytoma managed at the University of Chicago Medical Center between 1984 and 2009. Table 1 briefly summarizes their presentation and management. Two of these cases (cases 1 and 4) were published previously in detail but are presented to provide a more complete spectrum of presentation. View this table: Table 1. Summary of Cases ### Case 1 A 31-year–old black woman presented during gestational week 21 …

Effects of combining simvastatin with rosiglitazone on inflammation, oxidant stress and ambulatory blood pressure in patients with the metabolic syndrome: the SIROCO study

Aim: Individually, statins and thiazolidinediones (TZDs) show positive effects on atherosclerosis progression in cellular and animal models as well as patients with diabetes; however, their combined effects have not been studied. This study examines the effects of simvastatin combined with rosiglitazone on vascular inflammation, oxidant stress, ambulatory blood pressure (BP) and other atherosclerotic factors in patients with the metabolic syndrome.

Effects of nebivolol on aortic compliance in patients with diabetes and maximal renin angiotensin system blockade: the EFFORT study.

The beneficial effects of nebivolol on arterial stiffness and endothelial dysfunction are well documented in untreated hypertensive patients and differ from nonvasodilatory β‐blockers. This study tests the hypothesis that the addition of nebivolol in predominantly African American patients with type 2 diabetes already receiving maximally tolerated doses of renin‐angiotensin system (RAS) blockers will further improve large artery compliance. Patients with type 2 diabetes and hypertension on maximal RAS blockade (n=70) were randomized to nebivolol or metoprolol succinate daily. Doses were titrated until systolic blood pressure (SBP) was <130 mm Hg. Radial artery applanation tonometry and pulse wave velocity (PWV) analysis were used to derive central aortic pressures and hemodynamic indices at repeated visits at intervals during a 6‐month period. Both metoprolol succinate and nebivolol groups demonstrated reductions in brachial SBP (−8.2±4.3 mm Hg [P=.01] and −7.8±3.7 [P=.002], respectively) and aortic DBP (−2.4±1.8 [P=.039] and −4.0±2.9 mm Hg [P=.013], respectively). Aortic SBP decreased in the nebivolol group only (125.3±8 to 121.6±8.2, P=.025). There were no between group differences in aortic SBP, DBP, augmentation index, or PWV reduction. A significant increase in hemoglobin A1c was observed only in the metoprolol group. In patients with well‐controlled type 2 diabetes and hypertension treated with maximally tolerated RAS blockade, nebivolol does not offer significant reductions in aortic BP over metoprolol succinate but maintains a stable metabolic profile.

Management of Hypertension in the Elderly Population

Hypertension is common in people aged 65 and older. African Americans and women have a higher prevalence of hypertension than white individuals, and in those aged 70 and older, the hypertension was more poorly controlled than in those aged 60-69. The number of trials available in the elderly population compared with the general population are limited; hence, the database for strong recommendations as to goal blood pressure (BP) are limited. The American College of Cardiology with the American Heart Association has recently published a consensus report of management of hypertension in the elderly population. This review presents an overview of this consensus report and reviews specific studies that provide some novel findings regarding goal BP and progression of nephropathy. In general, the evidence strongly supports a BP goal of less than 150/80 mmHg. The evidence review for the consensus report supports a goal of <150/80 mmHg for the elderly with scant data in those over age 80. However, it was decided to set the goal to less than 140/90 mmHg unless the patient cannot tolerate it and then try for 140-145 mmHg. The data are scant at best for those over age 80 mmHg but some evidence exists for <150/80 mmHg. Diuretics and calcium antagonists are the most efficacious single agents for treatment; however, most patients will require two or more drugs to achieve such goals.

Sympathetic Activation in Resistant Hypertension: Theory and Therapy

Resistant hypertension defined as requiring 3 or more complementary antihypertensive drugs at maximally tolerated doses accounts for approximately 3% to 4% of all cases of hypertension. Its increased incidence over the past decade is related to the increase in obesity in the Western world. There are a number of dietary factors that affect sympathetic tone including sodium intake apart from increased body mass. This article discusses the mechanisms of sympathetic stimulation and activation in the context of animal models and human studies. In addition, there is a review of clinical trials with and without device therapy that summarizes the clinical findings. Effective management should be based on pathophysiologic principles and a focus on blood pressure reduction to levels well below 150/90 mm Hg because outcome trial evidence and Food and Drug Administration guidance supports this construct. The key to success of device-based therapy depends on identifying the cohort with true resistant hypertension that can benefit from therapies that are adjuncts to pharmacotherapy. Physicians need to concentrate on educating the patient on lifestyle modifications and themselves on use of proper combinations of antihypertensive medications. If this approach fails to result in a safe level of blood pressure then the patient should be referred to a board-certified clinical hypertension specialist.

Hypertension following kidney injury.

Arterial hypertension may result as a complication of trauma to the kidney with an incidence as high as 40%. Case reports since the 1940s document the development of resistant hypertension following falls and car accidents where the kidney was injured. Page and Engel first explained the pathophysiology of hyperreninemic hypertension secondary to kidney compression. The most common scenario is a healthy young person with new-onset hypertension and a history of blunt trauma. We present a case of resistant hypertension following trauma and its natural history.

Combination Therapy in Hypertension Treatment

Hypertension guidelines have recommended to lower blood pressures to at least 140/90 mmHg to prevent cardiovascular diseases. However, initiating monotherapy to hypertensive patients, especially with difficult-to-treat hypertension, fails to lower blood pressure to the desired goal. The formulation of single-pill combinations or fixed-dose combinations has made therapeutic management of hypertension less complicated. They have the same efficacy as the single agent, allow patient adherence, and at the same time lower the side effects if maximum doses of the single agent are given. However, cost still remains an issue since most of these drugs are not generic. In the future, there will be triple combination pills and even the polypill which show promise in the management of hypertension.

Can ambulatory blood pressure serve as a biomarker for presence of chronic kidney disease

I t is well established that poorly controlled blood pressure (BP) is a major risk factor for chronic kidney disease (CKD) development as well as increased cardiovascular morbidity and mortality [1]. Reduction in BP to levels below 130/80 mmHg has traditionally been a key strategy for reducing the rate of CKD progression and the cardiovascular disease risk [2,3]. Although the diagnosis and treatment of hypertension has been evaluated exclusively using seated resting BP in physician offices, home and 24-h ambulatory blood pressure monitoring (ABPM) are now being utilized as an accepted method for evaluating hypertension [4,5]. ABPM offers a better representation of total BP load over the 24-h period, is noninvasive, easily reproducible, accurate and portable. Studies using ABPM predict cardiovascular events even after adjustments of conventional office BP readings [6,7]. Historically, ABPM also allows for night-time evaluation of BP dipping status in the context of target organ damage as well as cardiovascular morbidity and mortality [8,9]. People with CKD, that is, stage 3 nephropathy and evidence of vascular inflammation such as presence of microalbuminuria, frequently have resistant hypertension and require an average of one or more additional medications to help achieve BP control [10,11]. The current study by Mathisen et al. [12] is unique in that it demonstrates an association between level of BP assessed by ABPM and changes in direct measurement of glomerular filtration rate (GFR) during the earliest stages of kidney disease. The results showed a positive correlation between daytime systolic and night-time SBP and DBP with GFR levels; the higher the measured BP, the higher the measured GFR in normotensive patients.