Current Hypertension Reports

The purpose of this review is to provide an overview of existing and emerging lifestyle treatments in the clinical management of primary elevated blood pressure and hypertension in pediatric patients. The authors hope to expand the knowledge base surrounding pediatric hypertension and update clinicians on best practices to improve outcomes. Elevated blood pressure is traditionally addressed with broad lifestyle recommendations such as limiting salt consumption and losing weight. This approach is not well adapted for pediatric patients. Novel and often underutilized approaches to the treatment of hypertension in pediatrics include psychological counseling for behavior modification, circadian nutrition, consistent use of interdisciplinary teams, manipulation of macronutrients, stress management, technology-infused interventions, and systemic changes to the food environment. Elevated blood pressure is a pervasive condition affecting cardiovascular disease and mortality risk. Increasingly, pediatric patients are presenting with elevated blood pressure with etiologies known to be affected by lifestyle behaviors. Weight management, dietary modifications, and daily physical activity are well-researched methods for improving individual blood pressure measurements. These strategies can sometimes be as effective as pharmacological interventions at lowering blood pressure. However, compliance with these individual recommendations is not consistent and has led to unsatisfactory results. There are emerging treatment trends that may provide non-traditional and more effective non-pharmacologic routes to blood pressure management in pediatric patients.

The prevalence of obesity in the United States remains high, exceeding 30% in most states. As this trend continues unhindered, we will continue see a persistent rise in obesity-related metabolic effects—hypertension, dyslipidemia, diabetes mellitus, and atherosclerosis. These diseases are also the leading causes of chronic kidney diseases and end-stage renal disease. The lipid nephrotoxicity hypothesis, proposed over three decades ago, suggested that proteinuria, decreased albumin levels, and the resultant hyperlipidemia may cause a glomerulosclerosis similar to atherosclerosis. More recent studies have demonstrated the role of oxidized high-density lipoprotein (HDL) and low-density lipoprotein (LDL) particles in the progression of kidney disease. Elucidation of the role of lipid-lowering therapies and the concomitant improvement in tubulointerstitial and glomerular diseases is a further evidence of the role of lipids in renal injury. Synergistic effects of lipid-lowering drugs and blockers of the renin-angiotensin-aldosterone system (RAAS) in renal protection have also been documented. Dyslipidemia in renal disease is usually characterized by elevated LDL cholesterol, low HDL cholesterol, and high triglycerides. After an initial glomerular injury, likely to be inflammatory, a series of self-perpetuating events occur. Increased glomerular basement permeability leads to loss of lipoprotein lipase activators, which results in hyperlipidemia. Circulating LDL has a charge affinity for glycoaminoglycans in the glomerular basement membrane and further increases its permeability. Substantial amounts of filtered lipoprotein cause proliferation of mesangial cells. Proximal tubules reabsorb some of the filtered lipoprotein, and the remainder is altered during passage through the nephron. If intraluminal pH is close to the isoelectric point of the apoprotein, luminal apoprotein will precipitate, causing tubulointerstitial disease. This review shows the evidence for the role of lipids in development of chronic renal disease, the pathophysiology of lipid nephrotoxicity, and strategies available to clinicians to slow the progression of disease.

Although obesity is a disease, most patients with obesity do not undergo effective treatment nor adhere to long-term care. We examine the barriers that patients with obesity confront when searching for effective treatment and propose an integrated care model of adiposity-related chronic diseases in a cardio-renal metabolic unit. The current care of obesity is fragmented between primary care providers, medical specialists and metabolic bariatric surgeons with little or no coordination of care between these providers. The current care of obesity heavily focuses on weight loss as the primary aim of treatment thereby reenforcing the weight stigma and turning patients away from effective therapy like metabolic bariatric surgery. An interdisciplinary cardio-renal metabolic unit that, besides weight loss, emphasizes prevention/remission of adiposity-related chronic diseases may deliver thorough and rewarding care to most patients with obesity.

Diagnosis of hypertension is critically dependent on accurate blood pressure (BP) measurement, especially in patients with chronic kidney disease (CKD), in whom early antihypertensive treatment is imperative to prevent cardiovascular events. Ambulatory BP monitoring (ABPM) has successfully identified hypertensive patients at increased risk, but its role in management of CKD patients is not well defined. Loss of the nocturnal decline in BP, which is common in CKD, is associated with adverse cardiovascular events. Increased BP variability has been documented as related to worse outcome, and patients on dialysis are subject to marked BP swings. Traditional measurement in the office fails to provide a thorough picture of the 24-hour BP pattern in CKD patients. Thus, ABPM appears mandatory to better define the hypertensive status in these subjects because it provides information on diurnal BP rhythm and variability and allows identification of subjects with white-coat and masked hypertension.

The hyperactivity of the brain renin-angiotensin system (RAS) has been implicated in the development and maintenance of hypertension in several types of experimental and genetic hypertension animal models. Among the main bioactive peptides of the brain RAS, angiotensin (Ang) II and Ang III display the same affinity for type 1 and type 2 Ang II receptors. Both peptides, injected intracerebroventricularly, similarly increase blood pressure (BP); however, because Ang II is converted in vivo to Ang III, the identity of the true effector is unknown. In this article, we review new insights into the predominant role of brain Ang III in the control of BP, underlining the fact that brain aminopeptidase A (APA), the enzyme-forming central Ang III, could constitute a putative central therapeutic target for the treatment of hypertension. This justifies the development of potent systemically active APA inhibitors, such as RB150, as prototypes of a new class of antihypertensive agents for the treatment of certain forms of hypertension.

Hypertension remains a significant risk factor for development of congestive heart failure CHF), with various mechanisms contributing to both systolic and diastolic dysfunction. The pathogenesis of myocardial changes includes structural remodeling, left ventricular hypertrophy, and fibrosis. Activation of the sympathetic nervous system and renin-angiotensin system is a key contributing factor of hypertension, and thus interventions that antagonize these systems promote regression of hypertrophy and heart failure. Control of blood pressure is of paramount importance in improving the prognosis of patients with heart failure.

Obesity is increasingly recognized as a global pandemic that threatens the health of millions of people. Obesity is considered to be an important cardiovascular risk factor, but there is increasing evidence that patients with elevated body mass index may be better off than others if they develop cardiovascular or renal disease. This phenomenon has been described as the "obesity paradox" or "reverse epidemiology." This article reviews some recent publications that have studied this phenomenon as it relates to heart failure, coronary artery disease, peripheral arterial disease, kidney disease, and a cohort of patients undergoing nonbariatric surgery.