Current Hypertension Reviews - Volume 7, Issue 3, 2011

The increase in the prevalence of obesity, which has been considered an epidemic by the World Health Organisation, is a serious, worldwide, health problem. Importantly, hypertension and diabetes, especially type 2 diabetes, are frequently associated with obesity, and together, constitute a significant burden, both in terms of patients' morbidity and health care costs. The driving forces linking hypertension, diabetes and obesity remain to be clarified due in part to the fact that environmental, genetic, life style and behavioural confounders are involved in generating the disease state. Both hypertension and diabetes affect the same major target organs. Importantly, taken in isolation, obesity, hypertension and diabetes are all associated with increased risks in the development of cardiovascular and renal complications; however, with the coexistence of diabetes and hypertension the risk is elevated more substantially. The purpose of this special issue is to present the current findings on “hypertension and cardiovascular-renal complications in diabetes”, especially focusing on the mechanisms linking the three conditions (hypertension, diabetes and cardiovascularrenal complications) with the main emphasis being on disease onset and development, and pharmacological treatment for hypertension in diabetes. Morales-Villegas reviewed cardiovascular risk factors widely including hypertension, diabetes, atherosclerosis and inflammation. Regarding the mechanisms, Sugimoto et al. discussed that insulin resistance plays a key role in metabolic syndrome as well as hypertension in obesity associated with activation of renin-angiotensin-aldosterone system, sympathetic nervous system and salt sensitivity, and unbalanced regulation of adipocytokines is also a major factor on progression of insulin resistance. They also proposed therapeutic approaches to hypertension in obesity or metabolic syndrome targeting on the insulin resistance. Masuo et al. reviewed the “epinephrine hypothesis”, which might explain how the adreno-medullary hormonal system could contribute to the development of hypertension by augmenting sympatho-neuronal norepinephrine release. Recently several investigations have shown that childhood obesity and birth-weight may relate to future cardiovascular risks, hypertension, metabolic syndrome, and obesity. Kong et al. investigated the relationships between birth-weight and components of metabolic syndrome in young school children with a longitudinal study. They found lower birth-weight had higher risk of clustering of metabolic syndrome components even in children aged 7-9 years. They concluded that monitoring growth throughout childhood is necessary to reduce the risk of metabolic syndrome. Stanley et al. discussed that the growing incidence of obesity and higher rates of metabolic syndrome in mental health patients placed this group of patients at much higher risk of type 2 diabetes and cardiovascular diseases. They suggested that those patients need not only psychotropic medications but also lifestyle modification. Lifestyle modification is the first line treatment for obesity and type 2 diabetes. Buranakijaroen et al. showed simple lifestyle modification could significant improvements on insulin resistance over a 4- month period, but this rebounded at 6 months. In this study, a simple instruction on mild losing weight and exercises provided by a trained nurse every 2 months had been found to affect on the insulin sensitivity in hypertensive patients with metabolic syndrome However, the effect was transient. Siegel et al. They discussed the benefit of treatment for hypertension in diabetes, particularly focused on the Action to Control Cardiovascular Risks in Diabetes Study (ACCORD). The combination of hypertension with obesity and diabetes, for a variety of reasons, renders the hypertension difficult to control, with patients frequently requiring two or more types of medications to achieve blood pressure goals. Masuo reviewed a wide range of pharmacological treatments for hypertension in obesity. A better understanding of the relationships and interactions between the physiological mechanisms of hypertension and diabetes may help in the development of appropriate clinical treatment of hypertension accompanied with diabetes. This special issue covered a wide range of “Hypertension and Diabetes” issues including, physiology and treatments, but all articles are very unique. The editor would like to thank the authors for submissions for our special issue and the reviewers for their help. I enjoyed editing the variety of articles. I hope that this special issue is useful for your clinical medicine, research and reducing a population of obesity worldwide.

In this article, we review relevant concepts in Preventive Cardiovascular Medicine. Among the most important concepts analyzed are the following. Ideal Cardiovascular Health: A new construct proposed in 2010 by the American Heart Association (AHA) as a motivational concept, with the aim of communicating the ideal profile of cardiovascular health to the general public. Cardiovascular Risk Factors: In the absence of an ideal cardiovascular health profile in the 99.99% of adults, an objective cardiovascular risk evaluation is an obligated task and one that cannot be postponed by any physician. Cardiovascular Risk Stratification: Cardiovascular event prediction system elaboration, like the Framingham, is based on the incorporation and pondering of the predictive value of immutable variables as are age, gender and other mutable variables that are susceptible to treatment like: hypercholesterolemia, hypertension, hyperglycemia and smoker. These predictive systems allowed cardiovascular risk calculation to treat determining factors and decrease the statistic probability of a fatal or disabling cardiovascular event. Cardiovascular stratification and therapeutic goals: Age is the main risk factor for cardiovascular events, for instance, a man older than 45, or a woman older than 55, even with a blood pressure, total cholesterol and glucose in adequate levels and no smoker will have a calculated cardiovascular risk over 0.5% per year. Any stratification of the cardiovascular risk is not transcendental without a preventive-therapeutic action. Up-today and before the ATP-IV guidelines publication, therapeutic goals are established according to the cardiovascular risk level calculated with the Framingham method 2008. Beyond population approaches that are investigating massive treatments (poly-pill or polycap), and independently from cardiovascular risk stratification method employed, cardiovascular risk assessment is the clinical approach with the greatest impact in a medical practice, this enables to establish strategies to fulfill our most important goal as doctors, which is to show all individuals a way to have long lives and with quality of life.

Insulin resistance (IR) is one of main causes of metabolic syndrome (Mets), which is clustered with several risk factors for cardiovascular disease. IR is also main cause of essential hypertension (EHT) as well as activation of renin-angiotensin-aldosterone system (RAAS), sympathetic nervous system (SNS) and salt-sensitivity. Recent researches reveal that IR is closely linked with RAAS, SNS and salt sensitivity especially in subjects with obesity. Unbalanced regulation of adipocytokines is also playing an important role on the progression of IR. In this review paper, we reviewed a role of IR in pathogenesis of EHT and therapeutic approaches to EHT with obesity or Mets targeting on the IR.

Epinephrine accounts for 80%, while norepinephrine accounts for 20% of the total hormone secreted from the adrenal medulla. Further, in certain situations epinephrine may be released as a co-transmitter with norepinephrine from postganglionic sympathetic nerves. Epinephrine is known as a prime mover in the “fight or flight” response with epinephrine elevating heart rate, augmenting neurogenic vasoconstriction, reducing blood flow to the skin and the kidneys, increasing the production of sweat, and widening the smaller bronchioles in the lungs. Its action raises blood-sugar levels by stimulating glucose production in the liver, and blood fatty-acid levels in adipose tissue. These effects on the cardiovascular system could perhaps play an important role in the onset and maintenance of hypertension, obesity and the metabolic syndrome (type 2 diabetes). The “epinephrine hypothesis” proposes that circulating epinephrine is taken up by sympathetic nerves, thereby promoting norepinephrine release during sympathetic nervous system stimulation. It is suggested that binding of co-released epinephrine to pre-synaptic β-adrenoceptors augments exocytotic release of norepinephrine and contribute to high blood pressure (hypertension). Thus, the “epinephrine hypothesis” might explain how the adreno-medullary hormonal system could contribute to the development of essential hypertension by augmenting sympathoneuroral norepinephrine release. There is evidence that the sympathetic nerves of hypertensive patients do release epinephrine as a co-transmitter. In this review, results will be presented which suggest that epinephrine is synthesized in situ in sympathetic nerve endings via the action of phenylethanolamine-N-methyltransferase (PNMT), which is induced by chronic mental stress exposure. Accordingly, this represents a biomarker of chronic mental stress, rather than a specific mechanism of hypertension, as proposed in the “epinephrine hypothesis”.

We investigated the relationships of birthweight and postnatal growth with the components of metabolic syndrome and their clustering in young schoolchildren in Korea. The subjects comprised 261 children aged 7-9 years who were recruited from an elementary school. Information on birthweight was obtained from their parents using a questionnaire, and data were also collected via anthropometric measurement, and biochemical examinations including blood. The current body mass index (BMI) and change in weight SD score were associated with clustering of metabolic risk factors. Those in the lowest birthweight group (<2.5kg) had an approximately sixfold increased risk of clustering of metabolic syndrome components compared to the others when adjusted for gender, age, current BMI, and maternal factors. Accelerated growth was also associated with an approximately tenfold increased risk for adverse effect regarding clustering of metabolic risk factors than those with normal growth patterns, even in children aged 7-9 years. Systolic and diastolic blood pressures (BPs) were the only components that were positively associated with weight SD score change and current BMI. The results of this study suggest that monitoring growth throughout childhood is necessary to reduce the risk of metabolic syndrome.

In Australia, rates of obesity in the general population are on the rise. The growing incidence of obesity and higher rates of metabolic syndrome in mental health patients places this group of people at a much higher risk for type 2 diabetes and cardiovascular disease. Treatment effects via psychotropic medications, and lifestyle factors such as diet and exercise suggests that attention needs to be drawn to this vulnerable population. Assessment and the ongoing monitoring of physical health is essential in the prevention of major physical illness in people with a mental disorder.

A simple instruction on the lifestyle modification study was conducted on 51 hypertensives with metabolic syndrome. Significant weight reductions from baseline, 67.7 ± 11.2 kg, was noted at the 2nd month, 66.8 ± 11.2 kg, (p <0.01), 4th month, 66.6 ± 11.3 kg, (p <0.01) and 6th month, 66.8 ± 11.5 kg, (p <0.01). Decrements of insulin levels from 13.5 ± 7.3 mU/L at baseline to 12.3 ± 6.6 mU/L at the 2nd month (p = 0.075) and to 11.7 ± 6.2 mU/ L at the 4th month (p = 0.025) were observed. HOMA-IR score was also improved from 3.6 ± 2.0 at baseline to 3.2 ± 1.7 at the 2nd month (p = 0.047) and to 3.1 ± 1.8 at the 4th month (p = 0.03). However, there was no significant change in the insulin levels and HOMA-IR at the 6th month when compared to those at baseline.

The prevalence of obesity, hypertension and type 2 diabetes mellitus-all part of the metabolic syndrome--is increasing in the US and worldwide. In this setting, it is important to understand the effects of antihypertensives on several components of the metabolic syndrome. Overall, has treatment of hypertension in diabetes been beneficial? To answer this question, the authors have reviewed pertinent clinical studies. The Action to Control Cardiovascular Risks in Diabetes Study (ACCORD) was a well-designed trial of 10,251 patients with type 2 diabetes mellitus that studied the effects of tight control of blood sugar, hypertension and lipids. Disappointingly, as compared with standard treatment, the use of intensive therapy to target normal glycated hemoglobin levels, tight lipid control by adding fenofibrate to a statin and aggressive blood pressure treatment with a goal of 120 mm Hg did not significantly reduce major cardiovascular events. Focusing on patients with hypertension, the authors compare these results to other studies of the same issues and speculate about reasons for the lack of benefit in ACCORD. Finally, the authors speculate on whether future treatment might be guided by genetic markers.

Obesity, hypertension and obesity-related hypertension are growing health problems. Several epidemiological studies have shown a high prevalence of cardiovascular complications and all cause of mortality in obesity and hypertension. Obesity and hypertension are important and independent risk factors for cardiovascular disease development. An integrated cardiovascular risk management approach involving aggressive blood pressure (BP) control should be adopted in patients at high cardiovascular risk (i.e. those with ischemic heart disease, end-organ damage, type 2 diabetes) and the use of well-tolerated antihypertensive agents with protective benefits beyond BP lowering. The identification and management of risk factors is an important part of the overall management of hypertensive patients. Given that obese patients are more predisposed to target organ damage development, stringent targets for blood pressure control have been set in clinical guidelines, including those of the Joint National Committee (JNC-7) [1], the World Health Organisation and the International Society of Hypertension (WHO/ISH) [2], the European Society of Hypertension (ESH) [3] and the Japanese Society of Hypertension (JSH-2009) [4]. Pertinently, clinical trials and real-life evidence suggest that these targets are difficult to achieve. Hypertension in obesity is characterized by stimulation of the renin-angiotensin-aldosterone system (RAAS), elevated sympathetic activity, insulin resistance and selective leptin resistance. Importantly, these characteristics, even in isolation constitute risk factors for cardiovascular disease development and progression. It is therefore imperative that pharmacological treatments should be selected based on favourable effects on these factors. Furthermore, in choosing an antihypertensive agent, effectiveness needs to be accompanied by favourable metabolic, cardioprotective, and renal protective properties. Recent pharmacogenetic studies have shown that several polymorphisms may contribute to antihypertensive effectiveness. Weight loss is recommended as the first line of treatment for hypertension associated with obesity. Indeed, lifestyle modification including a low caloric diet, reducing sedentary behaviour and exercise form the foundation of all therapy. For the subjects who are more severe obesity or inability to undertake an exercise program, bariatric surgery are recommended. Anti-obesity drugs have been developed but unfortunately some were associated with significant side effects and were recently withdrawn from the markets in the United States, Europe and Australia. Leptin administration has a theoretical basis in obesity therapy and, while it has been examined in overweight and obese human subjects and in animal models, the anti-obesity effects of leptin administration are controversial. The combination of high blood pressure with obesity, for a variety of reasons, renders the hypertension difficult to control, with patients frequently requiring two or more types of medications to achieve blood pressure goals. Many large cohort studies have compared the efficacies of antihypertensive drug classes in hypertensive patients with the metabolic syndrome, however, there are few systemic reviews of antihypertensive drug treatments for patients with obesity. Moreover the mechanisms underlying both obesity and hypertension remain to be elucidated therby making it difficult to achieve blood pressure goals. In this review I aim to provide a synthesis of the current data examining both pharmacological and nonpharmacological antihypertensive treatments in those patients with obesity-related hypertension.

Hypertension is common (prevalence up to 75 %) in patients with sporadic primary hyperparathyroidism and can be cured by parathyroidectomy. However, there is still uncertainty about the pathophysiology of parathyroid hypertension. The limited and partly controversial data available may be explained by the low prevalence of sporadic primary hyperparathyroidism, the chance of coexisting primary hypertension, and the low number of studies comparing pathogenic mechanisms before and after successful parathyroidectomy. Parathyroid hypertension is associated with reversible pathogenic mechanisms : a) higher plasma norepinephrine (NE) levels, suggesting sympathetic activation; b) a tendency to develop hyperaldosteronism regardless of largely normal plasma renin activity; c) functional and structural changes of blood vessels; 4) increased cytosolic free calcium and reduced intracellular magnesium levels in blood cells, and 5) increased secretion of a hypertensive parathyroid factor resulting in a generalized rise in intracellular cytosolic calcium. Total peripheral vascular resistance is increased in parathyroid hypertension and may be related, at least in part, to an imbalance between cardiovascular NE responsiveness and circulating NE levels. The majority of hypertensive patients with sporadic primary hyperparathyroidism have hypertension stage 1, but occasionally hypertensive crisis occurs in parathyroid hypertension. The death risk of hypertensive patients with primary hyperparathyroidism is 50 % higher than that of normotensive patients with primary hyperparathyroidism. Parathyroid hypertension can be normalized by antihypertensive therapy. Uncomplicated hypertension per se is not a generally accepted indication for parathyroidectomy.