The Role of Angiogenesis Inhibitors in Hypertension: Following "Ariadne's Thread".

Arterial hypertension (HT) is one of the most frequently recorded comorbidities among patients under antiangiogenic therapy. Inhibitors of vascular endothelial growth factor and vascular endothelial growth factor receptors are most commonly involved in new onset or exacerbation of pre-existing controlled HT. From the pathophysiology point of view, data support that reduced nitric oxide release and sodium and fluid retention, microvascular rarefaction, elevated vasoconstrictor levels, and globular injury might contribute to HT. The purpose of this review was to present recent evidence regarding the incidence of HT induced by antiangiogenic agents, to analyze the pathophysiological mechanisms, and to summarize current recommendations for the management of elevated blood pressure in this field.

Human Immunodeficiency Virus Infection And Hypertension. Is There a Connection?

Data support that hypertension (HTN) is prevalent among human immunodeficiency virus (HIV) patients contributing to increased risk of cardiovascular disease. Immunodeficiency and prolonged antiretroviral treatment along with common risk factors including older age, male gender, and high body mass index might conduce to greater incidence of HTN. The purpose of this review was to summarize recent evidence of the increased cardiovascular risk in these patents linking HIV infection to HTN.

Air pollution and arterial hypertension. A new risk factor is in the air.

Air pollution is one of the greatest environmental threats and has been implicated for several adverse cardiovascular effects including arterial hypertension (HTN). However, the exact relationship between air pollution exposure and HTN is still unclear. Air contamination provokes oxidative stress, systemic inflammation, and autonomic nervous system imbalance that subsequently induce endothelial dysfunction and vasoconstriction leading to increased blood pressure. The aim of this review was to describe the potential mechanisms by which air pollution contributes to HTN and to summarize the consequences of short- and long-term exposure.

Renal Fibromuscular Dysplasia: A Not So Common Entity of Secondary Hypertension.

Fibromuscular dysplasia is a rare noninflammatory vascular disease characterized by nonatheroslerotic stenosis predominantly seen in young women, whereas the majority of cases involve the renal arteries causing secondary hypertension. Most noninvasive screening tests are not quite sensitive or reproducible to rule out renal artery stenosis, but renal angiography usually confirms the diagnosis. Percutaneous renal artery angioplasty is the treatment of choice; however, it may not result in normalization of blood pressure if diagnosis is delayed. Continued follow-up is necessary since stenosis reoccurs.

Apelin and relaxin plasma levels in young healthy offspring of patients with essential hypertension.

Epidemiologic studies have shown that healthy offspring of hypertensive patients exhibit many features of the metabolic syndrome, such as hyperinsulinemia, insulin resistance, and lipid disorders, while hypoapelinemia and hyporelaxinemia may contribute to vascular damage that accelerates atherogenesis. The aim of this study was to determine apelin and relaxin plasma levels in the healthy offspring of hypertensive patients and to compare the findings with those of healthy offspring of healthy parents, matched for age, sex, and body mass index (BMI). Forty-six (24 men and 22 women) healthy offspring of hypertensive patients, mean age 18±3 years and BMI 22.4±1.4 kg/m(2) (group A), and 50 healthy offspring of healthy parents (28 men and 22 women), mean age 18±3.2 years and BMI 22.6±1.7 kg/m(2) (group B), were studied. The apelin and relaxin plasma levels (enzyme-linked immunosorbent assay method) were determined in the study population. The two groups were matched for age, sex, and BMI. Plasma apelin levels (6±3 vs 105 pg/mL, P<.001) and relaxin plasma levels (20±7 vs 29±8 pg/mL, P<.001) were significantly lower in group A compared with group B, respectively. Our findings suggest that healthy offspring of healthy parents have significantly lower plasma apelin and relaxin levels. This group of individuals needs closer follow-up and further examination.

Masked hypertension and atherogenesis: the impact of apelin and relaxin plasma levels.

Recent evidence demonstrates that masked hypertension (MH) is a significant predictor of cardiovascular disease, while apelin and relaxin are two novel factors with a significant role in vascular regulation. Apelin is an adipokine that elicits endothelium-dependent vasorelaxation and reduces arterial blood pressure, while relaxin is a protein hormone that induces the production of nitric oxide and vascular endothelial growth factor and inhibits endothelin and angiotensin II. This study aimed to investigate whether apelin and relaxin plasma levels are affected in patients with MH and compare the findings with those of healthy normotensives. One hundred-thirty (60 men, 70 women) healthy patients with a mean age of 45±12 years who had clinic blood pressure <140/90 mmHg were studied. The whole study population underwent 24-hour ambulatory blood pressure monitoring (ABPM). According to the ABPM recordings, 24 individuals (8 men, 16 women) had MH and the remaining 106 patients (52 men, 54 women) had normal ABPM recordings. Apelin and relaxin plasma levels were determined in both groups (enzyme-linked immunosorbent assay method). The apelin (220±121 vs 315±147 pg/mL, P=.001) and relaxin (35.2±6.7 vs 56.8±13.6 pg/mL, P<.001) plasma levels were significantly lower in the masked hypertensive group compared with normotensive controls. Our findings suggest that patients with masked hypertension have significantly lower apelin and relaxin levels. This observation may have prognostic significance for future cardiovascular events in patients with MH and needs further investigation.

A case report of Gordon's syndrome in a 20-year-old male with free medical family history.

Gordon's syndrome is a rare autosomal dominant disease that manifests in childhood. It is characterized by hypertension, hyperkalemic hyperchloremic metabolic acidosis, low renin and usually normal aldosterone levels, and it is sensitive to thiazide diuretics. A 20-year-old male with a history of diagnosed Gordon's syndrome was referred to a nephrology clinic for evaluation. The patient, who was under treatment with hydrochlorothiazide, had been diagnosed with Gordon's syndrome at the age of 11, when he presented hypertension and episodes of hyperkalemic hyperchloremic metabolic acidosis. However, none of his relatives had been diagnosed with this syndrome. Therefore, we assume that our patient might be a case of de novo gene mutation.

Hypertension crisis.

Hypertensive crises (76% urgencies, 24% emergencies) represented more than one fourth of all medical urgencies/emergencies. Hypertensive urgencies frequently present with headache (22%), epistaxis (17%), faintness, and psychomotor agitation (10%) and hypertensive emergencies frequently present with chest pain (27%), dyspnea (22%) and neurological deficit (21%). Types of end-organ damage associated with hypertensive emergencies include cerebral infarction (24%), acute pulmonary edema (23%) and hypertensive encephalopathy (16%), as well as cerebral hemorrhage (4.5%). The most important factor that limits morbidity and mortality from these disorders is prompt and carefully considered therapy. Unfortunately, hypertensive emergencies and urgencies are among the most misunderstood and mismanaged of acute medical problems seen today. The primary goal of intervention in a hypertensive crisis is to safely reduce BP. Immediate reduction in BP is required only in patients with acute end-organ damage (i.e. hypertensive emergency). This requires treatment with a titratable short-acting intravenous (IV) antihypertensive agent, while severe hypertension with no acute end-organ damage is usually treated with oral antihypertensive agents. Patients with hypertensive emergencies are best treated in an intensive care unit (ICU) with titratable IV hypotensive agents. The aim of this review is to summarize the details regarding the definition-impact, causes, clinical condition and management of hypertensive crises.

Coexistence of atherosclerosis and fistula as a cause of angina pectoris: a case report.

INTRODUCTION: Coronary artery fistulas are abnormal communications between a coronary artery and a cardiac chamber or a major vessel (vena cava, pulmonary vein, pulmonary artery). They are usually diagnosed by coronary arteriography. Clinical presentations are variable depending on the type of fistula, shunt volume, site of the shunt, and presence of other cardiac conditions. CASE PRESENTATION: This report describes a 46-year-old Greek female patient who was admitted to the hospital because of an acute coronary syndrome. She underwent coronary angiogram which showed a coronary artery fistula from the left anterior descending artery to the main pulmonary artery and severe coronary disease. The patient was referred for coronary artery bypass surgery and fistula closure operation. CONCLUSIONS: Coronary artery fistulas between left anterior descending artery and main pulmonary artery are very rare anomalies. This case report describes a patient with this anomaly combined with severe coronary disease, reviews the current literature and discusses the available options for treating this rare condition.

Resistant hypertension workup and approach to treatment.

Resistant hypertension is defined as blood pressure above the patient's goal despite the use of 3 or more antihypertensive agents from different classes at optimal doses, one of which should ideally be a diuretic. Evaluation of patients with resistive hypertension should first confirm that they have true resistant hypertension by ruling out or correcting factors associated with pseudoresistance such as white coat hypertension, suboptimal blood pressure measurement technique, poor adherence to prescribed medication, suboptimal dosing of antihypertensive agents or inappropriate combinations, the white coat effect, and clinical inertia. Management includes lifestyle and dietary modification, elimination of medications contributing to resistance, and evaluation of potential secondary causes of hypertension. Pharmacological treatment should be tailored to the patient's profile and focus on the causative pathway of resistance. Patients with uncontrolled hypertension despite receiving an optimal therapy are candidates for newer interventional therapies such as carotid baroreceptor stimulation and renal denervation.

Depression masked as paroxysmal hypertension episodes.

This paper describes a clinical picture frequently seen in specialty hypertension clinics, a patient with paroxysmal or intermittent hypertension not related to pheochromocytoma. A variety of diagnostic labels given to these patients is reviewed, including pseudopheochromocytoma and panic attacks. The clinical features, pathophysiology, diagnosis and treatment of these syndromes are outlined. It is proposed that successful management of these patients may be best achieved by collaborative care between a hypertension specialist and a psychiatrist, or clinical psychologist with expertise in cognitive-behavioral panic disorder management, stress-reduction techniques including controlled breathing, and effective treatment of anxiety. The use of drugs effective for treatment of panic disorder can also be helpful in managing those patients.

Hypertrophic and hypertensive hypertrophic cardiomyopathy--a true association?

The cardiomyopathies were previously defined as ''heart muscle diseases of unknown cause'' and were differentiated from specific heart muscle disease with known cause. With increasing understanding of etiology and pathogenesis, the difference between cardiomyopathy and specific heart muscle disease has become indistinct. The term specific cardiomyopathies are used to describe heart diseases that are associated with specific cardiac or systemic disorders. These were previously defined as specific heart muscle diseases. They included ischemic cardiomyopathy, valvular cardiomyopathy, hypertensive cardiomyopathy, inflammatory cardiomyopathy, metabolic cardiomyopathy, general system disease, muscular dystrophies, sensitivity and toxic reactions, and peripartal cardiomyopathy. The cardiomyopathies are therefore classified by the dominant pathophysiology or, if possible, by etiological/pathogenetic factors. Topol in 1985 described a syndrome called hypertensive hypertrophic cardiomyopathy that included severe concentric cardiac hypertrophy, a small left ventricular cavity, and supernormal indexes of systolic function without concurrent medical illness or ischemic heart disease. The aim of this review was to highlighted this syndrome from pathophysiological, clinical, diagnostical view and clear all the possible correlations with genetic, inflammatory, and other markers.

Association of passive smoking with masked hypertension in clinically normotensive nonsmokers.

BACKGROUND: We investigated ambulatory blood pressure (BP) levels among clinically normotensive nonsmokers exposed (PS) and not exposed (SF) to passive smoking aiming to evaluate the relative prevalence of masked hypertension (MH). METHODS: From 790 consecutive never-treated subjects who were self-referred to an outpatient hypertensive clinic, we excluded active smokers and those having a mean clinic BP >140/90 mm Hg. In the remaining population, echocardiography and routine biochemical profile assessment was performed, whereas by the implementation of additional exclusion criteria, all clinically normotensive subjects eligible to participate (i.e., 154 PS and 100 SF) underwent to ambulatory BP monitoring. RESULTS: PS with respect to SF subjects were younger, followed a less hygienic diet and consumed more alcohol (all P < 0.05). Moreover, PS in comparison with SF showed higher 24-h systolic BP, standing diastolic BP, and clinic heart rate (126 +/- 6 mm Hg vs. 122 +/- 5 mm Hg, 89 +/- 4 mm Hg vs. 84 +/- 4 mm Hg and 79 +/- 5 beats/min vs. 73 +/- 4 beats/min, respectively, P < 0.05 for all) and higher prevalence of MH (23% vs. 8%, P < 0.01). After adjustment for confounders determinants of MH remained passive smoking, weekly duration and intensity of passive smoke exposure, younger age, clinic heart rate, low physical activity score, and standing/sitting difference of diastolic BP and heart rate (P < 0.05 for all). CONCLUSIONS: MH is associated with passive smoking in a dose-related manner and low physical activity, increased heart rate and postural hemodynamic reaction may represent potential accelerators of that phenomenon.

Free leptin is associated with masked hypertension in nonobese subjects: a cross-sectional study.

The aim of the study was to investigate whether diverse clinical blood pressure phenotypes are associated with free leptin surrogates, as reflected by plasma leptin, human soluble leptin receptor, and their ratio (ie, free leptin index) in nonobese normoglycemic subjects. Three separate clinic blood pressure measurements and ambulatory blood pressure monitoring were implemented to divide 494 subjects (aged 44+/-5 years; 272 men; body mass index: <30 kg/m(2)) into hypertensives (n=166), white-coat hypertensives (n=82), masked hypertensives (n=66), and normotensives (n=180). Participants underwent echocardiography, while, from fasting venous blood samples, metabolic profile, plasma leptin, and its receptor levels were assessed. Hypertensives and masked hypertensives demonstrated higher levels of log (10)(leptin) and log (10)(free leptin index), as well as lower levels of log (10)(human soluble leptin receptor) with respect to normotensives. White-coat hypertensives had similar free leptin surrogates compared with normotensives. Younger age, 24-hour systolic and diastolic blood pressures, 24-hour heart rate, and left ventricle mass index were common correlates of free leptin surrogates. After adjustment for confounders, masked hypertensive and hypertensive with respect to normotensive phenotype were associated with log (10)(leptin) with odds ratios (95% CIs) of 1.31 (1.12 to 3.80) and 1.26 (1.09 to 2.24), respectively, log (10)(human soluble leptin receptor) with 0.65 (0.53 to 0.78) and 0.69 (0.57 to 0.84), respectively, and log (10)(free leptin index) with 2.46 (1.32 to 7.23) and 1.84 (1.26 to 3.73), respectively (P<0.05 for all of the cases). Free leptin surrogates are associated with masked hypertension in nonobese normoglycemic subjects. Free leptin is almost equally increased in masked and sustained hypertension, suggesting a similar leptin-related vascular impairment.

Masked hypertension and atherogenesis: the impact on adiponectin and resistin plasma levels.

Recent evidence suggests that masked hypertension (MH) is a predictor of cardiovascular disease and that hypoadiponectinemia and hyperesistinemia may contribute to chronic inflammatory process, insulin resistance, endothelial dysfunction, and accelerated atherogenesis. The aim of this study was to examine the adiponectin and resistin plasma levels in patients with MH and compare the findings with those of healthy normotensive persons matched for age, sex, body mass index, and other risk factors. Overall, 130 (60 men and 70 women) healthy persons (mean age, 45+/-12 years) who had clinic blood pressure values <140/90 mm Hg were studied. The study population underwent 24-hour ambulatory blood pressure monitoring (ABPM). According to the ABPM recordings, 24 individuals (8 men and 16 women) had MH (daytime systolic blood pressure >or=135 mm Hg or daytime diastolic blood pressure >or=85 mm Hg; group A) and the remaining 106 participants (52 men and 54 women) had normal ABPM findings (group B). Adiponectin and resistin plasma levels were determined in both groups by enzyme-linked immunosorbent assay. Significantly higher (P<.01) resistin levels (12+/-4 vs 6.8+/-3.6 ng/mL) were found in group A compared with group B, while the adiponectin plasma levels were significantly lower (P<.01) in group A compared with group B (6+/-2.3 vs 11+/-2.7 microg/mL). Findings suggest that patients with MH have lower adiponectin levels and higher resistin levels compared with normotensive individuals. This observation may have prognostic significance for future cardiovascular events in patients with MH.

On target to dual block RAS?

Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are thought to possess cardioprotective, cerebroprotective, and nephroprotective properties. Both classes of agents can prevent or reverse endothelial dysfunction and atherosclerosis, thereby potentially reducing the risk of cardiovascular events. Such a reduction has been shown with angiotensin-converting enzyme inhibitors in patients with coronary artery disease, but no such data are scarce with angiotensin receptor blockers (Valsartan in Acute Myocardial Infarction study). Both angiotensin-converting enzyme inhibitors and angiotensin receptor blockers have been shown to reduce damage in target organs, such as the heart and kidney, and to decrease cardiovascular mortality and morbidity in patients with congestive heart failure. These drugs (especially angiotensin receptor blockers) may successfully prevent atrial fibrillation and play a protective role in metabolic syndrome. In some clinical settings, combined therapy angiotensin-converting enzyme inhibitors with angiotensin receptor blocker (double blockade of the renin-angiotensin- aldosterone system) may appear the most effective.

Metoprolol succinate combination in the treatment of hypertension.

Metoprolol is a selective beta(1)-adrenergic antagonist extensively used since 1975. Metoprolol has proven its efficacy in reducing cardiovascular events and mortality in patients with hypertension and coronary heart disease. A recently developed controlled release/ extended-release formulation of metoprolol succinate was designed to provide relatively constant metoprolol plasma concentrations and beta(1)-blockade while retaining the convenience of once daily administration. A 100-mg metoprolol controlled/extended-release tablet contains 95 mg of metoprolol succinate and is considered to have equivalent activity of 100 mg metoprolol tartrate. After ingestion, the tablet disintegrates into individual pellets and each pellet acts as a diffusion cell releasing the drug at a relatively constant rate over a period of approximately 20 hours. The aim of this review was to determine the pharmacokinetic and pharmacodynamic properties of metoprolol succinate and to apply those properties in combination with other drugs mainly diuretics in the treatment of hypertension.

Low-dose fixed combination of bisoprolol/hydrochlorothiazide as first line for hypertension: a review of the rationale and clinical evidence.

Essential hypertension is a heterogeneous multifactorial disease. Data from the National Health and Nutritional Examination Survey and from the World Health Organization have clearly demonstrated that, worldwide, less than 30% of hypertensive patients are adequately controlled by our currently accepted blood pressure goals. Although monotherapy is often unable to achieve blood pressure goals, the use of fixed low-dose combination drugs as alternative treatment seems to be related to a better antihypertensive efficacy and higher response rates in the low range of doses as the result of complementary mechanisms of antihypertensive effects. Indeed clinical trials have shown that initial low-dose combination therapy is superior as compared with treatment by the stepped-care and the sequential monotherapy approach, while recently, low-dose combination therapy for initial antihypertensive therapy instead of the stepped-care approach or of sequential monotherapy has been recommended. This review summarizes the beneficial effect of low-dose bisoprolol/ hydrochlorothiazide combination in the treatment of patients with stage I and II hypertension.

Is it time to treat prehypertension?

Prehypertension, defined as blood pressure between 120-139/80-89 mmHg, is a major public health concern. The condition is very prevalent (30% of the adult population), is often associated with other cardiovascular risk factors and independently increases the risk of hypertension and subsequent cardiovascular events. The mechanism of elevated risk for cardiovascular events associated with prehypertension is presumed to be the same as that of hypertension. In the general population, prehypertension can be lowered by lifestyle modifications, but often not reliably. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC-7) recommendation for prehypertension management with optimal weight control (largely through diet and exercise) remains the mainstay, except for individuals with diabetes, chronic kidney disease, and perhaps known coronary artery disease, because of the shot-term cost considerations and unproven long-term prognosis. The recently published Trial of Preventing Hypertension (TROPHY) is the first study of pharmacologic intervention among those with prehypertension. Results from this trial demonstrated that angiotensin receptor blockade (ARB) retards age-related blood pressure increases in prehypertensive patients. In this review, we discuss the options for pharmacologic intervention of prehypertension, with a focus on the TROPHY trial results.

Bilateral fistulas: a rare cause of chest pain. Case report with literature review.

A coronary artery fistula is a direct communication between a coronary artery and one of the cardiac chambers or vessels around the heart. These fistulas are usually diagnosed by coronary arteriography. Clinical presentations are variable depending on the type of fistula, shunt volume, site of the shunt, and presence of other cardiac conditions. Bilateral coronary fistulas between coronary arteries and the pulmonary artery are very rare. This report describes a 51-year-old man without any previous medical history, who presented to our hospital one hour after the acute onset of severe substernal chest pain associated with shortness of breath and nausea. Coronary angiography revealed two fistulas arising from the left anterior descending and right coronary arteries and draining at exactly the same site in the pulmonary artery. There was no evidence of atherosclerotic coronary artery disease in either the left or right coronary arterial tree.