Clinical Significance of Altered Vascular Morphology and Function in Normotension.

PURPOSE OF REVIEW: To review current literature examining the presence of subclinical micro- and macrovascular alterations in normotensive individuals and their clinical significance in terms of hypertension prediction. Emphasis is placed on alterations that can be detected in peripheral vascular beds using non-invasive, easily applicable methodology, as these are in general easier to capture and evaluate in clinical practice compared to more complex invasive or functional tests. RECENT FINDINGS: Arterial stiffness, increased carotid intima-media thickness, and altered retinal microvascular diameters predict the progression from the normotensive to the hypertensive state. By contrast, there is substantial lack of relevant prospective studies for skin microvascular alterations. Although conclusions regarding causality cannot be safely deduced from available studies, detection of morphological and functional vascular alterations in normotensive individuals emerges as a sensitive indicator of progression to hypertension and hence increased CVD risk. An increasing amount of evidence suggests that early detection of subclinical micro- and macrovascular alterations would be clinically useful for the early identification of individuals at high risk for future hypertension onset. Methodological issues and gaps in knowledge need to be addressed before detection of such changes could guide the development of strategies to prevent new-onset hypertension in normotensive individuals.

Platelet microvesicles are associated with the severity of coronary artery disease: comparison between peripheral and coronary circulation.

Microvesicles (MVs) have recently emerged as markers of thrombosis. Furthermore, there is an unexplained residual thrombotic risk is observed in patients with acute coronary syndrome (ACS) and/or stable coronary artery disease (CAD), despite treatment. We measured platelet (PMVs) and erythrocyte (ErMVs) in patients with ACS and stable CAD, both in the peripheral and coronary circulation. We studied consecutive eligible patients during a coronary angiography. Blood samples were collected from the stem of the left coronary artery and femoral artery. PMVs were significantly increased in CAD patients compared to controls. ACS patients had also increased PMVs in coronary and peripheral circulation, compared to controls. Furthermore, ACS patients exhibited increased PMVs in coronary compared to peripheral circulation. Lastly, coronary PMVs were associated with the severity of CAD based on the SYNTAX score. No significant differences were observed in the levels of ErMVs among groups. Therefore, PMVs emerge as novel markers of thrombosis in CAD, further augmenting the vicious cycle of inflammation and thrombosis during ACS. Importantly, coronary PMVs may reflect the severity of CAD in this population.

Endothelial Dysfunction in Patients with Rheumatoid Arthritis: the Role of Hypertension.

PURPOSE OF REVIEW: To review the data on the role of endothelial dysfunction and the impact of hypertension as a potent mediator of cardiovascular disease in patients with rheumatoid arthritis (RA). RECENT FINDINGS: RA represents the most common autoimmune rheumatic disorder and is characterized by chronic systemic inflammation predisposing to cardiovascular complications. Cardiovascular mortality is increased among patients with RA and represents the leading cause of death. Although the exact prevalence is debated, hypertension is increased in RA. Hypertension acts synergistically with chronic inflammation and accounts, at least partially, for the increased cardiovascular morbidity in this group of patients. Endothelial dysfunction is considered a primary process in the pathogenesis of hypertension and cardiovascular diseases and contributes significantly to the development and progression of the associated micro- and macrovascular complications. Even though several studies in patients with RA have shown the presence of endothelial dysfunction with traditional methods, novel biochemical and vascular methods for the evaluation of endothelial dysfunction have been scarcely applied. In addition, it remains unclear whether and to which extent endothelial dysfunction in RA is present regardless of concomitant hypertension, even in well-controlled patients. Hypertension, endothelial dysfunction, and chronic systemic inflammation appear as a mutually reinforcing triad aggravating cardiovascular risk in patients with RA. Detection of endothelial dysfunction in patients with RA in the early stages further aiming at the development of novel therapeutic targets might contribute to prevention of cardiovascular complications and remains under investigation.

Increased thrombotic and impaired fibrinolytic response to acute exercise in patients with essential hypertension: the effect of treatment with an angiotensin II receptor blocker.

Essential hypertension (EH) is characterised by increased thrombotic tendency and impaired fibrinolytic activity. However, exercise-induced changes in coagulation and fibrinolysis have not yet been clarified. We aimed at determining thrombotic and fibrinolytic activity during exercise in patients with EH pre and post treatment with an Angiotensin II receptor blocker. Study 1 consisted of 30 untreated hypertensive (UH) and 15 normotensive (NT) individuals. The UH individuals who received treatment were included in study 2 and were followed up after a 3-month treatment period with valsartan. Thrombin-antithrombin (TAT) complexes and human plasminogen activator inhibitor-1 (PAI-1) were measured as markers of coagulation and fibrinolysis, respectively, at baseline, immediately after a treadmill exercise test and 30 min later. In UH, TAT and PAI-1 levels were significantly increased immediately after peak exercise and decreased 30 min later, as compared with baseline levels. At all time points, UH exhibited significantly higher TAT and PAI-1 levels compared with NT. No significant changes of TAT and PAI-1 levels were observed in NT and in patients post treatment. Acute high-intensity exercise results in impaired thrombotic and fibrinolytic response in untreated patients with EH. Angiotensin II receptor blockade with adequate blood pressure control greatly improves exercise-induced changes in coagulation and fibrinolysis in EH.

The impact of frequently encountered cardiovascular risk factors on sexual dysfunction in rheumatic disorders.

Traditional cardiovascular risk factors have been acknowledged as major contributors to sexual dysfunction in the general population. The purpose of this study was to explore their impact on sexual function in rheumatologic patients. A total of 557 consecutive rheumatologic patients, 449 females and 108 males, had their sexual function evaluated with the Female Sexual Functioning Index (FSFI) and the International Index of Erectile Function (IIEF) questionnaire respectively. Personal data regarding presence of cardiovascular risk factors were collected and analysed in association with the FSFI and IIEF scores. Mean age of the participants was 54.1 ± 14.1 years, mean body mass index was 27.5 ± 5.29 and mean systolic and diastolic blood pressure was 130.5 ± 19.82 and 79.5 ± 10.51 mmHg respectively. Hypertension was present in 39% of the participants, diabetes mellitus in 10.2%, dyslipidaemia in 33.6% and history of cardiovascular events in 8.6%, whereas smoking was recorded by 28.4% and alcohol consumption by 7.4%. Sexual dysfunction affected 68.6% of our study population (73.5% of females and 48.1% of males, p < 0.001). Logistic regression analysis revealed that age was the only factor associated with a significantly higher prevalence of sexual dysfunction (p < 0.001 for both genders, p = 0.013 in males and p < 0.001 in females). Increased age was identified as the only independent predictor of sexual dysfunction in our population. Apart from age, traditional cardiovascular risk factors failed to explain the increased prevalence of sexual dysfunction in these patients. Other contributing factors (physical and/or psychological) might account for the increased occurrence of sexual dysfunction in rheumatic disorders.

Neurofibromatosis type 1: should we screen for other genetic syndromes? A case report of co-existence with multiple endocrine neoplasia 2A.

BACKGROUND: NF 1 is a genetic disorder with an autosomal dominant pattern of inheritence. It is associated with neoplastic disorders mainly derived from the neural seath. However, the co-existence of NF1 with the full spectrum of MEN 2A has rarely been reported. The aim of the study was to investigate the presence of secondary neoplasias in a patient with diagnosed NF1, and in particular the presence of hyperparathyroidism and the possible co-existence with another pheochromocytoma-related syndrome. METHODS: We report a case of a 70 years old female patient who had NF1. The patient was referred to our center and was diagnosed with an isolated pheochromocytoma of the right adrenal gland for which she underwent right adrenalectomy. We further investigated for the presence of another pheochromocytoma-related syndrome and in particular for the presence of hyperparathyroidism and medullary thyroid cancer. Molecular screening for germline mutations of the genes NF1, RET and VHL has also been performed. RESULTS: The patient was further diagnosed with hyperparathyroidism and medullary thyroid cancer, having the full spectrum of the clinical picture of the MEN2A syndrome. The genetic testing revealed the germline mutation for NF1 but not for the RET proto-oncogene which is generally found in MEN2A cases. CONCLUSION: To our knowledge this is a rare case of co-existence of two pheochromocytoma-related genetic syndromes, and generates the question of whether all patients with these syndromes should undergo a thorough clinical and laboratory investigation for the possibility of another co-existing pheochromocytoma-related genetic syndrome.

The pathogenesis of arterial stiffness and its prognostic value in essential hypertension and cardiovascular diseases.

The elasticity of a given arterial segment of the aorta and of big elastic arteries is not constant but depends on its distending pressure. As distending pressure increases, there is greater recruitment of inelastic collagen fibers and thereby a reduction in elasticity. It also depends on structural changes in the medial layer of the elastic arteries (mainly aorta and major arterial conduits), and is largely the result of progressive elastic fibre degeneration.Aortic Pulse Wave Velocity (PWV), is the most robust marker of arterial stiffness, however additional useful information can also be provided by the Central Augmentation Index (AIx C), and pulse pressure. The presence of systemic inflammation in cardiovascular disease and in particular in essential hypertension affects arterial stiffness and increases PWV. Some pharmacological and non-pharmacological interventions may improve arterial stiffness and thereby decrease PWV.