Head and neck paragangliomas (HNPGLs) are neural crest-derived tumors. In comparison with paragangliomas located in the abdomen and the chest, which are generally catecholamine secreting (sPGLs) and sympathetic in origin, HNPGLs are, in fact, parasympathetic in origin and are generally nonsecreting. Overall, 79 consecutive patients with HNPGL were examined for mutations in SDHA, SDHB, SDHC, SDHD, SDHAF2, VHL, MAX, and TMEM127 genes by PCR/sequencing. According to a detailed family history (FH) and clinical, laboratory (including metanephrines), and instrumental examinations, patients were divided into three groups: a) patients with a positive FH for HNPGL (index cases only), b) patients with a negative FH and multiple HNPGLs (synchronous or metachronous) or HNPGL associated with an sPGL, and c) patients with negative FH and single HNPGL. The ten patients in group a) proved to be SDHD mutation carriers. The 16 patients in group b) proved to be SDHD mutation carriers. Among the 53 patients in group c), ten presented with germ-line mutations (three SDHB, three SDHD, two VHL, and two SDHAF2). An sPGL was found at diagnosis or followed up in five patients (6.3%), all were SDHD mutation carriers. No SDHC, SDHA, MAX, and TMEM127 mutations were found. In SDHD mutation carriers, none of the patients affected by HNPGL associated with sPGL presented missense mutations. In conclusion, a positive FH or the presence of multiple HNPGLs is a strong predictor for germ-line mutations, which are also present in 18.8% of patients carefully classified as sporadic. The most frequently mutated gene so far is SDHD but others, including SDHB, SDHAF2, and VHL, may also be affected.
Hypogonadal patients show impaired vascular reactivity, including endothelial-dependent vasodilation due to reduced nitric oxide availability. TS administration further impairs nitric oxide availability in these patients.
The progressive ageing of world population, and the increasing prevalence hypertension in elderly people are leading to the consideration that hypertension in the elderly is one of the main topic in hypertension treatment. Multiple mechanisms, including stiffening of large arteries, endothelial dysfunction, cardiac remodeling, autonomic dysregulation, renal aspects, contribute to the great prevalence of hypertension in the elderly and to increased cardiovascular morbidity and mortality. Treatment of hypertension can hardly put back older patients in a low risk category, especially if target organ damage is present. Nevertheless, blood pressure control can successfully prevent stroke, cognitive decline, coronary heart disease and heart failure, and reduce mortality in the elderly, and even in patients > 80 years, as recently demonstrated. Blood pressure should be lowered below 140/90 mmHg also in older patients. However the HYVET study suggests that a goal of 150/90 mmHg can be reasonable in patients aged 80 years or more. Drug treatment should be titrated with particular caution to adverse responses and excessive blood pressure lowering.
No abstract
Hypertension is universally considered the most detrimental among cardiovascular risk factors. Despite the overwhelming evidence of benefits deriving from lowering blood pressure, its control among the hypertensive population is still unsatisfactory. Resistant hypertension has a non negligible prevalence among hypertensive patients, and it is associated with a worse cardiovascular prognosis. There is need of new therapeutic approaches for reducing cardiovascular risk in this population. Sympathetic nervous system is known to play a major role in development and maintenance of essential hypertension, thus in the past decades several efforts have been made to counteract its overactivation. Novel non-pharmacological, promising approaches targeting sympathetic nervous system are now available, such as renal denervation and baroceptor-activating therapy. This review is aimed at describing essential clinical aspects of resistant hypertension, physiopatological basis of autonomic modulation as a target for hypertension treatment, and the available clinical evidence about efficacy and safety of device-based therapies for resistant hypertension. Present limitations and future perspectives were also considered.
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