Dimitris Flessas

Pathophysiology of resistant hypertension: the role of sympathetic nervous system.

Resistant hypertension (RH) is a powerful risk factor for cardiovascular morbidity and mortality. Among the characteristics of patients with RH, obesity, obstructive sleep apnea, and aldosterone excess are covering a great area of the mosaic of RH phenotype. Increased sympathetic nervous system (SNS) activity is present in all these underlying conditions, supporting its crucial role in the pathophysiology of antihypertensive treatment resistance. Current clinical and experimental knowledge points towards an impact of several factors on SNS activation, namely, insulin resistance, adipokines, endothelial dysfunction, cyclic intermittent hypoxaemia, aldosterone effects on central nervous system, chemoreceptors, and baroreceptors dysregulation. The further investigation and understanding of the mechanisms leading to SNS activation could reveal novel therapeutic targets and expand our treatment options in the challenging management of RH.

PREVALENCE, CHARACTERISTICS AND PREDICTIVE VALUE OF SEVERE RESISTANT HYPERTENSION FOR THE INCIDENCE OF CARDIOVASCULAR DISEASE

Results: The incidence of the composite end-point was 6.7% (156 patients) over the whole follow-up period [(61 patients with CAD, 21 patients with stroke, 78 patients with AF (44 paroxysmal and 34 permanent forms) and 16 with more than one event]. The prevalence of RH was 7.9%. Patients with severe RH compared to those without were older (by 4.4 years, p<0.001) and exhibited greater waist circumference (by 4.4 cm, p<0.001), body mass index (by 1 kg/m2, p=0.001) and prevalence of diabetes (by 7%, p=0.006), as well as increased left ventricular mass index (by 14.2 g/m2, p<0.001), glucose (by 10.2 mg/dl, p<0.001), creatinine (by 0.11 mg/dl, p=0.001) and triglycerides levels (by 25.2 mg/dl, p<0.001) and decreased potassium (by 0.11 meq/L, p=0.002) and HDL levels (by 2.2 mg/dl, p=0.038). Incidence of CAD (5.4% vs. 2.4%, log rank p=0.013), stroke (2.7% vs. 0.7%, log rank p=0.006), AF (7.1% vs. 3%, log rank p=0.004) and their composite (13% vs. 6.2%, log rank p<0.001) was signiicantly higher in patients with RH. By applying multivariate Cox regression analysis the presence of RH (HR 1.66, p=0.037) along with age (HR=1.059, p<0.001), male gender (HR 2.154, p<0.001) and smoking (HR=1.804, p=0.003) were independently associated with the incidence of the composite end-point. Conclusions: The presence of severe ofice RH among all traditional risk factors turned out to be a potent independent predictor of advanced cardiovascular disease in the setting of essential hypertension.

METABOLIC SYNDROME IS ACCOMPANIED BY INCREASED SYMPATHETIC NERVOUS SYSTEM ACTIVITY AND ARTERIAL STIFFNESS IN RESISTANT HYPERTENSION

Resistant hypertension is related to sympathetic overdrive and arterial stiffening, while there are scarce data whether metabolic syndrome further potentiates sympathetic activity and vascular abnormalities in this setting. The aim of this study was to assess the effect of the metabolic syndrome on

INCIDENCE OF CORONARY ARTERY DISEASE AND STROKE IN RELATION TO THE PHYSICAL COURSE OF RESISTANT HYPERTENSION: A TIME UPDATED ANALYSIS OF A 4 YEAR COHORT STUDY

Methods: In a prospective observational study, 1911 treated hypertensive patients (aged 59±11 years, 49% males) were followed for a mean period of 3.9±1.7 years. Four groups were created depending on presence or absence of RH at baseline and follow-up: never having RH, resolved RH, incident RH and persistent RH. Endpoint of interest was the composite of coronary artery disease and stroke. For the subjects with differential RH status at baseline and follow up a uniform distribution was assumed for the estimation of the time point of status change. A time updated Cox regression analysis was then applied to estimate hazards of the predefined outcome.

PREDICTORS AND CARDIOVASCULAR PROGNOSIS OF INCIDENT AND PERSISTENT RESISTANT HYPERTENSION: A 4-YEAR FOLLOW-UP STUDY

Little is known regarding the clinical course and prognosis of resistant hypertension (RHT). We evaluated predictors of persistent RHT and the associated cardiovascular risk. We studied 1,911 treated hypertensive patients (aged 59±11 years, 49% males) for a mean period of 3.9 years. At baseline,