Alexandros Kasiakogias

Periodontitis and blood pressure: The concept of dental hypertension

Chronic periodontitis is a common inflammatory disorder that is being contemplated as a risk factor for atherosclerotic complications. Current epidemiological evidence also supports its potential association with increases in blood pressure levels and hypertension prevalence. Furthermore, data from cross-sectional studies suggest that in hypertensive subjects periodontitis may enhance the risk and degree of target organ damage. A possible pathogenetic background of an effect of periodontitis on blood pressure should include the systemic generalization of the local oral inflammation, the role of the host immune response, the direct microbial effect on the vascular system and alterations in endothelial function. Inversely, the concept of hypertension unfavorably affecting periodontal tissues cannot be excluded. The two conditions share multiple common risk factors that should be readily controlled for when assessing a possible association. Thoroughly designed prospective and interventional trials are needed in order to determine the impact of periodontitis on blood pressure regulation and incident hypertension and its integration in the clinical approach of both dental and hypertensive patients.

Managing hypertension in obstructive sleep apnea: the interplay of continuous positive airway pressure, medication and chronotherapy.

Hypertension is highly prevalent and usually uncontrolled among patients with obstructive sleep apnea despite multiple interventions, namely lifestyle modifications, use of antihypertensive drugs and continuous positive airway pressure application. Main prognosticators of the blood pressure (BP) reduction with continuous positive airway pressure therapy are high levels of BP, severity of apnea and daytime sleepiness. The long-term effect of continuous positive airway pressure on BP is still inconclusive, and compliance issues constitute a major limitation. There is no clear evidence for preference for a specific type of antihypertensive drug, and selection should primarily be guided by the patients cardiometabolic profile and associated clinical conditions. Furthermore, as hypertensive patients with obstructive sleep apnea frequently exhibit a disturbed circadian BP pattern, chronotherapy emerges as a possible therapeutic supplement.

Dynamic resistant hypertension patterns as predictors of cardiovascular morbidity: a 4-year prospective study.

Objective: Little is known regarding the clinical course and prognosis of resistant hypertension (RHT). We evaluated predictors of persistent RHT and the associated cardiovascular risk. Methods: We studied 1911 treated hypertensive patients (aged 59±11 years, 49% men) for a mean period of 3.9 years. At baseline, clinical data were collected and patients underwent echocardiographic measurements, routine blood testing and additional workup for exclusion of secondary causes of RHT (office-based uncontrolled hypertension under at least three drugs including a diuretic or controlled hypertension under four or more drugs). Endpoint of interest was the composite of coronary artery disease and stroke. Main results: Four groups were identified depending on presence or absence of RHT at baseline and follow-up: 1153 patients (60%) never having RHT, 189 (10%) with resolved RHT, 204 (11%) with incident RHT and 365 (19%) with persistent RHT. Two-thirds of the patients with RHT at baseline remained resistant at the end of the study. Independent variables associated with both incident and persistent RHT were diabetes mellitus, history of cardiovascular disease, hypertension duration, SBP, left ventricular hypertrophy and glomerular filtration rate. Persistent RHT compared with never-having RHT was associated with a 2.2-fold increased risk for cardiovascular morbidity (95% CI: 1.21–4.05, P = 0.01) after adjustment for risk factors. Conclusion: In treated hypertensive patients, among prospective RHT dynamic patterns, persistent RHT is frequent and independently associated with adverse cardiovascular prognosis.

Effects of continuous positive airway pressure on blood pressure in hypertensive patients with obstructive sleep apnea: a 3-year follow-up.

Objective: Several studies have reported a small yet significant decrease in blood pressure (BP) with continuous positive airway pressure (CPAP) application in patients with obstructive sleep apnea (OSA). We investigated the long-term efficiency of CPAP in the management of hypertensive patients with OSA on top of conventional antihypertensive medication. Methods: We followed 91 nonsleepy patients (aged 54 ± 9 years, 69 men) with essential hypertension and newly diagnosed moderate-to-severe OSA (apnea–hypopnea index, 38 ± 24 events/h on polysomnography) for a mean period of 3.1 years, after switching them to antihypertensive treatment targeting office BP less than 140/90 mmHg (<130/80 mmHg in diabetic patients). Participants were defined as on-CPAP if they adhered to CPAP treatment during the whole follow-up period (N = 41), whereas those that did not follow CPAP therapy served as controls (N = 50). Results: By the end of follow-up, on-CPAP patients and controls exhibited similar SBP and DBP levels (133 ± 12 versus 133 ± 13 mmHg, 84 ± 9 versus 85 ± 9 mmHg, respectively, P > 0.05 for all), number of patients with controlled hypertension (71 versus 70%, P > 0.05), and number of antihypertensive drugs needed to achieve BP control (2.28 ± 1.09 versus 2.11 ± 0.72, P > 0.05). In a subgroup of patients (N = 34) in whom ambulatory BP monitoring was also performed, 24-h BP levels did not differ between the two groups (125 ± 10/76 ± 7 mmHg versus 123 ± 11/75 ± 10 mmHg, P > 0.05). In multiple regression models, CPAP application was not associated with changes in BP levels. Conclusion: In nonsleepy, hypertensive, OSA patients on conventional antihypertensive treatment, long-term CPAP application is not associated with lower BP levels or a need for less antihypertensive drugs for BP control.

Independent association of circulating resistin with glomerular filtration rate in the early stages of essential hypertension.

Resistin, a newly discovered protein, promotes endothelial dysfunction and proinflammatory activation, contributing to subclinical atherosclerosis in different clinical settings. In this study we sought to investigate the relationship of increased resistin levels with estimated glomerular filtration rate (eGFR), the most established marker of kidney impairment, in hypertensive subjects. Our population consisted of 132 untreated non-diabetic subjects with stage I–II essential hypertension (49 males, mean age=54 years, office blood pressure (BP)=159/100 mm Hg). In all patients eGFR was assessed by the Modification in Renal Disease equation and venous blood sampling was performed for estimation of resistin concentrations. The distribution of resistin was split by the median (4.63 ng ml−1) and accordingly subjects were stratified into those with high and low values. Hypertensive patients with high (n=66) compared to those with low resistin (n=66) exhibited lower eGFR values (77.1±9.4 vs 89.1±12.2 ml min−1 per 1.73m2, P<0.0001), even after adjustment for established confounders. In the total population, resistin was associated with 24-h systolic BP (r=0.244, P<0.05), serum creatinine (r=0.311, P=0.007) and eGFR (r=−0.519, P<0.0001). Multiple regression analysis revealed that age (b=0.379, P=0.01), body mass index (b=0.158, P=0.022), 24-h systolic BP (b=0.284, P=0.006) and resistin (b=0.429, P<0.0001) were independent predictors of eGFR (R2=0.436, P<0.0001). In essential hypertensive subjects, higher resistin levels are associated with renal function impairment, as reflected by decreased eGFR. Moreover, the independent association of resistin with eGFR suggests involvement of resistin in the progression of kidney damage in the early stages of hypertension.

Resistant Hypertension and Obstructive Sleep Apnea: The Sparring Partners

Enhanced target organ damage and cardiovascular morbidity represent common issues observed in both resistant hypertension and obstructive sleep apnea. Common pathophysiological features and risk factors justify their coexistence, especially in individuals with increased upper-body adiposity. Impaired sodium handling, sympathetic activation, accelerated arterial stiffening, and impaired cardiorenal hemodynamics contribute to drug-resistant hypertension development in obstructive sleep apnea. Effective CPAP therapy qualifies as an effective “add-on” to the underlying antihypertensive pharmacological therapy, and emerging evidence underlines the favorable effect of mineralocorticoid antagonists on both resistant hypertension and obstructive sleep apnea treatment.

Catheter-based renal denervation for resistant hypertension: Twenty-four month results of the EnligHTN I first-in-human study using a multi-electrode ablation system.

BACKGROUND Long term safety and efficacy data of multi-electrode ablation system for renal denervation (RDN) in patients with drug resistant hypertension (dRHT) are limited. METHODS AND RESULTS We studied 46 patients (age: 60 ± 10 years, 4.7 ± 1.0 antihypertensive drugs) with drug resistant hypertension (dRHT). Reduction in office BP at 24 months from baseline was -29/-13 mmHg, while the reduction in 24-hour ambulatory BP and in home BP at 24 months were -13/-7 mmHg and -11/-6 mmHg respectively (p<0.05 for all). A correlation analysis revealed that baseline office and ambulatory BP were related to the extent of office and ambulatory BP drop. Apart from higher body mass index (33.3 ± 4.7 vs 29.5 ± 6.2 kg/m(2), p<0.05), there were no differences in patients that were RDN responders defined as ≥10 mmHg decrease (74%, n=34) compared to non-responders. Stepwise logistic regression analysis revealed no prognosticators of RDN response (p=NS for all). At 24 months there were no new serious device or procedure related adverse events. CONCLUSIONS The EnligHTN I study shows that the multi-electrode ablation system provides a safe method of RDN in dRHT accompanied by a clinically relevant and sustained BP reduction.

Waist circumference compared with other obesity parameters as determinants of coronary artery disease in essential hypertension: a 6-year follow-up study

This study aimed to assess the predictive role of body mass index (BMI), waist circumference (WC) and the waist-to-hip ratio (WHR) for the incidence of coronary artery disease (CAD) in a cohort of essential hypertensive patients. We followed up 2266 essential hypertensive individuals (mean age, 57.8 years; males, 1083; office blood pressure (BP), 143/89 mm Hg) who were free of cardiovascular disease for a mean period of 6 years. All subjects had at least one annual visit and, at baseline, underwent blood sampling and a complete echocardiographic study to determine the left ventricular (LV) mass index. CAD was defined as a history of myocardial infarction or significant coronary artery stenosis that was revealed by angiography or a coronary revascularization procedure. The incidence of CAD throughout the follow-up period was 2.33%. Hypertensive individuals who developed CAD (n=53) had a greater baseline WC (101.1±11.7 vs. 96.4±12 cm, P=0.005), WHR (0.94±0.07 vs. 0.89±0.08 cm, P<0.0001) and LV mass index (117±26.8 vs. 103.3±27 g m−2, P<0.0001) compared with those without CAD at follow-up (n=2213), whereas no difference was observed compared with the baseline office BP and BMI values (P=NS for all). Using a multivariate Cox regression model, WC (hazard ratio (HR) 1.037, P=0.002) and LV mass index (HR 1.010, P=0.044) were found to be independent predictors of CAD. In essential hypertensive patients, WC could predict the future development of CAD, whereas BMI and WHR showed no independent prognostic value. These findings suggest that WC constitutes an easy clinical tool to assess risk in hypertension among individuals with obesity.

Evening versus morning dosing of antihypertensive drugs in hypertensive patients with sleep apnoea: a cross-over study

Objective: Beneficial effects of continuous positive airway pressure (CPAP) on both blood pressure (BP) levels and variability have been documented in patients with obstructive sleep apnoea (OSA). We investigated the relevant impact of different dosing times of antihypertensive drugs beyond CPAP application. Methods: In this prospective, cross-over trial, we included 41 patients with newly diagnosed hypertension and never treated OSA (apnoea-hypopnea index ≥15/h), without increased daytime somnolence (Epworth Score ⩽10 points). Patients first received treatment with valsartan or with a fixed combination of amlodipine and valsartan in a single morning dose for 8 weeks. In the following 8-week period, patients received the same therapeutic regimen in a single evening dose. Office and ambulatory BP were measured at baseline and after each treatment period. Results: Compared with morning administration, evening dosing induced a greater decrease in office SBP (by 3.7 ± 6.5 mmHg, P = 0.001). The decrease in 24-h SBP/DBP was significant and similar after morning and evening dosing (-16.4 ± 11/11.0 ± 7.5 and -18.4 ± 11/12.1 ± 7.5 mmHg, respectively, P < 0.001 for both). Evening compared with morning dosing further reduced night-time SBP/DBP by 4.4 ± 8.6/2.9 ± 5.6 mmHg (P = 0.007 and P = 0.006, respectively). Night-time dippers increased from 24% at baseline to 34% with morning dosing and to 61% with evening dosing. There was no significant interaction between concurrent CPAP application and drugs dosing time on BP changes. Conclusion: Evening dosing of antihypertensive drugs improves night-time BP and dipping status in nonsleepy patients with OSA, irrespective of CPAP application.

The role of matrix metalloproteinases in diabetes mellitus.

Diabetes mellitus (DM) is a leading risk factor for cardiovascular disease that adversely affects multiple vascular components from early in its course. Current evidence implicates matrix metalloproteinases (MMPs) and their endogenous inhibitors in diverse pathways associated with the development and progression of diabetic microvascular complications. In diabetic nephropathy, altered MMPs expression contributes to extracellular matrix deposition and glomerular hypertrophy that eventually lead to proteinuria and renal insufficiency. In diabetic cardiomyopathy, MMPs participate in the breakdown of collagen and elastin, myocardial remodelling as well as the vulnerability of the coronary plaque. The development of diabetic peripheral arterial disease is mediated by the impaired angiogenesis caused by the activity of MMPs. Experimental data support an integral role of MMPs in cerebral circulation and stroke volume in diabetes. An excess of MMPs may contribute in poor diabetic wound healing. Future research should further clarify the role of MMPs within the pathophysiological substrate of diabetes, as well as potential therapeutic options.