Kyriakos Dimitriadis

The incremental effect of obstructive sleep apnoea syndrome on arterial stiffness in newly diagnosed essential hypertensive subjects.

Objective Although obstructive sleep apnoea syndrome (OSAS) is accompanied by an increased atherosclerotic cardiovascular disease burden, its relationship with arterial stiffness is not yet well determined. We investigated whether essential hypertensive individuals with OSAS are characterized by increased arterial stiffness. Methods Our study population consisted of 46 consecutive patients with newly diagnosed untreated stage I–II essential hypertension suffering from OSAS (35 men, aged 49 ± 8 years) and 53 hypertensive individuals without OSAS, matched for age, sex, and smoking status. All subjects underwent polysomnography, echocardiography and aortic stiffness evaluation by means of carotid–femoral pulse wave velocity (c–fPWV) measurements. Results Hypertensive subjects with OSAS [apnoea/hypopnoea index (AHI) ≥ 5] compared with hypertensive subjects without OSAS (AHI < 5) demonstrated increased levels of body mass index (31.4 ± 4 versus 29.3 ± 4 kg/m2, P = 0.015), office systolic/diastolic blood pressure (151/99 versus 145/94 mmHg, respectively, P < 0.05, for both cases) and relative wall thickness (RWT; 0.46 ± 0.06 versus 0.42 ± 0.07, P = 0.010). Hypertensive subjects with OSAS compared with those without OSAS had significantly increased c–fPWV by 9% (8.56 ± 0.49 versus 7.85 ± 0.93 m/s, P = 0.001) and this difference remained significant even after adjustment for confounders (P = 0.04). In the total study population, c–fPWV was correlated with age (r = 0.35, P = 0.015), office systolic blood pressure (r = 0.30, P = 0.007), RWT (r = 0.30, P = 0.03), logAHI (r = 0.389, P = 0.0001) and minimum oxygen saturation (r = −0.418, P = 0.0001). Conclusions OSAS has a significant incremental effect on aortic stiffening in the setting of middle-aged essential hypertensive subjects. This finding suggests that the presence of OSAS in a hypertensive patient accelerates vascular damage, increasing cardiovascular risk.

Left ventricular diastolic dysfunction is accompanied by increased aortic stiffness in the early stages of essential hypertension: a TDI approach.

Objective To investigate the inter-relationship between aortic stiffness and left ventricular (LV) diastolic function in subjects with newly diagnosed uncomplicated essential hypertension. Methods We studied 106 consecutive newly diagnosed subjects (aged 51 years, 80 males) with stage I–II essential hypertension, and 50 normotensives matched for age, sex and body mass index. LV diastolic function was estimated by pulsed tissue Doppler imaging (TDI) echocardiography, averaging diastolic mitral annular velocity measurements (Emav, Amav, Emav/Amav ratio) from four separate sites (basal septal, lateral, anterior, and inferior LV wall). Moreover, aortic stiffness was evaluated by non-invasive carotid–femoral pulse wave velocity (c–f PWV) measurement. Results Hypertensives compared with normotensives exhibited greater LV mass index and Amav (110 versus 95 g/m2 and 10 versus 8.8 cm/s, respectively, P < 0.001 for both cases), and greater c–f PWV (8.47 versus 7.48 m/s, P < 0.03), as well as lower Emav and Emav/Amav values, (8.4 versus 10 cm/s and 0.82 versus 1.15, respectively, P < 0.001 for both cases). In the group of hypertensives, a univariate analysis revealed that c–f PWV was negatively associated with Emav (r = −0.305, P = 0.005), as well as with Emav/Amav ratio (r = −0.437, P < 0.001). Moreover, a multivariate analysis showed that the TDI-derived Emav/Amav ratio was significantly associated with age (P = 0.001), relative wall thickness (P = 0.006) and c–f PWV (P = 0.03), while the conventional Doppler-derived E/A ratio was significantly associated only with age (P = 0.001). Conclusions TDI-detected LV diastolic dysfunction is accompanied by increased aortic stiffness in newly diagnosed essential hypertension, suggesting that there may be a common pathophysiological pathway linking these two entities.

Left ventricular hypertrophy versus chronic kidney disease as predictors of cardiovascular events in hypertension : a Greek 6-year-follow-up study

Objectives We assessed the comparative prognostic role of left ventricular hypertrophy (LVH) and chronic kidney disease (CKD) for major cardiovascular events in a prospective observational study in Greek essential hypertensive patients. Methods We followed up 1652 hypertensive patients (mean age 54.3 years, 696 male patients, office blood pressure 147/93 mmHg) free of cardiovascular disease for a mean period of 6 years. CKD and echocardiographically detected LVH were evaluated at baseline along with five major traditional risk factors [age > 65 years, sex, current smoking, diabetes mellitus and dyslipidemia (low density lipoprotein > 160 mg/dl)]. End points of interest were the incidence of coronary artery disease, stroke, all-cause mortality and their composite. Results At the end of follow-up, coronary artery disease was the most prevalent (5.2%), followed by stroke (5%) and total mortality (3.1%). The presence of both LVH and CKD is associated with a 2.5-fold increase in coronary artery disease (P = 0.034), four-fold in stroke (P = 0.002) and 3.2-fold in the composite (P < 0.001), whereas the presence of LVH alone was associated with a 2.5-fold higher risk for stroke (P = 0.009) and 1.7-fold for the composite (P = 0.018). By multivariate Cox regression analysis, LVH (hazard ratio = 1.53, P = 0.036) and CKD (hazard ratio = 1.66, P = 0.039) turned out to be independent prognosticators of the composite end point, whereas age more than 65 years (hazard ratio = 4.59, P < 0.001) and the presence of LVH (hazard ratio = 2.01, P = 0.043) were the only predictors of stroke. Conclusions In hypertensive patients free of cardiovascular disease, CKD and LVH are both independent prognosticators of the composite end point of all-cause death and cardiovascular morbidity, whereas LVH but not CKD is a major predictor for stroke.

ADMA, C-Reactive Protein, and Albuminuria in Untreated Essential Hypertension: A Cross-sectional Study

BACKGROUND Asymmetric dimethylarginine (ADMA) and subclinical inflammation are associated with atherosclerosis progression, whereas microalbuminuria is an established index of hypertensive organ damage. STUDY DESIGN Cross-sectional. SETTING & PARTICIPANTS In an outpatient hypertensive unit, 296 nondiabetic and untreated participants with hypertension were studied. Participants with atherosclerotic cardiovascular disease, severe valvulopathy, congestive heart failure, presence of neoplastic or other concurrent systemic disease, atrial fibrillation, serum creatinine level > 1.5 mg/dL in men and > 1.4 mg/dL in women, and urinary albumin excretion > 300 mg/24 h were excluded. PREDICTORS ADMA and high-sensitivity C-reactive protein (hs-CRP) levels. OUTCOME VARIABLE Albuminuria assessed using albumin-creatinine ratio (ACR). MEASUREMENTS Participants underwent ambulatory blood pressure monitoring, echocardiography, routine assessment of metabolic profile, ADMA, and hs-CRP, whereas ACR was determined as the mean of 3 values in nonconsecutive morning spot urine samples. RESULTS 64 participants had an ACR of 30-300 mg/g. Stratification based on ADMA level showed that participants with hypertension in quartile [Q] 4 compared with those in Q3, Q2, and Q1 showed the highest ACRs (53.2 vs 31.2 vs 30.4 vs 16.7 mg/g; P < 0.008 for all). Moreover, stratification based on hs-CRP level showed that participants with hypertension in Q4 (69.8% had microalbuminuria) showed the highest ACRs (72.2 vs 25.6, 16.2, and 19.2 mg/g for Q3, Q2, and Q1, respectively; P < 0.008 for all). Stepwise regression analysis showed that age, 24-hour systolic blood pressure, hs-CRP level, ADMA level, and the interaction of hs-CRP with ADMA were independent predictors of ACR (R(2) = 0.674; P < 0.001). LIMITATIONS Cross-sectional study. CONCLUSIONS In patients with untreated essential hypertension, increased hs-CRP and ADMA levels are associated with microalbuminuria, suggesting the involvement of inflammation and endothelial dysfunction in vascular and kidney damage.

Subendocardial viability ratio as an index of impaired coronary flow reserve in hypertensives without significant coronary artery stenoses.

Subendocardial viability ratio (SEVR), calculated through pulse wave analysis, is an index of myocardial oxygen supply and demand. Our aim was to evaluate the relationship between coronary flow reserve (CFR) and SEVR in 36 consecutive untreated hypertensives (aged 57.9 years, 12 males, all Caucasian) with indications of myocardial ischaemia and normal coronary arteries in coronary angiography. CFR was calculated by a 0.014-inch Doppler guidewire (Flowire, Volcano, San Diego, CA, USA) in response to bolus intracoronary administration of adenosine (30–60 μg). SEVR was calculated by radial applanation tonometry, while diastolic function was evaluated by means of transmitral flow and tissue Doppler imaging. Hypertensive patients with low CFR (n=24) compared with those with normal CFR (n=12) exhibited significantly decreased SEVR by 24.5% (P=0.002). In hypertensives with low CFR, CFR was correlated with SEVR (r=0.651, P=0.001). After applying multivariate linear regression analysis, age, left ventricular mass index, Em/Am, 24-h diastolic blood pressure (BP) and SEVR turned out to be the only independent predictors of CFR (adjusted R2=0.718). Estimation of SEVR by using applanation tonometry may provide a reliable tool for the assessment of coronary microcirculation in essential hypertensives with indications of myocardial ischaemia and normal coronary arteries.

Association of obstructive sleep apnea with urinary albumin excretion in essential hypertension: a cross-sectional study.

BACKGROUND Microalbuminuria reflects a state of widespread vascular dysfunction, whereas obstructive sleep apnea (OSA) further promotes atherosclerotic damage in hypertension. STUDY DESIGN Cross-sectional. SETTING & PARTICIPANTS In an outpatient hypertensive unit, 62 untreated hypertensive patients (aged 48 +/- 7 years; office blood pressure [BP], 151 +/- 8/97 +/- 7 mm Hg) with OSA and 70 hypertensive patients without OSA (apnea hypopnea index [AHI] < or = 5) matched for age, sex, smoking status, body mass index, and 24-hour pulse pressure were studied. PREDICTOR VARIABLE Hypertension and OSA compared with hypertension without OSA. OSA defined as AHI greater than 5, documented by polysomnography. OUTCOME VARIABLE Albuminuria assessed by urinary albumin-creatinine ratio (ACR). MEASUREMENTS Participants underwent polysomnography, ambulatory BP monitoring, echocardiography, routine metabolic profile assessment, and glomerular filtration rate estimation, whereas ACR was measured from 2 nonconsecutive morning spot urine samples. RESULTS Hypertensive patients with OSA compared with those without OSA showed increased 24-hour diastolic BP (87 +/- 7 versus 85 +/- 7 mm Hg; P = 0.03) and nighttime pulse pressure (50 +/- 10 versus 45 +/- 10 mm Hg; P = 0.008), but did not differ regarding metabolic profile and estimated glomerular filtration rate. Albuminuria was greater by 57% in patients with OSA compared with those without OSA: log(10)ACR, 1.1 +/- 0.2 versus 0.7 +/- 0.4 mg/g; P < 0.001). In the entire study population, log10(ACR) correlated with log10(AHI) (r = 0.35; P < 0.001), minimum oxygen saturation during sleep (r = -0.33; P < 0.001), 24-hour pulse pressure (r = 0.38; P < 0.001), and nighttime pulse pressure (r = 0.21; P =0 .01). In a multivariable linear regression model, independent predictors of ACR were AHI (beta = 0.36; P < 0.001) and 24-hour pulse pressure (beta = 0.25; P = 0.01). LIMITATIONS Cross-sectional study. CONCLUSIONS Albuminuria increases within the normal range in hypertensive individuals with OSA compared with those without OSA proportionally to OSA severity independently of confounders. The association of upper-airway dysfunction with albuminuria and pulsatile hemodynamic load may provide an explanatory mechanism for the OSA-related risk in hypertension.

The diverse associations of uric acid with low-grade inflammation, adiponectin and arterial stiffness in never-treated hypertensives

The data regarding the role of serum uric acid (SUA) along with subclinical inflammation in the context of hypertensive vascular damage are rather scarce and controversial. Towards this end, we assess the links between SUA, high-sensitivity CRP (hs-CRP), adiponectin and carotid to femoral pulse wave velocity (c–f PWV) in 292 subjects with never-treated stage I–II essential hypertension. On the basis of the median SUA levels (0.31 mmol l−1), the study population was divided into subjects with low (n=149) and high (n=143) SUA values. By multiple regression analysis, it was revealed that SUA was independently associated with log hs-CRP (R2=0.098; P=0.02), log adiponectin (R2=0.102; P=0.03), waist circumference (R2=0.049; P=0.04), 24-h systolic blood pressure (SBP) (R2=0.179; P=0.001) and estimated glomerular filtration rate (R2=0.156; β (s.e.)=−0.169 (0.023); P=0.02). In addition, c–f PWV was independently associated with age (R2=0.116; P<0.0001), waist circumference (R2=0.088; P<0.0001), 24-h SBP (R2=0.167; P=0.001), log adiponectin (R2=0.07; P=0.006) and log hs-CRP (R2=0.06; P=0.034). In conclusion, SUA levels are independently associated with hs-CRP and adiponectin levels but not with c–f PWV in essential hypertensive patients. Increased SUA levels are accompanied by a state of pronounced inflammatory activation and hypoadiponectinemia that significantly impairs the arterial stiffness accelerating the vascular ageing process in this setting.

Exercise Blood Pressure Response, Albuminuria and Arterial Stiffness in Hypertension

BACKGROUND A hypertensive response to exercise is associated with high cardiovascular risk, whereas the data about its relation to surrogates of subclinical atherosclerosis are scarce. We investigated the relationships of a hypertensive response to exercise with urinary albumin excretion and arterial stiffness in hypertensives. METHODS There were 171 untreated males (mean age 52 years, all Caucasian) with stage I-II essential hypertension and a negative treadmill exercise test divided into those with a hypertensive response to exercise (n=48) (peak exercise systolic blood pressure > or =210 mm Hg) and to those with normal blood pressure response (n=123). Albumin-to-creatinine ratio values were determined as the mean of 3 nonconsecutive morning spot urine samples, and arterial stiffness was evaluated on the basis of carotid-to-femoral pulse wave velocity. RESULTS Patients with a hypertensive response to exercise compared with those with normal blood pressure response exhibited greater log albumin-to-creatinine ratio (1.52+/-0.59 vs 0.97+/-0.33 mg/g) and higher pulse wave velocity (8.7+/-1.6 vs 7.7+/-1.2 m/s), independent of potentially confounding demographic and clinical factors. Resting systolic blood pressure (odds ratio [OR] 1.11, 95% confidence interval [CI], 1.06-1.16), body mass index (OR 1.12, 95% CI, 1.02-1.23), resting heart rate (OR 0.96, 95% CI, 0.93-0.99), and albumin-to-creatinine ratio (OR 7.45, 95% CI, 2.54-21.83) were independently associated with a hypertensive response to exercise. CONCLUSION A hypertensive response to exercise is related to augmented albumin-to-creatinine ratio and arterial stiffness, reflecting accelerated subclinical atherosclerosis. The association of albumin excretion with exercise blood pressure response suggests that albuminuria constitutes an important factor in the interpretation of the hypertensive response to exercise-associated risk.

Catheter-based renal sympathetic denervation exerts acute and chronic effects on renal hemodynamics in swine

OBJECTIVES We investigated the acute and chronic effects of catheter-based renal sympathetic denervation (RSD) on renal hemodynamics assessed by average peak velocity (APV), renal blood flow (RBF), renal flow reserve (RFR) and resistive index (RI). BACKGROUND Sympathetic overdrive is accompanied by impaired RBF, whereas there is no data on the effects of transcatheter RSD on renal hemodynamic balance. METHODS Before and post-RSD (acutely and after 1 month), in 9 farm swines we measured APV by a 0.014-inch Doppler flow wire placed in the stem of the renal artery under baseline and hyperemic conditions, induced by intrarenal dopamine (50 μg/kg). RFR was calculated as the ratio of hyperemic to basal peak velocity, and RI was estimated as (peak systolic velocity-end-diastolic velocity)/peak systolic velocity. RSD was achieved via the lumen of the main renal artery with a specifically designed catheter connected to a radiofrequency generator according to prespecified algorithm. RESULTS APV and RBF increased acutely post ablation in all animals, compared to APV and RBF before ablation (61.44 ± 32.6 vs 20.44 ± 6.38 cm/s, p<0.001 and 407.4 ± 335.1 vs 161.1 ± 76.6 ml/min, p=0.003; respectively), whereas RFR and RI were reduced (1.51 ± 0.59 vs 2.85 ± 1.33, p<0.001 and 0.67 ± 0.07 vs 0.74 ± 0.07, p=0.005; respectively). One month post ablation APV and RBF compared to APV and RBF before ablation remained significantly higher whereas RFR and RI remained lower as compared to baseline. CONCLUSIONS Catheter-based RSD exerts acute and chronic effects on renal hemodynamics in a large animal model. If confirmed in humans RBF parameters may be used as direct markers of successful RSD.

Disturbed circadian blood pressure rhythm and C-reactive protein in essential hypertension.

We investigated the effect of the diverse definition criteria of the dipping and non-dipping status on the assessed differences in inflammatory activation between dippers and non-dippers with essential hypertension. 269 consecutive subjects (188 males, aged 50±7 years) with untreated stage I–II essential hypertension underwent ambulatory blood pressure (BP) monitoring and high-sensitivity C-reactive protein (hs-CRP) level determination. The population was classified into dippers and non-dippers based on the three following different definitions: true non-dippers (TND): non-dippers (nocturnal fall of systolic and diastolic BP of <10% of the daytime values, n=95) and dippers (the remaining subjects, n=174); true dippers and true non-dippers (TD–TND): non-dippers (nocturnal fall of systolic and diastolic BP<10%, n=95) and dippers (nocturnal fall of systolic and diastolic BP⩾10%, n=75); systolic non-dippers (SND): non-dippers (nocturnal systolic BP fall of <10% of the daytime values, n=145) and dippers (the remaining subjects, n=124). Non-dippers compared to dippers in the TND, TD–TND and SND classification exhibited higher levels of log hs-CRP (by 0.11 mg l−1, P=0.02; 0.13 mg l−1, P=0.03 and 0.14 mg l−1, P=0.02, respectively) and 24 h pulse pressure (PP) (by 4 mm Hg, P=0.006; by 5 mm Hg, P=0.003 and by 5 mm Hg, P<0.0001, respectively). Twenty-four hour PP and nocturnal systolic BP fall were independent predictors of log hs-CRP (P<0.05 for both) in multiple regression analysis. In conclusion, essential hypertensive non-dippers compared to dippers exhibit higher hs-CRP values, irrespective of the dipping status definition. Furthermore, ambulatory PP and nocturnal systolic BP fall interrelate and participate in the inflammatory processes that accompany non-dipping state.