Ioannis Andrikou

Relationships of CRP and P Wave Dispersion With Atrial Fibrillation in Hypertensive Subjects

BACKGROUND Although inflammation has been shown to be implicated in the pathophysiology of atrial fibrillation (AF), little is known about its involvement in the accompanying atrial electrical remodeling expressed by P wave dispersion (P(disp)). METHODS Fifty hypertensive subjects with documented paroxysmal AF (AF group) and 50 matched for body mass index, sex and office systolic blood pressure (BP) subjects with no history of AF (SR group) were subjected to electrocardiogram (ECG) and P(disp) assessment, hs-CRP determination, a complete echocardiographic study and 24-h ambulatory BP monitoring. RESULTS The AF as compared to the SR subjects were older by 14 years (P < 0.0001) and they exhibited lower office and 24-h diastolic BP (7 mm Hg, P < 0.0001 and by 8 mm Hg, P < 0.0001, respectively) and higher office and 24-h pulse pressure (by 4 mm Hg, P = 0.03 and 6 mm Hg, P = 0.001, respectively) mean values. A higher mean of left atrial (LA) diameter index (by 1.9 mm/m(2), P < 0.0001) and left ventricular mass index (by 16 g/m(2), P < 0.0001) were observed in the AF vs. SR group. P(disp) mean and hs-CRP median values were higher in the AF group (by 22 ms, P < 0.0005 and by 4.63 mg/l, P < 0.0005, respectively). Standard multiple and multiple logistic regression analysis identified log(10)(hs-CRP) as independent determinant of P(disp) and log(10)(CRP) and P(disp) as independent determinants of AF. CONCLUSIONS In hypertensive subjects hs-CRP and P(disp) are interrelated and associated with AF, suggesting an active implication of inflammation in the atrial electrophysiological remodeling predisposing to AF.

Similar levels of low-grade inflammation and arterial stiffness in masked and white-coat hypertension: comparisons with sustained hypertension and normotension.

ObjectiveThe clinical significance of masked hypertension (MHT) and white-coat hypertension (WCHT) remains controversial, whereas subclinical inflammation and arterial stiffness are associated with an adverse prognosis. We examined the interrelationships of MHT, WCHT, and sustained hypertension (SHT) with high-sensitivity C-reactive protein (hs-CRP) and arterial stiffness. MethodsOur population consisted of 291 untreated nondiabetic patients with MHT [office blood pressure (BP) <140/90 mmHg and daytime BP≥135/85 mmHg; n=32], WCHT (office BP≥140/90 mmHg and daytime BP <135/85 mmHg; n=81), SHT (office BP≥140/90 mmHg and daytime BP≥135/85 mmHg; n=178), and 44 age-matched and sex-matched control normotensives. ResultsSHT compared with WCHT, MHT, and normotension exhibited higher pulse wave velocity (PWV; 8.2±1.4 vs. 7.5±1.2 vs. 7.3±0.9 vs. 6.8±0.5 m/s, respectively; P<0.05) and hs-CRP (2.8±0.7 vs. 2.2±0.6 vs. 1.9±0.4 vs. 1.2±0.3 mg/l, respectively; P<0.05), independently of confounders. Of note, there was no difference between the MHT and WCHT groups with regard to hs-CRP and PWV levels (P=not significant). In hypertensives, hs-CRP was associated with 24-h systolic BP (r=0.350, P<0.0001) and PWV (r=0.228, P<0.0001), whereas PWV was associated with 24-h systolic BP (r=0.330, P<0.0001). ConclusionMHT and WCHT represent two states of equivalent subclinical vascular dysfunction reflected by hs-CRP and PWV. Moreover, MHT and WCHT are characterized by a higher degree of inflammatory activation and arterial stiffening compared with normotension and by a lesser degree compared with SHT. The association of 24-h BP with both hs-CRP and PWV underscores the dominant role of hemodynamic load on hypertensive damage progression.

Association of nighttime hypertension with central arterial stiffness and urinary albumin excretion in dipper hypertensive subjects

Both blood pressure (BP) non-dipping and nighttime hypertension have been associated with accelerated target-organ damage (TOD). However, increased nighttime BP in subjects with a dipping circadian BP profile has never been reported or associated with TOD. Here, we investigated the relationships of nighttime BP with indices of vascular and kidney damage in dipper hypertensive subjects. We studied 402 subjects with untreated stage I-II essential hypertension. According to ambulatory BP recordings, 127 dipper subjects were selected and subdivided into nighttime hypertensives (NH, n=69) (nighttime BP ⩾120/70) and nighttime normotensives (NN, n=50) (nighttime BP <120/70 mm Hg). All participants underwent echocardiographic examination and assessments of carotid-to-femoral pulse wave velocity (c-f PWV), albumin-to-creatinine ratio (ACR), metabolic profile and high sensitivity C-reactive protein (hs-CRP) level. Compared with NN dippers, NH dippers had higher c-f PWV (P<0.001), ACR values (P=0.01) and hs-CRP levels (P<0.001). Multiple regression analysis showed that nighttime BP was more correlated with c-f PWV and ACR than was daytime BP. Among dippers, nighttime BP is associated more closely with c-f PWV and ACR than is daytime BP. These findings imply that even in dippers, absolute nighttime BP values should be taken into account when predicting surrogate end points such as arterial stiffness and urinary albumin excretion.

Comparative Prognostic Role of Nighttime Blood Pressure and Nondipping Profile on Renal Outcomes

Different studies have addressed the predictive role of nighttime hemodynamics on cardiovascular and renal outcomes, although nocturnal blood pressure (BP) phenotypes (i.e. nondipping pattern and absolute nocturnal BP) have been found to be predictive of worse health outcomes. Furthermore, differences in both examined populations – ranging from healthy and younger subjects to those with overt cardiovascular disease – and study design (i.e. cross-sectional or longitudinal) make the interpretation of the suggested correlations difficult. Focusing on the kidney, we reviewed the literature addressing the impact of nocturnal BP phenotypes on renal outcomes in different populations by further dividing our search by study design. The evidence so far qualifies absolute nocturnal BP as a better predictor or determinant of kidney dysfunction as compared with the nondipping status. The magnitude of nocturnal hemodynamic load imposed at the glomerular level might be of higher prognostic value as compared with the integration of the pathophysiological mechanisms associated with impaired nocturnal BP variability. These findings underline the importance of nocturnal BP phenotypes, retrieved by ambulatory BP measurements, on age-dependent progressive kidney function decline and question whether, to what extent and in whom the reduced nocturnal BP or reverse nondipping BP profile to a normal pattern will be of benefit.

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.

Ambulatory Blood Pressure Monitoring in Resistant Hypertension

ABPM constitutes a valuable tool in the diagnosis of RH. The identification of white coat RH and masked hypertension (which may fulfill or not the definition of RH) is of great importance in the clinical management of such patients. Moreover, the various ABPM components such as average BP values, circadian BP variability patterns, and ambulatory BP-derived indices, such as ambulatory arterial stiffness index (AASI), add significantly to the risk stratification of RH. Lastly, ABPM may indicate the need for implementation of specific therapeutic strategies, such as chronotherapy, that is, administration-time dependent therapy, and the evaluation of their efficacy.

Left Ventricular Mass Index as a Predictor of New-Onset Microalbuminuria in Hypertensive Subjects: A Prospective Study

BACKGROUND We aimed to investigate the predictive role of left ventricular mass and its reduction on the development of new-onset microalbuminuria (MA) in newly diagnosed hypertensive patients. METHODS A total of 207 nondiabetic, normoalbuminuric patients without clinical organ damage (aged 50.8 ± 10.1 years, 132 male, 84 smokers) with baseline office blood pressure (BP) 148/96 mm Hg were followed for a mean period of 3.3 ± 1.3 years. At baseline and last follow-up visit, all patients underwent office and 24-h ambulatory BP monitoring, albumin to creatinine ratio (ACR) determination, and echocardiographic assessment of left ventricular mass index (LVMI). All patients were treated with antihypertensive therapy during the follow-up period. We defined MA as ACR between 20 and 300 mg/g for men and 30-300 mg/g for women, effective BP control as office BP <140/90 mm Hg in ≥75% of total number of visits, and LVMI reduction as the decline of LVMI at end-follow-up of ≥15% with respect to the baseline value. RESULTS Between baseline and last follow-up visit, LVMI decreased by 6.84 ± 21.5 g/m(2) (P < 0.01); 64.3% (n = 133) of participants achieved BP control during the follow-up period. Of the total population, 5.8% (n = 12) developed MA during follow-up. Cox-regression analysis, after adjustment for clinical variables, revealed that increase of LVMI by 1 s.d. (23.3 g/m(2)) conferred a 15% increased risk of new-onset MA, while LVMI reduction and BP control were both associated with almost 100% reduced risk of MA development. CONCLUSIONS LVMI and its reduction were qualified as predictors of new-onset MA in newly diagnosed hypertensive patients, beyond BP control.

Periodontal disease severity and urinary albumin excretion in middle-aged hypertensive patients.

To address whether periodontal disease indexes are associated with urinary albumin-to-creatinine ratio (UACR) in conditions of high and low systemic inflammation as reflected by levels of high-sensitivity C-reactive protein (hs-CRP) in untreated hypertensive patients, we studied 242 hypertensive patients 51 ± 9 years old (24-hour systolic/diastolic blood pressure [BP] 132 ± 10/83 ± 8 mm Hg) with varying severity of periodontal disease evaluated by 3 periodontal disease indexes (PDIs) (i.e., mean clinical loss of attachment, maximum probe depth, and gingival bleeding index). Patients underwent BP measurements, echocardiography, and periodontal examination, and from fasting blood samples we assessed metabolic profile and hs-CRP. From 2 nonconsecutive overnight spot urine samples we evaluated UACR. With respect to median hs-CRP and UACR levels (1.67 mg/L and 10 mg/g, respectively), the total population was divided into patients with low-UACR/low-hs-CRP (n = 65), low-UACR/high-hs-CRP (n = 63), high-UACR/low-hs-CRP (n = 51), and high-UACR/high-hs-CRP (n = 63). PDIs differed among the 4 groups, and those with high UACR had significantly higher 24-hour systolic BP compared to those with low UACR. UACR was determined by all periodontal disease indexes, hs-CRP, and the interaction of each periodontal disease index with hs-CRP. In addition, mean clinical loss of attachment was the strongest determinant of the high-UACR/high-hs-CRP pattern among all studied periodontal disease indexes. In conclusion, in untreated middle-aged hypertensive patients, periodontal disease indexes and hs-CRP have a synergistic effect on UACR levels independently of the underlying hemodynamic load.

A Hypertensive Response to Exercise Is Prominent in Patients With Obstructive Sleep Apnea and Hypertension: A Controlled Study

Blood pressure (BP) behavior during exercise is not clear in hypertensive patients with obstructive sleep apnea (OSA). The authors studied 57 men with newly diagnosed essential hypertension and untreated OSA (apnea‐hypopnea index [AHI] ≥5) but without daytime sleepiness (Epworth Sleepiness Scale score ≤10), and an equal number of hypertensive controls without OSA matched for age, body mass index, and office systolic BP. All patients underwent ambulatory BP measurements, transthoracic echocardiography, and exercise treadmill testing according to the Bruce protocol. A hypertensive response to exercise (HRE) was defined as peak systolic BP ≥210 mm Hg. Patients with OSA and control patients had similar ambulatory and resting BP, ejection fraction, and left ventricular mass. Peak systolic BP was significantly higher in patients with OSA (197.6±25.6 mm Hg vs 187.8±23.6 mm Hg; P=.03), while peak diastolic BP and heart rate did not differ between groups. Furthermore, an HRE was more prevalent in patients with OSA (44% vs 19%; P=.009). Multiple logistic regression revealed that an HRE is independently predicted by both the logAHI and minimum oxygen saturation during sleep (odds ratio, 3.94; confidence interval, 1.69–9.18; P=.001 and odds ratio, 0.94; confidence interval, 0.89–0.99; P=.02, respectively). Exaggerated BP response is more prevalent in nonsleepy hypertensives with OSA compared with their nonapneic counterparts. This finding may have distinct diagnostic and prognostic implications.

Nighttime vs. daytime blood pressure as a predictor of changes in left ventricular mass in hypertensive subjects

Left ventricular hypertrophy (LVH) conveys an increased risk of cardiovascular morbidity and mortality. We aimed to compare the prognostic value of daytime and nighttime blood pressure (BP) on the changes in LVH status in newly diagnosed hypertensive subjects. Three hundred and five hypertensive, nondiabetic subjects (mean age 51.1±10.2 years, 190 men) were prospectively studied for a mean period of 42±17 months. At baseline and last follow-up visit, all patients underwent office and ambulatory BP monitoring, as well as echocardiographic assessment. We defined the following: LVH development/LVH persistence as the new-onset LVH at the end of follow-up or the presence of LVH at both baseline and the end of follow-up; left ventricular mass index (LVMI) reduction as a decline in LVMI at the end of follow-up of ⩾15% compared with the baseline value. Multivariate Cox regression analyses revealed that baseline nighttime systolic BP was a significant predictor of LVH development/LVH persistence during follow-up (hazard ratio=1.066, P=0.02), whereas baseline daytime systolic BP was not. Moreover, the reduction of nighttime systolic BP is related to an almost threefold increase in the probability of LVMI reduction, independently of daytime BP reduction. In conclusion, nighttime BP constitutes a better prognosticator of left ventricular mass alterations over time in treated essential hypertensive patients than does daytime BP.