Olivier Ormezzano

Night-time and diastolic hypertension are common and underestimated conditions in newly diagnosed apnoeic patients

Background In newly diagnosed apnoeic patients without a history of hypertension, clinical hypertension is underdiagnosed in at least 40% of the cases. An increase in diastolic blood pressure is the most frequent pattern encountered. Objective To assess clinic and 24-h blood pressure, baroreflex sensitivity and left ventricular mass for identifying the prevalence, the type and the consequences of hypertension in newly diagnosed apnoeic patients. Patients and methods Fifty-nine unselected patients (age = 48 ± 12 years, body mass index = 28.1 ± 4.5 kg/m2) referred to a university hospital sleep laboratory for symptoms suggesting obstructive sleep apnoea were included. Diagnosis of apnoea was accepted when respiratory disturbance index was ≥15/h of sleep. Blood pressure was considered as normal by their general practitioner and all of them were free of any medication for hypertension. Echocardiography, 24-hour ambulatory blood pressure monitoring and assessment of the baroreflex sensitivity were performed. Results Forty-two percent of the apnoeic patients demonstrated a clinical hypertension, 34 subjects (58%) had a daytime hypertension, and 45 patients (76%) had a night-time hypertension, using 24-h monitoring. All the daytime hypertensives also had night-time hypertension. Forty-seven of the 59 patients (80%) were hypertensive either in the clinic or using 24-h recording. Diastolic and systolo-diastolic hypertension were the prominent types of hypertension observed both by clinic or ambulatory measurements. Respiratory disturbance index was significantly higher in apnoeic patients suffering isolated diastolic hypertension than in the normotensives (50.9 ± 26.5/h versus 36.0 ± 12.3/h, respectively; P = 0.02). The prevalence rate of left ventricular hypertrophy was high (between 15 and 20%) and occurred independently of associated hypertension. Baroreflex sensitivity was altered whatever the type of hypertension and decreased with the severity of obstructive sleep apnoea. Conclusion Hypertension is hugely underdiagnosed in apnoeic patients unknown to be hypertensive. Use of 24-h blood pressure monitoring allowed the diagnosis of twice as much hypertension than did clinical measurement. Even at the beginning of their history of hypertension, apnoeic patients exhibited chronic adaptations of their cardiovascular system, as shown by early changes in baroreflex sensitivity and an increased prevalence of left ventricular hypertrophy.

EVAluation of the prognostic value of BARoreflex sensitivity in hypertensive patients: the EVABAR study.

Aims The prognostic value of baroreflex sensitivity in hypertensive patients has not much been studied. Method A cohort of 451 hypertensive patients without cardiovascular history was studied for an average of 6.2 ± 2.8 years follow-up. Each patient had a baroreflex sensitivity measurement by the sequence method, which is represented by the slope of up-sequences (systolic blood pressure+/pulse interval+) and down-sequences (systolic blood pressure−/pulse interval−) of spontaneous fluctuations in systolic blood pressure and pulse interval. Results During the follow-up, there were 20 deaths from any cause and 30 patients presented a major adverse cardiovascular event. Deaths and major adverse cardiovascular events were associated with a reduction in baroreflex sensitivity (systolic blood pressure+/pulse interval+ and systolic blood pressure−/pulse interval−). In multivariate analysis, the reduction in baroreflex sensitivity systolic blood pressure+/pulse interval+ was associated with an increased risk of deaths from any cause (Odds ratio 1.23; 95% confidence interval 1.02–1.67, P = 0.04). A baroreflex sensitivity systolic blood pressure+/pulse interval+ under 4.5 ms/mmHg was associated with a 2.5-increased relative risk of major adverse cardiovascular event (95% confidence interval 1.11–5.93, P = 0.03). However, multivariate analysis showed that baroreflex sensitivity systolic blood pressure−/pulse interval− was not associated either with death or major adverse cardiovascular events. Conclusions Reduction in baroreflex sensitivity marked by a reduction in vagal reflexes is an independent marker of the risk of mortality and major adverse cardiovascular events in hypertensive patients.

Early cardiovascular abnormalities in newly diagnosed obstructive sleep apnea

Obstructive sleep apnea (OSA) is associated with high cardiovascular morbidity and mortality. Recent studies have shown that it is associated with atherosclerosis and left ventricular dysfunction markers. The aim of this study was to assess the cardiovascular effects of OSA depending on its severity, in patients without clinically diagnosed cardiovascular disease. One hundred thirty newly diagnosed, nondiabetic OSA patients (mean age 49 ± 10 years), without vasoactive treatment were included. They underwent clinical and ambulatory blood pressure measurements, echocardiography, carotid ultrasound examination, and a carotid–femoral pulse wave velocity (PWV) measurement. Seventy-five percent of the subjects were hypertensive according to the clinical or ambulatory measurement. More patients with the most severe forms (respiratory disturbance index >37/hour) had a nondipper profile (52% vs 34%; P = 0.025) and their left ventricular mass was higher (40 ± 7 vs 36 ± 8 g/m, p = 0.014). This last parameter was independently and inversely associated with mean nocturnal oxygen saturation (P = 0.004). PWV and carotid intima-media thickness did not differ between one OSA severity group to another, but the prevalence of carotid hypertrophy was higher when mean SaO2 was below 93.5% (29.5 vs 16%; P = 0.05). Our study shows that in OSA patients without clinically diagnosed cardiovascular disease, there is a significant left ventricular and arterial effect, which is even more marked when OSA is severe.

A polymorphism in the endothelin-a receptor gene is linked to baroreflex sensitivity

Background The baroreflex plays an essential role in regulating the cardiovascular system. However, very few studies have focused on the links between genetic polymorphisms and baroreflex sensitivity (BRS). Methods A total of 146 hypertensive individuals who had never been treated, and 105 healthy individuals (controls) were included in the study. The genotypes of 17 polymorphisms of 11 genes involved in the regulation of the cardiovascular system were studied. BRS was measured using a sequence method: BRS was evaluated as the slope of spontaneous increases [systolic blood pressure (SBP)+/reflex response (RR)+] or decreases (SBP−/RR−) in SBP and pulse interval by recording blood pressure (BP) continuously for 20 min. Results Following univariate analysis, the genetic polymorphism of endothelin receptor A EDNRA/C+1222T was found to be significantly correlated with the BRS (SBP−/RR−) level in both populations. In normotensive subjects, mean BRS values (SBP−/RR−) were 11.93 ± 3.69 ms/mmHg in EDNRA CC homozygotes, 9.94 ± 2.97 ms/mmHg in CT heterozygotes and 9.51 ± 3.16 ms/mmHg in TT homozygotes (P = 0.01). In hypertensive subjects, mean BRS values (SBP−/RR−) were 9.26 ± 3.59 ms/mmHg in EDNRA CC homozygotes, 9.03 ± 4.14 ms/mmHg in CT heterozygotes and 6.60 ± 2.42 ms/mmHg in TT homozygotes (P = 0.01). After adjustment for age, sex, SBP and diastolic blood pressure and body mass index, the EDNRA/C+1222T polymorphism remained significantly correlated with BRS in both normotensive (P = 0.01) and hypertensive (P = 0.01) subjects. Conclusions These results suggest that the endothelin system may be involved in the regulation of BRS in humans. In particular, the T allele of the EDNRA/C+1222T polymorphism is associated with a reduction in BRS in both healthy and hypertensive subjects.

Increased aortic root size is associated with nocturnal hypoxia and diastolic blood pressure in obstructive sleep apnea.

STUDY OBJECTIVES Obstructive sleep apnea (OSA) is known as a major cardiovascular risk factor, and high prevalence of OSA has been reported in patients with thoracic aortic dissection. The aim of our study was to assess the relationship between OSA, its vascular consequences, and aortic root size. DESIGN/PATIENTS 156 newly diagnosed apneic patients free of cardiovascular disease and medication were included. Patients underwent cardiac ultrasound for measuring aortic root diameter, polysomnography, office and 24-h ambulatory blood pressure (BP) measurements, baroreflex sensitivity (BRS), and arterial stiffness evaluation by carotid-to-femoral pulse wave velocity (PWV). MEASUREMENTS AND RESULTS In univariate analysis, greater aortic root size was associated with older age (P = 0.03) and severity of OSA as expressed by mean nocturnal oxygen saturation (SpO2) (P = 0.015). Moreover, greater aortic root size was associated with higher diastolic BP, measured both clinically (P = 0.0005) or by 24-h ambulatory BP monitoring (P = 0.02), and PWV (P = 0.03). Mean nocturnal SpO(2) was correlated with BRS (P = 0.0008), thus potentially influencing BP values and arterial stiffness. In multivariate stepwise regression analysis, diastolic BP was the only significant factor for aortic root size (P = 0.0003). CONCLUSIONS In OSA patients, nocturnal hypoxemia decreased BRS and increased diastolic BP, which was the main factor influencing aortic root size.

High Prevalence of Multiple Arterial Bed Lesions in Patients With Fibromuscular DysplasiaNovelty and Significance: The ARCADIA Registry (Assessment of Renal and Cervical Artery Dysplasia)

Fibromuscular dysplasia (FMD) commonly affects the renal and cervical arteries but has been described to affect other vascular beds as well. The prevalence of and clinical characteristics associated with multisite FMD (string-of-beds or focal stenoses affecting at least 2 vascular beds) are not known. In the prospective ARCADIA registry (Assessment of Renal and Cervical Artery Dysplasia), symptomatic patients with renal artery (RA) FMD underwent tomographic- or magnetic resonance-angiography from the aortic arch to the intracranial arteries and those with cervical FMD from the diaphragm to the pelvis. Of 469 patients (84.0% women), 225 (48.0%) had multisite FMD. In addition, 86 of 244 patients with single-site disease had dissections or aneurisms affecting other vascular beds, totaling 311 patients (66.3%) with lesions in >1 vascular bed. Among patients with a cerebrovascular presentation, the prevalence of RA lesions was higher in patients with than in those without hypertension (odds ratio, 3.4; 95% confidence interval, 1.99–6.15). Among patients with a renal presentation, the prevalence of cervical lesions was higher in patients with bilateral than in those with unilateral RA lesions (odds ratio, 1.9; 95% confidence interval, 0.99–3.57). In conclusion, FMD is a systemic arterial disease. At least 2 vascular beds were affected by dysplastic stenoses in 48.0% of cases and by dysplastic stenoses, aneurysms, and dissections in 66.1% of cases. RA imaging should be proposed to hypertensive patients with a cerebrovascular presentation. Cervical artery imaging should be considered in patients with a renal presentation and bilateral RA lesions. Clinical Trial Registration— URL: www.Clinicaltrials.gov. Unique identifier: NCT02884141.

Study of nycthemeral variations in blood pressure in patients with heart failure.

ObjectiveThe objective of this study was to describe and analyse the nycthemeral variations in blood pressure (BP) by ambulatory BP monitoring (ABPM) over 24 h in patients with heart failure (HF). MethodsThe study population included 50 stable HF patients hospitalized in a cardiology department for acute pulmonary oedema. Parameters studied were: New York Heart Association class, clinical resting BP and heart rate in sitting and then standing positions, ABPM parameters, distance covered during a 6-min walking test, echographic left ventricular ejection fraction (LVEF), natremia, kaliemia, creatininemia, plasma haemoglobin and N-terminal fragment of brain-type natriuretic peptide levels. ResultsClinical hypertension was noted in 20% of patients (10/50) and orthostatic hypotension in 16% (8/50). Nine of 50 patients (18%) were hypertensive during the day and 21 (42%) at night. Thirty-nine of the 50 patients (78%) are nondippers. Nondipper patients are more prevalent when the HF has been present for more than 24 months (95 vs. 67%, P=0.04). This prevalence does not differ depending on New York Heart Association class or LVEF. Furthermore, there exists: (i) a significant positive relationship (R=0.46, P=0.02) between the diastolic BP (DBP) over 24 h and the distance covered during the walking test; (ii) a significant negative relationship between the day–night differences (in mmHg) of the systolic BP (SBP) (R=−0.46, P=0.01) and DBP (R=−0.33, P=0.03) and the duration of HF, between the day–night difference of the DBP and the LVEF (R=−0.34, P=0.02) and (iii) between the day–night differences of the SBP (R=−0.48, P=0.001) and the DBP (R=−0.32, P=0.03) and natremia. The day–night difference of the SBP has a positive correlation with plasma haemoglobin level (R=0.32, P=0.03). ConclusionThis study confirms the feasibility of carrying out ABPM with an adapted device in HF patients with atrial fibrillation. ABPM allows diagnosis to be more precise than the clinical measuring of BP abnormalities, which have a pejorative prognosis (e.g. hypertension, hypotension, nondipper status).

Twenty-Four-Hour Blood Pressure Monitoring to Predict and Assess Impact of Renal Denervation: The DENERHTN Study (Renal Denervation for Hypertension).

The DENERHTN trial (Renal Denervation for Hypertension) confirmed the blood pressure (BP) lowering efficacy of renal denervation added to a standardized stepped-care antihypertensive treatment for resistant hypertension at 6 months. We report here the effect of denervation on 24-hour BP and its variability and look for parameters that predicted the BP response. Patients with resistant hypertension were randomly assigned to denervation plus stepped-care treatment or treatment alone (control). Average and standard deviation of 24-hour, daytime, and nighttime BP and the smoothness index were calculated on recordings performed at randomization and 6 months. Responders were defined as a 6-month 24-hour systolic BP reduction ≥20 mm Hg. Analyses were performed on the per-protocol population. The significantly greater BP reduction in the denervation group was associated with a higher smoothness index (P=0.02). Variability of 24-hour, daytime, and nighttime BP did not change significantly from baseline to 6 months in both groups. The number of responders was greater in the denervation (20/44, 44.5%) than in the control group (11/53, 20.8%; P=0.01). In the discriminant analysis, baseline average nighttime systolic BP and standard deviation were significant predictors of the systolic BP response in the denervation group only, allowing adequate responder classification of 70% of the patients. Our results show that denervation lowers ambulatory BP homogeneously over 24 hours in patients with resistant hypertension and suggest that nighttime systolic BP and variability are predictors of the BP response to denervation. Clinical Trial Registration— URL: https://www.clinicaltrials.gov. Unique identifier: NCT01570777.

Abdominal Aortic Calcifications Influences the Systemic and Renal Hemodynamic Response to Renal Denervation in the DENERHTN (Renal Denervation for Hypertension) Trial

Background The DENERHTN (Renal Denervation for Hypertension) trial confirmed the efficacy of renal denervation (RDN) in lowering daytime ambulatory systolic blood pressure when added to standardized stepped‐care antihypertensive treatment (SSAHT) for resistant hypertension at 6 months. Methods and Results This post hoc exploratory analysis assessed the impact of abdominal aortic calcifications (AAC) on the hemodynamic and renal response to RDN at 6 months. In total, 106 patients with resistant hypertension were randomly assigned to RDN plus SSAHT or to the same SSAHT alone (control group). Total AAC volume was measured, with semiautomatic software and blind to randomization, from the aortic hiatus to the iliac bifurcation using the prerandomization noncontrast abdominal computed tomography scans of 90 patients. Measurements were expressed as tertiles. The baseline‐adjusted difference in the change in daytime ambulatory systolic blood pressure from baseline to 6 months between the RDN and control groups was −10.1 mm Hg (P=0.0462) in the lowest tertile and −2.5 mm Hg (P=0.4987) in the 2 highest tertiles of AAC volume. Estimated glomerular filtration rate remained stable at 6 months for the patients in the lowest tertile of AAC volume who underwent RDN (+2.5 mL/min per 1.73 m2) but decreased in the control group (−8.0 mL/min per 1.73 m2, P=0.0148). In the 2 highest tertiles of AAC volume, estimated glomerular filtration rate decreased similarly in the RDN and control groups (P=0.2640). Conclusions RDN plus SSAHT resulted in a larger decrease in daytime ambulatory systolic blood pressure than SSAHT alone in patients with a lower AAC burden than in those with a higher AAC burden. This larger decrease in daytime ambulatory systolic blood pressure was not associated with a decrease in estimated glomerular filtration rate. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT01570777.

Ambulatory blood pressure variation in healthy subjects, hypertensive elderly and type 1 diabetic patients in relation to the sitting or standing position.

Received 27 August 2001 Accepted 04 September 200