Obstructive sleep apnea, circulating microRNAs, and risk of cardiovascular disease.

OBJECTIVE: while obstructive sleep apnea is strongly associated with incident cardiovascular diseases (CVD), the underlying mechanisms remain to be elucidated. This study aimed to compare the patterns of microRNAs expression between OSA and control patients with and without incident CVD. METHODS: 218 matched adult participants with and without OSA and with and without incident CVD were selected from two independent community-based prospective cohorts in France and Switzerland, and 168 microRNAs on average were detected per sample. OSA was diagnosed using the validated Berlin questionnaire in one study (Paris Prospective Study 3) and during a full-night polysomnography in the second study (HypnoLaus Study). RESULTS: there were 78 OSA patients (39 with and 39 without CVD) and 140 controls (70 with and 70 without CVD). Participants were male in 54.6% (n = 119) and mean age was 58.7 years (±9.2). Of the 183 miRNAs screened, a mean 168 assays were detected per sample, and 129 in all samples. There was no pattern of blood microRNAs expression that discriminated OSA patients with and without CVD events. CONCLUSIONS: this binational study failed to find any association between a large panel of microRNAs and OSA patients with and without incident CVD.

Oral Condition and Incident Coronary Heart Disease: A Clustering Analysis.

Poor oral health has been linked to coronary heart disease (CHD). Clustering clinical oral conditions routinely recorded in adults may identify their CHD risk profile. Participants from the Paris Prospective Study 3 received, between 2008 and 2012, a baseline routine full-mouth clinical examination and an extensive physical examination and were thereafter followed up every 2 y until September 2020. Three axes defined oral health conditions: 1) healthy, missing, filled, and decayed teeth; 2) masticatory capacity denoted by functional masticatory units; and 3) gingival inflammation and dental plaque. Hierarchical cluster analysis was performed with multivariate Cox proportional hazards regression models and adjusted for age, sex, smoking, body mass index, education, deprivation (EPICES score; Evaluation of Deprivation and Inequalities in Health Examination Centres), hypertension, type 2 diabetes, LDL and HDL serum cholesterol (low- and high-density lipoprotein), triglycerides, lipid-lowering medications, NT-proBNP and IL-6 serum level. A sample of 5,294 participants (age, 50 to 75 y; 37.10% women) were included in the study. Cluster analysis identified 3,688 (69.66%) participants with optimal oral health and preserved masticatory capacity (cluster 1), 1,356 (25.61%) with moderate oral health and moderately impaired masticatory capacity (cluster 2), and 250 (4.72%) with poor oral health and severely impaired masticatory capacity (cluster 3). After a median follow-up of 8.32 y (interquartile range, 8.00 to 10.05), 128 nonfatal incident CHD events occurred. As compared with cluster 1, the risk of CHD progressively increased from cluster 2 (hazard ratio, 1.45; 95% CI, 0.98 to 2.15) to cluster 3 (hazard ratio, 2.47; 95% CI, 1.34 to 4.57; P < 0.05 for trend). To conclude, middle-aged individuals with poor oral health and severely impaired masticatory capacity have more than twice the risk of incident CHD than those with optimal oral health and preserved masticatory capacity (ClinicalTrials.gov NCT00741728).

Masticatory Capacity and Mortality: The Preventive and Clinical Investigation Center (IPC) Cohort Study.

Poor oral health (OH) has been associated with mortality, but the association between OH components and mortality remains imprecise. The present observational study aimed to investigate if there is an association between oral masticatory efficiency and cardiovascular (CV) mortality in a large French subject cohort. The study was based on a cohort of 85,830 subjects aged between 16 and 94 y at recruitment. The follow-up extended from 2001 to 2014 and the mean follow-up was 8.06 ± 2.73 y. The number of deaths totaled 1,670. Full-mouth examinations were performed. Dental plaque, dental calculus, gingival inflammation, missing teeth, and masticatory units were recorded. Masticatory units represent the number of natural or prosthetic opposing premolars and molar pairs and can be considered an accurate indicator for masticatory efficiency. Causes of death were ascertained from death certificates. Cox regression analyses were used to calculate hazard ratios (HRs). In the fully adjusted model, the number of masticatory units <5 is associated with an HR of 1.72 (95% confidence interval [CI], 1.54 to 1.91) for all-cause mortality, HR of 1.41 (95% CI, 1.01 to 1.99) for CV mortality, HR of 1.76 (95% CI, 1.44 to 2.15) for cancer mortality, and HR of 1.85 (95% CI, 1.55 to 2.20) for non-CV and noncancer mortality. Significant statistical associations with the other oral variables were also found for all-cause mortality, cancer mortality, and non-CV and noncancer mortality in the adjusted models. Our study indicates that after full adjustment, all oral parameters are associated with all-cause, cancer, and non-CV and noncancer mortality. However, the low number of masticatory units is associated with an increased risk of CV mortality. We highlight the association of masticatory units and CV mortality.

Body Silhouette Trajectories Over the Lifespan and Insomnia Symptoms: The Paris Prospective Study 3.

Insomnia symptoms are highly prevalent and associated with several adverse medical conditions, but only few determinants, including non-modifiable ones, have been highlighted. We investigated associations between body silhouette trajectories over the lifespan and insomnia symptoms in adulthood. From a community-based study, 7 496 men and women aged 50-75 years recalled their body silhouette at age 8, 15, 25, 35 and 45, and rated the frequency of insomnia symptoms on a standardized sleep questionnaire. An Epworth Sleepiness Scale ≥11 defined excessive daytime sleepiness (EDS). Using a group-based trajectory modeling, we identified five body silhouette trajectories: a 'lean-stable' (32.7%), a 'heavy-stable' (8.1%), a 'moderate-stable' (32.5%), a 'lean-increase' (11%) and a 'lean-marked increase' (15.7%) trajectory. In multivariate logistic regression, compared to the 'lean-stable' trajectory, the 'lean-marked increase' and 'heavy-stable' trajectories were associated with a significant increased odd of having ≥1 insomnia symptoms as compared to none and of having a proxy for insomnia disorder (≥1 insomnia symptom and EDS). The association with the 'lean-marked increase' trajectory' was independent from body mass index measured at study recruitment. In conclusion, increasing body silhouette over the lifespan is associated with insomnia symptoms in adulthood, emphasizing the importance of weight gain prevention during the entire lifespan.

[Silhouettes at different age of life: Retrospective appreciation of corpulence and his impact on prevalence of hypertension at 60years]. / Silhouettes aux différents âges de la vie : méthode d'appréciation rétrospective de la corpulence et de son impact sur la prévalence de l'hypertension à 60 ans.

PURPOSE OF THE STUDY: In epidemiological studies, recall of weight and height are not readily available at different ages of life. In order to improve the knowledge of the weight history, Sörensen et al. in 1983, developed a tool from silhouettes allowing an individual to evaluate his corpulence at different ages of life. Validity studies showed that measured weight and size were correlated to 80% in the reported silhouette. Studies have also shown that silhouettes are a good way to trace the weight history in an individual's life. Very few epidemiological studies have used this tool. A French study revealed a decrease of the risk of breast cancer in obese girls between the age of 8 and adolescence. Another study showed that a low birth weight or a thin silhouette before adulthood was associated with an increased risk of diabetes. On the basis of these findings, it was interesting to evaluate the relationship between the silhouette at 20years and the risk of hypertension at the age of 60years. RESULTS: It was shown that the prevalence of hypertension at age 60 was higher among obese subjects at 20years than among thin subjects (45.3% vs 36.7% (P<0.05). CONCLUSION: The classification between slimness and obesity is relevant using this tool. The history of corpulence is an important element to consider in the determinants of pathology, especially in hypertension.

Cross-sectional analysis of deprivation and ideal cardiovascular health in the Paris Prospective Study 3.

AIMS: We hypothesised that deprivation might represent a barrier to attain an ideal cardiovascular health (CVH) as defined by the American Heart Association (AHA). METHODS AND RESULTS: The baseline data of 8916 participants of the Paris Prospective Study 3, an observational cohort on novel markers for future cardiovascular disease, were used. The AHA 7-item tool includes four health behaviours (smoking, body weight, physical activity and optimal diet) and three biological measures (blood cholesterol, blood glucose and blood pressure). A validated 11-item score of individual material and psychosocial deprivation, the Evaluation de la Précarité et des Inégalités dans les Centres d'Examens de Santé-Evaluation of Deprivation and Inequalities in Health Examination centres (EPICES) score was used. The mean age was 59.5 years (standard deviation 6.2), 61.2% were men and 9.98% had an ideal CVH. In sex-specific multivariable polytomous logistic regression, the odds ratio (OR) for ideal behavioural CVH progressively decreased with quartile of increasing deprivation, from 0.54 (95% CI 0.41 to 0.72) to 0.49 (0.37 to 0.65) in women and from 0.61 (0.50 to 0.76) to 0.57 (0.46 to 0.71) in men. Associations with ideal biological CVH were confined to the most deprived women (OR=0.60; 95% CI 0.37 to 0.99), whereas in men, greater deprivation was related to higher OR of intermediate biological CVH (OR=1.28; 95% CI 1.05 to 1.57 for the third quartile vs the first quartile). CONCLUSIONS: Higher material and psychosocial deprivation may represent a barrier to reach an ideal CVH. TRIAL REGISTRATION NUMBER: NCT00741728.

High level of depressive symptoms as a barrier to reach an ideal cardiovascular health. The Paris Prospective Study III.

We hypothesized that depression might represent a barrier to reach an ideal cardiovascular health (CVH) as estimated by the 7-item tool proposed by the American Heart Association. Between 2008 and 2012, 9,417 subjects 50-75 years of age were examined in a large health center and enrolled in the Paris Prospective Study III (PPS3). Participants with 0-2, 3-4 and 5-7 health metrics at the ideal level were categorized as having poor, intermediate and ideal CVH, respectively. Participants with a score ≥ 7 on the 13-item Questionnaire of Depression 2nd version, Abridged or who were on antidepressants were referred as having high level of depressive symptoms (HLDS). The mean age of the 9417 study participants was 59.57 (SD 6.28) years and 61.16% were males. A total of 9.55% had HLDS. Poor, intermediate and ideal CVH was present in 40.38%, 49.52% and 10.10% of the participants. In multivariate polytomous logistic regression analysis, HLDS was inversely associated with ideal CVH (odds ratio = 0.70; 95% CI: 0.55;0.90). This was driven by an association with the behavioural component of the CVH. Participants with HLDS had a substantial reduced chance of reaching an ideal CVH.

New techniques for assessing arterial stiffness.

Arterial stiffness is now included in the guidelines of the European Society of Hypertension. In this paper, we review the evidence for the predictive value of arterial stiffness. More than 11 longitudinal trials have proven the predictive value of aortic stiffness measured through carotid to femoral pulse wave velocity, beyond and above classical risk factors. Such evidence is scarcer for central pressure and local arterial stiffness. If we add this evidence to the easiness of performing such measure, carotid to femoral pulse wave velocity is the reference technique for assessing arterial stiffness. Its place in the investigation of patients remains to be precised.

Inheritance of arterial lesions in renal fibromuscular dysplasia.

We have previously shown that patients with renal fibromuscular dysplasia (FMD) have asymptomatic carotid lesions and that familial forms may occur. The objective of this study was to test whether carotid lesions could be detected in relatives of familial cases. High-resolution echotracking of the carotid artery was performed in 47 relatives of 13 cases from six families. This non-invasive investigation led to a semiquantitative arterial score that was compared with that obtained for 47 controls matched for age and sex and that for 125 sporadic cases. Familial resemblance was tested by using a generalized estimating equation approach taking into account the clustering of scores in families. As expected, FMD cases had a significantly higher score than controls (4.02 vs 2.52, P<10(-5)). Familial cases were not significantly different from sporadic cases. Of interest, the 47 apparently healthy relatives of familial cases had also a high carotid score (4.17), very significantly higher than that of controls (2.52, P<10(-5)) even though lower than the corresponding index FMD cases (4.81, P=0.01). Segregation analysis showed that 52% of the descendants of subjects with a score >4 had a score >4, a proportion consistent with autosomal-dominant transmission of the trait. Altogether these results strengthen the hypothesis of renal FMD being a systemic arterial disease and argue for a familial resemblance that may be due to a major genetic effect. The carotid score obtained by high-resolution echotracking may provide a non-invasive surrogate marker for renal FMD of potential value for use in linkage strategies on large pedigrees.

Arterial stiffness and enlargement in mild-to-moderate chronic kidney disease.

Chronic kidney disease (CKD) is associated with an increased risk of cardiovascular morbidity and mortality. Arterial stiffness and remodeling have been well documented in patients with end-stage renal disease, but little is known about arterial phenotype in CKD patients with moderate reduction in glomerular filtration rate (GFR). In total, 95 patients (58+/-15 years, mean+/-s.d.) with CKD and GFR measured by renal clearance of (51)Cr-ethylenediaminetetraacetate were compared to 121 hypertensive patients without CKD (59+/-11 years), and 57 normotensive subjects (56+/-6 years). Common carotid artery diameter, intima-media thickness (IMT), distensibility, and Young's elastic modulus were noninvasively determined with a high-definition echotracking system. Patients with CKD had a significantly larger carotid internal diameter than in hypertensives and normotensives (6.32+/-1.05, 5.84+/-0.74, and 5.50+/-0.64 m x 10(-3), respectively; P<0.001), resulting in 25% and 11% increases in circumferential wall stress, respectively, since no significant difference in IMT was observed. Carotid distensibility and elastic modulus did not significantly differ between CKD and hypertensives; normotensives had significantly higher distensibility and lower elastic modulus than CKD and hypertensive patients. Carotid-femoral pulse wave velocity was significantly higher in CKD patients than in hypertensives and normotensives. In multivariate analyses either involving the entire population or restricted to CKD patients, GFR was independently and strongly related to carotid diameter and elastic modulus. Arterial enlargement and increased arterial stiffness occur in parallel with the decline in renal function in patients with mild-to-moderate CKD.

[Arterial ageing and coronary artery disease: physiopathological and epidemiological data]. / Vieillissement artériel et maladie coronaire: données physiopathologiques et épidémiologiques.

Vascular remodelling describes any change in arterial structure or function during physiological (ageing) and pathological processes such as atherosclerosis and hypertension. Adaptive changes in the short-term may carry pathological consequences in the long-term. The effects of ageing are additive with those of hypertension. The consequences are different according to whether the small resistance arteries or the large arteries of conduction are taken into consideration. The resistance arteries undergo three types of changes: (1) concentric or entrophic remodelling; this is a reorganisation of the same amount of tissue around a smaller diameter; (2) a rarefaction of the arteriolar bed; this is a smaller density of arterioles per unit weight of tissue perfused; (3) early disease of endothelial function with a reduced bio-availability of NO. The global result is an increase in peripheral resistance, a reduced capacity for vasodilatation and tissue ischaemia under critical conditions of perfusion. The methods of investigation of these different factors are not sufficiently well developed for use in routine clinical practice. Disease of the large arteries is principally an excentric hypertrophy, an increase in rigidity and loss of compliance. The increase in rigidity depends on the arterial territory: it is important in the aorta, moderate for elastic arteries but paradoxically decreased for muscular arteries, reflecting the combined effect of vascular smooth muscle hypertrophy ( mainly in the periphery) and changes in the extracellular matrix (mainly in the elastic arteries). The increased arterial rigidity is accompanied by an increase in cardiac work, hypertrophy, decreased coronary perfusion, favourising myocardial ischaemia. Peripheral artery remodelling also occurs in the coronary network. Therefore, the predictive positive value of hypertrophy and, above all, of aortic rigidity for coronary artery disease has now been well established in many populations. This predictive value is a complement to risk algorithms (SCORE, Framingham) and further predicts the coronary risk. Remodelling and arterial rigidity constitute disease of the artery as a target organ. Arch Mal Coeur Vaiss

Diagnostic score for heparin-induced thrombocytopenia after cardiopulmonary bypass.

Heparin-induced thrombocytopenia (HIT) occurs in nearly 3% of patients treated with heparin after cardiopulmonary bypass (CPB). HIT carries a risk of severe thrombotic complications, and must be diagnosed rapidly. To identify simple criteria for estimating the probability of HIT after CPB, we retrospectively analyzed the files of 84 patients with suspected HIT after CPB and we analyzed the usefulness of several variables collected at the time of HIT suspicion to estimate HIT probability. HIT was confirmed in 35 cases and ruled out in 49 cases, on the basis of a platelet increment after heparin withdrawal, detection of heparin-dependent antibodies, and absence of other clear cause of thrombocytopenia. A biphasic platelet count from CPB to the first day of suspected HIT, an interval of >/= 5 days from CPB to the first day of suspected HIT, and a CPB duration of

Influence of tamoxifen on carotid intima-media thickness in postmenopausal women.

BACKGROUND: Intima-media thickness of the common carotid artery (IMT-CCA) is an early marker of atherosclerosis. Tamoxifen is a selective estrogen-receptor modulator with estrogen-like effects on cardiovascular risk factors but as-yet unexplored effects on carotid artery structure. The goal of this study was to determine the influence of tamoxifen on IMT-CCA in menopausal women. METHODS AND RESULTS: With a predefined calculation of the sample size, 67 menopausal women with cancer who were treated with tamoxifen for > or =1 year and 37 menopausal women with cancer who were never treated with tamoxifen were enrolled. IMT-CCA, internal diameter, and pulse pressure were determined with a high-definition echotracking device and applanation tonometry in a central core laboratory that was blinded to treatment. Both groups were similar for clinical characteristics, including cardiovascular risk factors. IMT and internal diameter were significantly lower in the tamoxifen group (mean duration of treatment, 2.4+/-0.9 years) than in the control group (609+/-117 microm versus 662+/-147 microm, P=0.04, and 4.89+/-0.60 mm versus 5.12+/-0.58 mm, P=0.03, respectively). Pulse pressure was not influenced by the use of tamoxifen. After adjustment for age, cardiovascular risk factors, carotid pulse pressure, duration of menopause, and previous use of hormone replacement therapy, IMT remained significantly lower among tamoxifen users (P<0.00001), with an impact on IMT (-70 microm) equivalent to spontaneous evolution with 12 years of aging (5 microm/y). CONCLUSION: The use of tamoxifen was associated with a significantly lower carotid IMT in menopausal women with cancer. Randomized trials are needed to confirm the cardioprotective effect of selective estrogen-receptor modulators in terms of prevention of atherosclerosis.

Arterial remodelling in Fabry disease.

AIM: The enzymatic defect in Fabry disease results in the slow systemic deposition of uncleaved glycosphingolipids in the lysosomes of vascular endothelium and smooth muscle cells, leading to ischaemic strokes, cardiomyopathy and renal failure. Whereas it is known that Fabry disease affects small blood vessels, little is known about its effects on peripheral large arteries. We therefore set out to compare parameters of arterial wall structure and function in a cohort of patients with Fabry disease and an age-matched control group. METHODS: Large artery phenotype was non-invasively investigated in 21 hemizygous patients with Fabry disease and 24 age-matched male controls. Common carotid and radial artery diameter, intima-media thickness (IMT) and distensibility were determined with high-definition echotracking systems and aplanation tonometry. RESULTS: Patients with Fabry disease had a significant twofold increase in radial artery IMT and distensibility, independent of body surface area, age and mean blood pressure. In both groups, older age at the time of examination was significantly associated with larger radial artery IMT. The relationship between age and radial IMT was 2.3-fold higher in patients with Fabry disease than in controls (p < 0.01). Carotid IMT was mildly but significantly increased in patients with Fabry disease (+18%), whereas distensibility was unchanged. CONCLUSION: This study presents evidence of a major increase in arterial wall thickness and distensibility, measurable at the site of a medium-sized artery, in a cohort of patients with classic Fabry disease.

Compressibility of the carotid artery in patients with pseudoxanthoma elasticum.

The arterial wall has generally been considered as noncompressible in in vitro studies. However, compressibility of the arterial wall (CAW) has never been studied in vivo in humans. Large interstitial proteoglycans play a major role in sustaining the compression generated by pulsatile forces. The aims of the present study were to develop an experimental methodology for the assessment of CAW in vivo in humans and to study CAW in patients with pseudoxanthoma elasticum (PXE), a genetic disease characterized by proteoglycan accumulation and fragmented, swollen, and calcified elastic fibers in connective tissues. We studied 19 female patients with PXE and 15 normal female control subjects matched for age and blood pressure. A high-resolution echo-tracking system was used for the continuous determination of internal diameter and wall thickness at the site of the common carotid artery. Matrices of the radiofrequency signal were analyzed with a dedicated software to measure carotid wall cross-sectional area every 4 milliseconds during 4 to 6 cardiac cycles. CAW was calculated as the stroke change in cross-sectional area. CAW was 44% higher in patients with PXE than in control subjects (6.8+/-2.6% versus 4.7+/-2.7%, respectively; P<0.05). In control subjects, CAW decreased with age in a linear manner (r=-0.75, P<0.01). In PXE patients, the relationship with age was not homogeneous: CAW tended to increase with age before 40 years (P=0.07) and significantly decreased with age in older patients (P<0.01). Carotid geometry and elastic properties did not differ between PXE patients and control subjects. In conclusion, CAW was measurable in vivo and noninvasively in humans. The higher CAW of PXE patients compared with that of control subjects suggests that proteoglycans are important determinants of compressibility.

Heart rate, arterial stiffness, and wave reflections in paced patients.

Elevated heart rate (HR) and pulse pressure (PP) have a cumulative effect on cardiovascular risk, with the exception of HR >/=100 bpm. How an increase in HR may influence the PP level has never been investigated. In 11 patients with pacemaker monitoring, aortic (pulse-wave analysis) and digital (photoplethysmographic device) blood pressure were measured at 3 different levels of HR, together with determinations of carotid dimensions (echo tracking technique), wave reflections (pulse-wave analysis), and aortic pulse-wave velocity. Increased HR is associated with the following: (1) a significant increase of digital systolic, diastolic, and mean blood pressure; (2) a significant reduction of digital and carotid PP, with a more pronounced reduction of the carotid than of the digital PP, resulting in a significant PP amplification; and (3) a reduction in the time required for the backward pressure wave to return toward the heart, without any change of arterial stiffness. Increased HR significantly enhances PP amplification, leading to an increase of peripheral blood pressure without comparable change in central blood pressure. These results are important to consider for a better understanding of cardiovascular risk and the mechanism of white-coat hypertension.

[Effect of acupuncture on radial artery hemodynamics. Two controlled studies in pre-exposed and naive healthy subjects]. / Effets de l'acupuncture sur l'hémodynamique de l'artère radiale. Deux essais contrôlés chez des patients pré-exposés et chez des sujets sains naïfs.

Palpation of the radial pulses is one of the most important techniques in traditional Chinese medicine. Two double-blind randomised trials of the effects of real and sham acupuncture on radial artery hemodynamics were conducted in 19 patients regularly exposed to acupuncture (sensitised subjects), and in 8 healthy subjects devoid of previous exposure (naive subjects), respectively. Radial artery diameter and pulse waveform was measured with a high-resolution echotracking system and aplanation tonometry, respectively, before and during a 20-minute's acupuncture period. In sensitised patients, arterial diameter significantly increased during real acupuncture, compared to the sham group (+7.5 +/- 2.8% vs -2.9 +/- 2.7%, respectively; p < 0.01). By contrast, in naive subjects, arterial diameter did not change during real or sham acupuncture. In both populations, no significant difference was observed between real and sham acupuncture, concerning the time-course of blood pressure, radial artery distensibility and pressure waveform. Our results demonstrate that real acupuncture can determine an objective vasodilatation of the radial artery in patients regularly exposed to acupuncture, but not in naive subjects.