The effect of camelina oil on vascular function in essential hypertensive patients with metabolic syndrome: a randomized, placebo-controlled, double-blind study.

BACKGROUND: The effects of a dietary supplementation with the vegetable ω-3 α-linolenic acid (ALA) on cardiovascular homeostasis are unclear. In this context, it would be interesting to assess the effects of camelina oil. OBJECTIVE: This study aimed to assess the cardiovascular and metabolic effects of camelina oil in hypertensive patients with metabolic syndrome. METHODS: In a double-blind, placebo-controlled randomized study, treated essential hypertensive patients with metabolic syndrome received, during 6 mo, either cyclodextrin-complexed camelina oil containing ≈ 1.5 g ALA/d (n = 40) or an isocaloric placebo (n = 41), consisting of the same quantity of cyclodextrins and wheat starch. Anthropometric data, plasma lipids, glycemia, insulinemia, creatininemia, TBARs, high-sensitivity C-reactive protein, and n-3, n-6, and n-9 fatty acids in erythrocyte membranes were measured. Peripheral and central blood pressures, arterial stiffness, carotid intima-media thickness, and brachial artery endothelium-dependent flow-mediated dilatation (FMD) and endothelium-independent dilatation were assessed. RESULTS: Compared with placebo, camelina oil increased ALA (mean ± SD: 0 ± 0.04 compared with 0.08 ± 0.06%, P <0.001), its elongation product EPA (0 ± 0.5 compared with 0.16 ± 0.65%, P <0.05), and the n-9 gondoic acid (GA; 0 ± 0.04 compared with 0.08 ± 0.04%, P <0.001). No between-group difference was observed for cardiovascular parameters. However, changes in FMD were associated with the magnitude of changes in EPA (r = 0.26, P = 0.03). Compared with placebo, camelina oil increased fasting glycemia (-0.2 ± 0.6 compared with 0.3 ± 0.5 mmol/L, P <0.001) and HOMA-IR index (-0.8 ± 2.5 compared with 0.5 ± 0.9, P <0.01), without affecting plasma lipids, or inflammatory and oxidative stress markers. Changes in HOMA-IR index were correlated with the magnitude of changes in GA (r = 0.32, P <0.01). Nutritional intake remained similar between groups. CONCLUSION: ALA supplementation with camelina oil did not improve vascular function but adversely affected glucose metabolism in hypertensive patients with metabolic syndrome. Whether this adverse effect on insulin sensitivity is related to GA enrichment, remains to be elucidated.

SPARTE Study: Normalization of Arterial Stiffness and Cardiovascular Events in Patients With Hypertension at Medium to Very High Risk.

[Figure: see text].

A case-control study indicates that coagulation imbalance is associated with arteriosclerosis and markers of endothelial dysfunction in kidney failure.

Endothelial dysfunction, one of many causes of arterial changes in end-stage kidney disease (kidney failure), is a likely link between early vascular aging and the risk of thrombosis or bleeding in this condition. To evaluate this, we compared links between arterial stiffness and endothelial/coagulation factors in 55 patients receiving hemodialysis therapy and 57 age-/sex-matched control individuals. Arterial stiffness was assessed from carotid-femoral pulse wave velocity, and coagulation status from the endogenous thrombin generating potential. Markers of endothelial dysfunction (von Willebrand factor, tissue factor pathway inhibitor), neutrophil extracellular traps and tissue factor-positive extracellular vesicles were higher in patients with kidney failure. Prothrombin fragments 1 and 2, and D-dimer markers of in vivo coagulation activation were also higher. However, in vitro in the presence of platelets, endogenous thrombin generating potential was lower and its downregulation by activated protein C impaired. Antiplatelet drugs did not affect these parameters. In multiple regression analysis, prothrombin fragments 1 and 2, D-dimer, factor VIII and monocyte-derived tissue factor-positive extracellular vesicles correlated with higher carotid-femoral pulse wave velocity. In patients with kidney failure, in vivo hypercoagulability occurred with reduced thrombin generation in platelet-rich plasma, likely explaining the opposing thrombotic and bleeding tendencies in patients with kidney failure. Importantly, arteriosclerosis is more closely related to a prothrombotic state. Thus, coagulation changes plus arterial stiffness highlight a major therapeutic challenge for anticoagulant and antiplatelet drug use.

Association Between Occupational, Sport, and Leisure Related Physical Activity and Baroreflex Sensitivity: The Paris Prospective Study III.

Physical activity (PA) is a preventative behavior for noncommunicable disease. However, little consideration is given as to whether different domains of PA have differing associations with health outcomes. We sought to determine the association between occupational, sport, leisure, and total PA with baroreflex sensitivity (BRS), distinguishing between neural (nBRS) and mechanical (mBRS) BRS. In a cross-sectional analysis of 8649 adults aged 50 to 75 years, resting nBRS (estimated by low-frequency gain, from carotid distension rate and heart rate) and mBRS (carotid stiffness) were measured by high-precision carotid echo-tracking. PA was self-reported using the validated Baecke questionnaire. The associations between PA and nBRS and mBRS were quantified using multivariate linear regression analysis, separately in the working and nonworking population. In working adults (n=5039), occupational PA was associated with worse nBRS (unstandardized ß=-0.02; [95% CI, -0.04 to -0.003]; P=0.022) whereas sport PA was associated with better nBRS (ß=0.04; [95% CI, 0.02-0.07]; P=0.003) and mBRS (ß=-0.05; [95% CI, -0.09 to -0.00001]; P=0.049). Neither leisure PA nor total PA was associated with nBRS or mBRS. In nonworking adults (n=3610), sport PA and total PA were associated with better mBRS (ß=-0.08; [95% CI, -0.15 to 0.02]; P=0.012 and ß=-0.05; [95% CI, -0.10 to 0.009]; P=0.018) but not nBRS. These findings suggest differential associations between domains of PA and BRS and may provide insights into the mechanisms underlying the association between occupational PA and cardiovascular disease.

Arterial Stiffness Gradient, Systemic Reflection Coefficient, and Pulsatile Pressure Wave Transmission in Essential Hypertension.

Arterial stiffness and impedance gradients are known to influence pressure wave propagation and macrovascular-microvascular interactions. We studied the association between the carotid-femoral arterial stiffness gradient and the systemic reflection coefficient (N=393); of this population, 246 also underwent assessment of forward/backward pressure wave propagation and microvascular pulsatile pressure transmission (MPPT). Hemodynamic parameters were measured noninvasively. From peripheral vascular resistance and characteristic impedance, we estimated the systemic reflection coefficient and MPPT on peripheral and cardiac microcirculation in age-matched, sex-matched and body mass index-matched individuals with (n=147) or without (n=98) hypertension. The arterial stiffness gradient, systemic reflection coefficient, and correlations between the arterial stiffness gradient and age or blood pressure were similar in both populations. MPPT was higher in hypertension (P<0.0001), and the subendocardial viability (Buckberg) index lower (P<0.0001). In both populations, the systemic reflection coefficient and arterial stiffness gradient were significantly associated with changes in MPPT and the subendocardial viability index. Despite similar systemic reflection coefficients, the carotid reflected pressure and MPPT were higher in hypertension. Maintaining the systemic reflection coefficient within normal ranges was, therefore, insufficient to compensate for higher carotid forward pressure waves which, in hypertension, were associated with increased aortic stiffness (P<0.0001) and higher stroke volume (P=0.0365). Independently of cardiovascular risk, hypertension-induced changes have a weighted effect on MPPT, although insufficient to compensate for increased forward pressure waves. In hypertension, elevated aortic stiffness negatively affects the arterial stiffness gradient and systemic reflection coefficient but positively affects forward pressure.

Increased carotid stiffness and remodelling at early stages of chronic kidney disease.

OBJECTIVE: Increased carotid stiffness and remodelling is reported in patients with moderate and advanced chronic kidney disease (CKD) and is associated with cardiovascular events. Here, we tested the hypothesis that carotid artery alterations start earlier, during mild CKD. METHODS: Within the Paris Prospective Study 3, a large prospective observational survey of nonreferred people aged 50-75 who received an extensive health check-up, there were 294 participants with glomerular filtration rate (GFR) of at least 45 and less than 60 ml/min per 1.73 m (Stage 3A CKD), 840 participants with GFR 60-89 ml/min per 1.73 m with proteinuria (Stage 2 CKD), 4666 participants with GFR 60-89 ml/min per 1.73 m without proteinuria and 3317 individuals with GFR at least 90 ml/min per 1.73 m at study recruitment. Carotid artery measurements were performed using a high-resolution echotracking device. RESULTS: Compared with patients with GFR at least 90 ml/min per 1.73 m, the carotid distensibility and strain progressively decreased (P for trend <0.0001), whereas carotid stiffness progressively increased (P for trend <0.0001) across GFR categories starting at early stage from GFR 60-89 ml/min per 1.73 m without proteinuria. Higher Young's elastic modulus was observed only for Stage 3A CKD, whereas carotid internal diastolic diameter did not differ between groups. CONCLUSION: The large arterial stiffening starts early during CKD, even in participants with a very mild reduction in renal function.

Carotid Artery Stiffness and Incident Depressive Symptoms: The Paris Prospective Study III.

BACKGROUND: Arterial stiffness may contribute to late-life depression via cerebral microvascular damage, but evidence is scarce. No longitudinal study has evaluated the association between arterial stiffness and risk of depressive symptoms. Therefore, we investigated the association between carotid artery stiffness and incident depressive symptoms in a large community-based cohort study. METHODS: This longitudinal study included 7013 participants (mean age 59.7 ± 6.3 years; 35.8% women) free of depressive symptoms at baseline. Carotid artery stiffness (high-resolution echo tracking) was determined at baseline. Presence of depressive symptoms was determined at baseline and at 4 and 6 years of follow-up, and was defined as a score ≥7 on the validated Questionnaire of Depression, Second Version, Abridged and/or new use of antidepressant medication. Logistic regression and generalized estimating equations were used. RESULTS: In total, 6.9% (n = 484) of the participants had incident depressive symptoms. Individuals in the lowest tertile of carotid distensibility coefficient (indicating greater carotid artery stiffness) compared with those in the highest tertile had a higher risk of incident depressive symptoms (odds ratio: 1.43; 95% confidence interval: 1.10-1.87), after adjustment for age, sex, living alone, education, lifestyle, cardiovascular risk factors, and baseline Questionnaire of Depression, Second Version, Abridged scores. Results were qualitatively similar when we used carotid Young's elastic modulus as a measure of carotid stiffness instead of carotid distensibility coefficient, and when we used generalized estimating equations instead of logistic regression. CONCLUSIONS: Greater carotid stiffness is associated with a higher incidence of depressive symptoms. This supports the hypothesis that carotid stiffness may contribute to the development of late-life depression.

Wave reflections in hypertension: role of sex, metabolic, and ethnic factors.

OBJECTIVES: Although the links between pulsatile hemodynamics and age are widely acknowledged in hypertension, the interactions of sex, ethnicity, and metabolic factors with hemodynamic parameters remain largely unknown. We investigated the effects of body weight, glycemia, and cholesterolemia on the carotid augmentation index (CAI) and potential changes over time, with particular focus on the roles of sex and ethnicity. METHODS: Baseline (V1) and repeat (V2) measurements (at ∼1.7 years) of wave reflections (calculated from CAI), brachial and carotid pulse pressure, and heart rate were assessed in 2530 normotensive and hypertensive men and women living in Paris but born in either France, Africa, or Asia. RESULTS: At V1, and in comparison with French-born individuals, African-born individuals had significantly higher CAI, cardiovascular risk, and body weight, whereas Asian-born individuals had similar CAI but lower body weight, and higher cardiovascular risk, triglyceridemia, and heart rate. Stepwise multiple regression showed similar effects of cholesterolemia on CAI in all populations, whereas only French-born individuals (insulin-resistant men and women) showed associations between hyperglycemia and potential CAI dysfunction. Repeat (V2) measurements highlighted significant interactions (P < 0.008) of sex and ethnicity with changes in CAI over time. In men, CAI changes did not differ as a function of ethnicity, whereas in African-born women, they were lesser than those of Asian-born (P < 0.03) and French-born (P < 0.02) women. CONCLUSION: In the French-born population, CAI changes are affected by diabetes and possibly insulin-resistance, independently of sex. In African-born and Asian-born populations, CAI is sex-specific. Elevated CAI in African-born women calls for close monitoring of cardiovascular risk.

Body Silhouette Trajectories Across the Lifespan and Vascular Aging.

Vascular aging is a major contributor to cardiovascular disease and can be quantified by higher carotid stiffness, intima-media thickness and diameter, and hypertension. Weight gain across the lifetime may be an important, modifiable determinant of vascular aging. We therefore aimed to assess lifetime body silhouette trajectories (a marker of weight change across the lifespan) in relation to vascular aging in late adulthood. We used cross-sectional data from a community-based cohort study (n=8243; age, 59.4; 38.7% women). A linear mixed model was used to assess trajectories of recalled body silhouettes from age 8 to 45 years. We assessed carotid artery properties (ultrasonography), resting hypertension (blood pressure ≥140/90 mm Hg or use of antihypertensives), and exaggerated exercise blood pressure, a marker of masked hypertension (systolic blood pressure ≥150 mm Hg during submaximal exercise) at study recruitment when the participants were 50 to 75 years of age. We identified 5 distinct body silhouette trajectories: lean stable (32.0%), lean increase (11.1%), moderate stable (32.5%), lean-marked increase (16.3%), and heavy stable (8.1%). Compared with individuals in the lean-stable trajectory, those in the moderate-stable, lean-marked increase, and heavy-stable trajectories had higher carotid stiffness, intima-media thickness and diameter (odds ratios between 1.23 and 2.10 for highest quartile versus lowest quartile of manifestations of vascular aging; P<0.05) and were more likely to have resting hypertension and exaggerated exercise blood pressure, after adjustment for potential confounders (odds ratios between 1.31 and 1.60; P<0.05). Vascular aging was most prominent among individuals who were lean in early life but markedly gained weight during young adulthood and among those who were heavy in early life and maintained weight.

Sex differences in adherence to antihypertensive treatment in patients aged above 55: The French League Against Hypertension Survey (FLAHS).

Despite the availability of efficient therapies to reduce the risk of cardiovascular complications, poor adherence to antihypertensive (anti-HTN) drugs is frequent, especially during the first year of treatment and among uncontrolled/resistant hypertensive patients. The aim of the study was to identify factors associated with adherence to anti-HTN treatment and to examine whether they differ across sex. A total of 2743 treated hypertensive participants to the cross-sectional Metascope survey (France, 2015) aged 55 years or more were included. The authors measured adherence to anti-HTN treatment using the 6-item Girerd compliance test. Variations in adherence were examined using the Rao-Scott statistics and Poisson regression. Overall, 63.6% of participants were adherent to anti-HTN treatment. Adherence was more frequent among women than men (69% vs 58%, P < 10-4 ). For both sexes, level of adherence was positively associated with age (P < 10-4 ), but inversely associated with number of anti-HTN tablets, number of tablets taken for metabolic diseases, history of cardiovascular diseases, number of other chronic diseases (all P < 10-4 ). The inverse relationship between adherence and the number of anti-HTN tablets significantly differed between sexes (P < 10-4 ): Adherence decreased sharply when taking two or more anti-HTN tablets in men, whereas the decrease in women was only observed when taking three or more anti-HTN tablets. This study suggests that adherence to anti-HTN treatment is higher among women, decreases with the number of tablets prescribed, and differentially so across sex. Reducing the number of tablets for anti-HTN treatment may improve adherence, especially among men and patients with multiple comorbidities.

Evaluation of exposure to effervescent drugs in a large health check-up population in France: a cross-sectional study.

OBJECTIVES: The relationship between high dietary sodium intake and hypertension is well established. Some drugs are associated with high-sodium content, particularly effervescent tablets (ETs). Despite a possible cardiovascular risk associated with the use of such drugs, observational data describing exposure to ETs in ambulatory subjects are lacking.This study aims to estimate the prevalence of exposure to ETs and to highlight factors associated with this exposure in a large French health check-up population. DESIGN: This was a cross-sectional study. SETTING AND PARTICIPANTS: Participants were French individuals who underwent medical check-ups at the Investigations Préventives et Cliniques centre between April and June 2017. RESULTS: In total, 1043 subjects were included in the study. The prevalence of exposure to ETs in the last 30 days was 26.9% (95% CI 24.2% to 29.6%). Exposure was frequent (ie, two ETs per week or more in the last 30 days) for 7.3% of subjects. Self-medication was the major source of exposure (93.8%). Paracetamol, aspirin, vitamins and betaine accounted for 95.3% of the ETs used. The factors associated with this exposure by multivariate analysis were: male gender, Overseas French origin, depression and body mass index ≥25 kg/m2. A diagnosis of hypertension or treatment with diuretics were not protective factors against exposure to ETs. CONCLUSION: Exposure to ETs is frequent in the general population, particularly through self-medication. Clinical conditions associated with low-salt requirements were not associated with lower exposure to ETs, suggesting a lack of awareness by practitioners and patients about this iatrogenic issue.

Common Carotid Artery Diameter and Risk of Cardiovascular Events and Mortality: Pooled Analyses of Four Cohort Studies.

Carotid arterial diameter enlargement is a manifestation of arterial remodeling and may be a risk factor for cardiovascular disease (CVD). We evaluated the association between carotid artery diameter and risk of stroke, coronary heart disease, CVD, and all-cause mortality and explored whether the associations could be explained by processes involved in arterial remodeling, that is, blood pressure-related media thickening, arterial stiffness, arterial wall stress, and atherosclerosis. We included 4887 participants (mean age 67±9 years; 54% women) from 4 cohort studies: Rotterdam Study, NEPHROTEST, Hoorn Study, and a study by Blacher et al. Common carotid artery properties were measured using echotracking. Incident cases were recorded based on medical records. We used Cox proportional hazard models adjusting for cardiovascular risk factors and estimates of processes underlying arterial remodeling. During follow-up (mean, 11 years), 379 (8%) individuals had a stroke, 516 had a (11%) coronary heart disease, 807 had a (17%) CVD, and 1486 (30%) had died. After adjustment for cardiovascular risk factors, individuals in the highest tertile of carotid diameter (diameter >8 mm) compared with those in the lowest tertile (diameter <7 mm) had a higher incidence of stroke (hazard ratio, 1.5; 95% confidence interval, 1.1-2.0). From all estimates of processes underlying arterial remodeling, adjustment for carotid intima-media thickness attenuated this association (hazard ratio after adjustment for intima-media thickness, 1.2; 95% confidence interval, 0.9-1.6). Larger carotid diameter was associated with risk of CVD and mortality but not clearly with coronary heart disease risk. We showed that a larger carotid diameter is associated with incident stroke, CVD, and mortality. Carotid intima-media thickness, a measure of blood pressure-related media thickening, partially explained the association with stroke incidence.

Pulse Wave Velocity and Prognosis in End-Stage Kidney Disease.

High pulse wave velocity (PWV) is a hallmark of end-stage kidney disease (ESKD) where it is considered useful for risk stratification. We investigated whether PWV adds meaningful prognostic information to 2 simple, well-validated, clinical risk scores specific to ESKD (the Annualized Rate of Occurrence scores) for predicting all-cause and cardiovascular mortality by applying state-of-the-art prognostic tests including discrimination (Harrell C-index), risk reclassification (integrated discrimination improvement), and calibration. We performed these analyses in the 2 largest ESKD cohorts with available PWV data, the Manhes-Hospital cohort in Paris (n=287 patients) and the Quebec Research Center cohort in Canada (n=246 patients). The Harrell C-index of the 2 clinical risk scores was consistently higher than that by PWV both for all-cause (Manhes cohort, 77.5% versus 73.7%; Quebec cohort, 61.5% versus 58.9%) and cardiovascular mortality (Manhes cohort, 77.9% versus 77.2%; Quebec cohort, 63.8% versus 60.3%). Furthermore, PWV provided a very modest increase in discriminatory power over and above clinical risk scores by Harrell C-index (from 0.5% to 1.8%) and in risk reclassification by Integrated Discrimination Improvement (from 0.9% to 5.1%) and actually worsened models calibration. In patients with ESKD, PWV has a prognostic power for all-cause and cardiovascular mortality inferior to that by simple clinical risk scores and only modestly improves the risk discrimination and reclassification by the same risk scores and worsens models calibration. Clinicians may better rely on available clinical risk scores rather than on PWV for risk stratification in the ESKD population.

Self-report assessment of severe periodontitis: Periodontal screening score development.

AIM: To derive from a validated questionnaire a periodontal screening score (PESS), intended as a user-friendly tool to identify individuals at risk of periodontitis in epidemiological studies. METHODS: A French 12-item self-reported questionnaire was developed by translating English questions previously used for periodontitis screening and surveillance. After a cognitive evaluation, the questionnaire was validated in a sample of 232 individuals (mean age: 46.1 ± 12.6 years) receiving full-mouth periodontal examination, including probing pocket depth and clinical attachment level recordings. Case definition was based on the American Academy of Periodontology/Centers for Disease Control and Prevention criteria. Logistic regression analyses and C-statistics were used to assess the validity and accuracy of the questionnaire and to develop the PESS. RESULTS: The sample was constituted of 109 individuals with severe periodontitis, who were compared with 123 individuals with no/moderate periodontitis. The questionnaire had moderate-to-high accuracy in identifying severe cases; the PESS (calculated on five self-report items, age, and smoking) showed a sensitivity of 78.9% and a specificity of 74.8%, with an area under the receiver operating characteristics curve of 0.821. CONCLUSION: The PESS represents a valuable and accurate tool to screen for severe periodontitis at the population level.

Self-reported body silhouette trajectories across the lifespan and excessive daytime sleepiness in adulthood: a retrospective analysis. The Paris Prospective Study III.

OBJECTIVES: Excessive daytime sleepiness (EDS) is a common sleep complaint in the population and is increasingly recognised as deleterious for health. Simple and sensitive tools allowing identifying individuals at greater risk of EDS would be of public health importance. Hence, we determined trajectories of body silhouette from early childhood to adulthood and evaluated their association with EDS in adulthood. DESIGN: A retrospective analysis in a prospective community-based study. PARTICIPANTS: 6820 men and women self-reported their silhouette at ages 8, 15, 25, 35 and 45 using the body silhouettes proposed by Stunkard et al. EDS was defined by an Epworth Sleepiness Scale score ≥11. MAIN OUTCOME MEASURE: Presence of EDS in adulthood. RESULTS: The study population comprised 6820 participants (mean age 59.8 years, 61.1% men). Five distinct body silhouettes trajectories over the lifespan were identified: 31.9% 'lean stable', 11.1% 'lean increase', 16.1% 'lean-marked increase', 32.5% 'moderate stable' and 8.4% 'heavy stable'. Subjects with a 'heavy-stable' trajectory (OR 1.24, 95% CI 0.94 to 1.62) and those with a 'lean-marked increase' trajectory (OR 1.46, 95% CI 1.18 to 1.81) were more likely to have EDS when compared with the 'lean-stable' group after adjusting for confounding. Further adjustment for birth weight strengthened the magnitude of the ORs. CONCLUSION: Increasing body silhouette and to a lesser extent constantly high body silhouette trajectory from childhood to adulthood are associated with increased likelihood of EDS, independently of major confounding variables. TRIAL REGISTRATION NUMBER: NCT00741728; Pre-results.

Hyperglycaemia is associated with cancer-related but not non-cancer-related deaths: evidence from the IPC cohort.

AIMS/HYPOTHESIS: Hyperglycaemia has been associated with the incidence of all and specific types of cancer, distinct from the risks related to diabetes. The relationships between blood glucose and mortality rates related to all and specific cancers were analysed in comparison with all-cause or non-cancer-related mortality rates in a large, general primary care population in France. METHODS: Between January 1991 and December 2008, 301,948 participants (193,221 men and 108,727 women), aged 16-95 years (mean ± SD 44.8 ± 12.0 years for men and 45.1 ± 14.2 years for women), had a health check at the IPC Centre. All data collected in standard conditions during the health checks-up were used for statistical analysis All examinations were performed under fasting conditions and included a blood glucose measurement. Participants with known diabetes (<9%) were excluded from the analysis. Participants were classified into quintiles based on their blood glucose measurement and were followed for a maximum of 17 years (mean ± SD 9.2 ± 4.7 years) to assess all-cause, cancer and non-cancer mortality rates. RESULTS: A non-linear relationship was observed between cancer mortality rates and blood glucose quintile after adjustment for age and sex. There was a significant association between the group with the highest blood glucose level and cancer-related death (multivariate Cox model, HR [95% CI] 1.17 [1.03, 1.34]), while the group with normoglycaemia showed no association with cancer-related deaths. We did not observe a relationship between blood glucose and all-cause or non-cancer mortality rates. An excess risk of death was observed in the highest blood glucose quintile for gastrointestinal cancer and leukaemia. Adjustments for diabetes and aspirin use did not modify the results. However, this excess risk disappeared with use of glucose-lowering agents (HR [95% CI] 1.03 [0.74, 1.43]). CONCLUSIONS/INTERPRETATION: Hyperglycaemia is associated with significantly higher rates of cancer-related deaths, particularly in gastrointestinal cancer and leukaemia, but not with non-cancer-related deaths. The association is retained when taking into account confounding factors, including chronic aspirin treatment.

Prevalence and characteristics of metabolic syndrome in adults from the French childhood leukemia survivors' cohort: a comparison with controls from the French population.

The prevalence of the metabolic syndrome among adults from the French LEA childhood acute leukemia survivors' cohort was prospectively evaluated considering the type of anti-leukemic treatment received, and compared with that of controls. The metabolic profile of these patients was compared with that of controls. A total of 3203 patients from a French volunteer cohort were age- and sex-matched 3:1 to 1025 leukemia survivors (in both cohorts, mean age: 24.4 years; females: 51%). Metabolic syndrome was defined according to the National Cholesterol Education Program's Adult Treatment Panel III criteria. Metabolic syndrome was found in 10.3% of patients (mean follow-up duration: 16.3±0.2 years) and 4.5% of controls, (OR=2.49; P<0.001). Patients transplanted with total body irradiation presented the highest risk (OR=6.26; P<0.001); the other treatment groups also showed a higher risk than controls, including patients treated with chemotherapy only. Odd Ratios were 1.68 (P=0.005) after chemotherapy only, 2.32 (P=0.002) after chemotherapy and cranial irradiation, and 2.18 (P=0.057) in patients transplanted without irradiation. Total body irradiation recipients with metabolic syndrome displayed a unique profile compared with controls: smaller waist circumference (91 vs 99.6 cm; P=0.01), and increased triglyceride levels (3.99 vs 1.5 mmol/L; P<0.001), fasting glucose levels (6.2 vs 5.6 mmol/L; P=0.049), and systolic blood pressure (137.9 vs 132.8 mmHg; P=0.005). By contrast, cranial irradiation recipients with metabolic syndrome had a larger waist circumference (109 vs 99.6 cm; P=0.007) than controls. Regardless of the anti-leukemic treatment, metabolic syndrome risk was higher among childhood leukemia survivors. Its presentation differed depending on the treatment type, thus suggesting a divergent pathophysiology. This study is registered at clinicaltrials.gov identifier: 01756599.

Association between individual and neighbourhood socioeconomic factors and masticatory efficiency: a cross-sectional analysis of the Paris Prospective Study 3.

BACKGROUND: There is a lack of evidence on the impact of socioeconomic factors on masticatory efficiency. The present study investigates the relationship between individual and neighbourhood socioeconomic factors (main exposure) and the number of masticatory units (MUs) used as surrogate of the masticatory efficiency (main outcome). METHODS: In this cross-sectional study nested in the Paris Prospective Study 3, 4270 adults aged 50-75 and recruited from 13 June 2008 to 31 May 2012 underwent a full-mouth examination. Number of MUs defined as pairs of opposing teeth or dental prostheses allowing mastication, number of missing teeth and gingival inflammation were documented. The individual component of the socioeconomic status was evaluated with an individual multidimensional deprivation score and education level. The neighbourhood component of the socioeconomic status was evaluated with the FDep99 deprivation index. Associations were quantified using marginal models. RESULTS: In multivariate analyses, having less than 5 MUs was associated with (1) the most deprived neighbourhoods (OR=2.27 (95% CI 1.63 to 3.17)), (2) less than 12 years of educational attainment (OR=2.20 (95% CI 1.66 to 2.92)) and (3) the highest individual score of deprivation (OR=3.23 (95% CI 2.24 to 4.65)). Associations with education and individual score of deprivation were consistent across the level of neighbourhood deprivation. Comparable associations were observed with the number of missing teeth. Associations with gingival inflammation were of lower magnitude; the relationship was present for deprivation markers but not for education. CONCLUSION: Poor masticatory efficiency is associated with low educational attainment and high deprivation scores.

Impaired baroreflex sensitivity, carotid stiffness, and exaggerated exercise blood pressure: a community-based analysis from the Paris Prospective Study III.

Aims: People with exaggerated exercise blood pressure (BP) have adverse cardiovascular outcomes. Mechanisms are unknown but could be explained through impaired neural baroreflex sensitivity (BRS) and/or large artery stiffness. This study aimed to determine the associations of carotid BRS and carotid stiffness with exaggerated exercise BP. Methods and results: Blood pressure was recorded at rest and following an exercise step-test among 8976 adults aged 50 to 75 years from the Paris Prospective Study III. Resting carotid BRS (low frequency gain, from carotid distension rate, and heart rate) and stiffness were measured by high-precision echotracking. A systolic BP threshold of ≥ 150 mmHg defined exaggerated exercise BP and ≥140/90 mmHg defined resting hypertension (±antihypertensive treatment). Participants with exaggerated exercise BP had significantly lower BRS [median (Q1; Q3) 0.10 (0.06; 0.16) vs. 0.12 (0.08; 0.19) (ms2/mm) 2×108; P < 0.001] but higher stiffness [mean ± standard deviation (SD); 7.34 ± 1.37 vs. 6.76 ± 1.25 m/s; P < 0.001) compared to those with non-exaggerated exercise BP. However, only lower BRS (per 1SD decrement) was associated with exaggerated exercise BP among people without hypertension at rest {specifically among those with optimal BP; odds ratio (OR) 1.16 [95% confidence intervals (95% CI) 1.01; 1.33], P = 0.04 and high-normal BP; OR, 1.19 (95% CI 1.07; 1.32), P = 0.001} after adjustment for age, sex, body mass index, smoking, alcohol, total cholesterol, high-density lipoprotein cholesterol, resting heart rate, and antihypertensive medications. Conclusion: Impaired BRS, but not carotid stiffness, is independently associated with exaggerated exercise BP even among those with well controlled resting BP. This indicates a potential pathway from depressed neural baroreflex function to abnormal exercise BP and clinical outcomes.