Clinical interaction between diabetes duration and aortic stiffness in type 2 diabetes mellitus.

Diabetes complications increase with disease duration. No study was performed on the relationship between aortic stiffness and diabetes duration, taking into account the respective influence of such factors on macro- and microcirculation. In total, 618 subjects with type 2 diabetes (259 men) attending the Department of Internal Medicine of Tizi Ouzou Hospital (Algeria) were studied in collaboration with Hotel-Dieu Hospital (Paris, France). Brachial blood pressure (BP), anthropometric, clinical and biological data were evaluated. Aortic stiffness was estimated by carotid-femoral pulse wave velocity (PWV). From lower to higher tertile of diabetes duration, age, BP and PWV (10.1±2.7 to 12.3±2.8 m s-1) increased, while diabetes control and renal function worsened (all P<0.01). Diabetes duration was independently associated with PWV (R2=0.035, P<0.0001), even after adjustment for age, BP, heart rate, cardiovascular events and metabolic syndrome. Diabetes duration was significantly correlated to the prevalence of microalbuminuria (OR (95% CL) 1.3 (1.06-1.63), P=0.01), independently of age, sex, BP and renal function. Increased aortic stiffness was independently associated with the prevalence of cardiovascular events (P<0.001), reaching its maximal value above the first 2 years of diabetes duration. In conclusion, diabetes duration is an independent determinant of aortic stiffness in subjects with type 2 diabetes, representing about 4% of PWV variability. Diabetes duration is associated with microvascular complications independently of renal function, and with macrovascular complications through the presence of increased aortic stiffness.

Pulse wave analysis with two tonometric devices: a comparison study.

Pulse wave analysis is a pivotal tool to estimate central haemodynamic parameters. Available commercial devices use applanation tonometry and have been validated against invasive catheterism. We previously observed differences on a radial second systolic peak (rSPB2) between two commonly used devices: SphygmoCor (AtCor, Australia) and PulsePen (DiaTecne, Italy). The aim of our study was to further quantify differences in radial and carotid signals from the two devices.We measured radial and carotid waveforms in 38 patients with minimal changes between systolic, diastolic blood pressure and heart rate.rSBP2, mean pressure, form factor and augmentation index were different with SphygmoCor providing lower values (mean differences: 2.2 ± 3.8 mmHg; 1.5 ± 1.7 mmHg; 3.2 ± 3.5%; 4.2 ± 8.4%, respectively). Carotid augmentation index and form factor were similar. However carotid systolic pressure (cSBP) from PulsePen was higher than cSBP from SphygmoCor (2.7 ± 4.4 mmHg, p < 0.001). For both carotid and radial signals, harmonics moduli were similar across the spectrum with the exception of the 1st harmonic.PulsePen and SphygmoCor sensors are not equivalent and provide different wave shapes despite similar harmonics content with more discrepancy on radial derived parameters than on carotid derived parameters. Further studies are required to compare invasive pressure parameters to indices derived from these two devices.

[Correlation between urinary catecholamines dosage and apnea-hypopnea index in a hypertension population: pilot study]. / Corrélation entre les dosages des dérivés methoxylés urinaires et l'index d'apnée-hypopnée dans une population d'hypertendus : étude pilote.

AIMS: Sleep disorders like obstructive sleep apnea in adults are associated with increased sympathetic activity, which induced high blood pressure and could be associated with resistant hypertension. Some studies have demonstrated that high urinary catecholamine levels in obstructive sleep apnea patients may be decreased with continuous positive airway pressure therapy. However, very few studies have demonstrated a correlation between apnea-hypopnea index and urinary catecholamine levels in hypertension patients. METHODS: In this pilot study, 20 hypertensive patients referred for hypertension work-up including night-time polygraphy and 24h urinary catecholamine dosage were included. RESULTS: Mean age was 51±11 years (30-76), 68% were males. Diagnosis of obstructive sleep apnea was confirmed in 13 patients at the end of the work-up. Mean apnea-hypopnea index was 14±9 (2-32). The only urinary catecholamine parameter significantly increased in patients with obstructive sleep apnea was 24h urinary normetanephrine (1931±1285 vs 869±293nmol/24h; P<0.05). However, this difference was not significant when this parameter was adjusted to 24h urinary creatinine. We observed a significant positive correlation between AHI and 24h urinary normetanephine (r=0.486; P=0.035). CONCLUSION: This pilot study confirms an isolated elevation of 24h urinary normetanephrine in hypertensive patients with obstructive sleep apnea and shows a significant correlation between sleep disorders expressed by apnea-hypopnea index and urinary catecholamines excretion.

Long-term predictors of impaired fasting glucose and type 2 diabetes in subjects with family history of type 2 diabetes: a 12-years follow-up of the Brisighella Heart Study historical cohort.

AIM: To identify and quantify the role of different risk factors in the long-term development of IFG and T2DM in a rural Italian population sample with family history of T2DM. METHODS: We selected a sample of 1271 adult subjects from among those 1851 consecutively visited during four consecutive Brisighella Heart Study surveys (1996-2008), then selecting those ones with a family history of T2DM. Thus, we obtained a final sample including 545 subjects and for which a full clinical and ematochemistry data set was available. RESULTS: The Cox-regression model better predicting the incident IFG and T2DM included age, gender, FPG, TG and SUA. The model best predicting the incident IFG status alone (without T2DM) is very similar to that predicting both IFG and T2DM, including the same predictors. Finally, the model best predicting T2DM (excluding IFG) simply includes FPG, BMI and ALT/AST ratio. Repeating the Cox-regression analysis using BMI as a covariate, TG appears to be also a significant predictor of T2DM (HR 1.018 95% CI 1.009-1.041, p=0.013). CONCLUSION: In a sample of subjects with a family history of diabetes the best long-term predictors of IFG are age, gender, FPG, TG and SUA, while those of T2DM are FPG and BMI.

[Pressure wave shape comparison between two non-invasive tonometric devices]. / Comparaison des signaux radial et carotidien mesurés par deux appareils tonométriques.

BACKGROUND AND AIM: Pulse wave analysis is a pivotal instrument to estimate central hemodynamic parameters. Applanation tonometry on radial and/or carotid arteries is usually used to detect pressure waveforms. Available commercial devices have been validated against invasive catheterism, showing a good agreement of harmonics pattern. In a previous investigation, we observed differences on radial second systolic peak (rSPB2) between two commonly used devices: SphygmoCor (AtCor, Australia) and PulsePen (Diatecne, Italy). The aim of our study was to further quantify differences on radial and carotid signals from the two devices. METHODS: We measured radial and carotid pressure waveforms in 38 patients where systolic, diastolic blood pressure and heart rate presented minimal changes between measurements. Waveforms were digitally extracted for off-line analysis. RESULTS: Radial rSBP2, mean arterial pressure, form factor and augmentation index were different with SphygmoCor providing lower values. Carotid augmentation index and form factor were similar. However, carotid systolic pressure (cSBP) from PulsePen was higher that cSBP from SphygmoCor (2.7 ± 4.4 mmHg, P<0.001). CONCLUSION: PulsePen and SphygmoCor sensors are not equivalent and provide different wave shapes. These differences on wave shape have important consequences on parameters computed from these waveforms with more discrepancy on radial derived parameters such as rSBP2 and mean arterial pressure than on carotid derived parameters. Further studies are required to compare invasive pressure parameters to indices derived from these two devices.

Aortic stiffness, inflammation, denutrition and prognosis in the oldest people.

Observational studies have shown that some of the classic CV risk factors, namely hypertension or hypercholesterolemia, become nebulous, or even act in the reverse direction, in the oldest people. We investigated whether in the elderly, increased aortic stiffness was associated with higher mortality risk, before and after adjustments on common geriatric confounders. In a cohort of 331 (86 men) subjects aged >70 years (mean age (± s.d.): 85 ± 7 years), aortic stiffness was assessed by carotid-femoral pulse wave velocity (PWV). Classical CV risk factors were determined simultaneously, in association with inflammation and denutrition parameters. One hundred and ten subjects died during a 2-year follow-up period. In crude analysis, a positive non-significant trend was observed between PWV and mortality risk. Multivariate Cox regression analysis showed that five parameters entered the prediction model: two were positively related to mortality risk, PWV (P = 0.008) and orosomucoide (P = 0.045), and three were related negatively, total cholesterol (P = 0.006), albumin (P = 0.026) and body weight (P = 0.035). Interaction analysis revealed that the effect of PWV on mortality was increased in the presence of renal dysfunction and increased inflammation. In conclusion, although marginally significant in crude analysis, PWV is a powerful determinant of prognosis in the oldest people taking into account inflammation and denutrition.

Aortic stiffness, inflammation, denutrition and type 2 diabetes in the elderly.

AIM: Observational studies in the elderly have shown that some of the classical cardiovascular (CV) risk factors are difficult to interpret. Thus, our study investigated whether increased aortic stiffness is associated with higher mortality risk in both the diabetic and non-diabetic elderly before and after adjusting for geriatric confounders such as inflammation (sedimentation rate, C-reactive protein, orosomucoid levels, leukocyte count) and denutrition parameters (body weight, body mass index [BMI], plasma albumin and prealbumin). METHODS: In a cohort of 324 (84 men) hospitalized elderly subjects, including 255 non-diabetic and 69 diabetic subjects, aortic stiffness was assessed by carotid-femoral pulse wave velocity (PWV) together with CV risk factors. Subjects were studied over a 2-year mean follow-up period, thus enabling evaluation of long-term all-cause mortality. RESULTS: A total of 105 subjects died during the follow-up. Kaplan-Meier curves showed a significantly higher mortality in the diabetics (P=0.024). Multivariate Cox analyses differed for non-diabetic subjects and diabetics. In the former, the hazard ratio (HR) for an increase of 1 SD (with confidence intervals) was 1.36 (1.07-1.72) for PWV, 0.73 (0.52-1.01) for plasma albumin and 0.63 (0.45-0.89) for BMI. In diabetic patients, the HR was 1.60 (1.02-2.50) for leukocyte count, 1.75 (1.03-2.96) for orosomucoid levels and 0.32 (0.15-0.68) for BMI. CONCLUSION: In this very elderly population, although marginally significant on crude analysis, PWV, but not systolic or pulse pressure, was a powerful determinant of total mortality after taking into account the important role of type 2 diabetes. In diabetics, inflammation and denutrition predominated over mechanical factors.

Cardiovascular prevention: relationships between arterial aging and chronic drug treatment.

Drugs acting on cardiovascular (CV) prevention are, by definition, interconnected with age-induced arterial changes. However, this question has been poorly investigated along long-term treatment. This goal requires a major prerequisite: to determine statistical links associating age-induced changes in arterial stiffness and wave reflections with drug classes acting on CV prevention. We studied 347 subjects where CV prevention involved hypertension, diabetes mellitus and hypercholesterolaemia; and included six drug classes: diuretics, ß-blocking agents, angiotensin II (ANGII) and calcium-channel (CCB) blockers, insulin therapy and statins. For each class, the total population was divided into two subgroups according to the presence or absence of the corresponding class. Statistical comparisons between subgroups involved brachial and central blood pressure measurements, aortic pulse wave velocity (PWV), augmentation index (AIx), used as a marker of wave reflections. Non-invasive measurements included tonometry and pulse wave analysis. Appropriate adjustments indicated among results the respective role of age, sex, mean blood pressure (MBP), standard risk factors and other confounding variables. CCB and statins did not exhibit statistical association with PWV or AIx. ß-Blocking agents were significantly linked with heart rate reduction and resulting increase in AIx and central pulse pressure (PP). Increased PWV independent of age, MBP, CV risk factors were noticed under diuretics, ANGII blockers and insulin, pointing to intrinsic modifications of the arterial wall. Treatment of CV prevention involves alterations of the arterial wall depending on drug class. ß-Blocking agents and insulin are associated with the higher increases of central PP.

Comparative study of methodologies for pulse wave velocity estimation.

Arterial stiffness, estimated by pulse wave velocity (PWV), is an independent predictor of cardiovascular mortality and morbidity. However, the clinical applicability of these measurements and the elaboration of reference PWV values are difficult due to differences between the various devices used. In a population of 50 subjects aged 20-84 years, we compared PWV measurements with three frequently used devices: the Complior and the PulsePen, both of which determine aortic PWV as the delay between carotid and femoral pressure wave and the PulseTrace, which estimates the Stiffness Index (SI) by analyzing photoplethysmographic waves acquired on the fingertip. PWV was measured twice by each device. Coefficient of variation of PWV was 12.3, 12.4 and 14.5% for PulsePen, Complior and PulseTrace, respectively. These measurements were compared with the reference method, that is, a simultaneous acquisition of pressure waves using two tonometers. High correlation coefficients with the reference method were observed for PulsePen (r = 0.99) and Complior (r = 0.83), whereas for PulseTrace correlation with the reference method was much lower (r = 0.55). Upon Bland-Altman analysis, mean differences of values +/- 2s.d. versus the reference method were -0.15 +/- 0.62 m/s, 2.09 +/- 2.68 m/s and -1.12 +/- 4.92 m/s, for PulsePen, Complior and Pulse-Trace, respectively. This study confirms the reliability of Complior and PulsePen devices in estimating PWV, while the SI determined by the PulseTrace device was found to be inappropriate as a surrogate of PWV. The present results indicate the urgent need for evaluation and comparison of the different devices to standardize PWV measurements and establish reference values.