Christine Perret-Guillaume

Heart rate as a risk factor for cardiovascular disease.

Almost all the epidemiological studies that aimed to answer the question of the relationship between heart rate and all-cause or cardiovascular morbidity and mortality reported that a high heart rate was associated with a higher risk of all-cause mortality and cardiovascular events. This relationship has been found to be generally stronger in men than among women. The increase in the cardiovascular risk, associated with the acceleration of heart rate, was comparable to the increase in risk observed with high blood pressure. It has been shown that an increase in heart rate by 10 beats per minute was associated with an increase in the risk of cardiac death by at least 20%, and this increase in the risk is similar to the one observed with an increase in systolic blood pressure by 10 mm Hg. It has also been shown that heart rate recorded in elderly men has a strong predictive value in survival to a very old age. Taken together, these results indicate that the risk associated with accelerated heart rate is not only statistical significant but also clinically relevant and that it should be taken into account in the evaluation of the patients. Although the association between elevated heart rate and cardiovascular morbidity and mortality has been demonstrated in a large number of epidemiological studies, tachycardia has remained a neglected cardiovascular risk factor until very recently. For the first time, the recent guidelines of the European Society of Cardiology and the European Society of Hypertension indicate than an accelerated heart rate is considered as an independent risk factor and potentially as a target for pharmacologic therapies, especially in high-risk patients.

A Simple Clinical Scale to Stratify Risk of Recurrent Falls in Community-Dwelling Adults Aged 65 Years and Older

Background Correct identification of people at risk for recurrent falls facilitates the establishment of preventive and rehabilitative strategies in older adults. Objective The purposes of this study were: (1) to develop and validate a simple clinical scale to stratify risk for recurrent falls in community-dwelling elderly people based on easily obtained social and clinical items and (2) to evaluate the added value of 3 clinical balance tests in predicting this risk. Design This was a prospective measurement study. Methods A population of 1,618 community-dwelling people over 65 years of age underwent a health checkup, including performance of 3 clinical balance tests: the One-Leg-Balance Test, the Timed “Up & Go” Test, and the Five-Times-Sit-to-Stand Test. Falls were recorded using a self-administered questionnaire that was completed a mean (SD) of 25±5 months after the visit. Participants were randomly divided into either group A (n=999), which was used to develop the scale, or group B (n=619), which was used to prospectively validate the scale. Results Logistic regression analysis identified 4 variables that independently predicted recurrent falls in group A: history of falls, living alone, taking ≥4 medications per day, and female sex. Thereafter, 3 risk categories of recurrent falls (low, moderate, and high) were determined. Predicted probability of recurrent falls increased from 4.1% to 30.1% between the first and third categories. This scale subsequently was validated with great accuracy in group B. Only the Five-Times-Sit-to-Stand Test provided added value in the estimation of risk for recurrent falls, especially for the participants who were at moderate risk, in whom failure on the test (duration of >15 seconds) doubled the risk. Limitations Falls were assessed only once, and length of follow-up was heterogeneous (18–36 months). Conclusions Clinicians could easily classify older patients in low-, moderate-, or high-risk groups of recurrent falls by using 4 easy-to-obtain items. The Five-Times-Sit-to-Stand Test provides added value to stratify risk for falls in people at moderate risk.

Pulse Wave Velocity Assessment by External Noninvasive Devices and Phase-Contrast Magnetic Resonance Imaging in the Obese

Carotid-femoral pulse wave velocity (PWV) is considered the gold-standard measurement of arterial stiffness. Obesity, however, can render inaccurate the measurement of PWV by external noninvasive devices. Phase-contrast MRI allows the determination of aortic PWV in multiple aortic locations with intra-arterial distance measurements, as well as the assessment of aortic mechanical properties. The purpose of this study was to assess the reliability of external carotid-femoral PWV values measured by well-validated external devices in comparison with MRI acquisitions of PWV and aortic mechanical properties in a population of obese subjects. PWV was measured with PulsePen and Complior II devices in 32 volunteers (18 men and 14 women), aged 46 to 65 years (mean: 55.7±5.1 years), presenting with isolated abdominal obesity, with a waist circumference >102 cm for men and >88 cm for women, and a body mass index between 27 and 35. These results were then compared with MRI PWV values and cross-sectional MRI thoracic aorta distensibility values. MRI PWV values were positively correlated with PWV measured by both PulsePen (r=0.47; P=0.005) and Complior (r=0.43; P=0.01). Aortic cross-sectional stiffness was positively correlated with PulsePen PWV (r=0.42; P=0.02). The same trend was also observed with Complior PWV (r=0.33; P=0.06). This is the first study comparing transcutaneous PWV measurements with MRI aortic elastic properties in obese subjects. Our results indicate that, for body mass index values ≤35 kg m−2, PWV measured externally with Complior or PulsePen validly reflect values obtained directly in the thoracic aorta through MRI.

Blood pressure and pulse wave velocity values in the institutionalized elderly aged 80 and over: baseline of the PARTAGE study.

Objective The aim of the longitudinal study PARTAGE (predictive values of blood pressure and arterial stiffness in institutionalized very aged population) was to determine the predictive value of blood pressure (BP) and arterial stiffness for overall mortality, major cardiovascular events and cognitive decline in a large population of institutionalized patients aged 80 and over. In the study herein, we present the baseline data values of this study. Methods A total of 1130 patients were recruited (878 women), living in French and Italian nursing homes. Clinical and 3-day self-measurements of BP were conducted. Aortic and upper limb pulse wave velocity were obtained using a PulsePen tonometer. Results Of this population, 76% of women and 60% of men had a known hypertension and over 91% of the patients were under antihypertensive treatment; 51% of the treated hypertensive patients were well controlled (systolic BP <140 mmHg). No significant differences were found between clinical and self-measured BP. With age, there was an increase in pulse pressure (P < 0.001) due to a decrease in diastolic BP (P < 0.001), without any increase in systolic BP. Aortic but not peripheral pulse wave velocity significantly increased with age (P < 0.005). Conclusion Baseline values obtained herein demonstrate that elderly patients living in nursing homes present hemodynamic characteristics which are different to those described in community-living elderly populations, and indicate the interest of assessing, in longitudinal studies, the role of BP and arterial stiffness in morbidity and mortality in this population.

Benefits of the RAS blockade: clinical evidence before the ONTARGET study.

Activation of the AT1 angiotensin II (Ang II) receptors has various effects including vasoconstriction, hypertrophy, and possibly hyperplasia of vascular smooth muscle cells and cardiomyocytes and increase in extracellular collagen matrix synthesis. These actions lead to the development of cardiovascular hypertrophy and fibrosis, as well as arterial stiffness, which are some key factors in the development of the cardiovascular and renal complications. In clinical studies, it has been shown that renin–angiotensin blockade has direct and specific implications in the evolution of heart failure, coronary disease, stroke, and hypertensive and diabetic renal disease. The beneficial cardiovascular and renal effects of blocking the renin–angiotensin–aldosterone system reported in numerous clinical trials may be at least partially related to the actions of these drugs on cardiovascular and renal fibrosis, and arterial stiffness. These effects are now well-established and lead the international medical societies to propose the use of the renin–angiotensin system (RAS) blockers as initial treatment (both angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers) in several cardiovascular, metabolic, and renal disorders such as hypertension, heart failure, and proteinuria.

Health-related quality of life in French adolescents and adults: norms for the DUKE Health Profile

BackgroundThe continual monitoring of population health-related quality of life (HRQoL) with validated instruments helps public health agencies assess, protect, and promote population health. This study aimed to determine norms for the French adolescent and adult general population for the Duke Health Profile (DUKE) questionnaire in a large representative community sample.MethodsWe randomly selected 17,733 French people aged 12 to 75 years old in 2 steps, by households and individuals, from the National Health Barometer 2005, a periodic population study by the French National Institute for Prevention and Health Education. Quality of life and other data were collected by computer-assisted telephone interview.ResultsNormative data for the French population were analyzed by age, gender and self-reported chronic disease. Globally, function scores (best HRQoL=100) for physical, mental, social, and general health, as well as perceived health and self-esteem, were 72.3 (SEM 0.2), 74.6 (0.2), 66.8 (0.1), 71.3 (0.1), 71.3 (0.3), 76.5 (0.1), respectively. Dysfunction scores (worst HRQoL=100) for anxiety, depression, pain and disability domains were 30.9 (0.1), 27.6 (0.2), 34.3 (0.3), 3.1 (0.1), respectively.ConclusionThe French norms for adolescents and adults for the DUKE could be used as a reference for other studies assessing HRQoL, for specific illnesses, in France and for international comparisons.

Tissue factor pathway inhibitor: a new link among arterial stiffness, pulse pressure, and coagulation in postmenopausal women.

Objective—To investigate in women older than 60 whether aortic stiffness or pulse pressure (PP) is associated with selected procoagulant or anticoagulant factors and to examine whether pulsatile stretch influences these factors in human vascular smooth muscle cells (VSMCs) in vitro. Methods and Results—Aortic pulse wave velocity (PWV) and carotid PP were studied in 123 apparently healthy postmenopausal women. PWV, PP, von Willebrand factor, and free tissue factor pathway inhibitor (TFPI), but not mean arterial pressure, increased with age. Free TFPI and PWV were positively correlated, even after adjustment for age and PP and other confounding parameters. In vitro, 5% or 10% pulsatile stretch (at 1 Hz) enhanced TFPI synthesis and secretion by VSMCs in a time-independent manner (1 to 48 hours) without changes in protein level of smooth muscle myosin heavy chain. Application of 5% static stretch had no effect. Conclusion—In postmenopausal women, free TFPI increases as vascular wall function deteriorates and PP increases. These findings are supported by the increase in TFPI synthesized by VSMCs in response to cyclic stress in vitro. They suggest that VSMCs require pulsatility to interfere with the coagulation process and highlight the relevance of plasma free TFPI levels to cardiovascular diseases.

Glomerular filtration rate estimated by Cockcroft-Gault formula better predicts anti-Xa levels than modification of the diet in renal disease equation in older patients with prophylactic enoxaparin.

OBJECTIVES Older people have an increased risk of low molecular weight heparin accumulation leading to an increased bleeding risk. The objective of this study was to assess whether reduced glomerular filtration rate (GFR), estimated by the Cockcroft-Gault or modification of the diet in renal disease (MDRD) equations, indicates drug accumulation by increased anti-Xa levels in older subjects receiving prophylactic enoxaparin treatment. DESIGN Cohort study. SETTING Acute geriatric units in Nancy Hospital. PARTICIPANTS Ninety-two consenting consecutive patients, 65 and older, confined to bed for an acute medical condition requiring enoxaparin for prevention of venous thromboembolism, and hospitalized for at least six days were enrolled. MEASUREMENTS Serum creatinine and peak plasma anti-Xa levels 3 to 4 hours after the daily injection of enoxaparin were measured at days 3, 6, 9 and 12 (first dose of enoxaparin at day one). Analyses of variance for repeated measures were used to evaluate significant predictors of peak anti-Xa activity in univariate and multivariate analyses. RESULTS A significant correlation was observed between anti-Xa activity and GFR estimated with the Cockcroft formula r=0.43. Following univariate analysis, the three factors associated with higher anti-Xa levels were a lower Cockcroft-Gault GFR (p=0.0002), female gender (p=0.0003) and a lower bodyweight (p<.0001). No significant association between anti-Xa levels and MDRD GFR (p=0.33) was observed. Following multivariate analysis, female gender (p=0.02), bodyweight (p=0.04) and Cockcroft GFR (p=0.05) remained independent determinants of anti-Xa levels. CONCLUSION In hospitalized patients older than 65 years old, the Cockcroft-Gault equation, in contrast to the MDRD equation, is able to predict the risk of higher anti-Xa levels.

Effect of Multimorbidity on Health-Related Quality of Life in Adults Aged 55 Years or Older: Results from the SU.VI.MAX 2 Cohort.

Introduction Multimorbid chronic diseases are usually considered separately in trials. Here, we aimed to describe overall multimorbidity patterns in adults aged 55 years or older and assess their effect on health-related quality of life (HRQoL). Methods We used data for 5,647 participants included in the SUpplémentation en VItamines et Minéraux AntioXydants 2 (SU.VI.MAX 2) population-based trial. HRQoL was assessed by the French versions of the Medical Outcome Study Short Form 36 and the Duke Health Profile. An exploratory factor analysis was used to determine multimorbidity patterns, and a multimorbidity score for each resulting pattern was calculated. Adjusted multiple linear regression was used to examine the association between the identified multimorbidity and HRQoL scores by gender and for each age group (55–59, 60–64, 65–69, ≥ 70 years). Results More than 63% of the sample reported two or more chronic conditions (from 55.8% for those 55–59 years to 74.4% for those ≥ 70 years). Multimorbidity was more common among women than men (67.3% vs 60%). Two different multimorbidity patterns were identified. Pattern A was represented mainly by mental illness and bone impairments. Pattern B was represented mainly by cardiovascular and metabolic disorders. After adjusting for covariates, a high pattern A score was associated with reduced HRQoL for the physical and mental components of each HRQoL questionnaire, and a high pattern B score was associated with reduced HRQoL for only the physical component of each questionnaire. These multimorbidity scores affected HRQoL differently by age group. Conclusion Our study used a novel methodological approach to account for multimorbidity patterns in determining the link with chronic conditions. These multimorbidity scores (counted and weighted) can be used in clinical research to control for the effect of multimorbidity on patients’ HRQoL and may be useful for clinical practice. Clinical Trial Registration Clinicaltrial.gov (number NCT00272428).

Which generic health related Quality of Life questionnaire should be used in older inpatients: Comparison of the Duke Health Profile and the MOS Short-Form SF-36?

OBJECTIVES The objective of our study was to compare advantages and limitations of two generic Quality of Life questionnaires administered in older inpatients. DESIGN Two validated generic health-related Quality of Life instruments : the MOS Short-Form 36 (9 dimensions, 36 items) and the Duke Health Profile (6 dimensions, 4 dysfunctions, 17 items) were administered to inpatients over 65 years. SETTING AND PARTICIPANTS The sample was drawn from the CliniQualVie program that assessed systematically Quality of Life among hospitalized inpatients (18-79 years) in 10 medical and surgical wards at Nancy University Hospital. RESULTS The two self-administered questionnaires were completed by 701 patients over 65 years at admission (mean age 71 +/- 4, 63% men). The proportion of patients who completed all items were 72.5% for the Duke and 66.9% for the SF-36 (p < .001). The Dukes internal consistency was low as compared with the SF-36, but other psychometric properties were comparable. Good correlations (Spearman) were observed between the two questionnaires for physical health (0.59, p < .0001), mental health (0.68, p < .0001) and health perception (0.56, p < .0001) scores. Low correlations were observed for the social score. CONCLUSIONS This is the first study to our knowledge to assess the interest of using the Duke Health Profile in a general elderly inpatients population as compared with the SF-36 questionnaire. Although these two questionnaires have four comparable dimensions, they differ in their content and psychometric properties. The Duke questionnaire, due to its better completion rate and despite some psychometric limitations may be useful in this population, particularly in the more frail patients.