Isabelle Macquin-Mavier

Antihypertensive drug classes have different effects on short-term blood pressure variability in essential hypertension

Increased blood pressure variability (BPV) contributes to end-organ damage, cardiovascular events and mortality associated with hypertension. In a cohort of 2780 hypertensive patients treated by either calcium channel blockers (CCBs), diuretics, angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs) or β-blockers alone or in combination, we compared indices of short-term BPV according to the different treatments. Short-term BPV was calculated as the standard deviation (s.d.) of 24 h, daytime or nighttime systolic blood pressure and diastolic blood pressure (SBP and DBP). Short-term BPV was compared between patients treated with a given antihypertensive class of interest (alone or in combination) and those not treated with this class, after controlling for ambulatory average blood pressure, heart rate, age, gender, propensity scores and carotid–femoral pulse wave velocity. Patients treated with CCBs (n=1247) or diuretics (n=1486) alone, or in addition to other drugs had significant lower s.d. of 24-h SBP compared with those not treated with these classes (mean differences in s.d. −0.50±0.50 mm Hg, P=0.001 and −0.17±0.15 mm Hg, P=0.05, respectively). There was no significant difference regarding treatment with or without ARBs, ACEIs and β-blockers. The combinations of CCBs with diuretics or ARBs on top of other treatments resulted in a lower 24-h SBP variability (mean differences in s.d. −0.43±0.17 mm Hg, P=0.02 and −0.44±0.19 mm Hg, P=0.005 vs. other combination uses, respectively). Antihypertensive drug classes have differential effects on short-term BPV with a greater reduction in patients treated with CCBs and diuretics. The combinations of CCBs with diuretics may be the most efficient treatments in lowering BPV.

Crucial importance of using a sliding calliper to measure distance for carotid-femoral pulse wave velocity assessment.

Background and objectives: In the past, different methods have been used to measure the carotid-femoral distance for the assessment of pulse wave velocity (PWV). However, the latest consensus published advises to use 80% of the direct straight carotid-femoral distance (D0.8) using either a flexible tape or a sliding calliper. We studied the influence of the use of a tape measure and a calliper on PWV values and provided equations to derive the straight D0.8 distance from previous methodologies. Methods: PWV was measured in patients referred for ambulatory blood pressure monitoring. Carotid-femoral, carotid-sternal notch, and sternal notch-femoral distances were measured with a tape and a sliding calliper. Results: Two hundred and fifty-nine patients (141 men and 118 women) were recruited consecutively. Their BMI ranged from 18 to 45 kg/m2 (28.4 ± 5.0, mean ± SD). As expected, distances measured with tape were longer (3.1 ± 1.3 cm for D0.8) leading to higher values of PWV (0.6 ± 0.3 m/s for PWV0.8). This difference was similar in men and women and depended for 20% on the BMI. Equations explaining more than 85% of variance can be used to convert tape carotid-femoral, carotid-sternal notch, and tape sternal notch-femoral distances to D0.8. Conclusion: It is crucial to use a sliding calliper to assess distances for PWV measurement. The overestimation with flexible tape depends on the BMI but not on the sex. Conversion equations between previous methods and the D0.8 method can be used.

First-line antiangiogenics for metastatic renal cell carcinoma: A systematic review and network meta-analysis

BACKGROUND Sunitinib, pazopanib, sorafenib, axitinib and bevacizumab are the five recommended antiangiogenic agents in first-line therapy for metastatic renal cell carcinoma (mRCC). Because these drugs underwent simultaneous clinical development, no direct efficacy and safety comparison was ever conducted, thus preventing optimal therapy choices. METHODS We performed a traditional and network meta-analysis to evaluate the efficacy and safety of mRCC-recommended first-line antiangiogenic agents. After a systematic review of Medline and Embase up to July 2014, we identified randomized clinical trials (RCTs) evaluating the outcomes of mRCC patients treated with sunitinib, pazopanib, sorafenib, axitinib and bevacizumab as first-line treatment. Endpoints of interest were response rate, progression-free survival (PFS), overall survival (OS), and safety. RESULTS We screened 769 abstracts and included nine RCTs with a total of 4282 patients. In the weighted pooled analysis, first-line antiangiogenic agents showed significant improvement in PFS (HR=0.6; 95% IC, 0.51-0.72) and OS (HR=0.85; 95% IC, 0.78-0.93) compared to control (placebo or interferon-alpha2a (INF)). Network meta-analysis showed no significant differences among antiangiogenic drugs in 6-month PFS, 1-year OS, disease control rate and drug-related safety for all-grade hypertension, diarrhea, weight-loss, nausea or anorexia. However, pazopanib showed a lower incidence of fatigue, anemia and hand foot skin reaction. CONCLUSIONS This meta-analysis confirms the benefits of first-line antiangiogenic therapy in mRCC, with an improvement in OS. Sunitinib, pazopanib, axitinib and bevacizumab + INF offer similar efficacy but different safety profiles which can help clinicians to better personalize treatment decisions in patients with mRCC.

Carotid–Femoral Pulse Wave Velocity Is Not Increased in Obesity

BACKGROUND There are conflicting results in the literature concerning the relationship between obesity and arterial stiffness, assessed by carotid-femoral pulse wave velocity (PWV). The discrepancies could be due to differences in carotid-femoral distance measurement and/or to the presence of pathologies frequently associated with obesity and which increase arterial stiffness. In this study, we examine the relationship between PWV and weight, without and with associated cardiovascular risk factors (diabetes and/or dyslipidemia). METHODS PWV was assessed with a Complior SP device (Alam Medical, France) in 2,034 patients referred for ambulatory blood pressure monitoring. The carotid-femoral distance used to calculate PWV was measured with a flexible tape and from the estimated straight carotid-femoral distance obtained with a published equation. RESULTS In the whole cohort, PWV did not differ significantly according to weight (9.6±2.1, 9.8±2.2 and 9.7±1.9 m/s in normal weight, overweight and obese subjects, respectively, with the distance measured with a tape). PWV was significantly higher in the four groups of patients with cardiovascular risk factors (e.g., 11.1±2.4, 11.0±2.7 and 10.4±2.0 m/s in normal weight, overweight, and obese subjects, respectively, in the group treated for diabetes and dyslipidemia) than in the group of patients without cardiovascular risk factors (8.5±1.6, 8.8±1.7 and 8.5±1.2 in normal weight, overweight, and obese subjects, respectively). There was no relationship between PWV value and weight status, whether or not there were cardiovascular risk factors, and whatever the distance used to calculate PWV. CONCLUSIONS In our cohort, obesity per se was not associated with increased arterial stiffness.

Heart rate increment analysis is not effective for sleep-disordered breathing screening in patients with chronic heart failure

Frequency domain analysis of heart rate variation has been suggested as an effective screening tool for sleep‐disordered breathing (SDB) in the general population. The aim of this study was to assess this method in patients with chronic congestive heart failure (CHF). We included prospectively 84 patients with stable CHF, left ventricular ejection fraction (LVEF) <45% and sinus rhythm. The patients underwent polygraphy to measure the apnoea/hypopnoea index (AHI) and simultaneous Holter electrocardiogram monitoring to measure the power spectral density of the very low frequency component of the heart rate increment, expressed as the percentage of total power spectral density [% very low frequency increment (%VLFI)]. %VLFI could be determined in 54 patients (mean age, 52.8 ± 12.3 years; LVEF, 33.5 ± 9.8%). SDB defined as AHI ≥15 h−1 was diagnosed in 57.4% of patients. Percent VLFI was not correlated with AHI (r = 0.12). Receiver‐operating characteristic curves constructed using various AHI cut‐offs (5–30 h−1) failed to identify a %VLFI cut‐off associated with SDB. The 2.4% VLFI cut‐off recommended for the general population of patients with suspected SDB had low specificity (35%) and low positive and negative predictive values (35% and 54%, respectively). Heart rate increment analysis has several limitations in CHF patients and cannot be recommended as an SDB screening tool in the CHF population.

Effectiveness of anti-psychotics and related drugs in the Huntington French-speaking group cohort.

Purpose: Huntingtons disease is a rare condition. Patients are commonly treated with antipsychotics and tetrabenazine. The evidence of their effect on disease progression is limited and no comparative study between these drugs has been conducted. We therefore compared the effectiveness of antipsychotics on disease progression. Methods: 956 patients from the Huntington French Speaking Group were followed for up to 8 years between 2002 and 2010. The effectiveness of treatments was assessed using Unified Huntingtons Disease Rating Scale (UHDRS) scores and then compared using a mixed model adjusted on a multiple propensity score. Results: 63% of patients were treated with antipsychotics during the survey period. The most commonly prescribed medications were dibenzodiazepines (38%), risperidone (13%), tetrabenazine (12%) and benzamides (12%). There was no difference between treatments on the motor and behavioural declines observed, after taking the patient profiles at the start of the drug prescription into account. In contrast, the functional decline was lower in the dibenzodiazepine group than the other antipsychotic groups (Total Functional Capacity: 0.41±0.17 units per year vs. risperidone and 0.54±0.19 vs. tetrabenazine, both p<0.05). Benzamides were less effective than other antipsychotics on cognitive evolution (Stroop interference, Stroop color and Literal fluency: p<0.05). Conclusions: Antipsychotics are widely used to treat patients with Huntingtons disease. Although differences in motor or behavioural profiles between patients according to the antipsychotics used were small, there were differences in drug effectiveness on the evolution of functional and cognitive scores.

Relationship Between Short-Term Blood Pressure Variability and Large-Artery Stiffness in Human Hypertension

Short-term blood pressure (BP) variability predicts cardiovascular complications in hypertension, but its association with large-artery stiffness is poorly understood and confounded by methodologic issues related to the assessment of BP variations over 24 hours. Carotid-femoral pulse wave velocity (cfPWV) and 24-hour ambulatory BP were measured in 911 untreated, nondiabetic patients with uncomplicated hypertension (learning population) and in 2089 mostly treated hypertensive patients (83% treated, 25% diabetics; test population). Short-term systolic BP (SBP) variability was calculated as the following: (1) SD of 24-hour, daytime, or nighttime SBP; (2) weighted SD of 24-hour SBP; and (3) average real variability (ARV), that is, the average of the absolute differences between consecutive SBP measurements over 24 hours. In the learning population, all of the measures of SBP variability showed a direct correlation with cfPWV (SD of 24-hour, daytime, and nighttime SBP, r=0.17/0.19/0.13; weighted SD of 24-hour SBP, r=0.21; ARV, r=0.26; all P<0.001). The relationship between cfPWV and ARV was stronger than that with 24-hour, daytime, or nighttime SBP (all P<0.05) and similar to that with weighted SD of 24-hour SBP. In the test population, ARV and weighted SD of 24-hour SBP had stronger relationships with cfPWV than SD of 24-hour, daytime, or nighttime SBP. In both populations, SBP variability indices independently predicted cfPWV along with age, 24-hour SBP, and other factors. We conclude that short-term variability of 24-hour SBP shows an independent, although moderate, relation to aortic stiffness in hypertension. This relationship is stronger with measures of BP variability focusing on short-term changes, such as ARV and weighted 24-hour SD.

Relationship Between Short-Term Blood Pressure Variability and Large-Artery Stiffness in Human HypertensionNovelty and Significance

Short-term blood pressure (BP) variability predicts cardiovascular complications in hypertension, but its association with large-artery stiffness is poorly understood and confounded by methodologic issues related to the assessment of BP variations over 24 hours. Carotid-femoral pulse wave velocity (cfPWV) and 24-hour ambulatory BP were measured in 911 untreated, nondiabetic patients with uncomplicated hypertension (learning population) and in 2089 mostly treated hypertensive patients (83% treated, 25% diabetics; test population). Short-term systolic BP (SBP) variability was calculated as the following: (1) SD of 24-hour, daytime, or nighttime SBP; (2) weighted SD of 24-hour SBP; and (3) average real variability (ARV), that is, the average of the absolute differences between consecutive SBP measurements over 24 hours. In the learning population, all of the measures of SBP variability showed a direct correlation with cfPWV (SD of 24-hour, daytime, and nighttime SBP, r=0.17/0.19/0.13; weighted SD of 24-hour SBP, r=0.21; ARV, r=0.26; all P<0.001). The relationship between cfPWV and ARV was stronger than that with 24-hour, daytime, or nighttime SBP (all P<0.05) and similar to that with weighted SD of 24-hour SBP. In the test population, ARV and weighted SD of 24-hour SBP had stronger relationships with cfPWV than SD of 24-hour, daytime, or nighttime SBP. In both populations, SBP variability indices independently predicted cfPWV along with age, 24-hour SBP, and other factors. We conclude that short-term variability of 24-hour SBP shows an independent, although moderate, relation to aortic stiffness in hypertension. This relationship is stronger with measures of BP variability focusing on short-term changes, such as ARV and weighted 24-hour SD.

Relationship Between Short-Term Blood Pressure Variability and Large-Artery Stiffness in Human HypertensionNovelty and Significance: Findings From 2 Large Databases

Short-term blood pressure (BP) variability predicts cardiovascular complications in hypertension, but its association with large-artery stiffness is poorly understood and confounded by methodologic issues related to the assessment of BP variations over 24 hours. Carotid-femoral pulse wave velocity (cfPWV) and 24-hour ambulatory BP were measured in 911 untreated, nondiabetic patients with uncomplicated hypertension (learning population) and in 2089 mostly treated hypertensive patients (83% treated, 25% diabetics; test population). Short-term systolic BP (SBP) variability was calculated as the following: (1) SD of 24-hour, daytime, or nighttime SBP; (2) weighted SD of 24-hour SBP; and (3) average real variability (ARV), that is, the average of the absolute differences between consecutive SBP measurements over 24 hours. In the learning population, all of the measures of SBP variability showed a direct correlation with cfPWV (SD of 24-hour, daytime, and nighttime SBP, r=0.17/0.19/0.13; weighted SD of 24-hour SBP, r=0.21; ARV, r=0.26; all P<0.001). The relationship between cfPWV and ARV was stronger than that with 24-hour, daytime, or nighttime SBP (all P<0.05) and similar to that with weighted SD of 24-hour SBP. In the test population, ARV and weighted SD of 24-hour SBP had stronger relationships with cfPWV than SD of 24-hour, daytime, or nighttime SBP. In both populations, SBP variability indices independently predicted cfPWV along with age, 24-hour SBP, and other factors. We conclude that short-term variability of 24-hour SBP shows an independent, although moderate, relation to aortic stiffness in hypertension. This relationship is stronger with measures of BP variability focusing on short-term changes, such as ARV and weighted 24-hour SD.

CRITICAL INFLUENCE OF PULSE WAVE TRAVEL DISTANCE AND BODY MASS INDEX ON CAROTID-FEMORAL PULSE WAVE VELOCITY VALUES: PP.10.384

Introduction: Carotid-femoral pulse wave velocity (PWV) is considered the reference standard for assessing arterial stiffness and its measurement is now recommended in various clinical conditions to evaluate the cardiovascular risk. However, there is no consensus about which arterial path length should be used or how this length should be measured. Methods: We compared PWV values obtained with two path lengths - distance between the carotid and femoral sites of measurement (CfPWV) and distance obtained by substracting the carotid-suprasternal notch distance from suprasternal notch-to-femoral distance ((SF-SC)PWV)- and with two methods of measurements - flexible tape meter or sliding caliper - in 258 consecutive patients. PWV values were obtained using the Complior system (Alam Medical, France). Results: PWV values were significantly lower with distances measured with the caliper than with the tape meter: 11.3 ± 2.4 vs. 12.0 ± 2.5 m/s for CfPWV (p < 0.001) and 8.0 ± 1.8 vs. 8.7 ± 2.0 m/s for (SF-SC)PWV (p < 0.001). (SF-SC)PWV was significantly lower than CfPWV: -3.3 ± 1.0 m/s with the tape meter or with the caliper, representing a difference of 27–29%. Differences between tape meter and caliper PWV measurements significantly correlated with BMI (ñ = 0.39 and ñ = 0.41 p < 0.001 for CfPWV and (SF-SC)PWV, respectively). Interestingly, the difference was significant in normal-weight patients for CfPWV (12.0 ± 2.6 vs. 11.4 ± 2.5 m/s, p < 0.001) and (SF-SC)PWV (8.2 ± 1.8 vs. 7.6 ± 1.7 m/s, p < 0.001) and increased with BMI (Table). These differences remained significant when analysis were stratified on gender. Similar results were obtained with waist circumference. Figure 1. No caption available. Conclusion: Values of carotid-femoral PWV differed by 3.3 ± 1.0 m/s according to the path length used and they were significantly greater when distances were measured with a ruler with regard to a slide caliper, independently from path lengths, BMI, waist circumference and gender. These results underline the need for guidelines about the methods used to measure the path length for PWV assessment.