Longitudinal Effect of Bariatric Surgery on Retinal Microcirculation and Target Organ Damage: the BASTOD Study.

PURPOSE: Obesity is associated with increased cardiovascular risk. Bariatric surgery (BS) improves the clinical and metabolic profile. Retinal caliber changes could precede cardiovascular events. Different studies have shown an improvement in retinal caliber after BS. The aim of this study was to examine retinal caliber and other cardiovascular target organ damage before and after BS. MATERIALS AND METHODS: Monocentric, prospective cohort study at the Montpellier University Hospital. Biologic features, vessel stiffness, echocardiograph variables, and retinal caliber at baseline and 6 and 12 months were assessed in consecutive patients with class 2 or 3 obesity undergoing BS. A mixed linear model adjusted for age and sex was used. RESULTS: We included 88 patients (75 women). The mean (SD) age was 43 years (11) and mean (SD) baseline weight 117 (21) Kg. Mean changes in the first year after BS were - 5.1 µm in central retinal vein equivalent (CRVE) (p < 0.0001), + 0.02 in arteriole-to-venule ratio (AVR) (p < 0.0001), - 1.4 mmol/L in glycemia (p < 0.0001), - 1.0 mg/L in natural logarithm of C-reactive protein (p < 0.0001), and - 54.0 g in left ventricular mass (p = 0.0005). We observed no significant improvement in arterial stiffness markers. Predictors of improvement in CRVE were high baseline weight (p = 0.030), male sex (p = 0.025), and no diabetes history (p Dynamic links between variations = 0.047). CONCLUSION: The retinal microvascular phenotype improved during the first year after bariatric surgery, with decreased CRVE and increased AVR. Factors associated with retinal microvascular plasticity were male sex, high baseline weight, and absence of diabetes. Longitudinal assessment of retinal vascular calibers may offer new insights into the pathophysiology of subclinical vascular processes.

Predictive risk factors for death in elderly patients after hospitalization for acute heart failure in an internal medicine unit.

To determine the predictive factors of mortality after hospitalization for acute heart failure (AHF) in an internal medicine department. Retrospective observational analysis conducted on 164 patients hospitalized for AHF in 2016-2017. Demographic, clinical and biological characteristics were assessed during hospitalization. The primary endpoint was the occurrence of all-cause death. Multivariate analysis was performed using the Cox model adjusted for age and renal function. The study population was mostly female (n = 106, 64.6%), elderly (82.9 years ± 10.0), with a preserved LVEF (86%). Mean Charlson comorbidity index was 6.5 ± 2.5. After a median follow-up of 17.5 months (IQR 6-38), 109 patients (65%) had died with a median time to death of 14 months (IQR 3-29). In univariate analysis, patients who died were significantly older, had lower BMI and renal function, and higher CCI and NT-proBNP levels (median of 4944 ng/l [2370-14403] versus 1740 ng/l [1119-3503], p < 0.001). In multivariate analysis, risk factors for death were lower BMI (HR 0.69, CI [0.53-0.90], p = 0.005), lower albuminemia (HR 0.77 [0.63-0.94], p = 0.009), higher ferritinemia (HR 1.38 [1.08-1.76], p = 0.010), higher uricemia (HR 1.28 [1.02-1.59], p = 0.030), higher NT-proBNP (HR 2.46 [1.65-3.67], p < 0.001) and longer hospital stay (HR 1.25 [1.05-1.49] p = 0.013). In elderly multimorbid patients, AHF prognosis appears to be influenced by nutritional criteria, including lower BMI, hypoalbuminemia, and hyperuricemia (independently of renal function). These results underline the importance of nutritional status, especially as therapeutic options are available. This consideration paves the way for further research in this field.

Relevance and feasibility of a systematic screening of multimorbidities in patients with chronic inflammatory rheumatic diseases.

OBJECTIVES: EULAR recently proposed to screen multimorbidities in chronic inflammatory rheumatic diseases. The aims of the study were to define the most common multimorbidities in chronic inflammatory rheumatic diseases, compare the screening approach performed in the clinic with the recent EULAR recommendations, validate the points to consider for the systematic standardized multimorbidity screening proposed by EULAR and assess feasibility of such a screening in a daily clinic. METHODS: Data were collected prospectively during a 1-day multimorbidity clinic. Diabetes, hypertension, CVD damage, chronic respiratory diseases, osteoporosis and preventive measures were assessed. The comparison with EULAR points to consider was performed retrospectively. RESULTS: We included 200 consecutive patients (157 with rheumatoid arthritis, 37 spondyloarthritis, and 6 connective tissue diseases or vasculitis). The most common multimorbidities already diagnosed in our patients were hypertension (26%) and diabetes (7.5%). Screening showed that 61.5% (CI95%: 54.6%-67.9%) patients presented at least one undiagnosed or uncontrolled diseases: diabetes (6%), hypertension (20.6%), dyslipidemia (16.1%) valvulopathies (16.8%), peripheral artery disease (4.5%); carotid stenosis (6.5%) and aortic aneurysm (5.5%). Overall, 39.9% patients had incomplete cancer screening and 52.8% incomplete vaccine schedule. Undiagnosed pulmonary obstruction and risk of sleep apnea were suspected in 15.5% and 40.1% patients, respectively. CONCLUSION: This study underlines the relevance of a systematic screening of multimorbidities in chronic inflammatory rheumatic diseases and its feasibility in a 1-day clinic. Spirometry and sleep apnea screening should be added to EULAR points to consider. The long-term impact of such screening needs to be evaluated.

Sodium excretion is higher in patients with rheumatoid arthritis than in matched controls.

OBJECTIVE: It was shown that sodium can promote auto-immunity through the activation of the Th17 pathway. We aimed to compare sodium intake in patients with rheumatoid arthritis (RA) vs. matched controls. METHODS: This case-control study included 24 patients with RA at diagnosis and 24 controls matched by age, gender and body mass index. Sodium intake was evaluated by 24-hr urinary sodium excretion. RESULTS: Sodium excretion was greater for patients with early RA (2,849±1,350 vs. 2,182±751.7mg/day, p = 0.039) than controls. This difference remained significant after adjustment for smoking and the use of anti-hypertensive and nonsteroidal anti-inflammatory drugs (p = 0.043). Patients with radiographic erosion at the time of diagnosis had a higher sodium excretion than those without (p = 0.028). CONCLUSION: Patients with early RA showed increased sodium excretion which may have contributed to autoimmunity.

Noninvasive evaluation of left ventricular elastance according to pressure-volume curves modeling in arterial hypertension.

End-systolic left ventricular (LV) elastance (Ees) has been previously calculated and validated invasively using LV pressure-volume (P-V) loops. Noninvasive methods have been proposed, but clinical application remains complex. The aims of the present study were to 1) estimate Ees according to modeling of the LV P-V curve during ejection ("ejection P-V curve" method) and validate our method with existing published LV P-V loop data and 2) test the clinical applicability of noninvasively detecting a difference in Ees between normotensive and hypertensive subjects. On the basis of the ejection P-V curve and a linear relationship between elastance and time during ejection, we used a nonlinear least-squares method to fit the pressure waveform. We then computed the slope and intercept of time-varying elastance as well as the volume intercept (V0). As a validation, 22 P-V loops obtained from previous invasive studies were digitized and analyzed using the ejection P-V curve method. To test clinical applicability, ejection P-V curves were obtained from 33 hypertensive subjects and 32 normotensive subjects with carotid tonometry and real-time three-dimensional echocardiography during the same procedure. A good univariate relationship (r2 = 0.92, P < 0.005) and good limits of agreement were found between the invasive calculation of Ees and our new proposed ejection P-V curve method. In hypertensive patients, an increase in arterial elastance (Ea) was compensated by a parallel increase in Ees without change in Ea/Ees In addition, the clinical reproducibility of our method was similar to that of another noninvasive method. In conclusion, Ees and V0 can be estimated noninvasively from modeling of the P-V curve during ejection. This approach was found to be reproducible and sensitive enough to detect an expected increase in LV contractility in hypertensive patients. Because of its noninvasive nature, this methodology may have clinical implications in various disease states.NEW & NOTEWORTHY The use of real-time three-dimensional echocardiography-derived left ventricular volumes in conjunction with carotid tonometry was found to be reproducible and sensitive enough to detect expected differences in left ventricular elastance in arterial hypertension. Because of its noninvasive nature, this methodology may have clinical implications in various disease states.

Retinal vascular caliber associated with cardiac and renal target organ damage in never-treated hypertensive patients.

OBJECTIVE: The aim of this study was to assess the relationship between retinal vascular caliber and target organ damage in HT patients. METHODS: Data were collected on cardiac, renal, vascular, and retinal variables in 88 consecutive never-treated HT subjects. Retinal vascular calibers were measured from fundus photographs by using a semi-automated computer-assisted program and summarized as CRAE and CRVE. RESULTS: Mean CRAE and CRVE were significantly lower in patients with left ventricular hypertrophy (left ventricular mass ≥110 g/m² for women, 125 g/m² for men) than in those with normal left ventricular (CRAE: 129.4±3.7 vs 138.2±2.3 µm; P=.04; CRVE: 195.6±4.4 vs 209.8±2.7 µm; P=.008). CRAE and CRVE were negatively correlated with urinary albumin excretion (ß±SE=-15.4±3.2, P<.0001 and ß±SE=-11.9±4.4, P=.001, respectively) but were not correlated with estimated glomerular filtration rate (P=.21 and P=.75, respectively), carotid-to-femoral pulse wave velocity (P=.24 and P=.14), or carotid augmentation index (P=.43 and P=.16). CONCLUSION: In never-treated HT patients, reduced CRAE and CRVE were associated with cardiac and renal preclinical damage, ie, left ventricular hypertrophy and albuminuria, but not estimated glomerular filtration rate or vascular stiffness.

Arterial stiffness: an independent determinant of adaptive glomerular hyperfiltration after kidney donation.

After kidney donation, the remaining kidney tends to hyperfiltrate, thus limiting the initial loss of renal function. The potential determinants of this adaptive glomerular hyperfiltration (GHF) and specifically the influence of arterial function are poorly known. In 45 normotensive healthy kidney donors [51 ± 10 yr (mean ± SD), 39 females], glomerular filtration rate (GFR) was measured as the clearance of continuously infused (99m)Tc-DTPA and timed urine collections at baseline, i.e., before donation, and 1 yr after donation. GHF was computed as postdonation GFR minus half of baseline GFR. Arterial function was assessed as baseline carotid-femoral pulse wave velocity (PWV) and carotid augmentation index (AIx). After kidney donation, no significant change in blood pressure (BP) was observed, but two subjects developed hypertension. GFR decreased from 107 ± 19 to 73 ± 15 ml·min(-1)·1.73 m(-2), and mean GHF was 20 ± 10 ml·min(-1)·1.73 m(-2). In univariate analysis, GHF was inversely correlated to age (r(2) = 0.24, P = 0.01), baseline PWV (r(2) = 0.23, P = 0.001), and Aix (r(2) = 0.11, P = 0.031). Nevertheless, GHF was not correlated to baseline peripheral or central BP. In multivariate analysis, baseline PWV, but not AIx, remained inversely correlated to GHF, independently of age, baseline mean BP, and GFR (model r(2) = 0.34, P < 0.001). In healthy subjects selected for renal donation, increased arterial stiffness is associated with decreased postdonation compensatory hyperfiltration.

Left ventricular mass changes after renal transplantation: influence of dietary sodium and change in serum uric acid.

BACKGROUND: We hypothesized that dietary sodium may modulate the effect of systolic blood pressure and other nonhemodynamic factors, such as high uric acid and renal dysfunction, on changes in the left ventricular mass after renal transplantation. The objective of the present 3-year follow-up longitudinal study was to assess the concomitant influence of these factors on changes in the left ventricular mass after renal transplantation. METHODS: Twenty-four-hour urinary sodium excretion, glomerular filtration rate (isotopic clearance), and left ventricular mass (echocardiography) assessment were done in 165 renal transplant patients during the first year and after a follow-up of 3 years after renal transplantation. RESULTS: At follow-up, therapy of hypertension was associated with normalization of blood pressure in 64% and a decrease in the prevalence of left ventricular hypertrophy from 66% to 56%. At baseline and follow-up, systolic blood pressure, sodium intake, and serum uric acid emerged as independent and significant determinants of the final left ventricular mass index. When the population was divided according to sex-specific tertiles of the final 24-hr urinary sodium excretion, the relationship between change in serum uric acid during follow-up, final left ventricular mass index, and final glomerular filtration rate was significant only on the highest tertile of 24-hr urinary sodium excretion. CONCLUSION: The decrease in the prevalence of left ventricular hypertrophy after renal transplantation is blunted by high sodium intake. Persistence of the left ventricular hypertrophy may result from the combined adverse influences of excessive dietary sodium intake and increased serum uric acid during follow-up despite pharmacological control of blood pressure.

Effect of early stage kidney disease on cardiac mass: comparison to post-donation renal function.

BACKGROUND/AIM: In chronic renal failure the increase in cardiovascular risk is in part related to the high prevalence of left ventricular hypertrophy. The aim of the present monocentric retrospective study was to evaluate the influence of the presence of parenchymal kidney disease on left ventricular geometry in normotensive (arterial pressure <140/90 mm Hg) patients (KD+, n = 50, mean age 39 ± 19 years) with mild to moderate renal failure (stage 2-3 chronic kidney disease). METHODS: Left ventricular geometry was estimated by echocardiography and compared to a group of healthy subjects with similarly reduced renal function as a consequence of renal donation (KD-, n = 63, mean age 52 ± 12 years). RESULTS: Subjects with and without kidney disease had similar blood pressure, body mass index and isotopic glomerular filtration rate. Left ventricular mass (LVM) indexed to body surface area was greater in KD+ as compared to KD- subjects and the difference was more pronounced in women than in men. The increase in LVM in KD+ patients was associated with lower albuminemia and hematocrit, and a higher plasma renin activity and aldosterone as compared to KD- subjects. In multivariate analysis, kidney disease emerged as an important determinant of LVM index independently of age, gender and blood pressure. CONCLUSION: This observation suggests that the presence of kidney disease has an independent amplifying effect on LVM which could be related to volume overload and/or prohypertrophic factors such as aldosterone.

Retinal vascular caliber is associated with renal function in apparently healthy subjects.

PURPOSE: To assess the relation between retinal vascular caliber and renal function. PATIENTS AND METHODS: Eighty apparently healthy subjects screened for cardiovascular risk factors (mean age 47 years, 51% female, 36% hypertensive, without diabetes or renal dysfunction) were recruited. Retinal vascular calibers were measured from fundus photographs and expressed as central retinal artery and venular equivalent. Renal function was assessed by measurement of glomerular filtration rate (urinary clearance of 99mTc-DTPA) and urinary albumin/creatinine ratio. RESULTS: Mean glomerular filtration rate was 117 ml/min/1.73m(2). Overall, central retinal artery and venular equivalent were positively correlated with glomerular filtration rate (r = +0.31, p = 0.005 and r = +0.30, p = 0.006, respectively). In addition, central retinal artery equivalent was negatively correlated with urinary albumin/creatinine ratio (r = -0.34, p = 0.002). No significant relationship was found between central retinal venular equivalent and urinary albumin/creatinine ratio (r = +0.12, p = 0.32). The observed relations between retinal vascular calibers and renal function parameters remained significant after adjusting for potential confounding factors. CONCLUSION: In apparently healthy subjects with normal renal function, retinal arteriolar and venular calibers were negatively correlated with kidney function, suggesting common determinants of these preclinical target organ damages.

Etanercept normalises left ventricular mass in patients with rheumatoid arthritis.

BACKGROUND: Cardiovascular mortality is increased in patients with rheumatoid arthritis (RA). RA is associated with an increased left ventricular mass index (LVMI), a strong marker of cardiovascular mortality, and vessel abnormalities. Experimental studies have suggested that tumour necrosis factor α (TNFα) may induce LV hypertrophy. OBJECTIVE: To study the effect of medium-term (3- and 6-months) treatment with the TNFα inhibitor etanercept (ETN) and synthetic disease-modifying antirheumatic drugs (sDMARDs) on LV morphological features and arterial stiffness in patients with RA. METHODS: Consecutive female patients with active RA requiring treatment with ETN (n=28) or sDMARDs (n=20) were included. Clinical and biological monitoring, echocardiography and pulse wave velocity (PWV) assessment were performed at inclusion and at 3 and 6 months after the start of treatment. Paired t tests and multivariate linear regression analysis were used. RESULTS: Mean LVMI tended to be higher at baseline in the ETN group than in the sDMARD group (96.5±19.8 vs 84.3±26.8 g/m2; p=0.11 for the ETN and sDMARD groups, respectively). In patients with ETN treatment, mean LVMI was significantly decreased at 3 and 6 months (-6.3±7.6 and -14.2±9.3 g/m2; p<0.001), with no change from baseline for patients with sDMARD treatment (-2.2±10.9 and -2.7±10.2 g/m2, respectively). Blood pressure (BP) and aortic PWV were not changed by either treatment. CONCLUSIONS: ETN induced a significant decrease in LVMI with medium-term treatment with no change in BP or PWV. TNFα may be an important factor of LV hypertrophy, which may explain the benefit of TNF inhibitors on cardiovascular morbidity and mortality in RA. These results need to be confirmed by larger studies and with other TNF inhibitors.

Treatment of hypertension with renin-angiotensin system inhibitors and renal dysfunction: a systematic review and meta-analysis.

BACKGROUND: To determine whether inhibitors of the renin-angiotensin system (RAS) reduce the incidence of renal dysfunction when compared to other antihypertensive treatments in patients with essential hypertension and no pre-existent renal disease. METHODS: The search strategy used the Cochrane Library, Medline, previous meta-analyses, and journal reviews. The selection criteria included randomized, controlled trials of antihypertensive drugs that compared a RAS inhibitor with another treatment in essential hypertension. Studies that specifically enrolled only patients with diabetes or renal disease were not included. The quality assessment and data extraction of studies were performed by two independent reviewers. Effects on dichotomous renal outcome (serum creatinine (SCreat) higher than a prespecified value, doubling of SCreat or end-stage renal disease) and secondary continuous marker of renal outcome (change in SCreat) were calculated using Peto's method. RESULTS: 33,240 patients met the inclusion criteria for studies with a dichotomous outcome and 10,634 patients for studies with a continuous outcome. The mean follow-up was 42 ± 13 months. Patients randomized to RAS inhibitors did not show a significant reduction in the risk of developing renal dysfunction as compared to other antihypertensive strategies (odds ratio = 1.05; 95% confidence interval (CI) 0.89-1.25; P = 0.54). There was no significant difference in change of SCreat between groups (mean difference = 0.0005 mg/dl; 95% CI -0.0068 to 0.0077 mg/dl; P = 0.91). CONCLUSION: In patients with essential hypertension and no pre-existent renal disease, prevention of renal dysfunction is not significantly different with RAS inhibitors when compared to other antihypertensive agents.

Early detection of isolated left ventricular diastolic dysfunction in high-risk differentiated thyroid carcinoma patients on TSH-suppressive therapy.

OBJECTIVE: L-Thyroxine-suppressive therapy benefits high-risk differentiated thyroid cancer patients by decreasing recurrence rates and cancer-related mortality. However, fully suppressed serum thyroid-stimulating hormone (TSH) implies a state of subclinical hyperthyroidism (SCH) with associated adverse cardiac effects. Because left ventricular (LV) diastolic dysfunction may be the first manifestation of more severe LV failure, and to balance the risks from thyroid cancer recurrence with risks of cardiac failure, the purpose of this study was to analyse new parameters of LV function in asymptomatic patients with exogenous SCH. DESIGN: Case-control study with 24 patients on TSH-suppressive therapy of short duration (≤ 4 years) after thyroid ablative therapy for differentiated thyroid carcinoma and 20 age- and sex-matched subjects. MEASUREMENTS: LV function [LV global strain and strain rate (SR) curves] was assessed by speckle tracking imaging echocardiography in each subject. RESULTS: Patients and controls do not differ in body mass index, systolic blood pressure and heart rate. No significant differences were observed in LV morphology (LV mass and relative wall thickness), cardiac output and parameters of LV systolic function between patients on suppressive therapy and controls. When compared with controls, patients with exogenous SCH had a significantly impaired longitudinal protodiastolic strain, SR and strain diastolic index but preserved radial strain and SR function. CONCLUSIONS: In subjects with SCH at the early phase of TSH-suppressive therapy, evidence of isolated longitudinal LV diastolic dysfunction was observed, despite a normal LV morphology. Further prospective studies to clarify the prognosis of picking-up early diastolic dysfunction in asymptomatic patients are needed before serial measurements could be recommended.

Dietary sodium, aldosterone, and left ventricular mass changes during long-term inhibition of the renin-angiotensin system.

In essential hypertension, the regression of left ventricular hypertrophy is an important goal of treatment. In addition to treatment-associated changes in blood pressure (BP), the roles of other determinants of left ventricular hypertrophy regression, including dietary sodium intake, deserve investigation. In the present study, the change in echographic left ventricular mass index (LVMI) was assessed in 182 patients with never-treated essential hypertension at baseline and after 3 years of treatment by angiotensin converting enzyme inhibitors or angiotensin II receptor antagonists given at recommended doses and associated with other antihypertensive agents. Treatment was associated with satisfactory control of BP (<140/90 mm Hg) in 64% of patients, and left ventricular hypertrophy prevalence decreased from 56% to 39%. Twenty-four-hour urinary sodium was positively related to LVMI at baseline and at the end of the study, independently of age, sex, and systolic BP. Supine plasma aldosterone concentration was correlated with LVMI only at baseline but not in multivariate analysis. In response to treatment, the percentage of change in LVMI was positively correlated with the absolute changes in systolic BP, urinary sodium, and plasma aldosterone concentration, independently of baseline LVMI. The population was divided into 3 tertiles according to final values of gender-specific urinary sodium. When, within each urinary sodium tertile, patients were divided into those with plasma aldosterone concentration below and above the median (11.6 ng/dL), LVMI progressively increased across sodium tertiles only in patients with high plasma aldosterone concentration. Systolic BP was similar across all of the groups. In conclusion, aldosterone requires the presence of high dietary salt for the expression of its unfavorable effect on the heart.

Glomerular hemodynamics and arterial function in normal individuals.

OBJECTIVE: To determine the relationship between arterial function (stiffness and wave reflection) and glomerular hemodynamics. METHODS: In 49 healthy normotensive individuals, glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured by urinary clearances of 99mTC-DTPA and 131I-hippuran, respectively. Filtration fraction was computed as GFR/ERPF. Arterial stiffness was estimated by carotid-femoral pulse wave velocity (PWV). Wave reflection was evaluated by carotid augmentation index (AIx), reflection magnitude and the round-trip travel time of the pressure wave. RESULTS: PWV and round-trip travel time were not independently correlated with any renal hemodynamic parameter or urinary albumin-creatinine ratio (UACR). AIx and reflection magnitude were directly correlated with filtration fraction (r = 0.35 and 0.37, respectively) and UACR (r = 0.43 and 0.53, respectively). When the population was divided into quartiles of reflection magnitude, filtration fraction and UACR progressively increased from the lowest to the highest quartile and after adjustment for age, mean arterial pressure, heart rate but also sex for UACR (P linear trend = 0.031 and 0.001, respectively). CONCLUSION: It is suggested that in normal individuals, the amplitude of wave reflection but not arterial stiffness is associated with signs evocative of increased glomerular pressure (filtration fraction and UACR), independently of systemic blood pressure.

Non-pressure-related effects of dietary sodium.

After the demonstration of a positive correlation between sodium intake and arterial pressure in large population studies, the effect of short-term reduction in sodium intake demonstrated the efficacy of this nonpharmacologic therapy. In addition, a positive relation between urinary sodium (the most reliable estimate of salt intake) and left ventricular hypertrophy was found; and in recent years it was shown that cardiovascular morbidity clearly progressed with increasing sodium intake, despite one contradictory study. The role of non-pressure-related effects of dietary sodium is discussed in order to bring more arguments for a large-scale attempt to reduce sodium intake by 30% to 50%.

Pulse pressure is an independent determinant of renal function decline during treatment of essential hypertension.

BACKGROUND: In large epidemiological studies and using serum creatinine or estimates of glomerular filtration rate (GFR), blood pressure has emerged as a predominant determinant of the age-associated decline in renal function. METHODS: The present longitudinal study (median follow-up period of 5.8 years) was conducted in 132 never-treated patients with essential hypertension at baseline. The effect of treatment on the GFR and effective renal plasma flow, estimated by urinary clearances of isotopic markers, was assessed. RESULTS: Satisfactory control of hypertension (<140/90 mmHg) was achieved in 57% of the population. During follow-up, the yearly change in the GFR was -1.72+/-0.21 ml/min per year (mean+/-SEM). In univariate regression analysis, the change in the GFR was correlated with baseline pulse pressure (r=-0.27, P=0.002), whereas no influence of systolic, diastolic or mean blood pressures, as well as baseline albuminuria or left ventricular mass index, was found. Multivariate logistic regression analysis showed that only baseline pulse pressure conveyed a significant odds ratio of accelerated decline of GFR (>median of 1.5 ml/min per year), independently of age, baseline GFR, mean blood pressure and other known cardiovascular risk factors. No influence of the type of antihypertensive treatment (64% of the population had received angiotensin-converting enzyme inhibitor) was detected. CONCLUSION: Pulse pressure (a marker of arterial stiffening) is suggested as an independent determinant of the treatment-associated decline in renal function in essential hypertension. No influence of target organ damage (albuminuria of left ventricular hypertrophy) was detected.

Estimation of renal function in subjects with normal serum creatinine levels: influence of age and body mass index.

BACKGROUND: The Cockcroft-Gault (CG) and simplified Modification of Diet in Renal Disease (MDRD) formulas are the most widely used estimates of renal function. The influence of age and body mass index (BMI) on the performance of these equations was analyzed in 850 subjects with serum creatinine levels less than 1.5 mg/dL (<133 micromol/L). METHODS: Glomerular filtration rate (GFR) was measured as urinary clearance of continuously infused technetium Tc 99m-labeled diethylene triaminopentaacetic acid. Performance was assessed as bias, precision, and accuracy. RESULTS: In the total population, the CG and MDRD calculations based on enzymatic measurement of serum creatinine (which is constantly less than that obtained by using the alkaline picrate [Jaffé] method) significantly underestimated GFR by 4.9 and 12.4 mL/min/1.73 m2 (0.08 and 0.21 mL/s/1.73 m2), respectively. In patients 65 years and older, underestimation by means of the CG formula was enhanced, whereas that by means of the MDRD formula was blunted, compared with the group younger than 65 years (-11.3 versus -3.7 mL/min/1.73 m2 [-0.19 versus -0.06 mL/s/1.73 m2] for CG and -3.7 versus -14.0 mL/min/1.73 m2 [-0.06 versus -0.23 mL/s/1.73 m2] for MDRD). GFR was underestimated to a large extent by means of the MDRD equation irrespective of BMI. Conversely, the underestimation by means of the CG formula found in lean people (-13.0 mL/min/1.73 m2 [-0.22 mL/s/1.73 m2]) was blunted in overweight people (BMI, 25 to 30 kg/m2) and reversed to overestimation (+10.1 mL/min/1.73 m2 [+0.17 mL/s/1.73 m2]) in obese subjects (BMI > 30 kg/m2). CONCLUSION: As suggested by estimations obtained using enzymatic serum creatinine measurement, the MDRD equation may be the estimation of choice in elderly patients, whereas the CG estimate is preferable in subjects younger than 65 years. Nevertheless, when obesity is present, no reliable estimation can be obtained by using the CG or MDRD formula.

Relative glomerular hyperfiltration in primary aldosteronism.

Experimental and clinical data suggest that primary aldosteronism (PA) may be associated with cardiovascular hypertrophy and fibrosis, in part independent of the BP level. Whether PA may also result in specific deleterious effects on the kidneys was less studied. In 25 patients with tumoral PA, renal studies (urinary excretion of proteins, GFR, and effective renal plasma flow [ERPF], as clearances of technetium-labeled diethylene triaminopentaacetic acid and 131I-ortho iodohippurate, respectively) were performed both before and 6 mo after surgical cure. A control group consisting of patients with essential hypertension (EH) was studied before and after 6 mo of antihypertensive therapy. At baseline, PA and EH patients were similar with respect to demographic data, duration and level of hypertension, and GFR and ERPF. Urinary excretion of albumin and beta2 microglobulin were higher in PA than EH (88 +/- 26 versus 39 +/- 12 and 0.91 +/- 0.23 versus 0.26 +/- 0.19 mg/24 h, respectively; both P < 0.05). Adrenalectomy was followed by a decrease in arterial BP (by 28 +/- 3/13 +/- 2 mmHg), urinary excretion of albumin and beta2 microglobulin (by 48 +/- 19 and 0.53 +/- 0.21 mg/24 h, respectively), and GFR and ERPF (by 15 +/- 3 and 54 +/- 15 ml/min per 1.73 m(2), respectively). In EH, a similar decrease in pressure was associated with a decrease in albuminuria but no change in GFR or ERPF. In 17 of the 25 PA patients who received a 6-mo treatment of spironolactone, both GFR and ERPF decreased in parallel with BP, similar to what was observed after surgery. These data suggest that PA was associated with relative hyperfiltration, unmasked after suppression of aldosterone excess.