Leonella Luzardo

24-h ambulatory recording of aortic pulse wave velocity and central systolic augmentation: a feasibility study

We assessed the feasibility of ambulatory pulse wave analysis by comparing this approach with an established tonometric technique. We investigated 35 volunteers (45.6 years; 51.0% women) exclusively at rest (R study) and 83 volunteers (49.9 years; 61.4% women) at rest and during daytime (1000–2000 h) ambulatory monitoring (R+A study). We recorded central systolic (cSP), diastolic (cDP) and pulse (cPP) pressures, augmentation index (cAI) and pulse wave velocity (PWV) by brachial oscillometry (Mobil-O-Graph 24h PWA Monitor) and radial tonometry (SphygmoCor). We applied the Bland and Altman’s statistics. In the R study, tonometric and oscillometric estimates of cSP (105.6 vs. 106.9 mm Hg), cDP (74.6 vs. 74.7 mm Hg), cPP (31.0 vs. 32.1 mm Hg), cAI (21.1 vs. 20.6%) and PWV (7.3 vs. 7.0 m s−1) were similar (P⩾0.11). In the R+A study, tonometric vs. oscillometric assessment yielded similar values for cSP (115.4 vs. 113.9 mm Hg; P=0.19) and cAI (26.5 vs. 25.3%; P=0.54), but lower cDP (77.8 vs. 81.9 mm Hg; P<0.0001), so that cPP was higher (37.6 vs. 32.1 mm Hg; P<0.0001). PWV (7.9 vs. 7.4 m s−1) was higher (P=0.0002) on tonometric assessment. The differences between tonometric and oscillometric estimates increased (P⩽0.004) with cSP (r=0.37), cAI (r=0.39) and PWV (r=0.39), but not (P⩾0.17) with cDP (r=0.15) or cPP (r=0.13). Irrespective of measurement conditions, brachial oscillometry compared with an established tonometric method provided similar estimates for cSP and systolic augmentation, but slightly underestimated PWV. Pending further validation, ambulatory assessment of central hemodynamic variables is feasible.

Setting thresholds to varying blood pressure monitoring intervals differentially affects risk estimates associated with white-coat and masked hypertension in the population

Outcome-driven recommendations about time intervals during which ambulatory blood pressure should be measured to diagnose white-coat or masked hypertension are lacking. We cross-classified 8237 untreated participants (mean age, 50.7 years; 48.4% women) enrolled in 12 population studies, using ≥140/≥90, ≥130/≥80, ≥135/≥85, and ≥120/≥70 mm Hg as hypertension thresholds for conventional, 24-hour, daytime, and nighttime blood pressure. White-coat hypertension was hypertension on conventional measurement with ambulatory normotension, the opposite condition being masked hypertension. Intervals used for classification of participants were daytime, nighttime, and 24 hours, first considered separately, and next combined as 24 hours plus daytime or plus nighttime, or plus both. Depending on time intervals chosen, white-coat and masked hypertension frequencies ranged from 6.3% to 12.5% and from 9.7% to 19.6%, respectively. During 91 046 person-years, 729 participants experienced a cardiovascular event. In multivariable analyses with normotension during all intervals of the day as reference, hazard ratios associated with white-coat hypertension progressively weakened considering daytime only (1.38; P=0.033), nighttime only (1.43; P=0.0074), 24 hours only (1.21; P=0.20), 24 hours plus daytime (1.24; P=0.18), 24 hours plus nighttime (1.15; P=0.39), and 24 hours plus daytime and nighttime (1.16; P=0.41). The hazard ratios comparing masked hypertension with normotension were all significant (P<0.0001), ranging from 1.76 to 2.03. In conclusion, identification of truly low-risk white-coat hypertension requires setting thresholds simultaneously to 24 hours, daytime, and nighttime blood pressure. Although any time interval suffices to diagnose masked hypertension, as proposed in current guidelines, full 24-hour recordings remain standard in clinical practice.

Estimation of Glomerular Filtration Rate Based on Serum Cystatin C versus Creatinine in a Uruguayan Population

Background. Estimation of glomerular filtration rate (eGFR) from biomarkers has evolved and multiple equations are available to estimate renal function at bedside. Methods. In a random sample of 119 Uruguayans (54.5% women; 56.2 years (mean)), we used Bland and Altmans method and Cohens kappa statistic to assess concordance on a continuous or categorical (eGFR < 60 versus ≥60 mL/min/1.73 m2) scale between eGFRcys (reference) and eGFR derived from serum creatinine according to the Modification of Diet in Renal Disease (eGFRmdrd) or the Chronic Kidney Disease Epidemiology Collaboration equations (eGFRepi) or from both serum cystatin C and creatinine (eGFRmix). Results. In all participants, eGFRmdrd, eGFRepi, and eGFRmix were, respectively, 9.7, 11.5, and 5.6 mL/min/1.73 m2 higher (P < 0.0001) than eGFRcys. The prevalence of eGFR <60 mL/min/1.73 m2 was the highest for eGFRcys (21.8%), intermediate for eGFRmix (11.8%), and the lowest for eGFRmdrd (5.9%) and eGFRepi (3.4%). Using eGFRcys as reference, we found only fair agreement with the equations based on creatinine (Cohens kappa statistic 0.15 to 0.23). Conclusion. Using different equations we reached clinically significant differences in the estimation of renal function. eGFRcys provides lower estimates, resulting in higher prevalence of eGFR <60 mL/min/1.73 m2.

Prevalence and Determinants of Masked Hypertension Among Black Nigerians Compared With a Reference Population

Hitherto, diagnosis of hypertension in sub-Saharan Africa was largely based on conventional office blood pressure (BP). Data on the prevalence of masked hypertension (MH) in this region is scarce. Among individuals with normal office BP (<140/90 mm Hg), we compared the prevalence and determinants of MH diagnosed with self-monitored home blood pressure (≥135/85 mm Hg) among 293 Nigerians with a reference population consisting of 3615 subjects enrolled in the International Database on Home Blood Pressure in Relation to Cardiovascular Outcomes. In the reference population, the prevalence of MH was 14.6% overall and 11.1% and 39.6% in untreated and treated participants, respectively. Among Nigerians, the prevalence standardized to the sex and age distribution of the reference population was similar with rates of 14.4%, 8.6%, and 34.6%, respectively. The mutually adjusted odds ratios of having MH in Nigerians were 2.34 (95% confidence interval, 1.39–3.94) for a 10-year higher age, 1.92 (1.11–3.31) and 1.70 (1.14–2.53) for 10- or 5-mm Hg increments in systolic or diastolic office BP, and 3.05 (1.08–8.55) for being on antihypertensive therapy. The corresponding estimates in the reference population were similar with odds ratios of 1.80 (1.62–2.01), 1.64 (1.45–1.87), 1.13 (1.05–1.22), and 2.84 (2.21–3.64), respectively. In conclusion, MH is as common in Nigerians as in other populations with older age and higher levels of office BP being major risk factors. A significant proportion of true hypertensive subjects therefore remains undetected based on office BP, which is particularly relevant in sub-Saharan Africa, where hypertension is now a major cause of death.

Relationship between office and home blood pressure with increasing age: The International Database of HOme blood pressure in relation to Cardiovascular Outcome (IDHOCO)

Home blood pressure (HBP) measurements are known to be lower than conventional office blood pressure (OBP) measurements. However, this difference might not be consistent across the entire age range and has not been adequately investigated. We assessed the relationship between OBP and HBP with increasing age using the International Database of HOme blood pressure in relation to Cardiovascular Outcome (IDHOCO). OBP, HBP and their difference were assessed across different decades of age. A total of 5689 untreated subjects aged 18–97 years, who had at least two OBP and HBP measurements, were included. Systolic OBP and HBP increased across older age categories (from 112 to 142 mm Hg and from 109 to 136 mm Hg, respectively), with OBP being higher than HBP by ∼7 mm Hg in subjects aged >30 years and lesser in younger subjects (P=0.001). Both diastolic OBP and HBP increased until the age of ∼50 years (from 71 to 79 mm Hg and from 66 to 76 mm Hg, respectively), with OBP being consistently higher than HBP and a trend toward a decreased OBP–HBP difference with aging (P<0.001). Determinants of a larger OBP–HBP difference were younger age, sustained hypertension, nonsmoking and negative cardiovascular disease history. These data suggest that in the general adult population, HBP is consistently lower than OBP across all the decades, but their difference might vary between age groups. Further research is needed to confirm these findings in younger and older subjects and in hypertensive individuals.

The Diurnal Profile of Central Hemodynamics in a General Uruguayan Population.

BACKGROUND No previous population study assessed the diurnal profile of central arterial properties. METHODS In 167 participants (mean age, 56.1 years; 63.5% women), randomly recruited in Montevideo, Uruguay, we used the oscillometric Mobil-O-Graph 24-h PWA monitor to measure peripheral and central systolic (SBP), diastolic (DBP), and pulse (PP) pressures and central hemodynamics standardized to a heart rate of 75 bpm, including aortic pulse wave velocity, systolic augmentation (first/second peak × 100), and pressure amplification (peripheral PP/central PP). RESULTS Over 24 hours, day and night, peripheral minus central differences in SBP/DBP and in PP averaged 12.2/-1.1, 14.0/-0.7, and 9.7/0.2mm Hg and 12.6, 14.7, and 9.5mm Hg, respectively (P < 0.001 except for nighttime DBP (P = 0.38)). The central-to-peripheral ratios of SBP, DBP, and PP were 0.89, 1.00, and 0.70 unadjusted, but after accounting for anthropometric characteristics decreased to 0.74, 0.97, and 0.63, respectively, with strong influence of height for SBP and DBP and of sex for PP. From day (10-20h) to nighttime (0-6h), peripheral (-10.4/-10.5 mm Hg) and central (-6.0/-11.3mm Hg) SBP/DBP, pulse wave velocity (-0.7 m/s) and pressure amplification (-0.05) decreased (P < 0.001), whereas central PP (+5.3mm Hg) and systolic augmentation (+2.3%) increased (P < 0.001). CONCLUSIONS The diurnal rhythm of central pressure runs in parallel with that of peripheral pressure, but the nocturnal fall in SBP is smaller centrally than peripherally. pulse wave velocity, systolic augmentation, and pressure amplification loop through the day with high pulse wave velocity and pressure amplification but low systolic augmentation in the evening and opposite trends in the morning.

Significance of white-coat and masked hypertension in chronic kidney disease and end-stage renal disease

Hypertension is a frequent and modifiable cardiovascular risk factor with a cyclic relationship with chronic kidney disease (CKD). The diagnosis, treatment, monitoring and control of high blood pressure are all mandatory not only in CKD but also in end-stage renal disease (ESRD). As demonstrated by studies using population and hypertensive patients, white-coat hypertension (WCHT) and masked hypertension (MHT) carry a particular degree of risk. The advantages of ambulatory techniques in the management and prognostic stratification of patients with CKD and ESRD have also been recognized. However, most of the evidence underlines the importance of nocturnal hypertension and neglects WCHT and MHT. The absence of specific reports involving untreated and treated patients hinders the ability to significantly discriminate WCHT from the white-coat effect and MHT from masked uncontrolled hypertension. The heterogeneous definitions that are used add additional difficulty in translating experimental evidence into clinical practice. Reaching a consensus in definitions is mandatory for designing future research. Cross-sectional studies underscore the frequency of misdiagnosis, potentially leading to undertreatment (MHT) and overtreatment (WCHT) in renal disease. The divergent prevalence of WCHT and MHT reported in CKD could be related to the diverse definitions of hypertension and the heterogeneity of the pathologies pooled under the CKD definition. Even in the absence of randomized clinical trials specifically addressing this issue, the scarce longitudinal studies confirm that WCHT carries a risk close to that of sustained normotension, whereas MHT is associated with a risk close or identical to that of sustained hypertension.

Reliable quantification of the potential for equations based on spot urine samples to estimate population salt intake: protocol for a systematic review and meta-analysis.

Background Methods based on spot urine samples (a single sample at one time-point) have been identified as a possible alternative approach to 24-hour urine samples for determining mean population salt intake. Objective The aim of this study is to identify a reliable method for estimating mean population salt intake from spot urine samples. This will be done by comparing the performance of existing equations against one other and against estimates derived from 24-hour urine samples. The effects of factors such as ethnicity, sex, age, body mass index, antihypertensive drug use, health status, and timing of spot urine collection will be explored. The capacity of spot urine samples to measure change in salt intake over time will also be determined. Finally, we aim to develop a novel equation (or equations) that performs better than existing equations to estimate mean population salt intake. Methods A systematic review and meta-analysis of individual participant data will be conducted. A search has been conducted to identify human studies that report salt (or sodium) excretion based upon 24-hour urine samples and spot urine samples. There were no restrictions on language, study sample size, or characteristics of the study population. MEDLINE via OvidSP (1946-present), Premedline via OvidSP, EMBASE, Global Health via OvidSP (1910-present), and the Cochrane Library were searched, and two reviewers identified eligible studies. The authors of these studies will be invited to contribute data according to a standard format. Individual participant records will be compiled and a series of analyses will be completed to: (1) compare existing equations for estimating 24-hour salt intake from spot urine samples with 24-hour urine samples, and assess the degree of bias according to key demographic and clinical characteristics; (2) assess the reliability of using spot urine samples to measure population changes in salt intake overtime; and (3) develop a novel equation that performs better than existing equations to estimate mean population salt intake. Results The search strategy identified 538 records; 100 records were obtained for review in full text and 73 have been confirmed as eligible. In addition, 68 abstracts were identified, some of which may contain data eligible for inclusion. Individual participant data will be requested from the authors of eligible studies. Conclusions Many equations for estimating salt intake from spot urine samples have been developed and validated, although most have been studied in very specific settings. This meta-analysis of individual participant data will enable a much broader understanding of the capacity for spot urine samples to estimate population salt intake.

Rabdomiólisis por hipopotasemia severa

Rhabdomyolysis results from acute necrosis of skeletal muscle fibers and consequent leakage of muscle constituents into the circulation. It ranges from an asymptomatic state to a severe condition associated with extreme elevations in creatine kinase and acute renal failure. Reported etiologies of rhabdomyolysis include alcohol abuse, drugs, muscle trauma and muscle overexertion. Less common causes include muscle enzyme deficiencies, electrolyte abnormalities, infectious causes, toxins and endocrine disorders. Hypokalemia is a rare cause of rhabdomyolysis. We report six patients aged 31 to 57 years (three women) with a severe hypokalemic rhabdomyolysis, secondary to chronic diarrhea in two patients, treatment with loop diuretics in one and Gitelman syndrome in three. Rhabdomyolysis may be underdiagnosed in the context of hypokalemia, because the neuromuscular symptoms can be attributed solely to the electrolyte disorder.

Calcium citrate improves the epithelial-to-mesenchymal transition induced by acidosis in proximal tubular cells

INTRODUCTION Epithelial-to-mesenchymal transition (EMT) is a key event in renal fibrosis. The aims of the study were to evaluate acidosis induced EMT, transforming-growth-factor (TGF) β1 role and citrate effect on it. METHODS HK2 cells (ATCC 2290) were cultured in DMEM/HAM F12 medium, pH 7.4. At 80% confluence, after 24 hr under serum free conditions, cells were distributed in three groups (24 hours): A) Control: pH 7.4, B) Acidosis: pH 7.0 and C) Calcium citrate (0.2 mmol/L) + pH 7.0. Change (Δ) of intracellular calcium concentration, basal and after Angiotensin II (10-6M) exposition, were measured to evaluate cellular performance. EMT was evaluated by the expression of α-smooth muscle actin (α-SMA) and E-cadherin by immunocytochemistry and/or Western blot. TGF-β1 secretion was determined by ELISA in cell supernatant. RESULTS At pH 7.0 HK2 cells significantly reduced E-cadherin and increased α-SMA expression (EMT). Supernatant TGF-β1 levels were higher than in control group. Calcium citrate decreased acidosis induced EMT and improved cells performance, without reduction of TGF-β production. CONCLUSIONS Acidosis induces EMT and secretion of TGF-β1 in tubular proximal cells in culture and citrate improves cellular performance and ameliorates acidosis induced EMT.