J. J. De La Cruz

Phase I-II Study of Paclitaxel, Cisplatin, and Gemcitabine in Advanced Transitional-Cell Carcinoma of the Urothelium

PURPOSE To determine the maximum-tolerated dose and the antitumor activity of a combination of paclitaxel, cisplatin, and gemcitabine in advanced transitional-cell carcinoma (TCC) of the urothelium. PATIENTS AND METHODS Patients with measurable, previously untreated, locally advanced or metastatic TCC and with Eastern Cooperative Oncology Group performance status < or = 2 and creatinine clearance > or = 55 mL/min were eligible. Cisplatin was given on day 1 at a fixed dose of 70 mg/m(2). Paclitaxel and gemcitabine were given on days 1 and 8 at increasing dose levels. Cycles were repeated every 21 days to a maximum of six cycles. RESULTS Sixty-one patients were registered. In phase I, 15 patients were entered at four different dose levels. Dose-limiting toxicity consisted of early onset (after the first cycle) grade 2 asthenia (two of six patients) and grade 3 asthenia (one of six patients) at dose level 4. A paclitaxel dose of 80 mg/m(2) and gemcitabine 1,000 mg/m(2) was recommended for phase II, and 46 additional patients were entered at this level for a total of 49 patients. Main nonhematologic toxicity was grade 2 asthenia in 18 patients, with early onset in five patients, and grade 3 in four patients. Grade 3/4 neutropenia and thrombocytopenia occurred in 27 (55%) and 11 (22%) patients, respectively. Overall, febrile neutropenia was seen in 11 patients, and one toxic death occurred because of neutropenic sepsis. The combination was active at all dose levels. In total, 58 of 61 eligible patients were assessable for response; 16 complete responses (27.6%) and 29 partial responses (50%) were observed for an overall response rate of 77.6% (95% confidence interval, 60% to 98%). The median survival time (MST) available for the phase I part of the study is 24.0 months. MST has not been reached for the whole group with the current follow-up. CONCLUSION This combination of paclitaxel, cisplatin, and gemcitabine is feasible and highly active in patients with advanced TCC of the urothelium. Further evaluation of this regimen in patients with TCC is warranted.

Systolic vs diastolic blood pressure: community burden and impact on blood pressure staging

Systolic blood pressure (SBP) is a more frequent cardiovascular risk factor than diastolic blood pressure (DBP), and has a greater impact on blood pressure staging, though this can vary with age, sex and country. Therefore this paper compares SBP and DBP in terms of community burden and impact on blood pressure staging, among Spains middle-aged population. Data were drawn from a cross-sectional study on a representative sample of the Spanish population aged 35–64 years. Blood pressure was determined under standardised conditions, and was classified as per WHO-ISH and JNC-VI criteria. Prevalence of SBP ⩾140 mm Hg was 34.1%, and that of DBP ⩾90 mm Hg, 30.9%. A total of 12% of subjects had isolated systolic hypertension (ISH) and 8.7% had isolated diastolic hypertension (IDH). Of treated hypertensives, 31% had their SBP controlled and 34% their DBP controlled. Of subjects not undergoing antihypertensive drug therapy, 60.8% had congruent SBP and DBP levels, 22.5% were up-staged on the basis of their SBP, and 16.7% were up-staged on the basis of their DBP. SBP alone thus correctly classified JNC-VI staging in 83.3% of subjects vs 77.5% for DBP alone. It was solely among the population >50 years of age, in both sexes, that systolic proved more frequent than diastolic hypertension, ISH greater than IDH prevalence, SBP worse than DBP control, and the percentage of SBP higher than that of DBP up-staged subjects. SBP constitutes a greater community burden than does DBP, and has a greater impact on blood pressure staging in Spains middle-aged population. However, the differential impact of SBP and DBP upon blood pressure burden and staging is favourable to SBP only among subjects >50 years old. These findings are in accordance with recent guidelines on hypertension management.

Dislipemia aterogénica: prevalencia y control en las unidades de lípidos

BACKGROUND AND OBJECTIVE Atherogenic dyslipidemia, which is characterized by increased triglyceride levels and reduced HDL cholesterol levels, is underestimated and undertreated in clinical practice. We assessed its prevalence and the achievement of therapeutic objectives for HDL cholesterol and triglyceride levels in patients treated at lipid and vascular risk units in Spain. PATIENTS AND METHOD This was an observational, longitudinal, retrospective, multicenter study performed in 14 autonomous Spanish communities that consecutively included 1828 patients aged ≥18 years who were referred for dyslipidemia and vascular risk to 43 lipid clinics accredited by the Spanish Society of Arteriosclerosis. We collected information from the medical records corresponding to 2 visits conducted during 2010 and 2011-12, respectively. RESULTS Of the 1649 patients who had a lipid profile in the first visit (90.2%), 295 (17.9%) had atherogenic dyslipidemia. The factors associated with atherogenic dyslipidemia were excess weight/obesity, not taking hypolipidemic drugs (statins and/or fibrates), diabetes, myocardial infarction and previous heart failure. Of the 273 (92.5%) patients with atherogenic dyslipidemia that had a lipid profile in the last visit, 44 (16.1%) achieved the therapeutic objectives for HDL cholesterol and triglyceride levels. The predictors of therapeutic success were normal weight and normoglycemia. CONCLUSION One of every 6 patients treated in lipid and vascular risk units had atherogenic dyslipidemia. The degree to which the therapeutic goals for HDL cholesterol and triglyceride levels were achieved in these patients was very low.

Incidence and risk factors of superficial and deep vein thrombosis associated with peripherally inserted central catheters in children

Essentials Pediatric studies on peripherally inserted central catheter (PICC)‐related thrombosis are scarce. This study analyzes incidence and risk factors for PICC‐related venous thrombosis in children. PICC‐related thrombosis is a common, and nearly always, asymptomatic complication. Echo‐guided insertion and a catheter to vein ratio < 0.33 may notably decrease this complication.

Heart rate and heart rate variability in resistant versus controlled hypertension and in true versus white-coat resistance.

Sympathetic nervous system has an important role in resistant hypertension. Heart rate (HR) is a marker of sympathetic activity, but its association with resistant hypertension has not been assessed. We aimed to evaluate differences in HR values and variability between resistant and controlled patients and between true and white-coat resistant hypertensives (RHs). We compared office and ambulatory HR, nocturnal dip and s.d. in 14 627 RHs versus 11 951 controlled patients (on ⩽3 drugs) and in 8730 true (24 h blood pressure (BP)⩾130 and/or 80 mm Hg) versus 4825 white-coat (24-h BP<130/80 mm Hg) RHs. After adjusting for age, gender, body mass index, diabetes status and beta blocker use, HR values and variability were significantly elevated in resistant versus controlled patients and in true versus white-coat RHs. In logistic regression models, after adjustment for confounders, office HR (odds ratio for each increase in tertile: 1.337; 95% confidence interval: 1.287–1.388; P<0.001), nocturnal dip (0.958; 0.918–0.999; P=0.035) and night time s.d. (1.115; 1.057–1.177; P=0.013) were all significantly associated with the presence of resistant hypertension. Moreover, night time HR (1.160; 1.065–1.265; P<0.001), nocturnal dip (0.876; 0.830–0.925; P<0.001) and 24-h s.d. (1.148; 1.092–1.207; P<0.001) were all significantly associated with true resistant hypertension. In conclusion, both increased HR and variability are associated with resistant hypertension and with true resistance. These suggest the involvement of the sympathetic nervous system in the development of resistance to antihypertensive treatment.

TRENDS IN ALBUMINURIA UNDER RENIN-ANGIOTENSIN SYSTEM SUPPRESSION: HT.3.05

Introduction: RAS suppression is considered as the therapy of choice, together with a strict BP control, to prevent the development and to impede the progression of albuminuria. Objective: We have reviewed the evolution of albuminuria in a group of 1433 patients (mean age 60.5 yr; 50.3% male), arriving in our unit as a consequence of arterial hypertension with varying degrees of associated cardiovascular risk factors. All had in common the existence of previous therapy with an ACEi or an ARB for a minimum of two years before arrival in the Unit. Results: When first seen 67.7% were normoalbuminuric (albumin-to-creatinine ratio [ACR] <10 mg/g for male, <15 mg/g for female), 11.9% exhibited high-normal values of albuminuria (ACR 10–20 mg/g for male, 15–30 mg/g for female), 16.4% were microalbuminuric (ACR 20–200 mg/g for male, 30–300 mg/g for female) and 4% had macroalbuminuria (ACR >200 mg/g for male, >300 mg/g for female). At that time measured creatinine clearance was 96.8 ± 49.6 and 54.1% had BP values below 140/90 mmHg. All of them were followed for three years during which RAS suppression was maintained, while BP control improved. At the end of follow-up, only 54.9% were normoalbuminuric, 16.1% presented high-normal albuminuria, 21.6% were microalbuminuric and 7.4% macroalbuminuric (p < 0.004). The changes were seen in non-diabetic (p < 0.005) but were more marked in diabetics with only 37.5% of patients being normoalbuminuric. Conclusions: These results indicate that albuminuria develops in the presence of chronic RAS suppression at adequate doses and progresses continuously. Long-term RAS suppression needs to be revisited in order to control this alteration.

EFFECTS OF AIR POLLUTION IN 24H AMBULATORY BLOOD PRESSURE MONITORING

Objective: INTRODUCTION: Air particulate matters and nitrogen and sulfur dioxide are the most worrying environmental pollutants, with the greatest impact on public health. There are studies that relate atmospheric pollution with the increase in office blood pressure, but there is no study that relates air pollution with 24 h ambulatory blood pressure (ABP). Objective: To know the relationship between ABP and classic atmospheric pollutants (PM10, PM2,5, NO2 and SO2) and the most recent measurement (ultrafine particles, PUF). Design and method: Observational study of temporary and geographical measures of polluants in individual patients (case-time series design) in centers of Primary Care and Units of Hypertension of a large urban area. Untreated > 18 years hypertensive patients were included, with a first valid ABP monitoring (ABPM) conducted between 2005–2014 and with at least one atmospheric pollution reader at < 3 km of radius of the center where the ABPM was performed. Analysis of regression of temporal series adjusted by individual variables (sociodemographic and risk factors) and ecological (environmental temperature). Results: Sample of 2,888 hypertensive patients. Mean age of 54.3 (SD 14,6) years and 50,1% are women. Body Mass Index (BMI) 28.8 kg/m2 (SD 6.4) and 16.9% of the sample smokes. Baseline 24 h ABPM 128.0 (12.7)/77.4 (9.7) mmHg. For each increase of 10 mg/m3 of PM10 an increase of 1.37 mmHg in 24 h diastolicBP (DBP) and 1.48 mmHg in daytime-DBP was observed, statistically significant. For each increase of 1 mg/m3 of PUF 24 h DBP increases in 1.46 mmHg and daytime-DBP in 1.56 mmHg, statistically significant. The calculation was adjusted by temporal variables of ABPM measures, sociodemographic variables and risk factors, and by environmental temperature. No association was found with any of the two pollutants and nighttime-DBP. No statistical relationship was detected between the PM2.5, NO2 and SO2 pollutants and ABPM, nor between any air pollutants and the office BP. Conclusions: The increase in the atmospheric concentration of PM10 and PUF particles the day prior to ABPM is significantly associated with an increase in 24 h DBP and daytime-DBP.

BLOOD PRESSURE (BP) OUTCOME IN PATIENTS WITH SECONDARY ANEMIA IN PERITONEAL DIALYSIS TREATED WITH METOXIPOLIETILENGLICOL-EPOETINA (MIRCERA®) (CAPRI STUDY): PP.9.379

Objectives: To study the outcome of BP in patients with secondary anemia related to End Stage Renal Disease (ESRD) in peritoneal dialysis (PD), treated with MIRCERA. Methods: Observational and prospective study performed in PD patients of several hospitals in Catalonian. We included 49 patients naive or treated previously with darboepoetina or Beta epoetina. They started MIRCERA after beginning PD, and we performed a follow-up of demographical and analytical data and BP for a 6 months. Results: Between the 49 patients, 17 are male (34.7%). Age = 58.5 ± 15.6 years. The etiology of ESRD was glomerulopathy 32,7%, in 28.6% Diabetes Mellitus,16.3% unknown, 10.2% polychystosis and other etiology: 12,2%. 14 have cardiovascular disease, 20 hypercholesterolemia,1 cerebrovascular disease and 2 oncological events. 65.3% patients start PD as first treatment, 18.4 % come from hemodialysis and 16.3% from kidney transplant failure. 93.9% have high BP, 85.7% on pharmacological treatment. 14 were treated with ACEI, 4 with ARAII and 20 with diuretics. The starting dose of Mircera was 50 μg once monthly in 4.1%, 75 in 26.5%, 100 μg in 24.5%, 150 μg in 20.4%, 200 in 10.2% and 250 in 8.2% of cases. We observe that 29.8% have Hb levels <11 g/dl, 51.1% between 11–12.99 g/dl and 19.1% ± 13 g/dl at the beginning of the study. At 6 months the distribution was 19.1%, 53.2% and 27.7% respectively and no significance differences were found. There were no differences in Mircera doses between the patients treated with ACEI or ARA II and they treated with other drugs. If we consider hypertension as SBP ± 140 and DBP ± 90 mmHg, at the beginning 63.3% were hypertensive and 49.0% (p = 0.046)at the end. Only 2 patients with initial normal BP (140/90) have an increase at 6months. 9 patients with initial hypertension decrease BP levels to normal range; (p global = 0.065, p per groups of doses = 0.859)).Table 2 Figure 1. No caption available. Figure 2. No caption available. Conclusions: Treatment with MIRCERA in PD patients allows a good control of anaemia without negative influence in the control of BP.

CONCORDANCE OF BP CONTROL ASSESSED BY OFFICE BP AND BY ABPM IN A LARGE COHORT OF TREATED HYPERTENSIVES: PP.14.06

Objective: To examine the concordance of blood pressure (BP) control by means of both office measurements and ambulatory BP monitoring (ABPM), in a large cohort of treated hypertensives from the Spanish Society of Hypertension ABPM Registry. Methods: A total of 43,499 hypertensives were analyzed. Office BP control was defined when BP <140/90 mmHg. Ambulatory BP control was considered by means of 3 different criteria: daytime BP <135/85 mmHg, 24-h BP <130/80 mmHg, and nightime BP <120/70 mmHg. Clinical characteristics were compared between patients with daytime BP below or above 135/85 mmHg. Results: Office BP control was 22.7%, daytime BP control was 52.0%, 24-h BP control was 44.8%, and nighttime BP control was 39.7%. Concordant control of BP was present in 17.4%, 15.7%, and 12.9%, by the 3 different criteria. The main source of difference between office and ABPM was the proportion of patients with isolated office resistance, the proportion of which, using the 3 aforementioned criteria was 34.5%, 29.1%, and 26.8%, respectively. When compared to patients with normal ABPM values, the presence of elevated daytime BP (higher than 135/85 mmHg) was associated (p < 0.001 for all comparisons) with male gender (57.5% vs 47.7%), diabetes (25.1% vs 20.9%), smoking (17.5% vs 12.5%), left ventricular hypertrophy on EKG (11.1 vs 9.1), and chronic kidney disease (3.0% vs 2.0%). Conclusions: BP control in the treated hypertensive population by using ABPM is twice as observed by office measurements. The proportion of patients with isolated office resistance (white coat) is relatively large. Normal values of ABPM in treated patients are more frequent in women, nondiabetic, and nonsmokers subjects, as well as in those without organ damage.

HOW HYPERCHOLESTEROLEMIA INFLUENCES ON BLOOD PRESSURE AND VASCULAR RISK PROFILE IN TREATED HYPERTENSIVE PATIENTS: PP.23.449

Objective: To assess the influence of hypercholesterolemia on 24-h blood pressure (BP) and vascular risk in hypertensive patients. Methods: We analyzed data from the Spanish Society of Hypertension ABPM Registry. Hypercholesterolemia was defined as a serum LDL-cholesterol ≥165 mg/dl or current treatment with statins. Definitions for other variables and risk stratification followed 2007 ESH-ESC guidelines. ABPM was performed under standardized conditions and conventional thresholds for ambulatory BP and definition of a non dipping BP were applied. Results: We identified 9,805 subjects with hypercholesterolemia. Mean age (SD) was 64.1 (11.0) and 53.7% were men. Control rates of ambulatory BP were 49.6% (24-h), 57.3% (daytime), and 41.7% (nighttime) despite a widespread use (71.3%) of antihypertensive combinations. A non-dipper pattern of BP was present in 61.5% of subjects. Among those treated with statins, the proportion of patients showing a serum LDL-cholesterol <100 mg/dl was 11.8%. Prevalences of concomitant risk factors and organ damage were smoking 13.2%, diabetes 35.2%, obesity 40.7%, left ventricular hypertrophy 14.0%, radiological evidence of atherosclerosis 9.1%, microalbuminuria 11.8%, coronary heart disease 16.0%, cerebrovascular disease 9.3%, congestive heart failure 3.1%, and chronic kidney disease 4.5%. Consequently, prevalence of patients stratified as having high or very high added risk was 74.4%. Conclusions: Hypercholesterolemia identified hypertensive patients with a 75% likelihood of being at high or very high added cardiovascular risk. More than 50% of hypercholesterolemic hypertensives had their ambulatory BP undercontrolled. Only 53.6% of these patients were receiving statins, being very low (11.8%) the control rate of LDL-cholesterol. Additional efforts should be done for control of global cardiovascular risk in hypertensive patients with hypercholesterolemia.