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Background: Essential hypertension arises from the combined effect of genetic and environmental factors. A pharmacogenomics approach could help to identify additional molecular mechanisms involved in its pathogenesis. Aim: The aim of SOPHIA study was to identify genetic polymorphisms regulating blood pressure response to the angiotensin II receptor blocker, losartan, with a whole-genome approach. Materials & methods: We performed a genome-wide association study on blood pressure response in 372 hypertensives treated with losartan and we looked for replication in two independent samples. Results: We identified a peak of association in CAMK1D gene (rs10752271, effect size -5.5 ± 0.94 mmHg, p = 1.2 × 10-8). CAMK1D encodes a protein that belongs to the regulatory pathway involved in aldosterone synthesis. We tested the specificity of rs10752271 for losartan in hypertensives treated with hydrochlorothiazide and we validated it in silico in the GENRES cohort. Conclusion: Using a genome-wide approach, we identified the CAMK1D gene as a novel locus associated with blood pressure response to losartan. CAMK1D gene characterization may represent a useful tool to personalize the treatment of essential hypertension. Original submitted 7 May 2014; Revision submitted 29 July 2014

Chronic kidney disease (CKD) is associated with various consequences to the cardiovascular system and metabolic profile. The classification into stages should be useful for the physician to anticipate and treat early the manifestations of this disease. We have reviewed the current evidence of the potential benefits from screening, monitoring and treating adult patients for CKD stages 1-3 to counter the progression of kidney damage towards end-stage renal disease. In particular, we advocate an integrated vision of kidney and cardiovascular diseases in clinical practice. A Medline/PubMed, Embase and Cochrane Library search from 2001 to 2013 was performed. All articles related to this topic were reviewed. The search strategy was limited to papers on adult patients in English and Italian. The resulting data was organized on the basis of the current guidelines (evidence-based medicine levels of evidence).

Objective: Evaluate the impact of antihypertensive drugs (AHD) on stroke and acute myocardial infarction (AMI) and death for 3 cohorts of patients: diabetics, high risk, and hypertensive. Methods: This was a retrospective cohort obervational study based on administrative database of 7 Italian Local Health Units. Newly treated patients with AHD were enrolled from 01/01/2004 to 06/30/2007. Drug utilization and incidence of death, stroke and AMI were measured until 12/31/2007. Results: The study enrolled 125,770 patients aged ≥ 18-year-old: 8516 diabetic, 8549 high risk, and 108,705 hypertensive. Diabetic and high risk patients were more frequently male (57.2%, 64.9% VS 46.6%) and older (66.4 ± 11.6, 67.5 ± 13.2 VS 61.6 ± 13.9) than hypertensive patients and were more treated with concomitant therapy. Drugs acting on the renin-angiotensin system were the more fre- quent choice in the three cohorts but with a dif- ferent prevalence (63.9%, 52.9%, 35.9% in dia- betic, hypertensive and high risk patients re- spectively). Adherent patients to AHD > 80% were 44.0% among diabetic patients, 48.4% among high risk, 35.2% among hypertensive. A Cox regression model showed that the risk of the combined outcome was determined by increasing age, male gender, presence of concomitant therapy, low adherence to AHD and first choice of AHD. Conclusions: An integrated analysis of prescription and hospital admission database has the great advantage that it uses routinely available data, it can be done quickly and by few staff, and it is less expensive than planned large scale survey.

Objective The present study investigated the effects of switching to different products of the same off-patent active substance (brand name or generic) on therapy discontinuation or substitution with another molecule of the same class, in patients with cardiovascular disease treated with statins and antihypertensives in a ‘real-world’ setting. Design A retrospective cohort study in a ‘real-world’ setting. Setting Analysis of data performed by integrating administrative databases that included approximately two million individuals who are assisted by the National Health System from three Local Health Units located in three different regions of Italy. Participants All patients aged ≥18 years with at least one prescription of simvastatin, ramipril or amlodipine in the period 1 January to 31 December 2010 were included and followed up for 2 years. Main outcome measures Prescription refills occurring during follow-up were evaluated. Frequency of discontinuation of therapy or substitution with another molecule of the same class (eg, from simvastatin to a different statin) during follow-up was identified. Results During follow-up, therapy discontinuation or substitution was found to be more frequent in patients switching to a different product of the same active substance compared with non-switching patients (11.5% vs 10.8% and 22.2% vs 20.8% (p=0.002), respectively, in the simvastatin group; 4.0% vs 3.5% and 24.6% vs 22.7% (p

Oral anticoagulant therapy is essential for the treatment and prevention of many thromboembolic disorders. The aim of the present study is to evaluate the level of anticoagulation intensity in patients treated with vitamin K antagonists (VKAs) in a clinical practice setting and to explore the relationship between anticoagulation intensity and adherence to VKA treatment. We conducted a retrospective cohort study using the administrative databases of three Italian Local Health Units. Patients were enrolled if they had filled at least one prescription for VKAs (ATC code B01AA) between January 1st, 2007 and June 30th, 2008. In the same period all determinations of the international normalised ratio (INR) were collected. The parameters evaluated were anticoagulation control and adherence to VKA treatment.The survey showed that only 47.9% and 56.3% of INR determinations, in VKA naïve and established patients respectively, were into the recommended range (2.0-3.0). Moreover, the percentage of INR determination below the recommended range was higher than the percentage of INR determination above the recommended range for both naïve and established patients. Moreover, adherence to VKA treatment was poor both in naïve and established patients and, consequently, anticoagulation control is poor. Also in patients with the highest adherence to VKA treatment, only about 60% of INR determinations were into the recommended range. Our findings evidence that the anticoagulation control in clinical practice settings is still unsatisfactory and it is necessary to evaluate interventions to increase the amount of time at which patients’ INR are within the recommended range.

Objective: To evaluate adherence to antihypertensive therapy (AHT) and the association between adherence to AHT, all-cause mortality, and cardiovascular (CV) morbidity in a large cohort of patients newly treated with antihypertensives in a clinical practice setting. Methods: An administrative database kept by the Local Health Unit of Florence (Italy) listing patient baseline characteristics, drug prescription, and hospital admission information was used to perform a population-based retrospective study including patients newly treated with antihypertensives, ≥18 years of age, with a first prescription between January 1, 2004 and December 31, 2006. Patients using antihypertensives for secondary prevention of CV disease, occasional spot users, and patients with early CV events, were excluded from the study cohort. Adherence to AHT was calculated and classified as poor, moderate, good, and excellent. A Cox regression model was conducted to determine the association among adherence to AHT and risk of all-cause mortality, stroke, or acute myocardial infarction. Results: A total of 31,306 patients, 15,031 men (48.0%), and 16,275 women (52.0%), with a mean age of 60.2 ± 14.5 years was included in the study. Adherence to AHT was poor in 8038 patients (25.7% of included patients), moderate in 4640 (14.8%), good in 5651 (18.1%), and excellent in 12,977 (41.5%). Compared with patients with poor adherence (hazard ratio [HR] = 1), the risk of all-cause death, stroke, or acute myocardial infarction was significantly lower in patients with good (HR = 0.69, P < 0.001) and excellent adherence (HR = 0.53, P < 0.001). Conclusions: These findings indicate that suboptimal adherence to AHT occurs in a substantial proportion of patients and is associated with poor health outcomes already in primary prevention of CV diseases. For health authorities, this preliminary evidence underlines the need for monitoring and improving medication adherence in clinical practice.

Large-scale clinical trials have shown that antihypertensive drugs reduce the risk for cardiovascular events. However, little is known about the effectiveness of these drugs in the primary care setting.The aim of this study was to investigate the frequency of cardiovascularevents during treatment with either of 2 of the most frequently prescribed antihypertensive drugs.This observational, longitudinal, cohort study considered the entirepopulation listed in the administrative databases of the Local Health Authority of Ravenna, Italy (356,000 residents). The demographic registry and the pharmaceutical and nosocomial databases were cross-linked to determine drug treatment, as well as the frequency of cardiovascular events on a patient-by-patient basis. Each patient aged18 years receiving a first prescription for amlodipine or enalapril in the period between January 1, 1996, and December 31, 2000, with ≥6 months of continuous treatment with the drug was included. The follow-up period varied from 6 months to 4.5 years.Of the 7500 patients analyzed (4092 women and 3408 men; mean[SD] age, 68.0 [12.4] years), 2231 (29.7%) were given amlodipine and 5269 (70.3%) were given enalapril. The observed rate of cardiovascular events was higher among patients treated with amlodipine (54 per 1000 patient-years vs 46 per 1000 patient-years; P = 0.007), with a hazard ratio 17% higher compared with enalapril (95% Cl, 5.0-24.0; P = 0.007). The result was also confirmed using Cox multivariate regression analysis. The combination of enalapril plus diuretic showed the lowest risk for cardiovascular events (0.73; 95% Cl, -36.0 to -16.0; P0.001).This analysis showed that treatment with enalapril was associatedwith a significantly lower frequency of cardiovascular events compared with amlodipine.

The objective of the research was to perform a clinical practice-based analysis of how long patients remain on various antihypertensive drugs. An administrative database listing of patient baseline characteristics, drug prescriptions, and hospital admissions was used. All new users of antihypertensive drugs,or =20 years of age, receiving a first prescription for diuretics, beta blockers, calcium channel blockers, angiotensin-converting enzyme inhibitors, or angiotensin II receptor antagonists between January 1, 2000, and December 31, 2000, were included and observed for 365 days. Persistence was defined as a duration of therapy273 days. A total of 14,062 patients were included in the study, 39.7% of whom remained on treatment (persistent patients). Persistent patients were more likely to be older, taking other drugs for concurrent disorders, hospitalized for cardiovascular diseases, and initially prescribed angiotensin II receptor antagonists. Persistent patients accounted for 80.6% of the overall cost for antihypertensive drugs. Factors associated with drug cost were age, pattern of persistence, number of prescribed classes, and specific medication at enrollment. Measuring persistence with treatment is needed to evaluate the appropriateness and the cost-effectiveness of drug use.

In spite of findings of large-scale clinical trials which showed an overall reduction of morbidity and mortality from coronary heart disease in patients treated with 3-hydroxy-3-metylglutaryl coenzyme-A reductase inhibitors (statins), relatively little is still known about the real prevalence of treatment in general practice setting, particularly in patients with a high cardiovascular risk. The objective of this study was to investigate among patients with cardiovascular risk profile estimated according to the Framingham Heart Prediction Risk Study, the percentage of those exposed to statins, and the proportion of patients reaching total cholesterol (TC) target levels. A cross-sectional analysis was conducted on a large cohort of patients listed in the administrative databases of the Local Health Unit of Ravenna (total resident population of 356,000). In 2001, every single patient who received a prescription for a statin, and/or with a recorded plasma TC level, and/or with a hospital admission for cardiovascular reasons (identified by ICD-9 code), and/or with a clinical appraisal based on the presence of cardiovascular risk factors, was defined eligible. Sebsequently, pharmaceutical, and nosocomial databases, were cross-linked with that of 50 general practitioners in order to assess the pharmacoutilization of statins on a patient-by-patient basis. A cohort of 9,208 patients with a well documented cardiovascular risk profile were analyzed. The mean age of those patients was 57 (SD=17) years and 42% of them was male. On the basis of raised TC levels and cardiovascular risk profiles, patients for whom a statin treatment was suggested amounted to 7,233. However, the number of those who received statins was significantly lower (n = 1,343), corresponding to 18.6%. In those exposed to statins, just a small group of patients reached a level of TC below 190 mg/dl (n = 271), equivalent to 20.2%. In the group of treated who did not achieve recommended TC target levels, 31.7% (n = 340) of patients was at very high cardiovascular risk. Moreover, among all patients with high plasma TC levels (n=5,890), there was a 45.7% (n = 2,690) who did not received any lipid lowering drug even though they had a high cardiovascular risk profile. Results from large population-based administrative databases suggest a remarkable level of undertreatment among patients with cardiovascular risk factors. Furthermore, many patients did not achieve recommended TC target levels with their statin treatment. Pharmacoutilization of statins in general practice reveals the need of a more careful pursuing of therapeutic goals.

A new class of anti-inflammatory agents, the selective inhibitors of cyclooxygenase-2 (COXIBs), has been recently introduced into the market for the treatment of osteoarthritis and reumatoid arthritis. Randomized and controlled clinical trials showed a similar efficacy and a better tolerability profile of COXIBs compared with conventional non-steroidal anti-inflammatory drugs (NSAIDs). The aim of this study was to perform a scientific literature review relating to the economic impact produced by COXIBs’ introduction. The research of references included the following databases: MEDLINE, EMBASE and the NHS (Economic Evaluation Database) of the York University. A total of 67 in extenso pubblications have been extracted. Of these 13 papers having the specific objective to evaluate the economic implications of COXIBs in comparison to conventional NSAIDs was analysed. In ten cases (77%), cost-effectiveness analyses were performed. The European context was considered in eight cases (62%), while that of North America and Asia were investigated in four and one case, respectively. The analysis of costs took always into account direct costs of the management of arthritis exclusively (drugs, and resources associated with the treatment of gastrointestinal side effects). Indirect and intangible costs were never considered. The results of this review highlight that the higher tollerability profile of COXIBs may generate a cost-saving. This cost-saving seems to be basically due to the reduced frequency of gastroprotective agents coprescription and also to a lesser appearance of severe gastrointestinal side effects compared with conventional NSAIDs. Besides the disease management improving, the cost-saving associated with COXIBs can completely or partially offset the net increase of expense induced by their higher price of purchase.

The aim of the paper was to perform a pharmacoepidemiological and pharmacoeconomic analysis of antihypertensive drug treatment. An administrative database kept by the Local Health Unit of Ravenna listing patient baseline characteristics, drug prescriptions and hospital admissions was used to perform a population-based cohort study. The study included all new users of antihypertensive drugs, 20 years of age or over receiving a first prescription for diuretics, beta-blockers, calcium channel-blockers, ACE inhibitors or angiotensin II antagonists (AIIAs) between January 1st, 2000 and December 31st, 2000. All prescriptions for anti-hypertensive drugs filled during the 12-months follow-up period were considered. Patients were classified as continuers, switchers and discontinuers on the basis of their prescription dynamics. A total of 14.062 patients were included in the study of whom only 39,7% resulted persistent at 12 months. Patients initially prescribed for AIIAs were more likely to continue antihypertensive treatment than those started on other drug classes as well as those with older age, concurrent drug therapies and previous hospitalisation for cardiovascular diseases. The overall cost of the study cohort for antihypertensive drugs amounted to 1.238.752,37 euros of which 80,6% was used for persistent patients. The annual average cost for antihypertensive drugs was 171,73 euro for continuers, 205,10 euros for switchers and 28,29 euros for discontinuers. Factors associated to drug cost were age, pattern of persistence, number of prescribed drug classes, and class prescribed at enrolment. Nonpersistence with antihypertensive pharmacotherapy induced a high cost for the consumption of antihypertensive drug since discontinuers are responsible for a significant percentage of drug resources allocated on subjects exposed to therapy. A correlation between drug therapy cost and persistence with treatment is needed to evaluate the appropriateness of drug utilization and to perform cost-effectiveness analyses between alternative pharmacological agents.

In this study, the persistence with treatment and resources allocated in antihypertensive pharmacotherapy has been evaluated. Administrative databases of the Local Health Unit of Ravenna listing patients baseline characteristics, drug prescriptions and hospital admissions were used to perform a population-based retrospective study. All new users 20 years old or over receiving a first prescription for diuretics, beta-blockers, calcium channel-blockers, ACE inhibitors or AII-Antagonists between January 1st, 1997 and December 31st, 1997 were included. A one-year follow-up for prescriptions of anti-hypertensive drugs were considered. According to duration of therapy, treated population was divided in persistent patients (continuers and switchers) and non-persistent patients. A total of 16,783 patients was included in the study of whom 64.9% were non-persistents. Persistence with treatment seems to be associated with the class of anti-hypertensive drug initially prescribed, and with patient-related factors. Patients initially prescribed for AII-Antagonists were more likely to persist than those starting on the other antihypertensive classes. Annual antihypertensive treatment cost accounted for • 1,076,053.55 of which 25.4% for non-persistent patients. An appropriate use of claims data may be considered as a powerful tool, providing detailed epidemiological and economic information concerning the antihypertensive treatment.

The Pandora Project is a longitudinal database--implemented by general practitioners since June 1997 in the Ravenna area (Italy)--providing information on patients with hypertension. Data from 1,651 patients were followed up for I year in order to investigate the cost of hypertension. Only direct medical costs were considered in the perspective of the National Healthcare System.At enrollment, 552 patients were classified as normotensive, 1,099 as hypertensive. After 1 year, among normotensive group, 352 patients remained normotensive and 200 became hypertensive; among hypertensive group, 323 patients became normotensive and 776 remained hypertensive. The average total cost per patient at follow-up was 779.59 Euros. About 46% of total cost was due to anti-hypertensive therapy, irrespective of the evolution of blood pressure levels registered, whilst other direct costs represented 54% of total patient cost in all cohorts. It is possible that co-morbidities play a significant role in this situation. Patient aged 80-89 years generate higher costs. Even if further investigation is needed on the burden of comorbidity on a per-patient cost of hypertension, this work provides evidence that the average total cost per patient is likely to increase with age and co-morbidities. Key words: cost-of-illness, costs, economics, hypertension.

Luca Degli Esposti, Stefania Saragoni, Stefano Buda, Ezio Degli EspostiClicon Srl Health, Economics and Outcomes Research, Ravenna, ItalyObjective: To investigate the criteria for prescribing a combination pill for hypertensive patients, and whether the combination pill improves medication adherence.Materials and methods: This was a retrospective cohort study, performed in three Italian local health units. We selected all adult subjects who received at least one prescription of antihypertensive drugs between September 1, 2011 and December 31, 2011 (the enrollment period). The date of the first antihypertensive claim was defined as the index date. For each patient, we documented the antihypertensive drug treatments and evaluated patients’ adherence to treatment, which was calculated, separately, as the proportion of days covered in the two 6-month periods preceding and following the index date. Only patients treated with olmesartan and/or amlodipine as a single therapy, or as a two-pill combination in the period prior the index date were included. Changes in adherence levels were compared in subjects who moved to the fixed combination of olmesartan/amlodipine after the index date and in subjects who did not.Results: A cohort of 21,008 subjects with a 6-month history of a prescription of olmesartan and amlodipine as two pills in a combination treatment, or as single-pill treatment, was obtained. Subjects treated with the two-pill combination treatment moved to the olmesartan/amlodipine fixed combination treatment more frequently than did subjects with a single-pill treatment (P

INTRODUCTION Venous thromboembolism (VTE) is a well-known complication of total hip replacement (THR) and total knee replacement (TKR). Various drugs have been introduced in an attempt to reduce the mortality as well as the short-term and long-term morbidity associated with the development of VTE. The aim of this study was to analyze drug utilization for thromboprophylaxis and the cost of illness in real clinical practice in patients with THR or TKR. MATERIALS AND METHODS A multicenter, retrospective, observational cohort study based on local health unit administrative databases was conducted. All patients (≥18 years old) discharged for THR/TKR procedures between January 1, 2007 and December 31, 2008 were included in the study. The date of first hospital discharge was the index date; patients were followed up for a period of 12 months. RESULTS A total of 10,389 patients were included: 3516 males (33.8%, 69.4 ± 10.4 years) and 6873 females (66.2%, 71.7 ± 9.0 years), of which 5483 (52.8%) were discharged for THR and 4906 (47.2%) for TKR. First antithrombotic treatments after discharge were enoxaparin (3937, 37.9%), heparin (3752, 36.1%), antiplatelet agents (658, 6.3%), vitamin K antagonists (276, 2.7%), fondaparinux (136, 1.3%), combinations (185, 1.8%), and no therapy (1445, 13.9%). Overall, we observed 2347 (22.6%) treatment changes; median duration of antithrombotic treatment was 23 days (range 11-47) for THR and 22 days (range 11-46) for TKR. During the follow-up period, we observed 129 cases of VTE (120 per 10,000 patients), five post-thrombotic syndrome (4.8 per 10,000 patients), and three heparin-induced thrombocytopenia (2.9 per 10,000 patients). Median cost for both THR and TKR was €9052.00 (range €8063.00-€9084.96), with a median length of stay of 9.0 days (range 6.0-12.0).

The primary aim of the STAR Study (Statins Target Assessment in Real practice) was to determine the LDLcholesterol reduction and to analyse patient’s and therapeutic factors associated to LDL-cholesterol target attainment in newly treated subjects with statins in an unselected population in clinical practice setting. Administrative databases (including pharmaceutical prescriptions and hospital admissions) and laboratory test databases (including LDL-cholesterol values) of five Local Health Units, distributed in Emilia Romagna, Toscana and Umbria, were linked. A retrospective cohort study was conducted and all subjects aged ≥18 years with a first prescription for statins (newly treated subjects) between January 1st, 2007 and June 30th, 2008 were included. All statin prescriptions over a 12 months follow-up period were considered and used to calculate adherence to treatment. Baseline and follow-up LDL-cholesterol, respectively, were defined according to the nearest determination to the first prescription for statins and to the end of the follow-up period. A total of 3.232 subjects was included, 1.516 males (47%) and 1.716 females (53%), with an average age equal to 65,9 ± 11,3 years. Among included subjects, 22,6% had a gap to LDL-cholesterol target

Luca Degli Esposti, Stefania Saragoni, Stefano Buda, Ezio Degli Esposti Health, Economics and Outcome Research, Clicon Srl, Ravenna, ItalyObjectives: To compare clinical outcomes and health care costs across three cohorts of uncontrolled diabetic patients who initiated treatment with one of the following: sulphonylureas (SU), thiazolidinediones (TZD) or sitagliptin (SITA).Materials and methods: We performed a retrospective study based on a linkage between administrative and laboratory databases maintained by three Italian local health units. The index period ranged from July 2008–June 2010. Patients were treatment-naïve to either SU, TZD, or SITA, but they were already treated with other oral hypoglycemic agents. Demographics and clinical characteristics were assessed at baseline. Adherence was measured by the medication possession ratio and adherent was defined a patient with a medication possession ratio of 80% or greater. We used a Poisson regression model to estimate the risk ratios for disease-related hospitalizations that occurred during the 18-month follow-up period. The total annual costs included all the pharmacological treatments and the direct costs due to hospitalizations and outpatient services.Results: We identified 928 patients treated with SU, 330 patients treated with TZD, and 83 patients treated with SITA. SITA patients were significantly younger and with fewer previous hospital discharges. The baseline mean glycated hemoglobin level was 8.1% for SU, 8.0% for TZD, and 8.3% for SITA patients. SITA-naïve patients resulted more adherent than the SU- and TZD-naïve patients (79.5% versus 53.2% and 62.8%, respectively; P

The Pandora Project was designed to develop a computer-assisted system to improve the appropriateness and effectiveness of hypertension treatment in clinical practice and to organize a database both for epidemiologic and economic assessments. The feasibility study was conducted by five general practitioners (GP) who enrolled 244 patients over a period of 6 months. The follow-up lasted 6 months. The computer system implemented provided a linkage among GP's office, hypertension unit, Ravenna Health Service databases, and a remote station. A total of 209 patients completed the follow-up period; 56% of patients were not normotensive despite the antihypertensive treatment. The prevalence of overweight, physical inactivity, and family history of high blood pressure and hypercholesterolemia was greater than 50%. Unplanned check-ups by GP occurred 9%. Six patients were admitted to the hospital eight times; 19 patients attended the casualty department 21 times. The mean total direct cost per patient was 567,800 Italian Lire (ITL) and increased to ITL 732,000 or to ITL 825,900 when lost productivity, calculated according to two different formulas, was added. This pilot study confirms the need and feasibility of implementing the Pandora Project in general practice in Ravenna.

Objective: To perform a time-trend analysis of adherence and cost of antihypertensive treatment over four years. Methods: A population-based retrospective cohort study was conducted. We included subjects ≥18 years, and newly treated for hypertension with diuretics, beta-blockers, calcium channel blockers, angiotensin-converting enzyme inhibitors, or angiotensin receptor blockers between 01 January 2004 and 31 December 2007. One-year adherence to antihypertensive therapy was calculated and classified as low, low-intermediate, intermediate, high-intermediate, and high. The direct cost of antihypertensive medications was evaluated. Results: We included data for a total of 105,512 patients. The number of newly treated subjects decreased from 27,334 in 2004 to 23,812 in 2007, as well as antihypertensive drug therapy cost which decreased from €2,654,166 in 2004 to €2,343,221 in 2007. On the other hand, in the same time frame, the percentage of adherent newly treated subjects increased from 22.9% to 28.0%. Compared with subjects initiated on angiotensin receptor blockers (odds ratio [OR] = 1), the risk of nonadherence was higher in those initiated on angiotensin-converting enzyme inhibitors (OR = 1.19), combination therapy (OR = 1.44), beta-blockers (OR = 1.56), calcium channel blockers (OR = 1.67), and diuretics (OR = 4.28). Conclusions: The findings of the present study indicate that suboptimal adherence to antihypertensive medication occurs in a substantial proportion of treated patients, and improvements in treatment adherence were obtained but are still unsatisfactory.

Increased sodium-lithium countertransport activity in red cells of IgA nephropathy patients. The aim of this work was to analyze Na,Li countertransport activity in the erythrocytes from patients with IgA nephropathy, in relationship with their blood pressure status and lipid profile Forty-nine patients (32 males, 17 females) with biopsy-proven IgA nephropathy and without significant impairment of renal function (serum creatinine ≤ 1.4 mg/dl) and 36 normal subjects (21 males, 15 females) were evaluated Twenty-nine patients with IgA nephropathy were normotensive and 20 hypertensive (diastolic pressure ≥ 95 mm Hg or treated by antihypertensive drugs). Na,Li countertransport was significantly higher in red cells from hypertensive than from normotensive patients (P = 0.002) and normal subjects (P = 0.0001), (values respectively 309 ± 17; 241 ± 12 and 211 ± 11 µmol/liter RBC/hr); normotensive patients with IgA nephropathy did not differ from controls regarding the Na,Li countertransport rate. A multiple stepwise logistic regression analysis with blood pressure status as the dependent variable and Na,Li countertransport activity, age, serum creatinine, proteinuria, cholesterol, triglycerides, plasma potassium and time from onset as independent variables, indicated an independent significant association for Na,Li countertransport (P = 0.002) proteinuria (P = 0.006), plasma potassium (P = 0.006) and age (P = 0.029). Other tested variables were not independently related to blood pressure status. Hyperlipidemic patients (plasma total cholesterol concentration >200 mg/dl and/or plasma triglycerides >172 mg/dl) had an erythrocyte Na,Li countertransport activity significantly higher than normolipidemic (P = 0.005) and controls (P = 0.001) (values respectively 295 ± 14; 226 ± 12 and 211 ± 11 µmol/liter RBC/hr). A high erythrocyte Na,Li counter-transport rate may be a marker of an increased risk of developing arterial hypertension, lipid abnormalities, and perhaps a more severe renal disease in IgA nephropathy.

The stabilization of systemic blood pressure is one of the most challenging tasks in the management of uremic patients. Continuous ambulatory peritoneal dialysis (CAPD) is associated with the development of hypotension in some patients [1–3]. Several pathogenetic mechanisms may be responsible for this type of dialysis-associated hypotension. Several authors have reported on the presence of autonomic dysfunction in uremic patients [4–8], and it has been postulated as a cause of hemodialysis-induced hypotension [4–8]. However, Marquez-Julio et al [3] have suggested that hypotension in CAPD patients may be due to the combined effect of an increased removal of sodium chloride and water and the loss of large concentrations of vasoconstrictive substances. In recent years, CAPD has been performed in a rapidly increasing number of diabetic patients with endstage renal disease [9]. It is well known that autonomic neuropathy is a long-term complication of diabetes mellitus [10–12]. The present study was undertaken first, to clarify whether or not hypotension in nondiabetic and diabetic CAPD patients is related to autonomic neuropathy and second, to see whether or not a functional lesion of the autonomic nervous system may be induced by peritoneal dialysis "per se".