Single nucleotide polymorphism (SNP) rs4291 of the angiotensin-converting enzyme (ACE) gene is associated with the response to losartan treatment in hypertensive patients.

Arterial hypertension is characterized by systolic pressure ≥ 140 mmHg and/or diastolic pressure ≥ 90 mmHg and its treatment consists of the use of antihypertensive drugs, as losartan and hydrochlorothiazide. Blood pressure is regulated by angiotensin-converting enzyme (ACE) and polymorphisms in the ACE gene are associated to a greater predisposition to hypertension and response to treatment. The aim of this study was to evaluate the association of genetic polymorphisms of ACE rs4363, rs4291 and rs4335 and the response to antihypertensive drugs in hypertensive patients from Ouro Preto/MG, Brazil. A case-control study was carried out with 87 hypertensive patients being treated with losartan and 75 with hydrochlorothiazide, who answered a questionnaire and had blood samples collected. Biochemical analyzes were performed on serum using UV/Vis spectrophotometry and identification of ACE variants rs4363, rs4291 and rs4335 was performed by real-time PCR using the TaqMan® system. Univariate logistic regression test was performed to compare categorical data in STATA 13.0 software. The results showed that there was an influence of ACE polymorphisms on the response to losartan, demonstrating that AT or TT genotypes of rs4291 were more frequent in the group of controlled AH (54.9%), indicating that these individuals are 2.8 times more likely to of being controlled AH (95% CI 1.12-6.80, p. =0.026) compared to those with AA genotype. In contrast, no influence of ACE polymorphisms on the response to hydrochlorothiazide was observed. In conclusion, the presence of the T allele of the rs4291 variant was associated to controled blood pressure when losartan was used as an antihypertensive agent. These results show the importance of pharmacogenetic studies to detect genetic characteristics, enabling therapeutic individuality and reducing costs for the healthcare system.

Effect of adding hydrochlorothiazide to usual treatment of patients with acute decompensated heart failure: a randomized clinical trial.

Acute decompensated heart failure (ADHF) is the leading cause of hospitalization in patients aged 65 years or older, and most of them present with congestion. The use of hydrochlorothiazide (HCTZ) may increase the response to loop diuretics. To evaluate the effect of adding HCTZ to furosemide on congestion and symptoms in patients with ADHF. This randomized clinical trial compared HCTZ 50 mg versus placebo for 3 days in patients with ADHF and signs of congestion. The primary outcome of the study was daily weight reduction. Secondary outcomes were change in creatinine, need for vasoactive drugs, change in natriuretic peptides, congestion score, dyspnea, thirst, and length of stay. Fifty-one patients were randomized-26 to the HCTZ group and 25 to the placebo group. There was an increment of 0.73 kg/day towards additional weight reduction in the HCTZ group (HCTZ: - 1.78 ± 1.08 kg/day vs placebo: - 1.05 ± 1.51 kg/day; p = 0.062). In post hoc analysis, the HCTZ group demonstrated significant weight reduction for every 40 mg of intravenous furosemide (HCTZ: - 0.74 ± 0.47 kg/40 mg vs placebo: - 0.33 ± 0.80 kg/40 mg; p = 0.032). There was a trend to increase in creatinine in the HCTZ group (HCTZ: 0.50 ± 0.37 vs placebo: 0.27 ± 0.40; p = 0.05) but no significant difference in onset of acute renal failure (HCTZ: 58% vs placebo: 41%; p = 0.38). No differences were found in the remaining outcomes. Adding hydrochlorothiazide to usual treatment of patients with acute decompensated heart failure did not cause significant difference in daily body weight reduction compared to placebo. In analysis adjusted to the dose of intravenous furosemide, adding HCTZ 50 mg to furosemide resulted in a significant synergistic effect on weight loss.Trial registration: The Brazilian Clinical Trials Registry (ReBEC), a publically accessible primary register that participates in the World Health Organization International Clinical Trial Registry Platform; number RBR-5qkn8h. Registered in 23/07/2019 (retrospectively), http://www.ensaiosclinicos.gov.br/rg/RBR-5qkn8h/ .

Association of urinary sodium/potassium ratio with structural and functional vascular changes in non-diabetic hypertensive patients.

Studies aiming to associate the sodium/potassium (Na/K) ratio with hypertension use 24-hour urinary excretion as a daily marker of ingestion. The objective of this study was to evaluate the association between urinary Na/K ratio and structural and functional vascular alterations in non-diabetic hypertensive patients. In hypertensive patients (n = 72), aged between 40 and 70 years, both sexes (61% women), in use of hydrochlorothiazide, we measured blood pressure, 24-hour urine sample collection, assessment of carotid-femoral pulse wave velocity (cf-PWV, Complior), central hemodynamic parameters (SphygmoCor), and post-occlusive reactive hyperemia (PORH). The participants were divided according to the tertile of 24-hour urinary Na/K ratio. Each group contained 24 patients. Systolic blood pressure was higher in T2 (133 ± 9 vs 140 ± 9 mmHg, P = .029). C-reactive protein (CRP) presented higher values in T3 as compared to T1 [0.20(0.10-0.34) vs 1.19 (0.96-1.42) mg/dL, P < .001]. Higher values in T3 were also observed for aortic systolic pressure (aoSP) [119(114-130) vs 135(125-147) mmHg, P = .002] and cf-PWV (9.2 ± 1.6 vs 11.1 ± 1.5 m/s, P < .001). The urinary Na/K ratio presented significant correlations with proteinuria (r = .27, P = .023), CRP (r = .77, P < .001), cf-PWV (r = .41, P < .001), and post-occlusive reactive hyperemia on cutaneous vascular conductance (PORH CVC) (r = -.23, P = .047). By multivariate linear regression, it was detected an independent and significant association of cf-PWV with urinary Na/K ratio (R2  = 0.17, P < .001) and PORH CVC with CRP (R2  = 0.30, P = .010). Our data indicated that increased urinary Na/K ratio in non-diabetic hypertensive patients was associated with higher degree of inflammation, raised peripheral and central pressure levels, and changes suggestive of endothelial dysfunction and arterial stiffness.

Association of obstructive sleep apnea with arterial stiffness and nondipping blood pressure in patients with hypertension.

Whether sex influences the association of obstructive sleep apnea (OSA) with markers of cardiovascular risk in patients with hypertension is unknown. In this study, 95 hypertensive participants underwent carotid-femoral pulse wave velocity, 24-hour ambulatory blood pressure monitoring, echocardiogram, and polysomnography after a 30-day standardized treatment with hydrochlorothiazide plus enalapril or losartan. OSA was present in 52 patients. Compared with non-OSA patients, pulse wave velocity values were higher in the OSA group (men: 11.1±2.2 vs 12.7±2.4 m/s, P=.04; women: 11.8±2.4 vs 13.2±2.2 m/s, P=.03). The proportion of diastolic dysfunction was significant in men and women with OSA. Compared with non-OSA patients, nondipping systolic blood pressure in OSA was higher in men (14.3% vs 46.4%) and in women (41.4% vs 65.2%). OSA was independently associated with pulse wave velocity (ß=1.050; P=.025) and nondipping systolic blood pressure (odds ratio, 3.03; 95% confidence interval, 1.08-8.55; P=.035) in the regression analysis. In conclusion, OSA is independently associated with arterial stiffness and nondipping blood pressure in patients with hypertension regardless of sex.

Diuretic, natriuretic and potassium-sparing effect of nothofagin isolated from Leandra dasytricha (A. Gray) Cogn. leaves in normotensive and hypertensive rats.

Active constituents from natural origin have long been used for the treatment of patients suffering from cardiovascular and renal diseases. This study therefore aimed to investigate the diuretic and natriuretic properties of nothofagin, a dihydrochalcone isolated from Leandra dasytricha (A. Gray) Cogn. leaves in normotensive and hypertensive rats. Male Wistar normotensive rats were orally treated with vehicle (1 ml/kg); hydrochlorothiazide (HCTZ; 25 mg/kg); ethyl acetate fraction from L. dasytricha (EALD; 3-30 mg/kg) and nothofagin (NOT; 0.3-3 mg/kg). Spontaneously hypertensive rats (SHR) received NOT (1 mg/kg), HCTZ (25 mg/kg) or vehicle. The cumulative diuretic index, urinary electrolytes excretion (Na+ and K+), pH, density and conductivity were measured at the end of the experiment (after 8 h). A7r5 and L929 cell lines were used to measure cell viability after exposure to NOT. Nitric oxide generation was quantified in A7r5 cell supernatant, and DPPH assay was used for evaluating the antioxidant properties of NOT. The urinary volume of normotensive rats were increased after the treatment with EALD, without any changes in Na+ or K+ excretion. NOT was able to induce diuresis and natriuresis, but not kaliuresis, in both normotensive and hypertensive rats. The reduction in prostanoids generation through cyclooxygenase inhibition, as well as the muscarinic receptor antagonism, fully avoided NOT-induced increases in diuretic index. NOT, which did not interfere with L929 or A7r5 cell viability, was able to stimulate nitric oxide generation in A7r5 cell, besides showing an antioxidant effect in scavenging the free-radical DPPH. Taken together, our study shows, for the first time, the diuretic, natriuretic and potassium-sparing effect of nothofagin in rats, which was associated with prostanoids generation, muscarinic receptor activation and antioxidant properties.

An association of losartan-hydrochlorothiazide, but not losartan-furosemide, completely arrests progressive injury in the remnant kidney.

We have previously shown that an association of losartan and hydrochlorothiazide, initiated 1 mo after 5/6 nephrectomy (Nx), reversed hypertension and albuminuria and promoted lasting renoprotection. In this new study, we investigated whether equal or even better protection could be obtained by combining losartan and furosemide. Nx was performed in 58 Munich-Wistar rats. One month later, tail-cuff pressure and albuminuria were markedly elevated. At this time, Nx rats were distributed among the following four groups: untreated Nx rats, Nx rats that received losartan, Nx rats that received losartan + hydrochlorothiazide, and Nx rats that received losartan + furosemide. Seven months later, Nx rats exhibited high mortality, severe hypertension, albuminuria, glomerulosclerosis, and interstitial fibrosis. Losartan treatment limited mortality and attenuated the renal and hemodynamic abnormalities associated with Nx. As previously shown, the losartan + hydrochlorothiazide association normalized tail-cuff pressure and albumin, prevented renal injury, and reduced mortality to zero. The losartan + furosemide treatment failed to reduce tail-cuff pressure or albumin to normal and prevented renal injury less efficiently than the losartan and hydrochlorothiazide regimen. The reasons for the differing efficacies of the losartan + furosemide and losartan + hydrochlorothiazide schemes are unclear and may include beneficial nondiuretic actions of thiazides, such as vasorelaxation and antiproliferative activity. These results refute the established concept that thiazides and thiazide-like diuretics are ineffective at advanced chronic kidney disease stages. Rather, they suggest that, in view of their renoprotective action, these compounds may even be preferable to loop diuretics in the management of hypertension in advanced chronic kidney disease.

Antihypertensive therapy increases natural immunity response in hypertensive patients.

AIMS: The aim of this work was to evaluate the effects of treatment of hypertension on the autoantibodies to apolipoprotein B-derived peptides (anti-ApoB-D peptide Abs) response, inflammation markers and vascular function. MAIN METHODS: Eighty-eight patients with hypertension (stage 1 or 2) were recruited and advised to receive perindopril (4mg), hydrochlorothiazide (25mg), or indapamide (1.5mg) for 12weeks in a blinded fashion. Office and 24-h ambulatory blood pressure monitoring (24h ABPM), flow-mediated dilatation (FMD), nitrate-induced dilatation (NID), titers of IgG and IgM anti-ApoB-D peptide Abs, hsCRP, and interleukins (IL-8 and IL-10) were evaluated at baseline and 12weeks after therapies. KEY FINDINGS: All treatments reduced office BP, and improved FMD (P<0.05 vs. baseline). The NID was improved only in the perindopril arm (P<0.05 vs. baseline). The 24h-ABPM was reduced with perindopril and hydrochlorothiazide therapies (P<0.05 vs. baseline), but not with indapamide, and this effect was followed by increase in titers of IgM Anti-ApoB-D peptide Abs (P<0.05 vs. baseline), without modifications in titers IgG Anti-ApoB-D peptide Abs and interleukins. Multivariable regression analysis has shown that change in the titers of IgM anti-ApoB-D peptide was associated with the changes in FMD (ß -0.347; P<0.05). SIGNIFICANCE: These findings shed light to a possible modulator effect of the antihypertensive therapy on the natural immunity responses and vascular function.

Thiazide Diuretics in the Management of Young Children with Central Diabetes Insipidus.

OBJECTIVE: To report our experience in treating infants and toddlers with central diabetes insipidus (DI) with thiazide diuretics. STUDY DESIGN: A retrospective chart review of all infants and toddlers who were treated with thiazide diuretics for central DI at the Mayo Clinic between 1996 and 2014. RESULTS: Our cohort consisted of 13 patients. The median age at the start of therapy was 6 months (IQR, 1-14 months). Eight patients were given chlorothiazide at a starting dose of 5-10 mg/kg/day, and 5 patients were treated with hydrochlorothiazide at a starting dose of 1-2 mg/kg/day. The median age at the cessation of thiazide therapy was 18 months (IQR, 11.5-39 months). The main reason for stopping was the lack of continued response, in addition to hypernatremia. There was no hospitalization secondary to hyponatremia and only 1 hospitalization secondary to hypernatremia while receiving thiazide therapy. Calcium was checked periodically in 7 of the 13 patients, and 2 of these 7 patients had persistent hypercalcemia. CONCLUSION: Thiazide diuretics appear to be safe and effective in treating infants with central DI. They can be continued after the introduction of solid food, and until a lack of response is observed.

Comparing clinical effectiveness and drug toxicity with hydrochlorothiazide and chlorthalidone using two potency ratios in a managed care population.

This study compared the clinical effectiveness and drug toxicity of chlorthalidone and hydrochlorothiazide. Electronic health records and claims data were used to identify patients initially prescribed chlorthalidone or hydrochlorothiazide. A total of 214 patients prescribed chlorthalidone 25 mg were matched with 428 patients prescribed hydrochlorothiazide 25 mg (1:1 potency ratio) and 214 patients prescribed hydrochlorothiazide 50 mg (1:2 potency ratio). Mean systolic blood pressure/diastolic blood pressure values at least 30 days after initial prescription were lower with chlorthalidone (132.2/74 mm Hg) compared with hydrochlorothiazide 25 mg (137.0/77.5 mm Hg) and hydrochlorothiazide 50 mg (138.6/78.5 mm Hg) (P<.05 for all comparisons). Goal systolic blood pressure/diastolic blood pressure values were achieved in a higher percentage of patients prescribed chlorthalidone (45.0%/78.3%) than with either hydrochlorothiazide 25 mg (32.1%/63.9%) or hydrochlorothiazide 50 mg (32.8%/68.9%) (P<.05 for all comparisons). Mean serum potassium was 3.94 mEq/L with chlorthalidone 25 mg, 4.13 mEq/L with hydrochlorothiazide 25 mg (P<.01 vs chlorthalidone), and 3.96 mEq/L with hydrochlorothiazide 50 mg. These findings indicate that chlorthalidone 25 mg is associated with a better antihypertensive response than hydrochlorothiazide 25 mg or 50 mg, without clinically significant differences in serum potassium.

Use of aliskiren in Latin America in a real-world setting: aliskiren in Latin America Study (ALAS).

BACKGROUND: Hypertension (HTN) is one of the major risk factors for cardiovascular disease in Western countries, and disease control is of major relevance in order to reduce cardiovascular morbidity and mortality. Different approaches have shown efficacy, and one of the proven therapies for HTN control is the blockade of the renin-angiotensin-aldosterone system, which may be accomplished by means of various drugs with different modes of action. Aliskiren is a novel direct renin inhibitor that reduces both angiotensin I and II blood levels. Different randomized clinical trials (phase II and III) have shown its safety and efficacy either alone or in combination with hydrochlorothiazide. However, although aliskiren has been on the market for some years, reports on the post-marketing experience with aliskiren in the real-world setting are lacking. METHODS: The Aliskiren in Latin America Study (ALAS) was designed with the aim of describing the effectiveness of aliskiren at reducing blood pressure (BP) values by prospectively assessing BP control in outpatient clinics in different countries in Latin America. A total of 435 sites in 5 Latin American countries (Mexico, Ecuador, Colombia, Argentina, and Venezuela) enrolled 4588 patients who had just been initiated on aliskiren (either alone or in combination with hydrochlorothiazide) based on their treating physicians' discretion, and they were followed for a 6-month period. Prior antihypertensive drugs could be continued if their doses were not modified along the study. RESULTS: At the end of the follow-up period, a statistically significant reduction in BP values was observed, with a mean systolic BP reduction of 29.2 mmHg and a mean diastolic BP reduction of 13.78 mmHg from baseline at the 6-month visit. CONCLUSION: The BP reduction levels and the low adverse event rate demonstrate the adequate efficacy and safety profile of aliskiren (alone or with hydrochlorothiazide).

Efficacy and safety of two ramipril and hydrochlorothiazide fixed-dose combination formulations in adults with stage 1 or stage 2 arterial hypertension evaluated by using ABPM.

BACKGROUND: Fixed-dose combinations of antihypertensive agents demonstrate advantages in terms of efficacy, tolerability, and treatment adherence. OBJECTIVE: This study was designed to compare the efficacy and safety of 2 ramipril and hydrochlorothiazide (HCTZ) fixed-dose combinations in patients with hypertension stage 1 or 2. Patients' blood pressure (BP) profiles were evaluated by using 24-hour ambulatory BP monitoring (ABPM). METHODS: This was a multicenter, prospective, randomized, open-label, parallel-group, noninferiority trial of adult patients (age ≥18 years) with hypertension stage 1 or 2 and systolic blood pressure (SBP) within 140 to 179 mm Hg or diastolic blood pressure (DBP) 90 to 109 mm Hg. After a 2-week washout period, eligible patients were randomized to receive 1 of 2 ramipril/HCTZ fixed-dose combination formulations (5/25 mg/d) for 8 weeks. The primary end point was the difference in 24-hour ABPM SBP/DBP mean reductions between groups after 8 weeks of treatment. The secondary end points were the changes in daytime and nighttime ABPM and in office BP. Safety profile and tolerability assessments included monitoring of adverse events. RESULTS: A total of 102 patients with hypertension (54 in group A [test formulation] and 48 in group B [reference formulation]), aged 27 to 85 years, completed the 8-week treatment period. The decreases in SBP and DBP according to 24-hour ABPM from baseline to week 8 were significant and similar in both groups. SBP decreased from 149.1 to 133.0 mm Hg (-16.1 mm Hg) in group A and from 146.2 to 130.6 mm Hg in group B (-15.6 mm Hg) (P = 0.8537); DBP was reduced by 8.8 mm Hg in group A and by 8.5 mm Hg in group B (P = 0.8748). Because the lower 95% CI limit for the difference between groups A and B of 3.96 mm Hg in SBP and 3.54 mm Hg in DBP was lower than that preestablished by the trial protocol (4 mm Hg), noninferiority of the test formulation was demonstrated compared with the reference formulation. For the secondary end points, there was no significant difference between groups in SBP and DBP during daytime or nighttime at the end of week 8. Office BP was significantly reduced in both treatment groups, with no significant differences between groups. The incidence of adverse events was 23.7% in group A and 21.7% in group B. CONCLUSIONS: Both treatment options were well tolerated and equally reduced BP. The results support the conclusion that group A (new fixed-dose combination of ramipril/HCTZ) was noninferior to group B (reference medication in Brazil). ISRCTN Register: ISRCTN05051235.

Preference of patient information leaflets over standard drug monographs by patients prescribed hydrochlorothiazide, nifedipine and enalapril.

Standard drug monographs (SDMs) have been described as deficient in providing information in a manner simplified enough for patient reading. The aim of this study was to design patient information leaflets for hydrochlorothiazide, nifedipine and enalapril with content indicated by patients as relevant and to evaluate them against the SDM. Patient information leaflet (PIL) for each drug was designed to contain information on name, use of drug, how it works, how it is to be taken, common side effects, storage, missed dose action, things to avoid and when to contact the physician. Appropriateness was assessed by 10 practising pharmacists. For each drug, 40 patients were recruited, of which 20 were given SDM and 20 PIL. The knowledge of each participant was examined before and after exposure to SDM or PIL, as well as opinion on ease of reading and attractiveness using Pearson s Chi-square analysis. The results showed that both SDM and PIL improved knowledge of common side effects when compared with responses before exposure (chi2 = 24.26 for SDM and 27.64 for PIL, p < 0.001) with no difference between the groups. Respondents receiving PILs were better able to recall "things to avoid" after exposure to PIL (chi2 =10.85, p < 0.001). After exposure to SDM or PIL, the respondents who received PIL were more aware of when to contact the physician, compared to the SDM group (chi2 = 8.41, p < 0.01). When compared with SDM, respondents receiving PIL were more likely to indicate that PIL was easy to read (chi2 = 20.00, p < 0.001), attractive (chi2 = 12.45, p < 0.001) and they were more likely to recommend distribution of their reading material to other patients (chi2 = 22.11, p < 0.001). We conclude that there is benefit in designing information leaflets that simplify language and medication information contained in SDMs, including better understanding of precautions to take while on medication and when to consult physicians.

Preference of patient information leaflets over standard drug monographs by patients prescribed hydrochlorothiazide, nifedipine and enalapril / Preferencia por los prospectos de información al paciente en lugar de las monografías estándar sobre medicamentos, por parte de los pacientes a quienes se les ha prescrito hidroclorotiazida, nifedipina y analapril

Standard drug monographs (SDMs) have been described as deficient in providing information in a manner simplified enough for patient reading. The aim of this study was to design patient information leaflets for hydrochlorothiazide, nifedipine and enalapril with content indicated by patients as relevant and to evaluate them against the SDM. Patient information leaflet (PIL) for each drug was designed to contain information on name, use of drug, how it works, how it is to be taken, common side effects, storage, missed dose action, things to avoid and when to contact the physician. Appropriateness was assessed by 10 practising pharmacists. For each drug, 40 patients were recruited, of which 20 were given SDM and 20 PIL. The knowledge of each participant was examined before and after exposure to SDM or PIL, as well as opinion on ease of reading and attractiveness using Pearson's Chi-square analysis. The results showed that both SDM and PIL improved knowledge of common side effects when compared with responses before exposure (χ² = 24.26for SDM and 27.64 for PIL, p < 0.001) with no difference between the groups. Respondents receiving PILs were better able to recall "things to avoid" after exposure to PIL (χ² =10.85, p < 0.001). After exposure to SDM or PIL, the respondents who received PIL were more aware of when to contact the physician, compared to the SDM group (χ² = 8.41, p < 0.01). When compared with SDM, respondents receiving PIL were more likely to indicate that PIL was easy to read (χ² = 20.00, p < 0.001), attractive (χ² = 12.45, p < 0.001) and they were more likely to recommend distribution of their reading material to other patients (χ² = 22.11, p < 0.001). We conclude that there is benefit in designing information leaflets that simplify language and medication information contained in SDMs, including better understanding of precautions to take while on medication and when to consult physicians.

Las monografías de medicamentos estandarizadas se han considerado deficientes a la hora de proporcionar información de manera suficientemente simple para que el paciente pueda entenderlas. El objetivo de este estudio fue disenar prospectos con información sobre la hidroclorotiazida, la nifedipina y el analapril con contenidos indicados como relevantes por los pacientes, y evaluarlos en comparación con las monografías estandarizadas de medicamentos (MEM). El prospecto de información para el paciente (PIP) fue disenado de modo que apareciera información sobre el nombre del medicamento, su uso, modo de operar, manera de tomarse, efectos secundarios comunes, almacenamiento, qué hacer en caso de perder una dosis, cosas que deben evitarse, y cuando debe contactarse el médico. Se evaluó la adecuación por parte de 10 farmacéuticos practicantes. Para cada medicamento, se reclutaron 40 pacientes, a 20 de los cuales se les dio monografías (MEM), en tanto que a 20 se les ofreció prospectos (PIP). El conocimiento de cada participante se examinó antes y después de la exposición a MEM o PIP, así como la opinión en cuanto a facilidad de lectura y grado de atracción, usando el análisis del Chi-cuadrado de Pearson. Los resultados mostraron que tanto MEM como PIP mejoraron el conocimiento sobre los efectos secundarios comunes, cuando se hacía una comparación con las respuestas antes de la exposición (χ² = 24.26para MEMy 27.64para PIP, p < 0.001) sin diferencia entre los grupos. Los encuestados que recibieron prospectos pudieron recordar mejor las "cosas a evitar" luego de la exposición a PIP (χ² =10.85, p < 0.001). Después de la exposición a MEM o PIP, los encuestados con PIP tenían mayor conciencia en cuanto a cuando contactar a un médico, en comparación con el grupo MEM (χ² = 8.41, p < 0.01). Cuando se les comparó con el grupo MEM, los encuestados que recibieron PIP mostraron por una parte mayor probabilidad de indicar que PIP era más fácil de leer (χ² = 20.00, p < 0.001) y atractivo (χ² = 12.45, p < 0.001), y por otra, una mayor tendencia a recomendar la distribución de su material de lectura a otros pacientes (χ² = 22.11, p < 0.001). Se llegó a la conclusión de que es beneficioso disenar prospectos que simplifiquen el lenguajey la información médica contenida en las monografias estándar del medicamento, incluyendo una mejor comprensión de las precauciones a tomar mientras se está bajo medicación, y sobre cuándo consultar al médico.

Diastolic function parameters are improved by the addition of simvastatin to enalapril-based treatment in hypertensive individuals.

OBJECTIVE: Diastolic dysfunction (DD) is a frequent condition in hypertensive patients whose presence increases mortality and whose treatment remains unclear. The aim of this study was to investigate in a prospective, double-blinded, placebo-controlled randomized design the additive effect of simvastatin on DD in enalapril-treated hypertensive patients with average cholesterol levels. METHODS: Hypertensive patients with DD and LDL-cholesterol <160 mg/dL underwent a run-in phase to achieve a systolic blood pressure (SBP) <135 mmHg and diastolic blood pressure (DBP) <85 mmHg with enalapril. Hydrochlorothiazide was added when need to achieve blood pressure control. Four weeks after reaching the optimum anti-hypertensive regimen patients were randomized to receive 80 mg simvastatin (n=27) or placebo (n=28) for a period of 20 weeks. Echocardiograms were performed before and after treatment with measurement of maximum left atrial volume (LAV), conventional and tissue Doppler velocities in early diastole (E, e') and late diastole (A, a'). RESULTS: After 20 weeks, the simvastatin group presented reduction in SBP (-4±2 mmHg, p=0.02), increase in E/A ratio (1.0±0.05 to 1.2±0.06, p=0.03) and decrease of LAV indexed to body surface area (24.5±0.9 to 21.1±0.8 ml/m(2), p=0.048), as compared with placebo arm. No change in systolic function and no correlation between the E/A ratio, LAV and changes in blood pressure or lipid profile were observed. CONCLUSIONS: The addition of simvastatin to enalapril in hypertensive patients with average cholesterol levels improves parameters of diastolic function independently of changes in blood pressure or cholesterol.

Inequalities in prescription of hydrochlorothiazide for diabetic hypertensive patients in Colombia.

OBJECTIVE: Evaluating differences in the suitable prescription of thiazides in hypertense patients, according to affiliation regime. MATERIALS AND METHODS: This was an analytical cross-sectional study. The database from a previous study was used regarding two groups of hypertense patients (subsidised regime and contributory regime) who had attended out-patient consultation between 01-09-2007 and 29-02-2008. Ideal therapy was evaluated in both groups. Univariate and multivariate analysis was carried out. RESULTS: 136 patients (contributory: 41.9 %; subsidised: 58.1 %). Subsidised regime patients were older (mean=68.8±10) than those from the contributory regime (mean=64.1±11.1) (t-test, p=0.0110). Prescribing antihypertensive drugs was ideal in 49/136 of the patients (36.0 %). Ideal prescription accounted for 24/79 (30 %) of the patients in the subsidised regime and 25/57 (43.8 %) in the contributory one (OR=1.79; 95 % CI:0.88-3.64). Older people (aged ≥ 65 yo) were at risk of receiving a non-ideal prescription (OR=2.12; 95 %CI:1.02-4.38) whilst this was not so in the subsidised regime (OR=1.62; 95 % CI:0.78-3.35). CONCLUSIONS: Ideal prescription of antihypertensive drugs was low in the population being studied. There were differences regarding age ideal prescription but not concerning affiliation regime. It is suggested that a longitudinal study be carried out in the future.

The influence of cognition, anxiety and psychiatric disorders over treatment adherence in uncontrolled hypertensive patients.

BACKGROUND: Poor adherence is estimated to cause 125 thousand deaths per year and is linked to 10% of all hospital stays in the U.S. Up to one third of elderly hypertensive patients don't have adherence, which is responsible for high proportion of hospitalizations. Hypertension is also related to poor performance in tests that assess cognitive functions. On the other hand, poor cognitive performance is associated with low adherence to treatment. OBJECTIVE: To assess the association between cognitive function, anxiety and psychiatric disorders with adherence to drug treatment in patients with hypertension. METHODOLOGY AND PRINCIPAL FINDINGS: This a cohort studies with 56 adult patients with uncontrolled hypertension who participated of all meetings of a pharmaceutical intervention in a randomized clinical trial of pharmaceutical care. Cognitive function was measured by the Mini Mental State Examination (Mini-mental). The memory was measured by digit and word spans, tower and church shadow test, short story test and metamemory. Anxiety and psychiatric disorders were evaluated by the State Trace Anxiety Inventory and the Self-Report Questionnaire, respectively. The participants were classified as adherent or non-adherent to the drug treatment, according to the identification of plasma levels of hydrochlorothiazide. All non-adherent patients (n = 12) and 35 out 44 (79.5%) patients with adherence to treatment had at least one memory test with an altered score (P = 0.180). Participants with an unsatisfactory score in the Mini-mental had six-fold higher risk of non-adherence to treatment when compared to those with a normal score (RR = 5.8; CI 95%: 1.6-20.8; P = 0.007). The scores of anxiety and psychiatric disorders were not associated with adherence to the pharmacological treatment. CONCLUSION: Cognitive deficit impairs adherence to drug therapy and should be screened as part of a program of pharmaceutical care to improve adherence to treatment.

Effects of losartan, in monotherapy or in association with hydrochlorothiazide, in chronic nephropathy resulting from losartan treatment during lactation.

We recently standardized a model (L(Lact)) of severe chronic kidney disease based on impaired nephrogenesis by suppression of angiotensin II activity during lactation (Machado FG, Poppi EP, Fanelli C, Malheiros DM, Zatz R, Fujihara CK. Am J Physiol Renal Physiol 294: F1345-F1353, 2008). In this new study of the L(Lact) model, we sought to gain further insight into renal injury mechanisms associated with this model and to verify whether the renoprotection obtained with the association of the angiotensin II receptor blocker losartan (L) and hydrochlorothiazide (H), which arrested renal injury in the remnant kidney model, would provide similar renoprotection. Twenty Munich-Wistar dams, each nursing six pups, were divided into control, untreated, and L(Lact) groups, given losartan (L; 250 mg·kg(-1)·day(-1)) until weaning. The male L(Lact) offspring remained untreated until 7 mo of age, when renal functional and structural parameters were studied in 17 of them, used as pretreatment control (L(Lact)Pre), and followed no further. The remaining rats were then divided among groups L(Lact)+V, untreated; L(Lact)+L, given L (50 mg·kg(-1)·day(-1)) now as a therapy; L(Lact)+H, given H (6 mg·kg(-1)·day(-1)); and L(Lact)+LH, given L and H. All parameters were reassessed 3 mo later in these groups and in age-matched controls. At this time, L(Lact) rats exhibited hypertension, severe albuminuria, glomerular damage, marked interstitial expansion/inflammation, enhanced cell proliferation, myofibroblast infiltration, and creatinine retention. L monotherapy normalized albuminuria and prevented hypertension and the progression of renal injury, inflammation, and myofibroblast infiltration. In contrast to the remnant model, the LH combination promoted only slight additional renoprotection, perhaps because of a limited tendency to retain sodium in L(Lact) rats.

Inequalities in prescription of hydrochlorothiazide for diabetic hypertensive patients in Colombia / Desigualdades en la prescripción de hidroclorotiazida en pacientes hipertensos diabéticos en Colombia

Objective Evaluating differences in the suitable prescription of thiazides in hypertense patients, according to affiliation regime. Materials and methods This was an analytical cross-sectional study. The database from a previous study was used regarding two groups of hypertense patients (subsidised regime and contributory regime) who had attended out-patient consultation between 01-09-2007 and 29-02-2008. Ideal therapy was evaluated in both groups. Univariate and multivariate analysis was carried out. Results 136 patients (contributory: 41.9 percent; subsidised: 58.1 percent). Subsidised regime patients were older (mean=68.8±10) than those from the contributory regime (mean=64.1±11.1) (t-test, p=0.0110). Prescribing antihypertensive drugs was ideal in 49/136 of the patients (36.0 percent). Ideal prescription accounted for 24/79 (30 percent) of the patients in the subsidised regime and 25/57 (43.8 percent) in the contributory one (OR=1.79; 95 percent CI:0.88-3.64). Older people (aged ≥ 65yo) were at risk of receiving a non-ideal prescription (OR=2.12; 95 percentCI:1.02-4.38) whilst this was not so in the subsidised regime (OR=1.62; 95 percent CI:0.78-3.35). Conclusions Ideal prescription of antihypertensive drugs was low in the population being studied. There were differences regarding age ideal prescription but not concerning affiliation regime. It is suggested that a longitudinal study be carried out in the future.

Objetivo Evaluar las diferencias en la adecuada prescripción de tiazidas en pacientes hipertensos, según régimen de afiliación. Materiales y métodos Estudio de corte transversal analítico. Se utilizó la base de datos de un estudio previo, dos grupos de pacientes hipertensos: régimen subsidiado y régimen contributivo que asistieron a consulta externa entre el 01-09-2007 y el 29-02-2008. Se evaluó terapia ideal en los dos grupos. Se realizó análisis univariado y multivariado. Resultados Se estudiaron 136 pacientes (contributivo: 41,9 por ciento; subsidiado: 58,1 por ciento). Los pacientes del régimen subsidiado fueron mayores (promedio= 68,8±10) que los del contributivo (promedio=64,1±11.1) (t-test, p=0,0110). La prescripción de antihipertensivos fue ideal en 49/136 (36,0 por ciento). En el régimen subsidiado la prescripción fue ideal en 24/79 (30 por ciento) y en el contributivo en 25/57 (43,8 por ciento) (OR: 1,79 IC95 por ciento (0,88-3,64)). La edad ≥65años fue riesgo de prescripción no ideal (OR: 2.12, IC95 por ciento(1,02-4,38)), mientras que no lo fue estar en el régimen subsidiado (OR=1,62, IC95 por ciento(0,78-3,35). Conclusiones La prescripción ideal de antihipertensivos es baja. Hay diferencias en la edad, en la prescripción ideal, mas no por régimen de afiliación. Se sugiere un estudio longitudinal en el futuro.

How to avoid discontinuation of antihypertensive treatment: The experience in São Paulo, Brazil.

OBJECTIVES: To evaluate the importance of providing guidelines to patients via active telephone calls for blood pressure control and for preventing the discontinuation of treatment among hypertensive patients. INTRODUCTION: Many reasons exist for non-adherence to medical regimens, and one of the strategies employed to improve treatment compliance is the use of active telephone calls. METHODS: Hypertensive patients (n=354) who could receive telephone calls to remind them of their medical appointments and receive instruction about hypertension were distributed into two groups: a) "uncomplicated" - hypertensive patients with no other concurrent diseases and b) "complicated" - severe hypertensive patients (mean diastolic ≥ 110 mmHg with or without medication) or patients with comorbidities. All patients, except those excluded (n=44), were open-block randomized to follow two treatment regimens ("traditional" or "current") and to receive or not receive telephone calls ("phone calls" and "no phone calls" groups, respectively). RESULTS: Significantly fewer patients in the "phone calls" group discontinued treatment compared to those in the "no phone calls" group (4 vs. 30; p<0.0094). There was no difference in the percentage of patients with controlled blood pressure in the "phone calls" group and "no phone calls" group or in the "traditional" and "current" groups. The percentage of patients with controlled blood pressure (<140/90 mmHg) was increased at the end of the treatment (74%), reaching 80% in the "uncomplicated" group and 67% in the "complicated" group (p<0.000001). CONCLUSION: Guidance to patients via active telephone calls is an efficient strategy for preventing the discontinuation of antihypertensive treatment.

Hiperparatiroidismo primario con normocalcemia, una asociación de diagnóstico complejo: a propósito de un caso clínico / Normocalcemic hyperparathyroidism: report of one case

We report a 59 years old female with a history of nephrolithiasis and progressive worsening of her bone mineral density. High serum PTH levels were detected, with normal serum calcium. Causes of secondary hyperparathyroidism were discarded. The patient was followed during six years, period in which she maintained elevated serum PTH and normal serum calcium. During the second year of follow up, hydrochlorothiazide was indicated. Serum calcium raised progressively and after six years, it became abnormally high. The patient was subjected to a total left lobe and subtotal right lobe thyroidectomy. The surgeon found a 1.6 mm diameter left parathyroid nodule. After surgery the patient is asymptomatic and is receiving levothyroxine supplementation.