Nocturnal blood pressure fall as predictor of diabetic nephropathy in hypertensive patients with type 2 diabetes.

BACKGROUND: Hypertensive patients with reduced blood pressure fall (BPF) at night are at higher risk of cardiovascular events (CVE). METHODS: We evaluated in hypertensive diabetic patients, if a reduced nocturnal BPF can precedes the development of diabetic nephropathy (DN). We followed 70 patients with normal urinary albumin excretion (UAE) for two years. We performed 24-hours ambulatory BP monitoring in baseline and at the end of the study. RESULTS: Fourteen (20%) patients (GI) developed DN (N = 11) and/or CVE (n = 4). Compared to the remaining 56 patients (GII) in baseline, GI had similar diurnal systolic (SBP) and diastolic BP (DBP), but higher nocturnal SBP (138 +/- 15 vs 129 +/- 16 mmHg; p < 0.05) and DBP (83 +/- 12 vs 75 +/- 11 mmHg; p < 0,05). Basal nocturnal SBP correlated with occurrence of DN and CVE (R = 0.26; P < 0.05) and with UAE at the end of the study (r = 0.3; p < 0.05). Basal BPF (%) correlated with final UAE (r = -0.31; p < 0.05). In patients who developed DN, reductions occurred in nocturnal systolic BPF (12 +/- 5 vs 3 +/- 6%, p < 0,01) and diastolic BPF (15 +/- 8 vs 4 +/- 10%, p < 0,01) while no changes were observed in diurnal SBP (153 +/- 17 vs 156 +/- 16 mmHg, NS) and DBP (91 +/- 9 vs 90 +/- 7 mmHg, NS). Patients with final UAE < 20 microg/min, had no changes in nocturnal and diurnal BP. CONCLUSIONS: Our results suggests that elevations in nocturnal BP precedes DN and increases the risk to develop CVE in hypertensive patients with T2DM.

Latin American guidelines on hypertension. Latin American Expert Group.

Hypertension is a highly prevalent cardiovascular risk factor in the world and particularly overwhelming in low and middle-income countries. Recent reports from the WHO and the World Bank highlight the importance of chronic diseases such as hypertension as an obstacle to the achievement of good health status. It must be added that for most low and middle-income countries, deficient strategies of primary healthcare are the major obstacles for blood pressure control. Furthermore, the epidemiology of hypertension and related diseases, healthcare resources and priorities, the socioeconomic status of the population vary considerably in different countries and in different regions of individual countries. Considering the low rates of blood pressure control achieved in Latin America and the benefits that can be expected from an improved control, it was decided to invite specialists from different Latin American countries to analyze the regional situation and to provide a consensus document on detection, evaluation and treatment of hypertension that may prove to be cost-utility adequate. The recommendations here included are the result of preparatory documents by invited experts and a subsequent very active debate by different discussion panels, held during a 2-day sessions in Asuncion, Paraguay, in May 2008. Finally, in order to improve clinical practice, the publication of the guidelines should be followed by implementation of effective interventions capable of overcoming barriers (cognitive, behavioral and affective) preventing attitude changes in both physicians and patients.

An 18-week, prospective, randomized, double-blind, multicenter study of amlodipine/ramipril combination versus amlodipine monotherapy in the treatment of hypertension: the assessment of combination therapy of amlodipine/ramipril (ATAR) study.

BACKGROUND: A combination of antihypertensive agents of different drug classes in a fixed-dose combination (FDC) may offer advantages in terms of efficacy, tolerability, and treatment compliance. Combination of a calcium channel blocker with an angiotensin-converting enzyme inhibitor may act synergistically to reduce blood pressure (BP). OBJECTIVE: The aim of this study was to compare the efficacy and tolerability of an amlodipine/ramipril FDC with those of amlodipine monotherapy. METHODS: This 18-week, prospective, randomized, double-blind study was conducted at 8 centers across Brazil. Patients with stage 1 or 2 essential hypertension were enrolled. After a 2-week placebo run-in phase, patients received amlodipine/ramipril 2.5/2.5 mg or amlodipine 2.5 mg, after which the doses were titrated, based on BP, to 5/5 then 10/10 mg (amlodipine/ramipril) and 5 then 10 mg (amlodipine). The primary end point was BP measured in the intent-to-treat (ITT) population. Hematology and serum biochemistry were assessed at baseline and study end. Tolerability was assessed using patient interview, laboratory analysis, and physical examination, including measurement of ankle circumference to assess peripheral edema. RESULTS: A total of 222 patients completed the study (age range, 40-79 years; FDC group, 117 patients [mean dose, 7.60/7.60 mg]; monotherapy, 105 patients [mean dose, 7.97 mg]). The mean (SD) changes in systolic BP (SBP) and diastolic BP (DBP), as measured using 24-hour ambulatory blood pressure monitoring (ABPM) and in the physician's office, were significantly greater with combination therapy than monotherapy, with the exception of office DBP (ABPM, -20.76 [1.25] vs -15.80 [1.18] mm Hg and -11.71 [0.78] vs -8.61 [0.74] mm Hg, respectively [both, P = 0.004]; office, -27.51 [1.40] vs -22.84 [1.33] mm Hg [P = 0.012] and -16.41 [0.79] vs -14.64 [0.75] mm Hg [P = NS], respectively). In the ITT analysis, the mean changes in ambulatory, but not office-based, BP were statistically significant (ABPM: SBP, -20.21 [1.14] vs -15.31 [1.12] mm Hg and DBP, -11.61 [0.72] vs -8.42 [0.70] mm Hg, respectively [both, P = 0.002]; office: SBP, -26.60 [1.34] vs -22.97 [1.30] mm Hg and DBP, -16.48 [0.78] vs -14.48 [0.75] mm Hg [both, P = NS]). Twenty-nine patients (22.1%) treated with combination therapy and 41 patients (30.6%) treated with monotherapy experienced > or =1 adverse event considered possibly related to study drug. The combination-therapy group had lower prevalence of edema (7.6% vs 18.7%; P = 0.011) and a similar prevalence of dry cough (3.8% vs 0.8%; P = NS). No clinically significant changes in laboratory values were found in either group. CONCLUSIONS: In this population of patients with essential hypertension, the amlodipine/ramipril FDC was associated with significantly reduced ambulatory and office-measured BP compared with amlodipine monotherapy, with the exception of office DBP. Both treatments were well tolerated.

Reproducibility of ambulatory blood pressure monitoring in hypertensive patients with type 2 diabetes mellitus.

OBJECTIVE: To evaluate the reproducibility of ambulatory blood pressure monitoring (ABPM) (SpaceLabs-90207) and placebo effect on ABPM. METHODS: Blood pressure was measured in the office and over two ABPM periods with an interval from one to ten months (mean 4.9 months), in 26 patients with type 2 diabetes mellitus and hypertension. Eleven patients (G1) had two ABPMs without taking antihypertensive drugs for 15 days, whereas G2 (N=15) had the second ABPM after administration of a placebo for 15 days. RESULTS: In the evaluation of the coefficient of variation (CV) of diurnal (awake) systolic BP (DSBP), of diurnal (awake) diastolic BP (DDBP), of 24-hour systolic BP (24hSBP) and of 24-hour diastolic BP (24hDBP), the values found were 4.6%, 3.9%, 5.0%, 4.0% for G1 and 4.3%, 5.1%, 3.7%, 5.1% for G2 respectively. We also determined the CV of nocturnal (sleep) systolic and diastolic BP (NSBP and NDBP) for G1 (7.7%; 8.2%) and G2 (5.6%; 6.3%). Heart rate CV during alertness and sleep were: G1=5.9% and 9.0%; G2=6.9% and 5.8% respectively. When the total number of 'patients was analyzed, all variables showed a strong correlation between the first and second ABPM measurements (DSBP, r = 0.76; P < 0.001; DDBP, r = 0.65; p < 0.001; 24hSBP, r = 0.77; p < 0.001; 24hDBP, r = 0.70; p < 0.001; NSBP, r = 0.62; p < 0.001; NDBP, r = 0.52; p < 0.01). Office systolic and diastolic BP and 24hSBP and 24hDBP also showed correlation (r = 0.65; p < 0.001; r = 0.57; p < 0.01). CONCLUSION: Mean of pressure levels measured by ABPM presented good reproducibility and were not affected by placebo.

Reprodutibilidade da medida ambulatorial da pressão arterial em pacientes hipertensos com diabete melito tipo 2 / Reproducibility of ambulatory blood pressure monitoring in hypertensive patients with type 2 diabetes mellitus

OBJETIVO: Avaliar a reprodutibilidade e o efeito placebo sobre a monitorização ambulatorial da pressão arterial (MAPA) (SpaceLabs-90207). MÉTODOS: Mensurou-se a PA no consultório e por meio de duas MAPA, realizadas em um intervalo de 1 a 10 meses (média de 4,9 meses), de 26 pacientes com diabetes tipo 2 e hipertensão. Onze pacientes (G1) realizaram as duas MAPA sem medicação anti-hipertensiva por 15 dias, enquanto o G2 (N = 15) fez a segunda MAPA em uso de placebo pelo mesmo período. RESULTADOS: Ao avaliarmos os coeficientes de variação (CV) da PA sistólica na vigília (PASV), PA diastólica na vigília (PADV), PA sistólica nas 24h (PAS24h) e PA diastólica nas 24h (PAD24h), encontramos valores de 4,6 por cento, 3,9 por cento, 5,0 por cento e 4,0 por cento no G1 e 4,3 por cento, 5,1 por cento, 3,7 por cento e 5,1 por cento no G2, respectivamente. Quanto ao CV da PA sistólica e diastólica durante o sono (PASS e PADS), encontramos 7,7 por cento e 8,2 por cento para G1, e 5,6 por cento e 6,3 por cento para G2, respectivamente. O CV da freqüência cardíaca na vigília e durante o sono foram: G1 = 5,9 por cento e 9,0 por cento, G2 = 6,9 por cento e 5,8 por cento, respectivamente. Analisando o total dos pacientes, todas as variáveis mostraram fortes correlações entre a primeira e a segunda MAPA (PASV, r=0,76; P<0,001; PADV, r=0,65; p<0,001; PAS24h, r=0,77; p<0,001; PAD24h, r=0,70; p<0,001; PASS, r=0,62; p<0,001; PADS, r=0,52; p<0,01). Ocorreram também correlações entre a PA sistólica e a diastólica de consultório e a PAS24h e PAD24h (r=0,65; p<0,001; r=0,57; p<0,01). CONCLUSÃO: A média dos níveis pressóricos avaliados pela MAPA apresentou boa reprodutibilidade e esses não foram afetados pelo efeito placebo.

OBJECTIVE: To evaluate the reproducibility of ambulatory blood pressure monitoring (ABPM) (SpaceLabs-90207) and placebo effect on ABPM. METHODS: Blood pressure was measured in the office and over two ABPM periods with an interval from one to ten months (mean 4.9 months), in 26 patients with type 2 diabetes mellitus and hypertension. Eleven patients (G1) had two ABPMs without taking antihypertensive drugs for 15 days, whereas G2 (N=15) had the second ABPM after administration of a placebo for 15 days. RESULTS: In the evaluation of the coefficient of variation (CV) of diurnal (awake) systolic BP (DSBP), of diurnal (awake) diastolic BP (DDBP), of 24-hour systolic BP (24hSBP) and of 24-hour diastolic BP (24hDBP), the values found were 4.6 percent, 3.9 percent, 5.0 percent, 4.0 percent for G1 and 4.3 percent, 5.1 percent, 3.7 percent, 5.1 percent for G2 respectively. We also determined the CV of nocturnal (sleep) systolic and diastolic BP (NSBP and NDBP) for G1 (7.7 percent; 8.2 percent) and G2 (5.6 percent; 6.3 percent). Heart rate CV during alertness and sleep were: G1=5.9 percent and 9.0 percent; G2=6.9 percent and 5.8 percent respectively. When the total number of 'patients was analyzed, all variables showed a strong correlation between the first and second ABPM measurements (DSBP, r = 0.76; P < 0.001; DDBP, r = 0.65; p < 0.001; 24hSBP, r = 0.77; p < 0.001; 24hDBP, r = 0.70; p < 0.001; NSBP, r = 0.62; p < 0.001; NDBP, r = 0.52; p < 0.01). Office systolic and diastolic BP and 24hSBP and 24hDBP also showed correlation (r = 0.65; p < 0.001; r = 0.57; p < 0.01). CONCLUSION: Mean of pressure levels measured by ABPM presented good reproducibility and were not affected by placebo.

Hyperglycemia and nocturnal systolic blood pressure are associated with left ventricular hypertrophy and diastolic dysfunction in hypertensive diabetic patients.

BACKGROUND: The aim of this study was to determine if hypertensive type 2 diabetic patients, when compared to patients with essential hypertension have an increased left ventricular mass index (LVMI) and a worse diastolic function, and if this fact would be related to 24-h pressoric levels changes. METHODS: Ninety-one hypertensive patients with type 2 diabetes mellitus (DM) (group-1 [G1]), 59 essential hypertensive patients (group-2 [G2]) and 26 healthy controls (group-3 [G3]) were submitted to 24-h Ambulatory Blood Pressure Monitoring (ABPM) and echocardiography (ECHO) with Doppler. We calculated an average of fasting blood glucose (AFBG) values of G1 from the previous 4.2 years and a glycemic control index (GCI) (percentual of FBG above 200 mg/dl). RESULTS: G1 and G2 did not differ on average of diurnal systolic and diastolic BP. However, G1 presented worse diastolic function and a higher average of nocturnal systolic BP (NSBP) and LVMI (NSBP = 132 +/- 18 vs 124 +/- 14 mmHg; P < 0.05 and LVMI = 103 +/- 27 vs 89 +/- 17 g/m2; P < 0.05, respectively). In G1, LVMI correlated with NSBP (r = 0.37; P < 0.001) and GCI (r = 0.29; P < 0.05) while NSBP correlated with GCI (r = 0.27; P < 0.05) and AFBG (r = 0.30; P < 0.01). When G1 was divided in tertiles according to NSBP, the subgroup with NSBP> or =140 mmHg showed a higher risk of LVH. Diabetics with NSBP> or =140 mmHg and AFBG>165 mg/dl showed an additional risk of LVH (P < 0.05; odds ratio = 11). In multivariate regression, both GCI and NSBP were independent predictors of LVMI in G1. CONCLUSION: This study suggests that hyperglycemia and higher NSBP levels should be responsible for an increased prevalence of LVH in hypertensive patients with Type 2 DM.

Role of vasopressin in 24-hour blood pressure regulation in diabetic patients with autonomic neuropathy.

To evaluate the role of vasopressin (AVP) on blood pressure (BP) in diabetic patients with autonomic neuropathy (AN), 10 patients were studied on a fixed sodium and potassium diet. On days 4 and 7, a 24-h BP monitoring, as well as blood and urine samples for sodium, potassium, creatinine, and osmolality determinations were obtained for every 4-h period; either placebo or an AVP-V1-antagonist (d(CH2)5Tyr(me)AVP; 0.5 mg; AVPi) were given iv at 1 PM. On placebo, systolic BP (SBP) showed a progressive elevation during the day, declining after 12 PM (8 AM to 12 AM 122+/-9; 12 AM to 4 PM 125+/-11; 4 PM to 8 PM 134+/-14; 8 PM to 12 PM 136+/-14; 12 PM to 8 AM 131+/-17 mm Hg). On AVPi this rise in SBP was blunted: 8 AM to 12 AM 125+/-122; 12 AM to 4 PM 121+/-21; 4 PM to 8 PM 126+/-16; 8 PM to 12 PM 129+/-14; 12 PM to 8 AM 124+/-12 mm Hg. Creatinine clearance and diureses were greater during the night, both with placebo and AVPi. Plasma osmolality did not change on either day, although serum sodium decreased after AVPi, reaching the lowest values at 4 PM to 8 PM period (137+/-4.7 v 131+/-3.8 mEq/L; P < .05). With placebo, fractional excretion of sodium (FENa) increased from 0.43%+/-0.32% during 12 h of orthostasis to 0.92%+/-1.05% during 12 h of recumbency (P < .02). With AVPi, the FENa on orthostasis did not differ from that with placebo, although BP values were lower and did not increase with recumbency (0.58+/-0.57 v 0.73%+/-0.49%; NS). In conclusion, our results show that in diabetic patients with AN, vasopressin participates in BP control by stimulating vascular and renal V1 receptors, which results in vasoconstriction and sodium reabsorption.

Obesidade, hipertensäo arterial e suas influências sobre a massa e funçäo do ventrículo esquerdo / Obesity, hypertension and your influence about the left ventricular function and mass

Para avaliar as influências da obesidade e da hipertensão sobre a massa de ventrículo esquerdo (MVE), estudamos 121 mulheres divididas em 4 grupos: não-obesas normotensas (n = 25), não-obesas hipertensas (n = 30), obesas normotensas (n = 24) e obesas hipertensas (n = 42) quanto a parâmetros antropométricos, ecocardiográficos e de monitorização ambulatorial da pressão arterial (MAPA). As pacientes obesas hiperten- sas apresentaram maior MVE que os outros grupos - não-obesas normotensas, não-obesas hipertensas e obesas normotensas (167 +/- 38,8 vs. 113 +/- 26,4; vs. 133 +/- 26,5; vs. 132 +/- 29,2g; p < 0,05, respectivamente) e maior diâmetro de átrio esquerdo (AE) quando comparadas aos grupos de não-obesas, tanto normotensas como hipertensas (36 +/- 4,3 vs. 33 +/- 5,1; vs. 35 +/- 3,9mm; p < 0,05, respectivamente). Obesas normotensas apresentaram MVE similar à do grupo não-obesas hipertensas (133 +/- 26,5 vs. 132 +/- 29,5g; NS) e aumento de AE quando comparadas às não-obesas normotensas (35 +/- 3,9 vs. 31 +/- 4,6mm; p < 0,05). Detectou-se correlação entre a circunferência da cintura e a razão cintura-quadril com os níveis pressóricos à MAPA, assim como entre estas medidas e parâmetros ecocardiográficos que avaliam a massa cardíaca; o índice de massa corporal só se correlacionou ao diâmetro do AE. A correção da MVE pela altura ao invés da superfície corpórea aumentou a prevalência de hipertrofia de VE nas obesas (10,6 vs. 36,7 por cento, p < 0,01), mas não nas não-obesas. Ausência de descenso noturno da pressão arterial sistólica à MAPA (non-dipper) foi mais prevalente nas pacientes obesas, hipertensas ou não; entretanto, as obesas hipertensas non-dippers não diferiram das dippers quanto à MVE. Nossos dados demonstram que a obesidade associada à hipertensão aumenta a MVE de modo mais importante do que as condições isoladamente. Concluímos, ainda, que pacientes obesas também apresentam alta freqüência de alterações do ritmo da pressão arterial de 24 horas, caracterizada por menor queda pressórica durante o sono.