Guilherme Gama

Influence of non-steroidal anti-inflammatory drugs on renal function and 24h ambulatory blood pressure-reducing effects of enalapril and nifedipine gastrointestinal therapeutic system in hypertensive patients.

Objective: To evaluate the influence of non-steroidal anti-inflammatory drugs (NSAIDs; aspirin and indomethacin) on the renal and antihypertensive effects of enalapril and nifedipine gastrointestinal therapeutic system (GITS) in patients with essential hypertension. Design and methods: In a crossover study, 18 patients on an unrestricted-salt diet were randomly assigned to receive either enalapril (20-40 mg/day) or nifedipine-GITS (30-60mg/day) for 4-8 weeks, followed by aspirin (100 mg/day for 2 weeks) and then indomethacin (75 mg/day for 1 week). Blood pressure was measured by 24 h ambulatory monitoring. Results: Enalapril and nifedipine-GITS significantly reduced blood pressure compared with placebo. Aspirin did not alter the antihypertensive effect of either drug. Indomethacin attenuated (by 45%) the antihypertensive effect of enalapril throughout the 24 h period of evaluation, but did not interfere with the effect of nifedipine. Furthermore, indomethacin significantly reduced the fractional excretion of sodium and plasma levels of prostaglandins in a similar way when added to either the enalapril or the nifedipine regimen. Conclusions: Vasodilatory prostaglandins are probably involved in the antihypertensive effects of enalapril but not of nifedipine, and this interaction seems to be independent of any indomethacin-induced decrease in renal sodium excretion. Nifedipine may be an appropriate drug to treat hypertensive patients requiring concomitant therapy with NSAID.

Sequential follow-up clinic and ambulatory blood pressure evaluation in a low risk population of white-coat hypertensive patients and in normotensives.

BackgroundIn subjects with white-coat hypertension (WCH) it is unclear how ambulatory blood pressure (ABPM) progresses over time and whether they exhibit an increased cardiovascular risk. MethodsWe prospectively evaluated the transition of clinic and ABPM values in 39 clinic and ABPM normotensive subjects (NT) (clinic BP<140/90 mmHg and awake BP<130/85 mmHg, ages 43.4±2.6 y) and in 79 untreated subjects (47.2±2.4 y) with WCH (clinic BP>140/90, awake ABP<130/85 mmHg) with no other major cardiovascular risk factors. Ambulatory blood pressure was evaluated at baseline and on at least two further occasions during follow-up. ResultsAt baseline all subjects were untreated and groups did not differ on values of metabolic parameters, BMI, left ventricular mass index, and ABPM values. Subjects were revaluated for ABPM half way through and at the end of follow-up, 35±3 and 86±4 months in NT and 49±4 and 90±4 months in WCH. Thirty-six WCH were on antihypertensive treatment (AH) after baseline until the end of follow-up (WCH-tr), whereas 43 WCH (WCH-untr) were free from AH throughout the study. In a similar way all groups showed a significant (p<0.01) progressive increase in 24-h ABPM systolic blood pressure (SBP)/diastolic blood pressure (DBP) from baseline throughout the follow-up in NT (+4.9/2.1±0.8/0.9 mmHg), average annual increase of 0.72/0.37 mmHg/y, in WCH-tr (+ 5.0/1.2±1.1/1.5 mmHg), average annual increase of 0.66/0.31 mmHg/y and in WCH-untr (+5.4/3.2±0.9/1.1 mmHg), average annual increase of 0.74/0.39 mmHg/y. During the follow-up office SBP/DBP (mmHg) significantly rose in NT (+5.7/3.9) but was reduced in WCH-tr (−7.8/5.2) and in WCH-untr (−4.7/1.1). Development of ambulatory hypertension (daytime BP >130 and/or >85 mmHg) occurred in 15.4% (6/39) of NT, in 22.7% (8/36) of WCH-tr and in 26.1% (11/43) of WCH-untr (NS). First cardiovascular events recorded were three in subjects with WCH and none in NT. ConclusionsAfter 7.4 years of follow-up, both the progressive increase in ABPM and the rate of transition to ambulatory hypertension in subjects with WCH (either treated or untreated), who were selected under strict criteria were similar to that of normotensive subjects. Also there was no evidence that WCH exhibited a clear higher risk of development cardiovascular events.

arterial distensibility in subjects with white-coat hypertension with and without diabetes or dyslipidaemia: comparison with normotensives and sustained hypertensives

Background Arterial distensibility can be assessed by measuring pulse‐wave velocity (PWV). Objective To determine whether diabetes, smoking and dyslipidaemia were associated with greater than normal stiffness of aortic walls in subjects with white‐coat hypertension. Methods Arterial distensibility was assessed by automatic measurement of carotid‐femoral PWV in 35 healthy normotensives, 46 white‐coat hypertensives (WCH, clinic blood pressures > 140/90 mmHg, daytime blood pressures < 130/85 mmHg) and 81 ambulatory hypertensives (clinic blood pressures > 140/90 mmHg, daytime blood pressures ≥ 130 mmHg systolic or ≥ 85 mmHg diastolic, or both) all matched for age, sex and body mass index. Nineteen normotensives (subgroup A), 28 WCH (subgroup A) and 37 ambulatory hypertensives (subgroup A) had only one or no other major cardiovascular risk factor whereas 16 normotensives (subgroup B), 18 WCH (subgroup B) and 44 ambulatory hypertensives (subgroup B) had also some combination of non‐insulin‐dependent diabetes, a smoking habit and dyslipidaemia. Results Both for the WCH and for ambulatory hypertensives diabetes and dyslipidaemia (subgroups B) were associated with higher (P < 0.04) PWV (11.6 ± 0.3 and 12.8 ± 0.3 m/s, respectively) than for subgroups A (9.3 ± 0.5 and 10.9 ± 0.6 m/s, respectively). In contrast, PWV for WCH in subgroup A (9.3 ± 0.5 m/s) did not differ (P > 0.35) from those for the normotensive subgroups A (9.2 ± 0.3 m/s) and B (9.6 ± 0.4 m/s). PWV was not correlated to levels of glycaemia, glycosylated haemoglobin and cholesterolaemia. Conclusions These results suggest that, both for ambulatory hypertensives and for WCH, diabetes and dyslipidaemia are associated with an impairment of arterial distensibility that can entail a greater than normal cardiovascular risk, which might dictate a more than usually stringent treatment of concomitant risk factors and possibly of high blood pressure. In contrast, PWV in WCH of the subgroup A did not differ from those in normotensives, reinforcing the hypothesis that WCH is associated with a benign cardiovascular outcome in the absence of other cardiovascular risk factors.

Differences in behavior profile between normotensive subjects and patients with white-coat and sustained hypertension

It has been hypothesized that white-coat hypertensives (WCHs) have lower cardiovascular risk than sustained hypertensives (HTs), but higher emotional reactivity. We evaluated 92 HT patients (clinic and daytime BP>140/90 mmHg), 52 WCHs (clinic BP>140190 and ambulatory daytime BP<134/ 85 mmHg), and 74 normotensive subjects (NTs, clinic BP<140/90 and ambulatory daytime BP<134/85 mmHg), aged between 24 and 72 years, and matched for educational level, age, gender, and weight for depression, psychopathology, well-being, and quality of life. HTs showed worse scores than WCHs and NTs on most of the psychological variables; no differences were found between WCHs and NTs except on physical mobility. Daytime BP variability was HTs>WCHs>NTs, whereas nighttime BP variability was HTs>WCHs=NTs. We conclude that HTs have worse psychological profiles than the other two groups. WCHs and NTs have similar psychological profiles, although WCHs have a higher daytime BP variability, which is not associated with higher emotional reactivity.

Accuracy of twenty-four-hour ambulatory blood pressure monitoring (night-day values) for the diagnosis of secondary hypertension

Objectives To determine the accuracy of 24-h ambulatory blood pressure monitoring, using the relationship between night-time and daytime values, in diagnosing secondary hypertension. Patients and methods A prospective study was performed in a referred population of 402 hypertensive patients (clinic systolic/diastolic blood pressure >140/90 mmHg). The ambulatory monitoring data included 24-h mean, awake (daytime) and sleeping (night-time) values. Secondary hypertension was diagnosed by standard procedures. To describe the accuracy of ambulatory blood pressure monitoring, receiver–operator characteristic curves were constructed, using sensitivity and specificity values for deciles of the distribution of overnight blood pressure falls (absolute and percentage). Measurements included the fall in nocturnal blood pressure, sensitivity (the percentage of those with secondary hypertension who were classified as non-dippers), specificity (the percentage of non-secondary hypertensives who were classified as dippers) and predictive values of ambulatory blood pressure monitoring. Results On average, overnight systolic/diastolic blood pressure fell in primary hypertensives (n = 290) by 20/18 mmHg (13%/19%), in white-coat hypertensives (n = 65, daytime ambulatory blood pressure <135/87 mmHg) by 17/15 mmHg (13%/19%) and in patients with secondary hypertension (n = 47, renal/renovascular and endocrine forms) by 13/11 mmHg (9%/12%). From receiver–operator characteristic curves, the nocturnal blood pressure fall of 15 mmHg showed the highest accuracy, with a sensitivity/specificity of 61%/69% (systolic) and 75%/62% (diastolic) whereas 10% (systolic) and 15% (diastolic) nocturnal falls had a sensitivity/specificity of 62%/74% (systolic) and 62%/70% (diastolic). The ambulatory blood pressure data had a high (>93%) negative predictive value for secondary hypertension. Conclusions Secondary hypertension is associated with a blunted nocturnal fall in blood pressure. Ambulatory blood pressure monitoring data are not critically important for the diagnosis and screening of secondary hypertension but may be helpful in excluding it.

G1 - Measurement of trough-to-peak ratios of four antihypertensive drugs on the basis of 24-h ambulatory blood pressure monitoring, different methods may give different results

With 24 h ambulatory blood pressure monitoring (ABPM), the trough-to-peak (T/P) ratios (corrected for placebo) of atenolol 100 mg, cilazapril 2.5 mg, enalapril 20 mg and nifedipine-GITS 30 mg administered once daily for 4 weeks were determined in four groups of hypertensive patients. T/P ratios were calculated by three different methods: directly from the curves that averaged all individual 24 h profiles (A); averaging all individual T/P ratios after ABPM data were averaged for each patient over either 1 h intervals (B) or 3 h intervals (C). Methods B and C produced different values of T/P which, for each drug, were significantly higher with method C. With method A, nifedipine appeared to have the higher T/P. With methods B and C (which in contrast to method A, permitted statistical comparisons), differences between nifedipine and the other drugs were not significant. Meanwhile, method B appears to adhere most closely to FDA guidelines by taking more into account the interindividual variability of BP profile. Thus, we suggest that precise guidelines for measuring T/P on the basis of ABPM are needed, whereas for the comparison between drugs, both the mean value of the T/P and its variance must be determined.