Association of renin-angiotensin system gene polymorphisms with antihypertensive responses to angiotensin-converting enzyme inhibition or angiotensin receptor blockade.
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Biomedical subjects
Publications and source records attributed to T D Mountokalakis.
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BACKGROUND AND AIMS: To provide a direct comparison of Helicobacter pylori-positive subjects bleeding from duodenal ulcer with H. pylori-negative ones, in terms of severity of bleeding and outcome. PATIENTS AND METHODS: A case-control study was prospectively conducted in 105 H. pylori-negative duodenal ulcer bleeders and same number of sex- and age-matched H. pylori-positive ones. RESULTS: NSAID consumption was more common among H. pylori-negative subjects (81%) compared to their H. pylori-positive counterparts (58.1%, P < 0.001). H. pylori-negative bleeders were found to need more often haemostasis (55.2% versus 31.4%, P < 0.001) or surgical intervention (15.2% versus 4.8%, P = 0.011) and to have a greater proportion of rebleeding (32.4% versus 13.3%, P = 0.001), a more prolonged hospitalisation (11.6 +/- 4.1 versus 6.2 +/- 1.5 days, P < 0.001) and a higher rate of in-hospital mortality (15.2% versus 3.8%, P = 0.005). In the overall population (N = 210), H. pylori negativity, among other known risk factors, emerged as independent predictor (odds ratio: 3.2; 95% CI: 1.5, 11.2; P = 0.004) of an unfavourable outcome (surgery or death). CONCLUSIONS: Duodenal ulcer bleeding in H. pylori-negative subjects appears to be more severe, to have a higher rate of rebleeding, and to lead more often to surgery or fatality compared to the vast majority of H. pylori-positive duodenal ulcer bleeders.
An algorithm has been proposed for the detection of white coat hypertension among subjects with elevated blood pressure (BP) on at least three clinic visits using home BP monitoring (screening test) and, if this is low, ambulatory BP monitoring (diagnostic test). This study aims to test this strategy in practice. The proposed algorithm was applied in 133 untreated subjects with elevated BP assessed in a previous prospective study using repeated clinic, home and ambulatory BP measurements. The proportions of detected and missed cases of white coat hypertension and the diagnostic value of the algorithm were calculated. By applying the algorithm, 99 subjects (74%) were found eligible for home measurements and 35 (26%) for ambulatory monitoring. There were 38 subjects with white coat hypertension (38%), of whom 15 (39%) were not detected by the proposed strategy. The sensitivity, specificity, and the positive and negative predictive value of the algorithm to diagnose white coat hypertension were 61, 81, 66 and 77%, respectively. Of the 34 subjects with normal BP on the third clinic visit, 15 (42%) had elevated home and/or ambulatory BP. These data suggest that, using the proposed strategy, many white coat hypertensives may remain undetected and may receive unnecessary long-term drug treatment. Therefore, more research is needed on the optimal strategy for detecting white coat hypertension in clinical practice.
This study investigated the differences in the effect of an angiotensin converting enzyme inhibitor (ACEI) compared with an angiotensin receptor blocker (ARB) on blood pressure (BP) and pulse pressure (PP) measured in the clinic (CBP and CPP, respectively), at home (HBP, HPP) and with ambulatory monitoring (ABP, APP). Twenty-seven hypertensive patients were randomised to receive lisinopril (20 mg) or losartan (50 mg) for 5 weeks, and were subsequently crossed-over to the alternative treatment for a second 5-week period. Measurements of CBP, 24-h ABP and 5-days HBP were performed before randomisation and at the end of each treatment period. All measurement methods showed that lisinopril was more effective than losartan in reducing BP. However, the difference between the two drugs was demonstrated with greater precision using HBP (P<0.001) than 24-h ABP (P<0.01), whereas the poorest precision for demonstrating this difference was provided by CBP (P<0.05). Lisinopril was also found more effective than losartan in reducing HPP (P=0.01) and 24-h APP (P=0.03) whereas no such a difference was detected using measurements of CPP. It was concluded that the antihypertensive drugs may differ in their effects not only on BP, but also on PP. HBP monitoring appears to be as reliable as 24-h ABP monitoring in detecting differences in the effect of drugs on both BP and PP. Clinic measurements seem to be the least reliable method, particularly in the detection of differences in PP.
PURPOSE: To develop a simple and reliable diagnostic tool for differentiation of cerebral infarction (CIF) from intracerebral haemorrhage (ICH) in order to aid clinicians to decide about starting antiplatelet therapy in settings where rapid access to computed tomography (CT) is lacking. METHODS: Thirty variables regarding each patient admitted with acute stroke were recorded and considered in a logistic regression analysis using ICH as end-point (internal study). CT was used as the golden standard. The score derived was validated with data from the next consecutive stroke patients and was compared with the three preexisting scores (external validation study). RESULTS: Amongst 235 patients (119 males, mean age 70.6 +/- 11.2 years) of the internal study, 43 (18.3%) had ICH. Four independent correlates of ICH were identified and used for the derivation of the following integer-based scoring system: number of points=6 * (neurological deterioration within 3 h from admission) + 4 * (vomiting) + 4 * (WBC > 12 000) + 3 * (decreased level of consciousness). In the external study [168 patients, 85 males, mean age 70.2 +/- 10.8 years, 31 (18.5%) with ICH], when the cut-offs < or =3 points for CIF and > or =11 points for ICH were used, sensitivity, specificity, and positive and negative predictive values of the score for detection of stroke type were 97, 99, 97 and 99%, respectively; exceeding noticeably the three previously proposed systems. CONCLUSIONS: The proposed model provides an easy to use tool for sufficiently accurate differentiation between haemorrhagic and nonhaemorrhagic stroke on the basis of information available to all physicians early after admission.
To test the hypothesis that the antihypertensive response to angiotensin converting enzyme (ACE) inhibition can predict the response to angiotensin II type I receptor (AT1R) antagonism, 33 hypertensive patients were randomized to receive lisinopril (20 mg) or losartan (50 mg) for 5 weeks. Patients were then crossed-over to the alternative treatment for a second 5-week period. Twenty-four-hour ambulatory BP (ABP) was measured before randomization and on the final day of each period. The agreement in ABP response between the two drugs was assessed using the following approaches: Subjects were classified as responders and nonresponders using as a threshold an arbitrary level of response (ABP fall > or = 10 mm Hg systolic or > or = 5 mm Hg diastolic) or the median ABP response achieved by each of the drugs. Disagreement between the two drugs in the responders-nonresponders classification was expressed as the proportion of subjects whose ABP responded to one of the drugs only. Lisinopril was more effective than losartan in reducing ABP (mean difference 4.7+/-8.1/3.3+/-5.7 mm Hg, systolic/diastolic, P < .05). Disagreement in the antihypertensive response between the two drugs was found in 39%/33% of subjects for systolic/diastolic ABP using the arbitrary response criterion (33%/39% using the median response criterion). Significant correlations were found between the responses to lisinopril and losartan (r = 0.47/0.59, systolic/diastolic, P < .01). We conclude that in more than one third of hypertensive subjects, the BP response to ACE inhibition fails to predict the response to AT1R antagonism and vice versa. These data suggest that there are differences between these two drug classes that are not only of theoretical but also of practical significance.
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To evaluate reference values of home blood pressure (HBP) a cross-sectional community study was conducted on 694 adult subjects (aged > or = 18 years) of the village Didima in southern Greece (participation rate 76.4%). Clinic blood pressure (CBP) was measured on two visits (triplicate measurements, mercury sphygmomanometer) and HBP on 3 workdays (duplicate morning and evening measurements, oscillometric devices; Omron HEM 705CP). After exclusion of 132 subjects (103 treated hypertensives and 29 with incomplete data), 562 subjects were analyzed (mean +/- SD aged 51.2 +/- 17.2 years, 42.7% men). Average HBP (120.0 +/- 17.8/72.6 +/- 8.8 mm Hg, systolic/diastolic) was strongly correlated (P < .0001) with CBP (118.7 +/- 17.7/73.8 +/- 10.5 mm Hg). Systolic CBP was 1.3 mm Hg lower than HBP (P < .01, 95% confidence interval 0.4, 2.2), whereas diastolic CBP was 1.2 mm Hg higher than HBP (P < .0001, 95% confidence interval 0.6, 1.7). The threshold of HBP normality determined using three different approaches was 1) 139.7/83.0 mm Hg (systolic/diastolic) using the distribution criterion (95th percentile of the HBP distribution among 476 normotensive subjects); 2) 139.7/85.8 mm Hg using the correspondence criterion (the percentiles of the CBP distribution that correspond to CBP > or = 140/90 mm Hg were estimated, and the levels of BP that correspond to these same percentiles on the HBP distribution were calculated); and 3) 137.4/82.7 mm Hg using the regression criterion (calculation of the levels of HBP that correspond to CBP of 140/90 mm Hg using the regression equation between HBP and CBP). Overall, the findings of the three criteria suggest that average HBP < 137/82 mm Hg might be considered as probably normal, > 140/86 mm Hg as probably abnormal, and within these limits as borderline. Until mortality-based prospective data are available, this approach might be useful in the interpretation of HBP in clinical practice.
OBJECTIVE: To investigate whether measurement of blood pressure at home (HBP) and by ambulatory monitoring (ABP) are reliable alternatives to the traditional strategy for the diagnosis of hypertension based on blood pressure measurement on repeated clinic visits (CBP). DESIGN: Comparison of the diagnosis of hypertension based on HBP (on six workdays) or ABP monitoring (two occasions) with that based on CBP (five visits within 3 months). SETTING: Outpatient hypertension clinic. PARTICIPANTS: We enrolled 133 individuals with a diastolic CBP of 90-115 mmHg on the initial visit. MAIN OUTCOME MEASURES: CBP, HBP and ABP values, and the diagnosis of hypertension. RESULTS: Hypertension was diagnosed in 70, 63 and 56% of individuals using the CBP, ABP and HBP methods respectively (P = 0.04). Agreement in the diagnosis of hypertension between all three methods was found in 59% of individuals. Disagreement between CBP and ABP was found in 27%, between CBP and HBP in 29% and between ABP and HBP in 26% of individuals. The sensitivity, specificity and positive and negative predictive values of ABP to diagnose hypertension correctly were 76, 67, 85 and 53% respectively; for HBP the respective values were 69, 77, 88 and 51%. The same parameters for HBP compared with ABP in the detection of white-coat hypertension were 61, 79, 48 and 86% respectively. CONCLUSIONS: Indiscriminate use of HBP or ABP monitoring in the evaluation of all individuals with high blood pressure will probably result in confusion and therefore should be discouraged. However, in the detection of white-coat hypertension, HBP appears to be useful as a screening test, which, if positive, requires confirmation with ABP monitoring.
The study was designed to assess the antihypertensive effect of combined angiotensin-converting enzyme (ACE) inhibition and angiotensin II type 1 receptor (AT1) antagonism in patients with essential hypertension. Twenty patients with uncontrolled ambulatory diastolic blood pressure (BP) after 6 weeks of ACE inhibitor monotherapy (benazepril, 20 mg, o.d.) were randomized to receive double-blind valsartan, 80 mg, o.d. (AT1 antagonist) or matching placebo for 5 weeks while continuing to receive background benazepril. Then patients crossed over to the alternative regimen for a second 5-week period. The 24-h ambulatory BP was monitored on the final day of the benazepril monotherapy period and on the final day of each double-blind treatment period. Valsartan added to benazepril produced a significant antihypertensive effect with a benefit over placebo of 6.5 +/- 12.6/4.5 +/- 8.0 mm Hg (systolic/diastolic) for average awake ambulatory BP (p < 0.05), 7.1 +/- 9.4/5.6 +/- 6.5 mm Hg for asleep BP (p < 0.01), and 6.8 +/- 9.7/4.9 +/- 6.8 mm Hg for average 24-h ambulatory BP (p < 0.01). Pulse rate was unaffected. Plasma active renin was higher on the benazepril-valsartan combination compared with benazepril-placebo (p < 0.05). There was no change in routine biochemical variables when valsartan was added to benazepril. Six patients reported mild dizziness or fatigue (three also with placebo). These data suggest that in hypertensive patients uncontrolled with an ACE inhibitor, the addition of an AT1 antagonist provides a powerful and safe antihypertensive drug combination.
To assess the prevalence and the levels of awareness, treatment, and control of hypertension in the rural population of Greece, a cross-sectional survey of the total population age > or =18 years of the village Didima was conducted. The survey included an interview and blood pressure (BP) measurement on two clinic visits. Hypertension was defined as systolic BP > or = 140 mm Hg and or diastolic BP > or = 90 mm Hg or current treatment with antihypertensive drugs. The same BP threshold was used for the assessment of hypertension control. A total of 694 inhabitants participated (response rate 76.4%), and 665 were analyzed. The prevalence of hypertension was 28.4% (men 30.2%, women 27.1%). Of the subjects age > or =65 years, 50% had hypertension. Although 73% of participants were measuring their BP at least once a year, overall, 39.2% of hypertensives were unaware of the diagnosis (men 50%, women 30.5%), 6.3% were aware but not treated (men 4.8%, women 7.6%), 27.5% were treated but not controlled (men 22.6%, women 31.4%), and 27% were treated and controlled (men 22.6%, women 30.5%). These results suggest that, in the rural population of Greece, hypertension is a common risk factor with considerable potential for improvement in levels of control.
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The objective of the study was to investigate whether home blood pressure (HBP) is a reliable alternative to ambulatory blood pressure (ABP) for the detection of the white coat effect (WCE). Hypertensive patients were randomized to measure HBP for 2 weeks or ABP for 24 h. The alternative measurement was then performed. Clinic blood pressure (CBP) was measured in the beginning and end of the study. Subjects with a difference of > or = 20 mm Hg systolic or > or = 10 mm Hg diastolic BP between CBP and awake ABP or CBP and HBP, were classified as clinic reactors. A total of 189 patients completed the study (79 on stable antihypertensive treatment). There was no difference in the magnitude of WCE assessed using the ABP or the HBP method (mean discrepancy, systolic BP: -1.5 +/- 11.7 mm Hg, 95% CI -3.2, 0.2; diastolic BP: 0.9 +/- 7.0, 95% CI -0.1, 1.9). A strong association existed between WCE calculated using the HBP or the ABP method (r = 0.64/0.59 systolic/diastolic, P < .001). The proportion of patients classified as clinic reactors was identical using the HBP or the ABP method (25.9%). Agreement between methods in the classification of clinic reactors was found in 147 patients (78%). The sensitivity and specificity of the HBP method to classify correctly clinic reactors (ABP method used as the standard) were 57% and 85%, respectively, whereas its positive and negative predictive value were 57% and 85%. These results indicate that HBP is not appropriate as an alternative to ABP diagnostic testing in the detection of WCE. Nevertheless, HBP appears useful as a screening test for the detection of this phenomenon.
OBJECTIVE: To determine the minimum number of self-measurements of blood pressure at home (HBP) necessary to provide the maximum clinically important benefit. METHODS: Hypertensive patients were randomly allocated to monitor HBP for 2 weeks (6 work days, duplicate measurements, twice daily) or ambulatory blood pressure for 24 h. The alternative measurement was then performed. Clinic blood pressure was measured at the beginning and the end of the study. Criteria for reliability of HBP were the stabilization of mean HBP, its variability (SD) and the correlation coefficient r for relationship of HBP with ambulatory blood pressure. The reproducibility of HBP was quantified using test-re-test correlations and the SD of differences between average HBP values of different days. RESULTS: We studied 189 patients (79 being administered stable antihypertensive treatment). Average HBP (137.5 +/- 16.2/85.9 +/- 9.9 mmHg) was lower than average clinic blood pressure (P<0.001) and higher than 24 h and night-time ambulatory blood pressures (P<0.001). There was no difference between HBP and daytime ambulatory blood pressure. On day 1 HBP was higher than it was on each of days 2-6, with no difference among days 2-6. When data for the initial day for monitoring of HBP were excluded from analysis, average HBP was reduced. Only a modest improvement in the reliability of HBP on day 2 (reductions in mean HBP and its SD and an increase in r with ambulatory blood pressure) was achieved by averaging more readings taken on succeeding days. At least two monitoring days were needed for the reproducibility of HBP to be superior to that of clinic blood pressure. CONCLUSIONS: These results suggest that determining average HBP of the second and third work days, is the minimum programme that provides a reliable estimate of HBP.
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Blood pressure (BP) during siesta declines to levels similar to those of night time sleep. The objective of the study was to assess the effect of siesta on 24-h ambulatory BP (ABP) data. Two different approaches were employed for the definition of day and night periods: (1) actual patient reported day and night intervals (ACT) with siesta period analysed as a third time period; and (2) arbitrary day and night time intervals (ARB) with the presence of siesta being ignored. A total of 203 24-h ABP recordings were analysed, with a siesta during ABP monitoring reported in 154 of them. Mean siesta BP was very close to ACT night time BP. Among recordings with a siesta, ACT daytime BP was higher and night time BP lower than the corresponding ARB BPs (P < 0.001). The magnitude of night time BP drop was greater with ACT intervals, resulting in a lower percentage of non-dippers (P < 0.001). Among 49 recordings without a siesta, differences between ACT and ARB BPs were less pronounced for daytime but not for night time. Differences in the magnitude of nocturnal BP drop between ACT and ARB periods, although statistically significant, did not affect the prevalence of non-dippers. In conclusion, analysis of 24-h BP profiles by using ARB instead of ACT day and night intervals results in underestimation of the nocturnal BP drop and overestimation of the proportion of non-dippers. This bias is more pronounced in patients who take a siesta during ABP monitoring.
The study was designed to investigate whether a long-acting dihydropyridine calcium antagonist has additional antihypertensive effect when combined with currently used low-dose thiazide diuretic therapy. After 6 weeks with open chlorthalidone monotherapy at 25 mg daily, hypertensive patients with trough diastolic BP 90-115 mm Hg were randomly assigned to receive double-blind lacidipine, 4 mg daily or matching placebo for 4 weeks, while continuing to receive background chlorthalidone. Then patients crossed over to the alternative regimen for a second 4-week period. Clinic and 24-h ambulatory blood pressure (BP) were measured on the final day of chlorthalidone monotherapy and on the final day of each double-blind treatment. Seventeen patients completed the study [mean age, 51.0 +/- 6.9 (SD) years]. Clinic BP was lower with lacidipine versus placebo (systolic, p < 0.01; diastolic, p < 0.05). Daytime ambulatory BP was reduced with lacidipine (p < 0.05), whereas nighttime BP was unchanged. Mean 24-h ambulatory diastolic BP also was reduced on lacidipine (p < 0.05). Heart rate was increased on lacidipine during both daytime (p < 0.01) and nighttime (p < 0.05). In conclusion, when added to chlorthalidone, lacidipine produced a significant reduction in clinic and ambulatory BP during daytime but not nighttime. This was associated with increased heart rate. Modem long-acting dihydropyridines may produce small but clinically significant additive antihypertensive effects in patients uncontrolled on low-dose thiazide monotherapy.
Home blood pressure (HBP) measurement is becoming increasingly popular as an additional source of information for the practicing physician. Whether HBP measured with a fully automated oscillometric device (oHBP) is more reliable than HBP measured with an aneroid sphygmomanometer and a stethoscope (sHBP) remains unclear. We compared sHBP with oHBP using as a reference method daytime ambulatory blood pressure (ABP), as this is believed to be a better index of an individual's overall level of pressure. Forty-six hypertensive patients measuring HBP with aneroid devices were retrained by a standard 30 min protocol that included training in the technique of measurement, checking patients' devices, and testing patients' performance in stethoscopic measurement. Patients were randomized to measure for 2 weeks either sHBP using their own calibrated aneroid devices or oHBP using a validated fully automated oscillometric device (Omron HEM-705CP). Then 24 h ABP monitoring was performed (SpaceLabs 90207) and patients crossed over for a second 2 week period by using the alternative HBP measurement technique. Mean sHBP was not different from mean oHBP, and there was a close correlation between them (r = 0.82/0.76 for systolic/diastolic BP, P < .001). Daytime ABP was not different from oHBP or sHBP and was closely related to both of them (oHBP, r = 0.59/0.72 systolic/diastolic BP, P < .001; sHBP, 0.50/0.65, P < .001). Age was significantly related with diastolic ABP-sHBP difference (r = 0.33, P < .05). These results suggest that HBP measured with validated fully automated oscillometric devices is equally reliable in predicting average ABP as that measured with calibrated aneroid sphygmomanometers used by very carefully trained patients. In clinical practice, HBP monitoring by using reliable automated devices is probably more feasible than to achieve a high standard of stethoscopic HBP measuring technique.