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.

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.

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.

The present study was aimed at reviewing the medical literature devoted to the clinical applications of self-blood pressure monitoring (SBPM) and at providing some recommendations regarding the use of SBPM for diagnostic purposes. The lack of reliability of conventional blood pressure (BP) measurement is largely related to the extreme variability of BP over time. SBPM provides a large number of readings and can be used to predict the results of repeated clinical measurements. The use of SBPM in the diagnosis of white coat hypertension can be proposed as a screening test: if it gives a positive result (a low home BP), it should be confirmed by ambulatory BP monitoring (ABPM). SBPM could improve patients' compliance with medication. Last, SBPM may be cost-effective for the management of hypertensive patients, by reducing costs of medication, number of clinic visits and costs of cardiovascular morbidity. Compared with ABPM, SBPM seems to have a less value for the initial diagnosis of hypertension and for predicting prognosis. In contrast, it should be of more value for the long term follow-up of patients with white coat hypertension and for the evaluation of treatment efficacy in patients with sustained hypertension. The use of SBPM in diabetic hypertensives, in pregnant women and in the elderly is encouraged, but needs further evaluation.

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.

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.

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.

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.

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.

It has consistently been reported that older AIDS patients have a shortened survival compared with younger patients. The aim of the present study was to investigate whether this difference in survival is caused by differences in the pattern of the complicating diseases. Information on patient follow-up after the AIDS diagnosis was obtained by retrospective case note review. The 6,546 patients were followed from the time of AIDS diagnosis as part of the multicentre AIDS in Europe study, which examined AIDS cases diagnosed at 52 centres in 17 European countries between 1979 and 1989. Occurrence of AIDS-defining events and demographic variables were recorded for all patients, and CD4 lymphocyte count at the time of AIDS diagnosis for approximately half the patients. After adjusting for imbalances in other variables, persons > or = 50 years of age had a significantly higher risk of contracting AIDS wasting syndrome, AIDS dementia complex and oesophageal candidiasis after the initial AIDS diagnosis, compared with age group 30-39 years [relative risk (RR) 95% confidence interval (CI)], 3.23 (2.70-3.75 CI); 2.48 (2.16-2.80 CI); 1.55 (1.26-1.83 CI), respectively]. Shortened survival after the time of AIDS diagnosis was associated with older age. After adjusting for pattern of complicating diseases, the age effect remained unchanged. Older age predisposes to AIDS-related wasting syndrome, AIDS dementia complex and oesophageal candidiasis. Independent of these differences, older age is significantly associated with shortened survival, suggesting that factors such as severity of complicating diseases or the capability of handling serious infections, rather than disease pattern, are responsible for the shortened survival.

To investigate the reliability of home blood pressure (HBP) measurement as it is generally used in practice, we studied 50 consecutive newly referred hypertensive patients that were measuring HBP for at least 6 months before referral. No specific instructions on the technique of HBP measurement were given to the patients. HBP was compared to clinic BP (CBP) by using daytime ambulatory BP (ABP) as a reference method. The technique of HBP measurement used by the patients was assessed on the basis of a detailed questionnaire and the accuracy of the devices was tested against a mercury column. There was no difference between the degree of similarity of ABP with HBP or CBP (mean value of discrepancies and correlation coefficients) for systolic BP (SBP) and little difference for diastolic BP (DBP). However, the variability of discrepancies between HBP and ABP was equal to the corresponding variability between CBP and ABP, indicating that HBP was not better predictor of ABP than CBP. Although patients measured HBP more frequently than generally recommended, poor standardisation of measurement and wrong technique were particularly common. In conclusion, in the present study HBP measurement offered no advantage over CBP in predicting ABP. The theoretical advantages of HBP may be partially offset by incorrect technique and less standardised conditions of measurement. Without patients education and regular maintenance of devices HBP offers no advantage over CBP and should not be used. (This article is based on data presented at the 7th European Hypertension Society Meeting in Milan, June 1995).

One hundred and seventy-four patients with advanced colorectal cancer were treated with 5-fluorouracil (5-FU), mitomycin-C (MIT-C) and Adriamycin (ADR) (FAM). The total response rate was 26.4%. A higher response rate (37%) was observed in patients with liver metastases only, compared to other sites of metastases (p < 0.02). Complete remission were achieved only in patients with liver metastases (15%). Male patients with liver metastases had a higher response rate than females (p < 0.03). Twenty-five patients previously treated unsuccessfully with 5-FU and MIT-C showed a response rate of 28% when ADR was added to the regimen. The patients' median survival was 11 months (range: from 3 to > or = 60 months). The median survival of patients with liver metastases was 11 months and that of responders (20 months) was significantly longer than that of nonresponders (7 months; p < 0.0001). These results suggest that the FAM combination might be considered an eligible chemotherapy schedule for patients with liver metastatic disease from colorectal cancer.

The effect of the cytotoxic drug 5-fluorouracil (5-FU) on plasma lipid levels was studied in patients and animals. Seven patients with metastatic carcinoma of the colon and three with advanced breast cancer were treated with 5-FU monotherapy by i.v. push at a dose of 500 mg/m2/d for 3-5 consecutive days. The animal group comprised 9 rabbits treated with 5-FU by i.v. push at 12-18 mg/kg/d for 2 consecutive days. Measurements of serum lipid levels were performed before and 2 and 4 weeks after 5-FU administration. No obvious change of diet, body weight and bowel habits occurred during the study period. A significant reduction of total plasma cholesterol was observed in both patients and animals. The triglyceride levels were also reduced in the rabbits. Maximal cholesterol-lowering effect was observed in patients and rabbits with higher baseline cholesterol levels. The results suggest that 5-FU might interfere with lipid metabolism.