The optimal home blood pressure monitoring schedule based on the Didima outcome study.

This study investigated the optimal schedule for home blood pressure (HBP) monitoring that has the greatest prognostic ability and provides the most reliable assessment of HBP. The Didima study assessed the value of HBP (duplicate morning and evening measurements, 3 days) in predicting cardiovascular events in the general population (662 adults, 8.2+/-0.2 years follow-up). Criteria for the optimal monitoring schedule were stabilization of mean HBP, its variability (standard deviation (s.d.)) and hazard ratios (HRs) of cardiovascular events per 1 mm Hg HBP increase. By averaging more readings (1-12), there was a progressive decline in average HBP and its s.d. and increase in HR, with most of these benefits achieved on the second day (8 readings) and little additional benefit obtained on the third day (12 readings). The first day gave higher and more unstable HBP values (higher s.d.) with less prognostic ability (lower HR). The first HBP readings per occasion gave higher values but with similar prognostic ability as the second readings taken 1 min later. There was little difference in average HBP between morning and evening readings with no prognostic superiority of morning readings. In conclusion, by averaging more readings the average HBP and its variability are reduced and the prognostic ability improved. Any aspect of HBP monitoring (first or second readings, morning or evening) has similar prognostic ability. The first day gives higher and unstable values with lower prognostic ability and should be better discarded. These data validate the HBP monitoring schedule proposed by the European Society of Hypertension.

Unreliable oscillometric blood pressure measurement: prevalence, repeatability and characteristics of the phenomenon.

Oscillometric devices are being widely used for ambulatory, home and office blood pressure (BP) measurement. However, even successfully validated oscillometric devices fail to provide accurate measurements in some patients. This study investigated the prevalence, the reproducibility and the characteristics of the phenomenon of unreliable oscillometric BP (UOBP) measurement. A total of 5070 BP measurements were obtained simultaneously (Y connector) using a professional oscillometric device (BpTRU) and a mercury sphygmomanometer in 755 patients (1706 visits). UOBP readings were defined as those with >10 mm Hg difference (systolic or diastolic) between the two methods. UOBP was found in 15% of systolic and 6.4% of diastolic BP measurements. In all, 18% of the participants had UOBP in their first but not their second visit, or the reverse. However, 49% of these participants had at least one more UOBP visit after their second visit within the study database. Patients with persistent UOBP were more likely to be female and had lower arm circumference. The systolic BP discrepancy between the two methods was associated with pulse pressure (r=0.41) and inversely with diastolic BP (r=0.40) and arm circumference (r=0.30), whereas the diastolic discrepancy with diastolic BP (r=0.61) and inversely with pulse pressure (r=0.32). There was a consistent significant trend for larger systolic BP discrepancy and smaller diastolic from the lower to the higher pulse pressure quintile (P<0.0001). A decreasing arm circumference was a significant predictor of persistent UOBP. These data suggest that the UOBP measurement is particularly common, not very reproducible and mainly affected by pulse pressure and arm circumference.

C-peptide, IGF-I, sex-steroid hormones and adiposity: a cross-sectional study in healthy women within the European Prospective Investigation into Cancer and Nutrition (EPIC).

OBJECTIVES: The risk of some cancers is positively associated with body weight, which may influence circulating levels of sex-steroid hormones, insulin and IGF-I. Interrelationships between these hormones and the associations with adiposity were evaluated in healthy women participating in the European Prospective Investigation into Cancer and Nutrition (EPIC). METHODS: A cross-sectional analysis was performed on anthropometric and hormonal data from 743 pre- and 1217 postmenopausal women. Body mass index (BMI) and waist circumference were used as indicators of adiposity. C-peptide, Insulin Growth Factor (IGF)-I, Insulin Growth Factor binding protein (IGFBP)-3, androgens, estrogens and sex hormone binding globulin (SHBG) were measured by immunoassays; free sex steroid concentrations were calculated. RESULTS: BMI and waist circumference were positively correlated with estrogens in postmenopausal women and with C-peptide, free testosterone and inversely with SHBG in all women. C-peptide and IGF-I were inversely correlated with SHBG, and positively with free sex steroids in postmenopausal women. IGF-I was positively associated with postmenopausal estrogens and androgen concentrations in all women. CONCLUSIONS: Sex-steroid concentrations appear to be regulated along several axes. Adiposity correlated directly with estrogens in postmenopausal women and with insulin, resulting in lower SHBG and increased levels of free sex steroids. Independent of adiposity and insulin, IGF-I was associated with decreased SHBG levels, and increased concentrations of androgens and postmenopausal estrogens.

Circulating soluble E-cadherin levels are of prognostic significance in patients with multiple myeloma.

BACKGROUND: The epithelial transmembrane molecule E-cadherin (E-Cad) is the prime mediator of epithelial cell-cell adhesion, through homotypic interactions. It also participates in the maintenance of cytoskeletal structure and cell-cell signalling, while there are no published reports of expression of E-Cad in non-epithelial tissues. We examined whether the circulating levels of soluble E-Cad in newly diagnosed patients with multiple myeloma (MM) are of prognostic significance. PATIENTS AND METHODS: We used an ELISA method to determine the levels of circulating soluble E-cadherin (sE-Cad) in 21 newly diagnosed patients with MM and in 29 healthy volunteers, as a control group. RESULTS: MM patients demonstrated increased circulating levels of sE-Cad, compared with controls (p<0.0001). Increased circulating sE-Cad levels correlated with LDH levels at diagnosis (p<0.001) and poor prognosis. Multivariate analysis demonstrated that sE-Cad levels are an independent prognostic factor of survival (p<0.0207). CONCLUSION: Our data suggest that adhesion molecules play a role in the pathogenesis of MM, establish sE-Cad as an independent marker of survival and, finally, provide evidence of non-epithelial production of E-Cad in MM patients.

Dietary and lifestyle factors in relation to plasma insulin-like growth factor I in a general population sample.

There is evidence that the insulin-like growth factor system (IGF), particularly IGF-I, is important in human carcinogenesis. We studied in a general, though not strictly random population sample of 620 adults, the relationship of IGF-I to demographic, lifestyle and dietary factors, the latter ascertained through an extensive validated questionnaire. Plasma IGF-I levels declined significantly with age and the decline was more evident among women than among men. Tobacco smoking, body mass index and regular physical activity were unrelated to this hormone and a positive association with height was not statistically significant. Neither protein nor carbohydrate intake was related to plasma IGF-I levels but there was inconsistent evidence that ethanol intake may be inversely associated with plasma IGF-I and saturated and polyunsaturated lipids may be positively associated with it. The findings are evaluated in conjunction with evidence indicating that the incidence of cancer is lower among women than among men, height is a risk factor for several forms of cancer, and saturated and polyunsaturated lipids have been more closely linked to human and animal carcinogenesis than monounsaturated lipids.

Assessment of drug effects on blood pressure and pulse pressure using clinic, home and ambulatory measurements.

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.

Does the antihypertensive response to angiotensin converting enzyme inhibition predict the antihypertensive response to angiotensin receptor antagonism?

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.

Additive hypotensive effect of angiotensin-converting enzyme inhibition and angiotensin-receptor antagonism in essential hypertension.

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.

Diagnosis of hypertension using home or ambulatory blood pressure monitoring: comparison with the conventional strategy based on repeated clinic blood pressure measurements.

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.