Hilde Celis

Daytime and Nighttime Blood Pressure as Predictors of Death and Cause-Specific Cardiovascular Events in Hypertension

Our aim was to assess the prognostic significance of nighttime and daytime ambulatory blood pressure and their ratio for mortality and cause-specific cardiovascular events in hypertensive patients without major cardiovascular disease at baseline. We performed a meta-analysis on individual data of 3468 patients from 4 prospective studies performed in Europe. Age of the subjects averaged 61±13 years, 45% were men, 13.7% smoked, 8.4% had diabetes, and 61% were under antihypertensive treatment at the time of ambulatory blood pressure monitoring. Office, daytime, and nighttime blood pressure averaged 159±20/91±12, 143±17/87±12, and 130±18/75±12 mm Hg. Total follow-up amounted to 23 164 patient-years. We used multivariable Cox regression analysis to assess the hazard ratios associated with 1 standard deviation higher blood pressure. Daytime and nighttime systolic blood pressure predicted all-cause and cardiovascular mortality, coronary heart disease, and stroke, independently from office blood pressure and confounding variables. When these blood pressures were entered simultaneously into the models, nighttime blood pressure predicted all outcomes, whereas daytime blood pressure did not add prognostic precision to nighttime pressure. Appropriate interaction terms indicated that the results were similar in men and women, in younger and older patients, and in treated and untreated patients The systolic night–day blood pressure ratio predicted all outcomes, which only persisted for all-cause mortality after adjustment for 24-hour blood pressure. In conclusion, nighttime blood pressure is in general a better predictor of outcome than daytime pressure in hypertensive patients, and the night–day blood pressure ratio predicts mortality, even after adjustment for 24-hour blood pressure.

Regression of Left Ventricular Mass by Antihypertensive Treatment: A Meta-Analysis of Randomized Comparative Studies

Blood pressure–lowering therapy reduces left ventricular mass, but the question of whether differences exist among drug classes has not been fully resolved. Our aim was to compare the effects of diuretics, &bgr;-blockers, calcium channel blockers, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers on left ventricular mass regression in patients with hypertension on the basis of prospective, randomized comparative studies. We performed meta-analyses, involving pooled pairwise comparisons of the drug classes and of each class versus other classes statistically combined, and meta-regression analyses to identify the determinants of the regression. The 75 relevant publications involved 84 pairwise comparisons and 6001 patients. Regression of left ventricular mass was significantly less (P=0.01) with &bgr;-blockers (9.8%) than with angiotensin receptor blockers (12.5%), but none of the other analyzable pairwise comparisons between drug classes revealed significant differences (P>0.10). In addition, &bgr;-blockers showed less regression than the other 4 classes statistically combined (P<0.01), and regression was more pronounced with angiotensin receptor blockers versus the others (P<0.01). In multivariable meta-regression analysis on all of the treatment arms, &bgr;-blocker treatment was a significant and negative predictor of the regression (−3.6%; P<0.01), but this was not the case for the other drug classes, including angiotensin receptor blockers. In conclusion, &bgr;-blockers show less regression of left ventricular mass, whereas angiotensin receptor blockers may induce larger regression. The inferiority of &bgr;-blockers appears to be more convincing than the superiority of angiotensin receptor blockers.

The epidemiology of the association between hypertension and menopause

Menopause is a normal aging phenomenon in women and consists of the gradual transition from the reproductive to the non-reproductive phase of life. The median age at the menopause is currently around 50 years. As a result of the increasing life expectancy in the first and second worlds, many women will be postmenopausal for over one-third of their lives. The influence of menopause per se on blood pressure remains uncertain. Recent experimental and epidemiological evidence supports the hypothesis that oestrogen deficiency may induce endothelial and vascular dysfunction and potentiate the age-related increase in systolic pressure, possibly as a consequence of a reduced compliance of the large arteries. However, the latter hypothesis requires further investigation.

Cardiovascular Risk In White-coat and Sustained Hypertensive Patients

We compared cardiovascular outcome between patients with white-coat and sustained hypertension who had previously participated in the Ambulatory Blood Pressure Monitoring and Treatment of Hypertension (APTH) trial. Baseline characteristics, including office and ambulatory blood pressure (BP), were measured during the 2-month run-in period of the APTH trial. During follow-up, information on the occurrence of major cardiovascular events (death, myocardial infarction, stroke and heart failure), achieved office BP and treatment status was obtained. At entry, 326 patients had sustained hypertension (daytime ambulatory BP S 140 mmHg systolic and/or S 90 mmHg diastolic) and 93 had daytime ambulatory BP below these limits and were classified as white-coat hypertensives. During 2088 patientyears of follow-up (median follow-up 5.3 years), all major cardiovascular events ( n = 22) occurred in the patients with sustained hypertension (rate 12.7 per 1000 patient-years, p = 0.02 for between-group difference). Furthermore, multiple Cox regression confirmed that after adjustment for important covariables, daytime ambulatory BP - but not office BP at entry - significantly and independently predicted cardiovascular outcome. After additional adjustment for office BP, daytime ambulatory BP still predicted the occurrence of major cardiovascular events. Although white-coat hypertension was less frequently associated with antihypertensive drug treatment during follow-up, it carried a significantly better prognosis than sustained hypertension.

Prognostic Significance of Electrocardiographic Voltages and Their Serial Changes in Elderly With Systolic Hypertension

The aim of the present study was to assess the prognostic value of ECG voltages at baseline and their serial changes during follow-up in a large prospective study with standardized follow-up and strictly defined end points. Patients who were 60 years old or older, with systolic blood pressure of 160 to 219 mm Hg and diastolic pressure <95 mm Hg, were randomized into the double-blind placebo-controlled Systolic Hypertension in Europe trial. Active treatment consisted of nitrendipine, which could be combined with or replaced by enalapril, hydrochlorothiazide, or both. At the end of the double-blind part of the trial (median follow-up, 2.0 years), follow-up was extended and all patients received active study drugs (median total follow-up, 6.1 years). Electrocardiography was performed at baseline and yearly thereafter. Electrocardiographic left ventricular mass was prospectively defined as the sum of 3 voltages (RaVL+SV1+RV5), which averaged 3.1±1.0 mV. The adjusted relative hazard rate, associated with a 1 mV higher sum at baseline, amounted to 1.10 and 1.15 for all-cause and cardiovascular mortality and to 1.21 and 1.18 for strokes and cardiac events, respectively (P≤0.01 for all). A 1-mV decrease in electrocardiographic voltages during follow-up independently predicted a lower incidence of cardiac events (relative hazard rate: 0.86; P≤0.05), but not of stroke or mortality. In conclusion, electrocardiographic voltages at baseline and their serial changes during follow-up predict subsequent events in older patients with systolic hypertension.

Influence of cholesterol lowering on plasma membrane lipids and cationic transport systems

Background In order to determine whether alterations in membrane lipids affect transmembrane cationic transport systems in erythrocytes and platelets, cationic fluxes and intracellular cationic concentrations were measured in hypercholesterolaemic patients before and during administration of an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase. Methods After a 1-month run-in placebo period on a lipid-lowering diet the patients were treated, in a double-blind manner, with either placebo (n=25) or pravastatin (n=25) for 6 months. Placebo or pravastatin (10 mg during the first month, 20 mg during the second month and 40 mg during the remaining 4 months) was administered once a day in the evening. Results Compared with the placebo group, the erythrocyte and platelet membrane cholesterol content was reduced in the patients treated with pravastatin. The intra-erythrocyte and intraplatelet Na+ concentration was reduced during pravastatin administration, whereas the activity of the erythrocyte and platelet Na+-K+ pump was increased. However, the intra-erythrocyte and intraplatelet K+, Mg2+ and cytosolic Ca2+ concentrations, and water content, as well as the activities of the erythrocyte Na+-Li+ countertransporter and Na+, K+ cotransporter, and Na+ and K+ leakage, were not changed during pravastatin treatment. Conclusions The present data show that cholesterol lowering in hypercholesterolaemic patients may result in a significant decrease in erythrocyte and platelet membrane cholesterol content. These changes in membrane cholesterol are accompanied by an increase in activity of the Na+-K+ pump and a decrease in intra-erythrocyte and intraplatelet Na* concentrations.

For how many days should blood pressure be measured at home in older patients before steady levels are obtained

This study investigated the period of time that blood pressure (BP) should be measured at home in older patients in order to obtain steady BP values. Thirty-six men and 38 women (⩾60 years) were recruited at one family practice. At one office visit the family physician measured supine, sitting and standing BPs three times consecutively in each position. During 10 consecutive days, BP was measured at home five times daily. The supine and standing BPs were measured once in the morning and in the evening and the sitting BP once at noon. These home BP values were averaged over the first day (1-day), over the first 3 days (3-day) and all 10 days (10-day) of measurements. In both the supine (−5.1 mm Hg) and sitting (−3.8 mm Hg) positions the 10-day average systolic home BP was significantly lower than the corresponding office BP. The opposite was observed for the 10-day average standing home BP values (+7.3/+3.4 mm Hg). Comparison of the 3-day and 10-day average home BP values showed only a significantly lower 10-day than 3-day systolic BP level in the supine position (−1.1 mm Hg, 95% CI −1.9 to −0.2 mm Hg). Repeated measures ANOVA, showed a small but significant decrease over time only for the supine systolic home BP (−0.29 mm Hg per day, 95% CI −0.49 to −0.08 mm Hg per day). We conclude that in older subjects, 3 days of home measurements may suffice to obtain steady values for the sitting and standing BPs. A longer interval might be required for the supine BP.

Prognostic significance of various characteristics of out-of-the-office blood pressure.

After the initial investigations by Perloff et al. [1,2], our knowledge on the prognostic significance of out-of-theoffice blood pressure measurements has tremendously increased in the last decade [3–27]. Blood pressure was most often assessed by use of ambulatory blood pressure monitoring [1–7,9–25,27], although in some reports blood pressure was measured at the patients’ home [8,26,27]. Studies have been performed in the general population [5,6,8,9,14,19], in elderly [16,22], in hypertensive patients in general, with or without treatment [1–4,7,11,17,18,21,23,24,26,27], in older patients with systolic–diastolic or isolated systolic hypertension [12,13,15,20,25] and in refractory hypertension [10]. In the current issue of the journal, Björklund et al. [28] extend our knowledge by assessing the prognostic significance of ambulatory blood pressure in 70-year-old men who participated in a prospective longitudinal population-based follow-up study in Uppsala, Sweden.

Transfer of cadmium from a sandy acidic soil to man : a population study

This population study included 230 subjects (age range 20-83 years) who consumed vegetables grown in kitchen gardens on a sandy acidic soil (mean pH approximately 6.3). The study investigated the association between the Cd (cadmium) levels in blood and urine and the Cd concentration in the soil (range 0.2-44 ppm). Seventy-six subjects were current smokers and 122 participants lived in a district with known Cd pollution. Urinary Cd in the 230 subjects averaged 8.7 nmole/24 hr, (range 1.3 to 47 nmole/24 hr) after age adjustment positively correlated with the Cd level in the soil; a twofold increase of the Cd concentration in the soil was accompanied by a 7% rise in urinary Cd in men (R2 = 0.05; P = 0.04) and by a 4% rise in women (R2 = 0.02; P = 0.05). Blood Cd averaged 11.5 nmole/liter (range 1.8-41 nmole/liter) and was negatively associated with the Cd level in the soil. After adjustment for significant covariates (smoking and serum gamma-glutamyl transpeptidase in both sexes, and age and serum ferritin in women), a twofold increase in the Cd concentration in the soil was accompanied by a 6% decrease in blood Cd in men (R2 = 0.03; P = 0.09) and by a 10% decrease in women (R2 = 0.06; P less than 0.01). In conclusion, in a rural population, consuming vegetables grown on a sandy acidic soil, 2 to 4% of the variance of urinary Cd was directly related to the Cd level in the soil. The negative correlation with blood Cd, a measure of more recent exposure, was biased by the implementation of preventive measures in the polluted district.

The Trough-to-Peak Ratio as an Instrument to Evaluate Antihypertensive Drugs

The U.S. Food and Drug Administration designed the trough-to-peak ratio as an instrument for the evaluation of long-acting antihypertensive drugs, but the ratios are usually reported without accounting for interindividual variability. This study investigated how the trough-to-peak ratio would be affected by interindividual and intraindividual variability and by smoothing of the diurnal blood pressure profiles. The ambulatory blood pressure was recorded on placebo in 143 hypertensive patients (diastolic pressure on conventional measurement > 95 mm Hg). After 2 months, the recordings were repeated on 10 mg (n = 66) or 20 mg (n = 77) lisinopril given once daily between 7 and 11 PM. The baseline-adjusted trough-to-peak ratios were determined from diurnal blood pressure profiles with 1-hour precision. Lisinopril reduced (+/- SD) the 24-hour pressure by 16 +/- 17 mm Hg for systolic and 10 +/- 10 mm Hg for diastolic (P < .001). According to the usual approach, disregarding interindividual variability, the trough-to-peak ratio was 0.72 for systolic pressure and 0.67 for diastolic pressure. In the 143 patients the ratios were not normally distributed. They were the same on both lisinopril doses. When interindividual variability was accounted for, the median trough-to-peak ratio was 0.34 (P5 to P95 interval, -0.46 to 0.87) for systolic pressure and 0.26 (-0.44 to 0.84) for diastolic pressure. In 66 patients examined twice on 10 mg lisinopril at a median interval of 32 days, the trough-to-peak ratios were characterized by large intraindividual variability.(ABSTRACT TRUNCATED AT 250 WORDS)