Lia E. Bang

24-h ambulatory blood pressure in 352 normal Danish subjects, related to age and gender

UNLABELLED The study was conducted to determine age and sex stratified normal values for 24-h ambulatory blood pressure. A sample of 352 healthy subjects (all white) were randomly selected from the community register and stratified by sex and age groups in decades from 20 to 79 years of age. Persons with a history of hypertension, cerebral apoplexy, diabetes, myocardial or renal disease, and who were taking blood pressure-influencing medication were excluded. Ambulatory blood pressure was recorded over 24 h, with measurements taken every 15 min from 07:00 to 22:59, and every 30 min from 23:00 to 6:59. Systolic blood pressure increased only slightly with age and was significantly higher in men than in women. The diastolic blood pressure increased only slightly with age in both sexes until the 50 to 59 years age group and declined thereafter. The diastolic blood pressure was not different for the two sexes. Both systolic and diastolic blood pressure were approximately 15% lower during the night regardless of age or sex. Ambulatory blood pressure during the daytime was on an average of 5 mm Hg lower than office blood pressure, but the mean difference between the two measurements increased with age. The variability of the difference also increased with age. IN CONCLUSION Normal values for ambulatory blood pressure are presented in a randomly selected age- and gender-stratified population. Differences between office blood pressure and ambulatory blood pressure increased with age suggesting that the previously observed higher blood pressure seen in the elderly partly might be explained by a greater impact of white coat hypertension in older people.

On the Mechanisms of Blunted Nocturnal Decline in Arterial Blood Pressure in NIDDM Patients With Diabetic Nephropathy

Nondiabetic hypertensive patients lacking the normal nocturnal decline in arterial blood pressure have enhanced cardiovascular complications. Since cardiovascular morbidity and mortality are increased in non-insulindependent diabetes mellitus (NIDDM), we performed a prospective cross-sectional case-controlled study comparing the diurnal variation in arterial blood pressure, prevalence of dippers, cardiac autonomic nervous function (beat-to-beat variation during deep breathing), and extracellular fluid volume (51Cr-labeled EDTA) in 55 NIDDM patients with diabetic nephropathy (group 1), 55 NIDDM patients with normoalbuminuria (group 2), and 22 nondiabetic control subjects (group 3). All antihypertensive treatments were withdrawn at least 2 weeks before the study. The nocturnal blood pressure reduction (daytime-to-nighttime)/daytime (mean ± SE) was impaired in group 1 (6.6 ± 1.5%) and group 2 (11.1 ± 1.4%) as compared with group 3 (17.6 ± 1.7%), and it was impaired in group 1 as compared with group 2 (JP <0.05 for each comparison). The prevalence of dippers (95% confidence interval) was lower in group 1 (42% [29–56]) as compared with group 2 (58% [44–71]; P = 0.08) and group 3 (86% [65+97]; P < 0.001) and in group 2 as compared with group 3 (P < 0.01). Abolished beat-to-beat variation was more prevalent in group 1 (63% [50–76]) as compared with group 2 (15% [7–27]) and with group 3 (5% [0–23]) (P < 0.001). Nocturnal blood pressure reduction was associated with beat-to-beat variation during deep breathing (r = 0.22, P < 0.01). Extracellular fluid volume (mean ± SE) was higher in group 1 (15.9 ± 0.5 1/m2) as compared with group 3 (14.1 ± 0.8 1/m2) (P < 0.05) with group 2 between the two (15.1 ± 0.4 1/m2). Extracellular fluid volume was not associated with the degree of nocturnal blood pressure reduction. In conclusion, NIDDM patients with and without diabetic nephropathy have blunted nocturnal decline in arterial blood pressure, a condition that might enhance the strain on the microvascular and cardiovascular system. The high prevalence of autonomic neuropathy may also contribute to the increased cardiovascular morbidity and mortality characteristically found in these patients.

Macro-microangiopathy and endothelial dysfunction in NIDDM patients with and without diabetic nephropathy

Summary The Steno hypothesis suggests that albuminuria reflects widespread vascular damage (proliferative retinopathy and severe macroangiopathy) due to a generalized vascular (endothelial) dysfunction. We assessed this concept in NIDDM (non-insulin-dependent diabetic) patients with (13 female/39 male, age 60 ± 7 years, group 1) and without (12 female/41 male, age 61 ± 7 years, group 2) diabetic nephropathy compared to matched non-diabetic subjects (7 female/15 male, age 58 ± 8 years, group 3). A 12-lead ECG was recorded and coded blindly using the Minnesota Rating Scale; the World Health Organization cardiovascular questionnaire was used to assess past and present evidence of myocardial infarction, angina pectoris, stroke, and peripheral vascular disease (digital systolic blood pressure determination). The degree of diabetic retinopathy was scored from fundus photography. The following variables were measured: transcapillary escape rate of albumin (initial disappearance of intravenously injected 125I-labelled human serum albumin), plasma concentrations of prorenin (radioimmunoassay) and serum concentrations of von Willebrand factor (enzyme-linked immunoadsorbent assay). Prevalence of ischaemic heart disease (ECG reading) (49/20/5)% and peripheral vascular disease as indicated by reduced systolic blood pressure on big toe (69/30/14)% was significantly higher in group 1 vs group 2 (p < 0.01) and in group 2 vs group 3 (p < 0.01), respectively. The prevalence and severity of retinopathy was higher in group 1 vs 2 (p < 0.01). Transcapillary escape rate of albumin (%/h) was elevated in group 1 and 2 as compared to control subjects: 7.9 (4.3–13.7); 7.4 (3.7–16.4) vs 6.0 (3.4–8.7), (p < 0.005), respectively. Plasma prorenin activity (IU/ml) was raised in group 1 and group 2 as compared to group 3: 272 (59–2405); 192 (18–813), and 85 (28–246), p < 0.001, respectively. Serum von Willebrand factor (IU/ml)was elevated in group 1 as compared to group 2 and 3: 2.07 (0.83–4.34); 1.60 (0.30–2.99) and 1.50 (1.00–2.38), p < 0.001, respectively. Our study demonstrated that NIDDM patients with and without albuminuria had increased transcapillary escape of albumin and raised prorenin activity, whereas only those with albuminuria had increased von Willebrand factor. Patients with NIDDM may have abnormal endothelial function in the absence of albuminuria. [Diabetologia (1996) 39: 1590–1597]

Glomerular hyperfiltration in microalbuminuric NIDDM patients

Summary Glomerular hyperfiltration and microalbuminuria are both regarded as risk factors for the development of diabetic nephropathy in insulin-dependent diabetic patients. Information on glomerular hyperfiltration is scarse in microalbuminuric non-insulin-dependent diabetic (NIDDM) patients. Therefore, we performed a cross-sectional study of glomerular filtration rate (single i. v. bolus injection of 51Cr-EDTA, plasma clearance for 4 h) in 158 microalbuminuric NIDDM patients compared to 39 normoalbuminuric NIDDM patients and 20 non-diabetic control subjects. The groups were well-matched with regard to sex, age and body mass index. The uncorrected (ml/min) and the adjusted (ml · min–1· 1.73 m–2) glomerular filtration rate were both clearly elevated in the microalbuminuric patients: 139 ± 29 and 117 ± 24 as compared to 115 ± 19 and 99 ± 15; 111 ± 23 and 98 ± 21 in normoalbuminuric NIDDM patients and control subjects, respectively (p < 0.001). The glomerular filtration rate (ml · min–1· 1.73 m–2) in NIDDM patients who had never received antihypertensive treatment was also clearly elevated in the microalbuminuric patients (n = 96): 119 ± 22 as compared to 100 ± 14 and 98 ± 21 in normoalbuminuric NIDDM patients (n = 27) and control subjects (n = 20), respectively (p < 0.001). Glomerular hyperfiltration (elevation above mean glomerular filtration rate plus 2 SD in normoalbuminuric NIDDM patients) was demonstrated in 37 (95 % confidence interval 30–45)% of the microalbuminuric patients. Multiple regression analysis revealed that HbA1 c, 24-h urinary sodium excretion, age and known duration of diabetes were correlated with glomerular filtration rate in microalbuminuric NIDDM patients (r2 = 0.21, p < 0.01). Our cross-sectional study indicates that NIDDM patients at high risk of developing diabetic nephropathy are also characterized by an additional putative risk factor for progression, glomerular hyperfiltration. [Diabetologia (1996) 39: 1584–1589]

Left ventricular hypertrophy in non-insulin-dependent diabetic patients with and without diabetic nephropathy

The aim of our cross‐sectional case–control study was to evaluate putative mechanisms of the increased cardiac morbidity and mortality in NIDDM patients with or without diabetic nephropathy. Fifty‐one NIDDM patients with diabetic nephropathy (38 males, age 61 ± 8 years, group 1), 53 NIDDM patients with normoalbuminuria (42 males, 61 ± 7 years, group 2), and 22 non‐diabetic control subjects (15 males, 58 ± 8 years, group 3) were investigated. Previous antihypertensive treatment was withdrawn 2 weeks before the study. Left ventricular mass index (LVMI) and systolic function were determined by echocardiography. LVMI was elevated, mean ± SE, in group 1: 157 ± 6 g m−2, and in group 2: 139 ± 7 g m−2, as compared with group 3: 95 ± 5 g m−2 (p < 0.001, for both), and in group 1 as compared with group 2 (p = 0.05). The prevalence of left ventricular hypertrophy (LVH) (LVMI > 131 g m−2 in men and > 100 g m−2 in women) was much higher in group 1: 75 % (95 % CI, 60–86), and group 2: 51 % (95 % CI, 37–65), as compared with group 3: 9 % (95 % CI, 1–29) (p < 0.001, for both), and in group 1 as compared with group 2 (p < 0.01). Shortening fraction of the left ventricle, % ± SE, was relatively reduced in group 1: 32.5 ± 1.1 %, and group 2: 33.4 ± 1.1 %, as compared with group 3: 41.2 ± 1.2 % (p < 0.01, for both). In a subgroup of 26 normoalbuminuric normotensive NIDDM patients, LVMI was higher than in 14 normotensive non‐diabetic control subjects: 137 ± 10 g m−2 vs 96 ± 7 g m−2, respectively (p < 0.005). The prevalence of LVH was 42 % (95 % CI, 23–63) and 14 % (95 % CI, 2–43) (p = 0.07) in these two groups, respectively. In conclusion, normotensive and hypertensive NIDDM patients with and without diabetic nephropathy frequently suffer from LVH and relatively reduced systolic function which may constitute independent risk factors for fatal and non‐fatal cardiac events. © 1997 John Wiley & Sons, Ltd.

Opposite effects of losartan and atenolol on natriuretic peptides in patients with hypertension and left ventricular hypertrophy: a LIFE substudy.

Background Secretion of natriuretic peptides is related to cardiac wall stress and influenced by the renin–angiotensin system. Therefore, we investigated the influence of blood pressure (BP) reduction with losartan versus atenolol on N-terminal pro-atrial natriuretic peptide (Nt-proANP) and N-terminal pro-brain natriuretic peptide (Nt-proBNP). Methods In 183 patients with hypertension and electrocardiographic left ventricular (LV) hypertrophy, enrolled in the LIFE Study, we measured BP and serum Nt-proANP and Nt-proBNP by immunoassay after 2 weeks of placebo treatment and after 1, 2, 4, 6, 12, 24, 36 and 48 months of randomized treatment with losartan- or atenolol-based antihypertensive regimens. Results There was no significant difference in BP at any time point between the two treatment groups. In patients treated with losartan, median Nt-proANP decreased gradually throughout the study, reaching significance after 6 months of treatment (1125–1060 pmol/l, P < 0.001), and Nt-proBNP decreased within the first month (24.7–18.7 pmol/l, P < 0.01) and stayed reduced throughout the study. During losartan-based antihypertensive treatment, Nt-proANP and Nt-proBNP as a percentage of baseline values were correlated to reductions in systolic BP (r = 0.11, P < 0.01 and r = 0.10, P = 0.01) and diastolic BP (r = 0.17, P < 0.001 and r = 0.07, P = 0.09). In atenolol-treated patients, Nt-proANP (1100–1640 pmol/l, P < 0.001) and Nt-proBNP (20.0–37.7 pmol/l, P < 0.001) increased during the first month, and remained elevated throughout the study. During atenolol-based antihypertensive treatment, changes in Nt-proANP (r = −0.16, P < 0.001) and Nt-proBNP (r = −0.07, P = 0.08) were negatively related to change in heart rate. Conclusion Nt-proANP and Nt-proBNP were reduced in parallel with BP in losartan-treated patients whereas they increased in parallel with decreased heart rate in atenolol-treated patients.

Do we undertreat hypertensive smokers? A comparison between smoking and non-smoking hypertensives.

The acute effect of smoking is a rise in blood pressure and heart rate. Nevertheless, in several epidemiologic studies, smokers tend to have a slightly lower office blood pressure than non-smokers. We studied the 24 h ambulatory blood pressure consecutively in hypertensive smokers (≥10 cigarettes per day, n  = 26) and hypertensive non-smokers (n  = 26) to test the hypothesis that smoking is associated with a rise in ambulatory blood pressure. There was no difference between smokers and non-smokers in office blood pressure (153.8 ± 22.2/98.5 ± 10.6 vs 149.0 ± 16.1/96.9 ± 11.6 mmHg). However, we found a statistically significant higher daytime systolic and diastolic blood pressure in smokers (153.7 ± 16.2/96.1 ± 9.5 vs 145.0 ± 12.1/90.1 ± 10.0 mmHg) than in non-smokers. Differences were also found for office–daytime differences and when studying patients on pharmacological antihypertensive treatment separately. Daytime heart rate was also significantly higher in smokers (86.6 ± 9.4 vs 76.0 ± 10.9). We conclude that smokers tend to be undertreated in that they have a higher daytime blood pressure than do non-smokers, a difference that is not recognized by measuring office blood pressure alone. We therefore recommend 24 h ambulatory blood pressure measurement in smokers with essential hypertension.

No impact of blood pressure variability on microalbuminuria and left ventricular geometry: analysis of daytime variation, diurnal variation and ‘white coat’ effect

ObjectiveTo investigate the influence of blood pressure variability on target organ involvement. MethodsUsing a cross‐sectional study of a hypertension clinic at a district general hospital, 420 patients with newly diagnosed untreated essential hypertension referred on a consecutive basis from general practice and 146 normal subjects drawn at random from the Danish National Register underwent a variety of measurements which included: echocardiography with determination of left ventricular mass index and relative wall thickness and early morning urine albumin/creatinine ratio. Mean, standard deviation and coefficient of variation of automated clinic values; daytime, night‐time and full 24‐h period were extracted from 24‐h ambulatory blood pressure (ABP) monitoring. ‘White coat’ effect and dip were calculated. Hypertensives were classified into subjects with high or low variability, into ‘white coat’ hypertensives or established hypertensives and into dippers or non‐dippers. ResultsStandard deviation of daytime blood pressure (BP) was positively associated with target organ damage and BP level, which was not the case when variability was expressed as a coefficient of variation. Patients with high variability exhibited no more significant target organ damage than patients with low variability, but patients with established hypertension had significantly more target organ damage than the ‘white coat’ hypertensives. The ‘white coat’ effect as such was not associated with increased target organ involvement. Non‐dippers had significantly more cardiac target organ damage than dippers, but the difference disappeared after correction for different 24‐h BP level. ConclusionBP variability data obtained by non‐invasive ABP monitoring does not seem to improve the information inherent in the BP level.

Retinol-binding protein and transferrin in urine: New markers of renal function in essential hypertension and white coat hypertension?*

We studied the 24 h urinary excretion of albumin, transferrin, immunoglobulin G, and retinol-binding protein in individuals with essential hypertension, white coat hypertension, and normotension. In 56 individuals, we measured the 24 h ambulatory blood pressure (AMBP). The individuals could be divided into three groups: 26 hypertensives, 14 white coat hypertensives, and 16 normotensives. Daytime AMBP values were (median values with range in parentheses, mm Hg): hypertensives 158/105 (198 to 121/95 to 120), white coat hypertensives 141/83 (161 to 129/72 to 90), and normotensives 123/75 (148 to 102/63 to 86). We determined with immunochemical methods the 24 h urinary excretions of albumin, transferrin, and immunoglobulin G, all markers of glomerular dysfunction, and retinol-binding protein, a marker of impaired proximal tubular function. We found a significantly higher excretion of albumin and transferrin in hypertensives (P < .0000/P < .0001) and in white coat hypertensives (P < .003/P < .02) compared to normotensives. Out of 26 hypertensives, seven had microalbuminuria (> or = 30 to < 300 mg albumin/ 24 h). Two cases of microalbuminuria were found among the 14 white coat hypertensives. Immunoglobulin G excretion was not significantly increased in any of the hypertensive groups. Retinol-binding protein excretion was significantly higher in hypertensive patients (P < .007), whereas no elevation was observed in persons with white coat hypertension. In hypertensives, a significant correlation was found between urinary excretion of albumin and transferrin and office blood pressure and systolic AMBP. There was no significant correlation between the urinary excretions of IgG and retinol-binding protein and blood pressures in any of the three groups. Our findings indicate that patients with white coat hypertension, like hypertensives, have a selective type of glomerular dysfunction. However, proximal tubular dysfunction was seen only in hypertensives. Urinary excretions of albumin, transferrin, and retinol-binding protein may be useful as markers of glomerular and tubular dysfunction in essential hypertension.

Losartan versus atenolol on 24‐hour ambulatory blood pressure. A LIFE substudy

Objective. The Losartan Intervention For Endpoint reduction in hypertension (LIFE) study showed that losartan‐based treatment reduced risk of the composite endpoint of cardiovascular death, stroke and myocardial infarction compared with atenolol‐based treatment in patients with hypertension and left ventricular hypertrophy with similar office blood pressure (BP) reduction. Our aim was to investigate the effect of losartan‐ and atenolol‐based treatment on 24‐h ambulatory BP and heart rate (HR) in LIFE. Methods: In 110 patients, 24‐h ambulatory BP and heart rate were recorded at baseline and 1 year after randomization. Results: Ambulatory BP was comparably reduced throughout the 24‐h period after 1 year of losartan‐ vs atenolol‐based antihypertensive treatment. Office and ambulatory BP were comparably reduced in the follow‐up period. Early morning surge in BP was similar between groups. Non‐dipping status was more frequent in the losartan group (p = 0.01). From baseline to Year 1 the 24‐h HR profile for the losartan group was unchanged, but, as expected, there was a significant decrease in daytime HR in the atenolol group, which was not as large during early night‐time. Conclusion: There were no differences in 24‐h BP burden and HR that could explain the difference in outcome in favor of losartan vs atenolol in the LIFE study.