Rudolph Schutte

Bone resorption and environmental exposure to cadmium in women: A population study

Background Environmental exposure to cadmium decreases bone density indirectly through hypercalciuria resulting from renal tubular dysfunction. Objective We sought evidence for a direct osteotoxic effect of cadmium in women. Methods We randomly recruited 294 women (mean age, 49.2 years) from a Flemish population with environmental cadmium exposure. We measured 24-hr urinary cadmium and blood cadmium as indexes of lifetime and recent exposure, respectively. We assessed the multivariate-adjusted association of exposure with specific markers of bone resorption, urinary hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP), as well as with calcium excretion, various calciotropic hormones, and forearm bone density. Results In all women, the effect sizes associated with a doubling of lifetime exposure were 8.4% (p = 0.009) for HP, 6.9% (p = 0.10) for LP, 0.77 mmol/day (p = 0.003) for urinary calcium, –0.009 g/cm2 (p = 0.055) for proximal forearm bone density, and –16.8% (p = 0.065) for serum parathyroid hormone. In 144 postmenopausal women, the corresponding effect sizes were –0.01223 g/cm2 (p = 0.008) for distal forearm bone density, 4.7% (p = 0.064) for serum calcitonin, and 10.2% for bone-specific alkaline phosphatase. In all women, the effect sizes associated with a doubling of recent exposure were 7.2% (p = 0.001) for urinary HP, 7.2% (p = 0.021) for urinary LP, –9.0% (p = 0.097) for serum parathyroid hormone, and 5.5% (p = 0.008) for serum calcitonin. Only one woman had renal tubular dysfunction (urinary retinol-binding protein > 338 μg/day). Conclusions In the absence of renal tubular dysfunction, environmental exposure to cadmium increases bone resorption in women, suggesting a direct osteotoxic effect with increased calciuria and reactive changes in calciotropic hormones.

Validation of the Finometer device for measurement of blood pressure in black women

The improved Finapres apparatus, known as the Fino-meter, measures finger blood pressure noninvasively on a beat-to-beat basis and gives waveform measurements similar to intra-arterial recordings. The Finometer measures brachial pressure and corrects for finger pressure accordingly. It also corrects for the hydrostatic height of the finger with respect to the heart level. The objective was to validate the Finometer according to the revised British Hypertension Society (BHS) protocol and the criteria of the Association for the Advancement of Medical Instrumentation (AAMI). We carried out a main validation test using a subject group of 102 black women, which was also divided into smaller groups, namely 24 hypertensives, 25 obese normotensive and 35 lean normotensive women. Finometer and mercury sphygmomanometer blood pressure (BP) measurements were taken early in the morning before breakfast, after the subjects stayed overnight in a research unit. Within the whole subject group, the Finometer satisfied the AAMI criteria for accuracy and achieved an overall A/B grading according to the BHS criteria. The sphygmomanometer measurements were 128±20/78±12 mmHg compared to 130±20/78±11 mmHg for the Finometer. The average differences between the mercury sphygmomanometer and Finometer readings for systolic and diastolic BP were, respectively, −1.83±6.8 and 0.88±7.5. Systolic readings of the Finometer device differed by less than 5 mmHg for 64%, by less than 10 mmHg for 86% and differed by less than 15 mmHg for 96% of all readings. A total of 63% of all diastolic readings of the Finometer by less than 5 mmHg, 85% by less than 10 mmHg and 94% of all readings differed by less than 15 mmHg. On the basis of these results, the Finometer device satisfied the validation criteria of AAMI and received an A/B grading according to the BHS protocol. It can therefore be recommended for measurements in the clinical set-up and for research purposes.

Within-Subject Blood Pressure Level—Not Variability—Predicts Fatal and Nonfatal Outcomes in a General Population

To assess the prognostic significance of blood pressure (BP) variability, we followed health outcomes in a family-based random population sample representative of the general population (n=2944; mean age: 44.9 years; 50.7% women). At baseline, BP was measured 5 times consecutively at each of 2 home visits 2 to 4 weeks apart. We assessed within-subject overall (10 readings), within- and between-visit systolic BP variability from variability independent of the mean, the difference between maximum and minimum BP, and average real variability. Over a median follow-up of 12 years, 401 deaths occurred and 311 participants experienced a fatal or nonfatal cardiovascular event. Overall systolic BP variability averaged (SD) 5.45 (2.82) units, 15.87 (8.36) mmHg, and 4.08 (2.05) mmHg for variability independent of the mean, difference between maximum and minimum BP, and average real variability, respectively. Female sex, older age, higher-mean systolic BP, lower body mass index, a history of peripheral arterial disease, and use of &bgr;-blockers were the main correlates of systolic BP variability. In multivariable-adjusted analyses, overall and within- and between-visit BP variability did not predict total or cardiovascular mortality or the composite of any fatal plus nonfatal cardiovascular end point. For instance, the hazard ratios for all cardiovascular events combined in relation to overall variability independent of the mean, difference between maximum and minimum BP, and average real variability were 1.05 (0.96–1.15), 1.06 (0.96–1.16), and 1.08 (0.98–1.19), respectively. By contrast, mean systolic BP was a significant predictor of all end points under study, independent of BP variability. In conclusion, in an unbiased population sample, BP variability did not contribute to risk stratification over and beyond mean systolic BP.

Are behavioural risk factors to be blamed for the conversion from optimal blood pressure to hypertensive status in Black South Africans? A 5-year prospective study

BACKGROUND Longitudinal cohort studies in sub-Saharan Africa are urgently needed to understand cardiovascular disease development. We, therefore, explored health behaviours and conventional risk factors of African individuals with optimal blood pressure (BP) (≤ 120/80 mm Hg), and their 5-year prediction for the development of hypertension. METHODS The Prospective Urban Rural Epidemiology study in the North West Province, South Africa, started in 2005 and included African volunteers (n = 1994; aged > 30 years) from a sample of 6000 randomly selected households in rural and urban areas. RESULTS At baseline, 48% of the participants were hypertensive (≥ 140/90 mmHg). Those with optimal BP (n = 478) were followed at a success rate of 70% for 5 years (213 normotensive, 68 hypertensive, 57 deceased). Africans that became hypertensive smoked more than the normotensive individuals (68.2% vs 49.8%), and they also had a greater waist circumference [ratio of geometric means of 0.94 cm (95% CI: 0.86-0.99)] and greater amount of γ-glutamyltransferase [0.74 U/l (95% CI: 0.62-0.88)] at baseline. The 5-year change in BP was independently explained by baseline γ-glutamyltransferase [R(2) = 0.23, β = 0.13 U/l (95% CI: 0.01-0.19)]. Alcohol intake also predicted central systolic BP and carotid cross-sectional wall area (CSWA) at follow-up. Waist circumference was another predictor of BP changes [β = 0.18 cm (95% CI: 0.05-0.24)] and CSWA. HIV infection was inversely associated with increased BP. CONCLUSIONS During the 5 years, 24% of Africans with optimal BP developed hypertension. The surge in hypertension in Africa is largely explained by modifiable risk factors. Public health strategies should focus aggressively on lifestyle to prevent a catastrophic burden on the national health system.

Home Blood Pressure Variability as Cardiovascular Risk Factor in the Population of Ohasama

Blood pressure variability based on office measurement predicts outcome in selected patients. We explored whether novel indices of blood pressure variability derived from the self-measured home blood pressure predicted outcome in a general population. We monitored mortality and stroke in 2421 Ohasama residents (Iwate Prefecture, Japan). At enrollment (1988–1995), participants (mean age, 58.6 years; 60.9% women; 27.1% treated) measured their blood pressure at home, using an oscillometric device. In multivariable-adjusted Cox models, we assessed the independent predictive value of the within-subject mean systolic blood pressure (SBP) and corresponding variability as estimated by variability independent of the mean, difference between maximum and minimum blood pressure, and average real variability. Over 12.0 years (median), 412 participants died, 139 of cardiovascular causes, and 223 had a stroke. In models including morning SBP, variability independent of the mean and average real variability (median, 26 readings) predicted total and cardiovascular mortality in all of the participants (P⩽0.044); variability independent of the mean predicted cardiovascular mortality in treated (P=0.014) but not in untreated (P=0.23) participants; and morning maximum and minimum blood pressure did not predict any end point (P≥0.085). In models already including evening SBP, only variability independent of the mean predicted cardiovascular mortality in all and in untreated participants (P⩽0.046). The R 2 statistics, a measure for the incremental risk explained by adding blood pressure variability to models already including SBP and covariables, ranged from <0.01% to 0.88%. In a general population, new indices of blood pressure variability derived from home blood pressure did not incrementally predict outcome over and beyond mean SBP.

Leptin is independently associated with systolic blood pressure, pulse pressure and arterial compliance in hypertensive African women with increased adiposity: the POWIRS study

High leptin levels are often observed in human obesity and are implicated in obesity-related hypertension. Leptin levels have been found to be higher in hypertensive obese African-American women compared to normotensive African-American women, but a direct association between leptin and blood pressure could not be obtained. Additionally, increased adiposity has been associated with higher aortic stiffness in obese African-American women, but leptin was not included in the study. The effects of leptin on cardiovascular function in African women have not yet been determined. We hypothesised that leptin is directly associated with blood pressure and decreased arterial compliance and that leptin levels are significantly higher in hypertensive overweight/obese African women compared to normotensive overweight/obese African women. A case–case control study was performed which included 98 African women. The subjects were divided into lean normotensive (lean NT), overweight/obese normotensive (OW/OB NT) and overweight/obese hypertensive (OW/OB HT). The Finometer apparatus was used to obtain a more elaborate cardiovascular profile. Serum leptin and insulin levels as well as the HOMA-IR index were determined. Various anthropometric measures were obtained. Leptin levels were elevated (P⩽0.05) in the OW/OB NT and HT groups compared to the lean NT group, but were similar in the OW/OB NT and HT groups. After adjusting for obesity, insulin resistance, hyperinsulinaemia and age, a direct positive correlation was obtained between leptin and systolic blood pressure (SBP) (P⩽0.05; r=0.68) in the OW/OB HT group. Additionally, leptin also correlated negatively with arterial compliance (P⩽0.05; r=−0.76) and positively with pulse pressure (P⩽0.05; r=0.71) in the OW/OB HT group. In conclusion, even though leptin levels were the same in OW/OB HT and NT African women, leptin was directly and positively associated with SBP and pulse pressure and negatively with CW only in OW/OB HT African women, independent of obesity, insulin-resistance, hyperinsulinaemia and age.

Conventional and behavioral risk factors explain differences in sub-clinical vascular disease between black and Caucasian South Africans: the SABPA study

OBJECTIVES There is an emerging burden of cardiovascular disease among urban black Africans in South Africa, which has been largely explained by the transition from traditional African lifestyles to more westernized behavior. We examined the role of health behaviors in explaining the excess burden of sub clinical vascular disease seen in black Africans compared to Caucasians. METHODS This was a cross-sectional study, comprising of urban African teachers (n=192 black, 206 Caucasian) working for one of the four Kenneth Kaunda Education districts in the North West Province, South Africa. Conventional cardiovascular risk factors, 24 h ambulatory blood pressure and objectively measured physical activity (Actical® accelerometers), smoking (confirmed by serum cotinine), and alcohol (serum gamma glutamyl transferase) were assessed. The main outcome was a marker of sub-clinical vascular disease, mean carotid intima media thickness (mCIMT), measured using high resolution ultrasound. RESULTS Compared with Caucasians, the black Africans demonstrated higher mCIMT (age and sex adjusted β=0.044, 95% CI, 0.024-0.064 mm). The blacks also had higher 24h systolic and diastolic blood pressure, triglycerides, adiposity, and C-reactive protein. In addition, blacks were less physically active (790.0 kcal/d vs 947.3 kcal/d, p<0.001), more likely to smoke (25% vs 16.3%, p=0.002), and demonstrated higher alcohol abuse (gamma glutamyl transferase, 66.6 μ/L vs 27.2 μ/L, p<0.001) compared with Caucasians. The difference in mCIMT between blacks and Caucasians was attenuated by 34% when conventional risk factors were added to the model and a further 18% when health behaviors were included. CONCLUSION There is an excess burden of sub clinical vascular disease seen in black Africans compared to Caucasians, which can be largely explained by health behaviors and conventional risk factors.

Inflammation, obesity and cardiovascular function in African and Caucasian women from South Africa: the POWIRS study

The integrated relationship between inflammation, obesity and cardiovascular disease is currently a subject of much research interest. These specific relationships, however, have not been studied in-depth in South African population groups in order to determine the role of ethnicity. It is known that Africans, compared to Caucasians, suffer from a high prevalence of hypertension. It was therefore hypothesized that the levels of inflammatory markers (high-sensitivity C-reactive protein (hsCRP), fibrinogen and leptin) are higher in Africans compared to Caucasians and are notably associated with cardiovascular dysfunction in Africans. Apparently healthy African (N=102) and Caucasian (N=115) women, matched for age and body mass index (BMI), were recruited. Leptin, hsCRP, fibrinogen and lipid levels, waist circumference (WC), BMI, systolic and diastolic blood pressure, cardiac output (CO), total peripheral resistance (TPR) and Windkessel compliance were measured. Results showed that the levels of leptin, hsCRP and fibrinogen were significantly higher (P<0.05) in the African women. The inflammatory markers correlated strongly with cardiovascular parameters, age and obesity (BMI, WC) in both groups, but after adjusting for age and obesity, none of the correlations were significant anymore. Multiple regression analyses (with leptin, hsCRP or fibrinogen as dependent variable) showed that only leptin levels of African women were explained by cardiovascular parameters (BP, TPR and CO). In conclusion, even though African women had significantly higher leptin, hsCRP, fibrinogen and blood pressure levels than Caucasian women, no cardiovascular parameters explained the variation in the inflammatory markers (except for leptin levels of African women).

Comparison of central pressure estimates obtained from SphygmoCor, Omron HEM-9000AI and carotid applanation tonometry

Background The Omron HEM-9000AI is the first automated tonometer to provide an estimate of central SBP (cSBP), which is considered to be more predictive of cardiovascular events than brachial pressure. However, considerable differences between the cSBP estimate of Omron and that of SphygmoCor have been reported, but not explained. This study assesses the sources of differences between both cSBP estimates and provides a handle on which estimate is closest to reality. Method For this purpose, aortic cSBP derived from calibrated carotid SBP was used as device- and algorithm-independent reference. Radial, brachial and carotid applanation tonometry were performed in 143 black South Africans, aged 39–91 years. Each individual was measured with an Omron HEM-9000AI and a SphygmoCor. Results When using both devices as advocated by their manufacturers, the corresponding cSBP estimates correlated strongly (r = 0.99, P < 0.001), but the Omron estimate was 18.8 (4.3) mmHg higher than the SphygmoCor estimate. Aortic SBP was in between both estimates: 11.7 (5.5) mmHg lower than cSBP-Omron and 7.1 (5.0) mmHg higher than cSBP-SphygmoCor. Alternative calibration of the radial SphygmoCor-curves with radial instead of brachial pressures yielded a cSBP that was 3.0 (4.2) mmHg lower than aortic SBP. The shape of the recorded pressure waves was similar in both devices: less than 5% of the observed cSBP difference was caused by differences in wave shape. Conclusion The results from this study demonstrate that the considerable difference between the central pressure estimates of Omron HEM-9000AI and SphygmoCor is due to algorithm differences, and suggest that the overestimation by Omron HEM-9000AI is larger than the underestimation by SphygmoCor.

Arterial Stiffness Profiles: Investigating Various Sections of the Arterial Tree of African and Caucasian People

In Africans, arterial stiffness progression seems more pronounced compared to Caucasians. We compared the arterial stiffness profiles of different age groups and focused on muscular arteries and two more central arterial segments in African and Caucasian people from South Africa. In African (N = 374) and Caucasian (N = 376) participants (20–70 years), we measured carotid-radial (C-R) and carotid-dorsalis pedis (C-DP) pulse wave velocity (PWV) and aortic characteristic impedance (Zao). Major findings were that normotensive and high-normal/hypertensive (HT) Caucasians indicated increased trends of C-R PWV with aging (P = .029 and P = .067), not seen in the African groups (P = .122 and P = .526). Both ethnic groups showed significant increases of C-DP PWV and Zao with aging. High-normal/hypertensive Africans had significantly stiffer arteries than hypertensive Caucasians for almost all age groups, and for all stiffness measures. African C-R PWV correlated significantly with blood pressure (BP), but not with age. Opposite results were observed for Caucasians. In conclusion, the stiffness of muscular arteries is already elevated in young Africans, in both those with normal or elevated BP. This is possibly due to an earlier deterioration during childhood, or perhaps already present from birth. Also, in Caucasians stiffness seems more age-related, while in Africans it seems to be more pressure-related.