Endoscopic decompression for chronic compartment syndrome of the forearm in motocross racers.

PURPOSE: Sporting activities that involve repetitive stress to muscle compartments can elicit chronic exertional compartment syndrome. Its occurrence in the lower leg muscle compartments is most common, but other locations are less well known and the pathophysiology is not completely understood. In motocross racers, chronic exertional compartment syndrome can occur in the muscles of the lower arm. Currently, the only accepted treatment of correctly diagnosed chronic exertional compartment syndrome is surgical release of the fascia, which successfully relieves pain and allows patients to return to full activity. Open decompression is considered as the gold standard of treatment. This clinical paper describes our new endoscopic technique and investigates the functional outcome after surgery. METHODS: We report on a series of 154 chronic exertional compartment syndromes afflicted motocross racers treated with an endoscopic release of the lower arm muscles. An MRI scan before and after strenuous exercise of the hand flexors (repetitive grip until exhaustion for 15 min) was performed to confirm the clinical diagnosis of chronic exertional compartment syndrome. Symptom severity before and after surgery was assessed using a visual analogue scale. RESULTS: Preoperative symptom severity scores were 1.1 ± 0.3 before exercise and 7.4 ± 1.5 after exercise. Post-operatively, these were 1.0 ± 0.2 and 1.7 ± 0.9. The pre- versus post-operative symptom scores after exercise were significantly different (p < 0.0001). No perioperative complications occurred, and at 6 weeks, all of the racers resumed their sportive activities. CONCLUSION: It can be concluded that endoscopic release of the superficial compartment of the forearms of motocross racers diagnosed with chronic exertional compartment syndrome is a valuable treatment option, with mild post-operative pain and fast recovery.

Determining the clinical utility of a breath test for screening an asbestos-exposed population for pleural mesothelioma: baseline results.

Pleural mesothelioma (PM) is an aggressive cancer of the serosal lining of the thoracic cavity, predominantly caused by asbestos exposure. Due to nonspecific symptoms, PM is characterized by an advanced-stage diagnosis, resulting in a dismal prognosis. However, early diagnosis improves patient outcome. Currently, no diagnostic biomarkers or screening tools are available. Therefore, exhaled breath was explored as this can easily be obtained and contains volatile organic compounds, which are considered biomarkers for multiple (patho)physiological processes. A breath test, which differentiates asbestos-exposed (AEx) individuals from PM patients with 87% accuracy, was developed. However, before being implemented as a screening tool, the clinical utility of the test must be determined. Occupational AEx individuals underwent annual breath tests using multicapillary column/ion mobility spectrometry. A baseline breath test was taken and their individual risk of PM was estimated. PM patients were included as controls. In total, 112 AEx individuals and six PM patients were included in the first of four screening rounds. All six PM patients were correctly classified as having mesothelioma (100% sensitivity) and out of 112 AEx individuals 78 were classified by the breath-based model as PM patients (30% specificity). Given the large false positive outcome, the breath test will be repeated annually for three more consecutive years to adhere to the 'test, re-test' principle and improve the false positivity rate. A low-dose computed tomography scan in those with two consecutive positive tests will correlate test positives with radiological findings and the possible growth of a pleural tumor. Finally, the evaluation of the clinical value of a breath-based prediction model may lead to the initiation of a screening program for early detection of PM in Aex individuals, which is currently lacking. This clinical study received approval from the Antwerp University Hospital Ethics Committee (B300201837007).

Age dependency of central and peripheral systolic blood pressures: cross-sectional and longitudinal observations in European populations.

BACKGROUND: As arteries become stiffer with ageing, reflected waves move faster and augment late systolic pressure. We investigated the age dependency of peripheral and central systolic pressure, pressure amplification (peripheral systolic blood pressure - central systolic blood pressure), and peripheral and central systolic augmentation (maximal systolic pressure minus the first peak of the pressure wave). METHODS: We randomly recruited 1420 White Europeans (mean age, 41.7 years). peripheral systolic blood pressure and central systolic blood pressure were measured by means of an oscillometric sphygmomanometer and pulse wave analysis, respectively. RESULTS: In cross-sectional analyses (731 women, 689 men), central systolic blood pressure and central systolic augmentation increased more with age than peripheral systolic blood pressure and peripheral systolic augmentation. These age-related increases were greater in women than men. The age-related decrease in pressure amplification was similar in both sexes. In longitudinal analyses (208 women, 190 men), the annual increases in central systolic blood pressure and central systolic augmentation were steeper (p < 0.001) than those in peripheral systolic blood pressure and peripheral systolic augmentation with no sex differences (p ≥ 0.068), except for peripheral systolic augmentation, which was larger in women (p = 0.002). Longitudinally, pressure amplification decreased more with age in women than men (p = 0.012). In multivariable-adjusted analyses, age was the overriding determinant of peripheral systolic blood pressure and central systolic blood pressure. CONCLUSION: With ageing, peripheral systolic blood pressure approximates to central systolic blood pressure. This might explain why in older subjects peripheral systolic blood pressure becomes the main predictor of cardiovascular complications.

Urinary nitric oxide metabolites and individual blood pressure progression to overt hypertension.

Baseline blood pressure (BP) is the strongest known determinant of progression to hypertension, but for an individualized prediction of the incidence of hypertension, the identification of additional biomarkers is crucial. In animal models of hypertension, renal nitric oxide (NO) handling modifies the systemic BP responses prior to the development of hypertension. This study aimed to evaluate whether urinary NO metabolites (NOx) predict the progression of hypertension in normotensive subjects. Among 62 participants enrolled in the Flemish Study on Environment, Genes and Health Outcomes, we assessed progression to hypertension over 4.6 years. In a case-control design, 49 normotensive subjects including 10 subjects with high-normal blood pressure were enrolled of whom 25 remained normotensive (controls), whereas 24 'progressed' to hypertension (progressors). Thirteen hypertensive patients served as negative controls. Urinary NOx concentration, renal function and the urinary excretion of electrolytes were assessed at baseline and follow-up. At baseline, progressors showed higher BP values than controls and urinary NOx concentration was significantly lower in progressors as compared to the normotensive controls (p < 0.01). In all initially normotensive subjects baseline urinary NOx concentration was associated with follow-up BP (r = -0.55, p < 0.001) and the relative increase of BP over time (r = -0.47, p < 0.001). In progressors baseline urinary NOx was associated with follow-up BP (r = -0.52, p < 0.009) and the relative increase of BP over time (r = -0.44, p = 0.033). Baseline urinary NOx and BP were independent predictors for the relative BP increase. A urinary NOx threshold of <130.5 mg/L predicted 75% of all progressors. In context with high-normal baseline BP, 87.5% of all progressors were identified. These findings indicate that urinary NO metabolites are associated with BP development in normotensive subjects. Moreover, urinary NOx predicts the progression to hypertension independent of baseline BP suggesting urinary NOx as a biomarker for individual new-onset hypertension.

Heritability of left ventricular structure and function in Caucasian families.

AIMS: The aim of this study was to investigate the heritability as well as genetic and environmental correlations of left ventricular (LV) structural and functional traits in complex pedigrees of a Caucasian population. METHODS AND RESULTS: We randomly recruited 459 white European subjects from 52 families (50% women; mean age 45 years). LV structure was measured by M-mode and 2D echocardiography and LV function was measured by conventional Doppler and tissue Doppler imaging (TDI). Other measurements included blood pressure, anthropometric, and biochemical measurements. We estimated the heritability of LV traits while adjusting for covariables, including sex, age, body height and weight, systolic and diastolic blood pressures, and heart rate. With full adjustment, heritability of LV mass was 0.23 (P= 0.025). The TDI-derived mitral annular velocities Ea and Aa showed moderate heritability (h(2)= 0.36 and 0.53, respectively), whereas the mitral inflow A peak had weak heritability (h(2) = 0.25) and the E peak was not heritable (h(2) = 0.11). We partitioned the total phenotypic correlation when it reached significance, into a genetic and an environmental component. The genetic correlations were 0.61 between the E and Ea peaks and 0.90 between the A and Aa peaks. CONCLUSION: Our study demonstrated moderate heritability for LV mass as well as the mitral annular Ea and Aa peaks. We also found significant genetic correlations between the E and Ea peaks and between the A and Aa peaks. Our current findings support the ongoing research to map and detect genetic variants that contribute to the variation in LV mass and other LV structural and functional phenotypes.

Rationale and design of the Newer Versus Older Antihypertensive Agents in African Hypertensive Patients (NOAAH) trial.

BACKGROUND: Sub-Saharan Africa experiences an epidemic surge in hypertension. Studies in African Americans led to the recommendation to initiate antihypertensive treatment in Blacks with a diuretic or a low-dose fixed combination including a diuretic. We mounted the Newer versus Older Antihypertensive Agents in African Hypertensive Patients (NOAAH) trial to compare in native African patients a fixed combination of newer drugs, not involving a diuretic, with a combination of older drugs including a diuretic. METHODS: Patients aged 30-69 years with uncomplicated hypertension (140-179/90-109 mmHg) and two or fewer associated risk factors are eligible. After a 4-week run-in period off treatment, 180 patients will be randomized to once daily bisoprolol/hydrochlorothiazide 5/6.25 mg or amlodipine/valsartan 5/160 mg. To attain and maintain blood pressure below 140/90 mmHg during 6 months of follow-up, the doses of bisoprolol and amlodipine in the combination tablets will be increased to 10 mg/day with the possible addition of α-methyldopa or hydralazine. NOAAH is powered to demonstrate a 5-mmHg between-group difference in sitting systolic pressure with a two-sided p-value of 0.01 and 90% power. NOAAH is investigator-led and complies with the Helsinki declaration. RESULTS: Six centers in four sub-Saharan countries started patient recruitment on September 1, 2010. On December 1, 195 patients were screened, 171 were enrolled, and 51 were randomized and followed up. The trial will be completed in the third quarter of 2011. CONCLUSIONS: NOAAH (NCT01030458) is the first randomized multicenter trial of antihypertensive medications in hypertensive patients born and living in sub-Saharan Africa.

Determinants of arterial properties in Chinese type-2 diabetic patients compared with population-based controls.

OBJECTIVE: To our knowledge, few studies compared the association of brachial-ankle pulse wave velocity (baPWV) with cardiovascular risk factors among Chinese with type-2 diabetes mellitus and non-diabetic controls. This study addresses this issue. METHODS: We measured baPWV (OMRON VP1000) in 413 diabetic patients from Shanghai city (mean age: 58.7 years; 57% women) and 354 controls randomly recruited from the population of JingNing county, Zhejiang Province. We used stepwise multiple regression to identify covariables of baPWV and introduced interaction terms in the models to compare slopes. We expressed association sizes for continuous variables for a 1-SD increase in the dependent variable. RESULTS: Adjusted baPWV was higher in diabetic patients than controls (1678 vs 1583 cm/sec; P= 0.018). In diabetic patients, baPWV was independently correlated with female sex (-61 cm/sec; P = 0.061), age (+107 cm/sec; P < 0.0001), height (-51 cm/sec; P = 0.012), systolic pressure (+99 cm/sec; P < 0.0001), and the HDL-to-total cholesterol ratio (-38 cm/sec; P = 0.0004). In controls, the explanatory variables were female sex (-74 cm/sec; P = 0.045), age (+138 cm/sec; P < 0.0001), height (-262 cm/sec; P < 0.0001), systolic pressure (+202 cm/sec; P < 0.0001), but not the HDL-to-total cholesterol ratio (P = 0.48). Explained variance of baPWV was 34% and 61% in diabetic patients and controls, respectively. The associations of baPWV with age, height and systolic pressure were steeper (P < 0.04) in controls than diabetic patients. CONCLUSION: Sex, age, height and systolic pressure were the main determinants of baPWV in Chinese, irrespective of whether they had diabetes or not, but these associations were tighter in population-based controls without diabetes.

Fatal and nonfatal outcomes, incidence of hypertension, and blood pressure changes in relation to urinary sodium excretion.

CONTEXT: Extrapolations from observational studies and short-term intervention trials suggest that population-wide moderation of salt intake might reduce cardiovascular events. OBJECTIVE: To assess whether 24-hour urinary sodium excretion predicts blood pressure (BP) and health outcomes. DESIGN, SETTING, AND PARTICIPANTS: Prospective population study, involving 3681 participants without cardiovascular disease (CVD) who are members of families that were randomly enrolled in the Flemish Study on Genes, Environment, and Health Outcomes (1985-2004) or in the European Project on Genes in Hypertension (1999-2001). Of 3681 participants without CVD, 2096 were normotensive at baseline and 1499 had BP and sodium excretion measured at baseline and last follow-up (2005-2008). MAIN OUTCOME MEASURES: Incidence of mortality and morbidity and association between changes in BP and sodium excretion. Multivariable-adjusted hazard ratios (HRs) express the risk in tertiles of sodium excretion relative to average risk in the whole study population. RESULTS: Among 3681 participants followed up for a median 7.9 years, CVD deaths decreased across increasing tertiles of 24-hour sodium excretion, from 50 deaths in the low (mean, 107 mmol), 24 in the medium (mean, 168 mmol), and 10 in the high excretion group (mean, 260 mmol; P < .001), resulting in respective death rates of 4.1% (95% confidence interval [CI], 3.5%-4.7%), 1.9% (95% CI, 1.5%-2.3%), and 0.8% (95% CI, 0.5%-1.1%). In multivariable-adjusted analyses, this inverse association retained significance (P = .02): the HR in the low tertile was 1.56 (95% CI, 1.02-2.36; P = .04). Baseline sodium excretion predicted neither total mortality (P = .10) nor fatal combined with nonfatal CVD events (P = .55). Among 2096 participants followed up for 6.5 years, the risk of hypertension did not increase across increasing tertiles (P = .93). Incident hypertension was 187 (27.0%; HR, 1.00; 95% CI, 0.87-1.16) in the low, 190 (26.6%; HR, 1.02; 95% CI, 0.89-1.16) in the medium, and 175 (25.4%; HR, 0.98; 95% CI, 0.86-1.12) in the high sodium excretion group. In 1499 participants followed up for 6.1 years, systolic blood pressure increased by 0.37 mm Hg per year (P < .001), whereas sodium excretion did not change (-0.45 mmol per year, P = .15). However, in multivariable-adjusted analyses, a 100-mmol increase in sodium excretion was associated with 1.71 mm Hg increase in systolic blood pressure (P.<001) but no change in diastolic BP. CONCLUSIONS: In this population-based cohort, systolic blood pressure, but not diastolic pressure, changes over time aligned with change in sodium excretion, but this association did not translate into a higher risk of hypertension or CVD complications. Lower sodium excretion was associated with higher CVD mortality.

Association between left ventricular mass and telomere length in a population study.

Experimental studies have implicated telomere dynamics in cardiomyocyte size and replication potential; shorter telomeres mark attenuated proliferation and increased apoptosis. The authors examined whether this translates into an impact of telomere length (TL) on left ventricular (LV) mass in the general population. In 334 randomly selected Flemish participants (mean age = 46.5 years; 52.5% women), they measured TL in circulating leukocytes using quantitative polymerase chain reaction, expressing it as telomere/genomic DNA ratio (T/S). After a median 7.4 years of follow-up (interquartile range, 6.2-8.5) during 1996-2007, they measured LV mass by echocardiography. In multivariable-adjusted analyses accounting for sex, age, body weight and height, systolic blood pressure, and antihypertensive drug use, LV mass and LV mass index significantly increased with mean leukocyte TL in the entire population and in the 198 normotensive subjects. For a 1-standard-deviation increment in T/S ratio, LV mass (mean = 170 g) and LV mass index (mean = 92 g/m(2)) increased by 5.20 g (P = 0.003) and 2.70 g/m(2) (P = 0.004), respectively, in all subjects and by 8.03 g (P = 0.0001) and 3.74 g/m(2) (P = 0.0007) in normotensive subjects. There were corresponding associations with LV wall thicknesses (P < 0.007) but not LV internal diameter (P = 0.26) in normotensive subjects. Longer mean leukocyte TL is associated with increased LV mass, particularly in normotensive subjects. This association could have a biologic basis related to the role of TL in determining cardiomyocyte size and replication potential.

Cadmium exposure in the population: from health risks to strategies of prevention.

We focus on the recent evidence that elucidates our understanding about the effects of cadmium (Cd) on human health and their prevention. Recently, there has been substantial progress in the exploration of the shape of the Cd concentration-response function on osteoporosis and mortality. Environmental exposure to Cd increases total mortality in a continuous fashion without evidence of a threshold, independently of kidney function and other classical factors associated with mortality including age, gender, smoking and social economic status. Pooled hazard rates of two recent environmental population based cohort studies revealed that for each doubling of urinary Cd concentration, the relative risk for mortality increases with 17% (95% CI 4.2-33.1%; P < 0.0001). Tubular kidney damage starts at urinary Cd concentrations ranging between 0.5 and 2 µg urinary Cd/g creatinine, and recent studies focusing on bone effects show increased risk of osteoporosis even at urinary Cd below 1 µg Cd/g creatinine. The non-smoking adult population has urinary Cd concentrations close to or higher than 0.5 µg Cd/g creatinine. To diminish the transfer of Cd from soil to plants for human consumption, the bioavailability of soil Cd for the plants should be reduced (external bioavailability) by maintaining agricultural and garden soils pH close to neutral (pH-H(2)O of 7.5; pH-KCL of 6.5). Reducing the systemic bioavailability of intestinal Cd can be best achieved by preserving a balanced iron status. The latter might especially be relevant in groups with a lower intake of iron, such as vegetarians, and women in reproductive phase of life. In exposed populations, house dust loaded with Cd is an additional relevant exposure route. In view of the insidious etiology of health effects associated with low dose exposure to Cd and the current European Cd intake which is close to the tolerable weekly intake, one should not underestimate the importance of the recent epidemiological evidence on Cd toxicity as to its medical and public health implications.

Association between carotid diameter and the advanced glycation end product N-epsilon-carboxymethyllysine (CML).

BACKGROUND: Nepsilon-carboxymethyllysine (CML) is the major non-cross linking advanced glycation end product (AGE). CML is elevated in diabetic patients and apparent in atherosclerotic lesions. AGEs are associated with hypertension and arterial stiffness potentially by qualitative changes of elastic fibers. We investigated whether CML affects carotid and aortic properties in normoglycemic subjects. METHODS: Hundred-two subjects (age 48.2+/-11.3 years) of the FLEMENGHO study were stratified according to the median of the plasma CML level (200.8 ng/ml; 25th percentile: 181.6 ng/ml, 75th percentile: 226.1 ng/ml) into "high CML" versus "low CML" as determined by ELISA. Local carotid artery properties, carotid intima media thickness (IMT), aortic pulse wave velocity (PWV), blood pressure and fetuin-A were analyzed. In 26 patients after carotidectomy, CML was visualized using immunohistochemistry. RESULTS: According to the CML median, groups were similar for anthropometric and biochemical data. Carotid diameter was enlarged in the "high" CML group (485.7+/-122.2 versus 421.2+/-133.2 microm; P<0.05), in particular in participants with elevated blood pressure and with "high" CML ("low" CML: 377.9+/-122.2 microm and "high" CML: 514.5+/-151.6 microm; P<0.001). CML was associated fetuin-A as marker of vascular inflammation in the whole cohort (r=0.28; P<0.01) and with carotid diameter in hypertensive subjects (r=0.42; P<0.01). CML level had no effect on aortic stiffness. CML was detected in the subendothelial space of human carotid arteries. CONCLUSION: In normoglycemic subjects CML was associated with carotid diameter without adaptive changes of elastic properties and with fetuin-A as vascular inflammation marker, in particular in subjects with elevated blood pressure. This may suggest qualitative changes of elastic fibers resulting in a defective mechanotransduction, in particular as CML is present in human carotid arteries.

Fetuin-A and arterial stiffness in patients with normal kidney function.

AIM: To evaluate the association between fetuin-A level (AHSG), its encoding gene (Thr256Ser) and arterial function in subjects with normal kidney function. INTRODUCTION: The aortic pulse wave velocity (aPWV) is a predictor for cardiovascular mortality. Fetuin-A is a calcification inhibitor and correlates negatively with increased vascular stiffness in dialysis patients. The fetuin-A polymorphism (Thr256Ser) is associated with reduced fetuin levels and accelerated vascular calcification in dialysis patients. Little is known about the role of fetuin-A as an independent predictor for the development of arterial stiffness in healthy subjects. MATERIALS AND METHODS: We studied 116 subjects with normal kidney function (age 47+/-12 years, 50 females and 66 males) of the FLEMENGHO study. Calcium measurements, plasma fetuin-A, its encoding gene (Thr256Ser) and indexes of arterial stiffness, such as aPWV and arterial distensibility, were determined. RESULTS: Fetuin-A levels were negatively correlated with aPWV (r=-0.21, p=0.029). After an adjustment for multiple covariables, fetuin-A levels were independently associated with aPWV (r=-0.30, p=0.022) in males but not in females. Male fetuin-A SerSer carrier had lower fetuin-A levels and higher aPWV (fetuin-A: 61.9+/-29.0 microg/ml; aPWV: 14.3+/-0.9 m/s) as compared to ThrThr (fetuin-A: 109.9+/-54.9 microg/ml; aPWV: 6.4+/-1.3 m/s) and ThrSer carrier (fetuin-A: 100.8+/-52.5 microg/ml; aPWV: 6.6+/-1.3 m/s). Other calcium variables were not significantly associated with arterial stiffness. CONCLUSION: With respect to common calcium variables, only fetuin-A level showed an inverse relation with aPWV in men with normal renal function. Male fetuin-A SerSer carriers demonstrate particularly high aortic stiffness, possibly implying a status of increased cardiovascular risk.

Altered molecular weight forms of adiponectin in hypertension.

An important link between adiponectin and hypertension has been proposed in clinical studies. In the circulation, adiponectin is predominantly present in multimeric complexes, of which high-molecular weight (HMW) adiponectin is thought to represent the biological active form. The authors investigated which role the different multimeric adiponectin isoforms play in context with hypertension as compared to total adiponectin levels. Fifty (19 normotensive/31 hypertensive) patients were included in the study. Total adiponectin and adiponectin multimers were determined by enzyme-linked immunosorbent assay and western blot. The authors analyzed associations between adiponectin multimer levels and blood pressure. Total adiponectin concentrations were not significantly different between hypertensive and normotensive patients (6.8+/-2.3 vs 7.5+/-4.2 microg/mL). HMW adiponectin was significantly lower (P<.05) and low-molecular weight adiponectin was significantly higher (P<.01) in hypertensive than in normotensive persons (3.8+/-1.7 vs 5.2+/-3.0 microg/mL and 0.9+/-0.5 vs 1.8+/-0.9, respectively). Low molecular weight was an independent predictor for the presence of hypertension (effect coefficient: 0.160-0.445; P<.001) in multivariate analyses. These results suggest that the composition of the molecular weight forms of adiponectin in hypertension are characterized by reduced HMW adiponectin, the proposed major active form of adiponectin, and increased low-molecular weight adiponectin. Moreover, the latter represents an independent predictor of prevalent hypertension, suggesting an association between adiponectin multimer composition and hypertension.

Left ventricular strain and strain rate in a general population.

AIMS: Strain and strain rate (SR) are measures of deformation that reflect left ventricular (LV) function. To our knowledge, no previous study described these indexes in a general population. We therefore described peak-systolic strain and SR of the LV in the general population and derived diagnostic thresholds for these measurements in a healthy subgroup. METHODS AND RESULTS: In 480 subjects enrolled in a family-based population study (50.5% women; mean age, 50.5 years; 37.2% hypertensive), we measured: (i) end-systolic longitudinal strain and peak-systolic SR from the basal portion of the LV inferior and inferolateral free walls; (ii) radial deformation of the LV inferolateral wall. Longitudinal (mean, 22.9%) and radial (59.2%) strain and longitudinal (1.31 s(-1)) and radial (3.40 s(-1)) SR decreased with age (P

Is oral vitamin D a risk factor for prosthetic loosening?

High counts of wear particles and activated macrophages are strong predictors of prosthetic loosening in total joint arthroplasty patients. The tissue response, dominated by macrophages, with production of inflammatory mediators and matrix-degrading enzymes, triggers a self-accelerating cycle of osteolysis, ultimately resulting in failure of the arthroplasty, high treatment cost and poor patient outcome. Vitamin D is frequently used as a treatment for osteoporosis, but might also contribute to osteolysis in inflammatory joints. Here, we review the effects of extrarenal vitamin D3 activation by macrophages in the joint space. The summarized pathways contribute to increased bone resorption in the setting of the inflammatory micro-environment at the bone-prosthesis interface. If further evidence confirms a role of oral vitamin D3 as a risk factor for aseptic loosening, this might influence the current treatment strategies for patients at risk for this condition.

Diagnostic thresholds for ambulatory blood pressure monitoring based on 10-year cardiovascular risk.

BACKGROUND: Current diagnostic thresholds for ambulatory blood pressure (ABP) mainly rely on statistical parameters derived from reference populations. We determined an outcome-driven reference frame for ABP measurement. METHODS AND RESULTS: We performed 24-hour ABP monitoring in 5682 participants (mean age 59.0 years; 43.3% women) enrolled in prospective population studies in Copenhagen, Denmark; Noorderkempen, Belgium; Ohasama, Japan; and Uppsala, Sweden. In multivariate analyses, we determined ABP thresholds, which yielded 10-year cardiovascular risks similar to those associated with optimal (120/80 mm Hg), normal (130/85 mm Hg), and high (140/90 mm Hg) blood pressure on office measurement. Over 9.7 years (median), 814 cardiovascular end points occurred, including 377 strokes and 435 cardiac events. Systolic/diastolic thresholds for optimal ABP were 116.8/74.2 mm Hg for 24 hours, 121.6/78.9 mm Hg for daytime, and 100.9/65.3 mm Hg for nighttime. Corresponding thresholds for normal ABP were 123.9/76.8, 129.9/82.6, and 110.2/68.1 mm Hg, respectively, and those for ambulatory hypertension were 131.0/79.4, 138.2/86.4, and 119.5/70.8 mm Hg. After rounding, approximate thresholds for optimal ABP amounted to 115/75 mm Hg for 24 hours, 120/80 mm Hg for daytime, and 100/65 mm Hg for nighttime. Rounded thresholds for normal ABP were 125/75, 130/85, and 110/70 mm Hg, respectively, and those for ambulatory hypertension were 130/80, 140/85, and 120/70 mm Hg. CONCLUSIONS: Population-based outcome-driven thresholds for optimal and normal ABP are lower than those currently proposed by hypertension guidelines.

Prognostic accuracy of day versus night ambulatory blood pressure: a cohort study.

BACKGROUND: Few studies have formally compared the predictive value of the blood pressure at night over and beyond the daytime value. We investigated the prognostic significance of the ambulatory blood pressure during night and day and of the night-to-day blood pressure ratio. METHODS: We did 24-h blood pressure monitoring in 7458 people (mean age 56.8 years [SD 13.9]) enrolled in prospective population studies in Denmark, Belgium, Japan, Sweden, Uruguay, and China. We calculated multivariate-adjusted hazard ratios for daytime and night-time blood pressure and the systolic night-to-day ratio, while adjusting for cohort and cardiovascular risk factors. FINDINGS: Median follow-up was 9.6 years (5th to 95th percentile 2.5-13.7). Adjusted for daytime blood pressure, night-time blood pressure predicted total (n=983; p<0.0001), cardiovascular (n=387; p<0.01), and non-cardiovascular (n=560; p<0.001) mortality. Conversely, adjusted for night-time blood pressure, daytime blood pressure predicted only non-cardiovascular mortality (p<0.05), with lower blood pressure levels being associated with increased risk. Both daytime and night-time blood pressure consistently predicted all cardiovascular events (n=943; p<0.05) and stroke (n=420; p<0.01). Adjusted for night-time blood pressure, daytime blood pressure lost prognostic significance only for cardiac events (n=525; p> or =0.07). Adjusted for the 24-h blood pressure, night-to-day ratio predicted mortality, but not fatal combined with non-fatal events. Antihypertensive drug treatment removed the significant association between cardiovascular events and the daytime blood pressure. Participants with systolic night-to-day ratio value of 1 or more were older, at higher risk of death, and died at an older age than those whose night-to-day ratio was normal (> or =0.80 to <0.90). INTERPRETATION: In contrast to commonly held views, daytime blood pressure adjusted for night-time blood pressure predicts fatal combined with non-fatal cardiovascular events, except in treated patients, in whom antihypertensive drugs might reduce blood pressure during the day, but not at night. The increased mortality in patients with higher night-time than daytime blood pressure probably indicates reverse causality. Our findings support recording the ambulatory blood pressure during the whole day.

Effects of genetic variation in adducin on left ventricular diastolic function as assessed by tissue Doppler imaging in a Flemish population.

BACKGROUND: We investigated the possible association between left ventricular diastolic function and the ADD1 Gly460Trp and ADD3 IVS11 +386A>G polymorphisms alone and in combination. METHODS: In a family-based population study (473 subjects; 50.5% women; mean age 50.5 years), we measured early (Ea) and late (Aa) diastolic peak velocities of the mitral annulus by tissue Doppler imaging. In multivariate-adjusted analyses, we investigated phenotype-genotype associations, while accounting for confounders and family structure. RESULTS: Lateral Ea/Aa ratio was higher in ADD1 Trp allele carriers than in GlyGly homozygotes (1.51 vs. 1.40; P = 0.005) and was lower in ADD3 A allele carriers than in GG homozygotes (1.42 vs. 1.55; P = 0.005). The effects of ADD1 on the lateral Ea and Ea/Aa weakened with older age (P < 0.05). The best fitting model for lateral Ea and Ea/Aa included ADD1, ADD3, and the three-way interaction term of both genes with age. Below the age of 50 years, the lateral Ea/Aa ratio was higher in ADD1 Trp allele carriers than in GlyGly homozygotes (1.91 vs. 1.73; P = 0.006), particularly in the presence of ADD3 GG homozygosity (2.46 vs. 1.80; P = 0.0008). In older subjects, these phenotype-genotype associations were not significant (P > 0.20). Transmission of the ADD1 Trp allele to offspring was associated with higher lateral Ea (+0.91; P = 0.026) and Ea/Aa ratio (+0.23; P = 0.0008). CONCLUSION: Our population-based study demonstrated that left ventricular diastolic relaxation is modulated by genetic variation in ADD1 and ADD3. This association was more prominent in younger subjects in whom longstanding environmental factors and ageing are less likely to mask genetic effects.

Reproducibility of the ambulatory arterial stiffness index in hypertensive patients.

BACKGROUND: We studied the repeatability of the ambulatory arterial stiffness index (AASI), which can be computed from 24-h blood pressure (BP) recordings as unity minus the regression slope of diastolic on systolic BP. METHODS: One hundred and fifty-two hypertensive outpatients recruited in Nijmegen (mean age = 46.2 years; 76.3% with systolic and diastolic hypertension) and 145 patients enrolled in the Systolic Hypertension in Europe (Syst-Eur) trial (71.0 years) underwent 24-h BP monitoring at a median interval of 8 and 31 days, respectively. We used the repeatability coefficient, which is twice the SD of the within-participant differences between repeat recordings, and expressed it as a percentage of four times the SD of the mean of the paired measurements. RESULTS: Mean AASI (crude or derived by time-weighted or robust regression) and 24-h pulse pressure (PP) were similar on repeat recordings in both cohorts. In Nijmegen patients, repeatability coefficients of AASI and PP were approximately 50%. In Syst-Eur trial patients, repeatability coefficient was approximately 60% for AASI and approximately 40% for PP. For comparison, repeatability coefficients for 24-h systolic and diastolic BP were approximately 30%. Differences in AASI between paired recordings were correlated with differences in the goodness of fit (r2) of the AASI regression line as well as with differences in the night-to-day BP ratio. However, in sensitivity analyses stratified for type of hypertension, r2, or dipping status, repeatability coefficients for AASI did not widely depart from 50 to 60% range. CONCLUSION: Estimates of mean AASI were not different between repeat recordings, and repeatability coefficients were within the 50-60% range.

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/cm(2) (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/cm(2) (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 microg/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.