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).

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.

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.

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.

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.

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.

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.

Are blood pressure and diabetes additive or synergistic risk factors? Outcome in 8494 subjects randomly recruited from 10 populations.

It remains unknown whether diabetes and high blood pressure (BP) are simply additive risk factors for cardiovascular outcome or whether they act synergistically and potentiate one another. We performed 24-h ambulatory BP monitoring in 8494 subjects (mean age, 54.6 years; 47.0% women; 6.9% diabetic patients) enrolled in prospective population studies in 10 countries. In multivariable-adjusted Cox regression, we assessed the additive as opposed to the synergistic effects of BP and diabetes in relation to a composite cardiovascular endpoint by testing the significance of appropriate interaction terms. During 10.6 years (median follow-up), 1066 participants had a cardiovascular complication. Diabetes mellitus as well as the 24-h ambulatory BP were independent and powerful predictors of the composite cardiovascular endpoint. However, there was no synergistic interaction between diabetes and 24-h, daytime, or nighttime, systolic or diastolic ambulatory BP (P for interaction, 0.07P0.97). The only exception was a borderline synergistic effect between diabetes and daytime diastolic BP in relation to the composite cardiovascular endpoint (P=0.04). In diabetic patients, with normotension as the reference group, the adjusted hazard ratios for the cardiovascular endpoint were 1.35 (95% confidence interval (CI), 0.87-2.11) for white-coat hypertension, 1.78 (95% CI, 1.22-2.60) for masked hypertension and 2.44 (95% CI, 1.92-3.11) for sustained hypertension. The hazard ratios for non-diabetic subjects were not different from those of diabetic patients (P-values for interaction, 0.09P0.72). In conclusion, in a large international population-based database, both diabetes mellitus and BP contributed equally to the risk of cardiovascular complications without evidence for a synergistic effect.

Association of echocardiographic left ventricular structure with the ACE D/I polymorphism: a meta-analysis.

INTRODUCTION: : In a previous meta-analysis, we derived pooled estimates for the association of left ventricular mass (LVM) and hypertrophy (LVH), as diagnosed by electrocardiography or echocardiography, with the ACE D/I polymorphism. We updated this meta-analysis until May 2009 only considering echocardiographic phenotypes. METHODS: : We computed pooled estimates from a random-effects model. RESULTS: : Across 38 studies, both DD homozygotes (n = 2440) and DI heterozygotes ( n = 4310) had higher (p ≤ 0.002) LVM or LVM index than II homozygotes (n = 2229). Across 21 studies with available data, this was due to increased mean wall thickness (MWT) with no difference in left ventricular internal diameter (LVID). Standardised differences (DD versus II) were 0.39 (p < 0.001) for LVM, 0.34 (p = 0.009) for MWT, and 0.066 (p = 0.26) for LVID. Across 16 studies (4894 participants), the pooled odds ratios of LVH (versus II homozygotes) were 1.11 (p = 0.29) and 1.02 (p = 0.88) for the DD and DI genotypes, respectively. Sensitivity analyses were confirmatory. CONCLUSIONS: : Our meta-analysis supports the hypothesis that the enhanced ACE activity associated with the D allele is associated with higher LV mass. Smaller sample size might explain the lack of significant association with LVH.

Ambulatory blood pressure monitoring in 9357 subjects from 11 populations highlights missed opportunities for cardiovascular prevention in women.

To analyze sex-specific relative and absolute risks associated with blood pressure (BP), we performed conventional and 24-hour ambulatory BP measurements in 9357 subjects (mean age, 52.8 years; 47% women) recruited from 11 populations. We computed standardized multivariable-adjusted hazard ratios for associations between outcome and systolic BP. During a course of 11.2 years (median), 1245 participants died, 472 of cardiovascular causes. The number of fatal combined with nonfatal events was 1080, 525, and 458 for cardiovascular and cardiac events and for stroke, respectively. In women and men alike, systolic BP predicted outcome, irrespective of the type of BP measurement. Women compared with men were at lower risk (hazard ratios for death and all cardiovascular events=0.66 and 0.62, respectively; P<0.001). However, the relation of all cardiovascular events with 24-hour BP (P=0.020) and the relations of total mortality (P=0.023) and all cardiovascular (P=0.0013), cerebrovascular (P=0.045), and cardiac (P=0.034) events with nighttime BP were steeper in women than in men. Consequently, per a 1-SD decrease, the proportion of potentially preventable events was higher in women than in men for all cardiovascular events (35.9% vs 24.2%) in relation to 24-hour systolic BP (1-SD, 13.4 mm Hg) and for all-cause mortality (23.1% vs 12.3%) and cardiovascular (35.1% vs 19.4%), cerebrovascular (38.3% vs 25.9%), and cardiac (31.0% vs 16.0%) events in relation to systolic nighttime BP (1-SD, 14.1 mm Hg). In conclusion, although absolute risks associated with systolic BP were lower in women than men, our results reveal a vast and largely unused potential for cardiovascular prevention by BP-lowering treatment in women.

Responses of the ambulatory arterial stiffness index and other measures of arterial function to antihypertensive drugs.

We investigated the effects of different antihypertensive drugs on the ambulatory arterial stiffness index (AASI), pulse pressure (PP), the arterio-ventricular coupling index (AVCI) and aortic pulse wave velocity (aPWV). After a 4-week placebo period, 94 and 107 patients with uncomplicated hypertension were randomly assigned to treatment with atenolol (AT) at dosage of 50 mg per day or perindopril/indapamide (PER/IND) at dosage of 2/0.6 mg per day for 1 year. From each patient's 24-h ambulatory blood pressure (BP) recording, we determined the 24-h systolic and diastolic BPs. We computed PP as the difference between 24-h systolic and diastolic BP, AASI as unity minus the regression slope of diastolic on systolic BP, and AVCI as (T/τ)/(1+2T/3τ), where T is the heart period in seconds and τ is the decay time of aortic BP during diastole. On AT compared with PER/IND, with adjustments applied for covariables, 24-h systolic BP (-9.5 vs. -13.7 mm Hg; P=0.009) and 24-h PP (-1.02 vs. -6.53 mm Hg; P<0.001) decreased less and AVCI lengthened more (+0.019 vs. -0.008; P<0.001). The changes in AASI (-0.001 vs. -0.014; P=0.44) and aPWV (-0.89 vs. -0.69 m s(-1); P=0.45) were similar in the two treatment groups. AASI and aPWV showed significant concordance (r=0.21, P=0.003) after adjustment for covariables. On administration of antihypertensive drugs with different hemodynamic profiles, AASI and aPWV behaved similarly. The similarity in the findings for aPWV and AASI support the use of AASI as an index reflecting the arterial stiffness.

Predictive role of the nighttime blood pressure.

Numerous studies addressed the predictive value of the nighttime blood pressure (BP) as captured by ambulatory monitoring. However, arbitrary cutoff limits in dichotomized analyses of continuous variables, data dredging across selected subgroups, extrapolation of cross-sectional studies to prospective outcomes, and lack of comprehensive adjustments for confounders make interpretation of the literature difficult. We reviewed prospective studies with total mortality or a composite cardiovascular end point as an outcome in relation to the level and the circadian profile of systolic BP. We analyzed studies in hypertensive patients (n = 23 856) separately from those in individuals randomly recruited from populations (n = 9641). We pooled summary statistics and individual subject data, respectively. In both patients and populations, in analyses in which nighttime BP was additionally adjusted for daytime BP and vice versa, nighttime BP was a stronger predictor than daytime BP. With adjustment for the 24-hour BP, both the night-to-day BP ratio and dipping status remained significant predictors of outcome but added little prognostic value over and beyond the 24-hour BP level. In the absence of conclusive evidence proving that nondipping is a reversible risk factor, the option whether or not to restore the diurnal blood pressure profile to a normal pattern should be left to the clinical judgment of doctors and should be individualized for each patient. Current guidelines on the interpretation of ambulatory BP recording need to be updated.

The metabolic syndrome and carotid intima-media thickness in relation to the parathyroid hormone to 25-OH-D(3) ratio in a general population.

BACKGROUND: Parathyroid hormone (PTH) and vitamin D interactively regulate calcium fluxes across membranes, and thereby modulate insulin sensitivity, blood pressure, and arterial calcification. We hypothesized that lower calcium intake as reflected by circulating PTH and 25-OH-D3 might be associated with the metabolic syndrome (MS) and arterial calcification. METHODS: In a random population sample (n = 542; 50.5% women; mean age, 49.8 ± 13.1 years), we measured MS prevalence (International Diabetes Federation (IDF) and American Heart Association (AHA) criteria), PTH and 25-OH-D3, serum and 24-h urinary calcium, MS components, carotid intima-media thickness (CIMT), and calcium intake from dairy products. We assessed associations in multivariable-adjusted analyses, using linear and logistic regressions. RESULTS: The prevalence of MS was 21.0% (IDF criteria) and 23.6% (AHA criteria). MS prevalence, blood pressure, waist circumference, body mass index, fasting blood glucose, insulin and triglycerides, and CIMT increased (P ≤ 0.042) across quartiles of the PTH/25-OH-D3 ratio, whereas serum and 24-h urinary calcium decreased (P ≤ 0.029). Waist circumference and fasting blood glucose decreased across quartiles of habitual calcium intake (P ≤ 0.04). In models that included MS (IDF) and PTH/25-OH-D3, the regression coefficients relating CIMT to PTH/25-OH-D3 ratio and MS were +51 µm (P = 0.013) and +19 µm (P = 0.45), respectively. Multivariable-adjusted analyses were confirmatory. CONCLUSIONS: MS prevalence and CIMT were positively associated with PTH/25-OH-D3. CIMT was not associated with MS. Prospective studies and intervention trials should address the causality of these associations.

Persistence of mortality reduction after the end of randomized therapy in clinical trials of blood pressure-lowering medications.

Long-term follow-up of clinical trials of blood pressure-lowering medications has suggested a continuation of event reduction after study completion. We evaluated the persistence of mortality benefit of these agents after the end of clinical trials, when all of the patients were advised to take the same open-label therapy. We performed a meta-analysis of randomized clinical trials using blood pressure-lowering medications, used in patients with hypertension, myocardial infarction, or left ventricular systolic dysfunction, (n=18; 132 854 patients; 11 988 deaths) when a second report describing results after the end of the trial was available. During the randomized (first) phase, 80% (interquartile range: 75% to 83%) of the patients randomized to receive active therapy actually received it compared with 16% (interquartile range: 7% to 22%) of those randomized to control. In this phase, mortality was lower in the intervention group (odds ratio: 0.84 [95% CI: 0.79 to 0.90]; P<0.0001). Mortality was also lower during the open-label follow-up (second) phase (odds ratio: 0.85 [95% CI: 0.79 to 0.91]; P<0.0001), when all of the patients were advised to take the same therapy, and rates of receiving active therapy were similar in the 2 groups (59% [interquartile range: 46% to 77%], among those originally randomized to active, and 43% [interquartile range: 20% to 68%], in the control). Several sensitivity analyses indicated stability of the effects. In studies of antihypertensive medications, a decrease in overall mortality persists after the end of trial phase, when most patients in both the intervention and control groups receive active therapy. These analyses imply that earlier intervention would result in better clinical outcomes.

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.

Blood pressure variability in relation to outcome in the International Database of Ambulatory blood pressure in relation to Cardiovascular Outcome.

Ambulatory blood pressure (BP) monitoring provides information not only on the BP level but also on the diurnal changes in BP. In the present review, we summarized the main findings of the International Database on Ambulatory BP in relation to Cardiovascular Outcome (IDACO) with regard to risk stratification based on BP variability. The predictive accuracy of daytime and nighttime BP and the night-to-day BP ratio depended on the disease outcome under study and treatment status, and differed for fatal outcomes compared with the composite of fatal and nonfatal diseases. An exaggerated morning surge, exceeding the 90th percentile of the population, is an independent risk factor for mortality and cardiovascular and cardiac events. Conversely, a sleep-trough or preawakening morning surge in systolic BP below 20 mm Hg is probably not associated with an increased risk of death or cardiovascular events. BP variability as captured by the average of the daytime and nighttime s.d. weighted for the duration of the daytime and nighttime interval (s.d.(dn)) and the average real variability (ARV(24)) predicted the outcome, but improved the prediction of the composite of all cardiovascular events by only 0.1%. In conclusion, the IDACO observations support the concept that BP variability adds to risk stratification, but above all highlight that 24-h ambulatory BP level remains the main predictor to be considered in clinical practice.

Prognostic value of isolated nocturnal hypertension on ambulatory measurement in 8711 individuals from 10 populations.

BACKGROUND: We and other investigators previously reported that isolated nocturnal hypertension on ambulatory measurement (INH) clustered with cardiovascular risk factors and was associated with intermediate target organ damage. We investigated whether INH might also predict hard cardiovascular endpoints. METHODS AND RESULTS: We monitored blood pressure (BP) throughout the day and followed health outcomes in 8711 individuals randomly recruited from 10 populations (mean age 54.8 years, 47.0% women). Of these, 577 untreated individuals had INH (daytime BP <135/85 mmHg and night-time BP ≥120/70 mmHg) and 994 untreated individuals had isolated daytime hypertension on ambulatory measurement (IDH; daytime BP ≥135/85 mmHg and night-time BP <120/70 mmHg). During follow-up (median 10.7 years), 1284 deaths (501 cardiovascular) occurred and 1109 participants experienced a fatal or nonfatal cardiovascular event. In multivariable-adjusted analyses, compared with normotension (n = 3837), INH was associated with a higher risk of total mortality (hazard ratio 1.29, P = 0.045) and all cardiovascular events (hazard ratio 1.38, P = 0.037). IDH was associated with increases in all cardiovascular events (hazard ratio 1.46, P = 0.0019) and cardiac endpoints (hazard ratio 1.53, P = 0.0061). Of 577 patients with INH, 457 were normotensive (<140/90 mmHg) on office BP measurement. Hazard ratios associated with INH with additional adjustment for office BP were 1.31 (P = 0.039) and 1.38 (P = 0.044) for total mortality and all cardiovascular events, respectively. After exclusion of patients with office hypertension, these hazard ratios were 1.17 (P = 0.31) and 1.48 (P = 0.034). CONCLUSION: INH predicts cardiovascular outcome in patients who are normotensive on office or on ambulatory daytime BP measurement.