Background-Few population studies addressed the prognostic significance of aortic pulse wave velocity (APWV) above and beyond other cardiovascular risk factors. Methods and Results-We studied a sex-and age-stratified random sample of 1678 Danes aged 40 to 70 years. We used Cox regression to investigate the prognostic value of APWV, office pulse pressure (PP), and 24-hour ambulatory PP while adjusting for mean arterial pressure (MAP) and other covariates. Over a median follow-up of 9.4 years, the incidence of fatal and nonfatal cardiovascular end points, cardiovascular mortality, and fatal and nonfatal coronary heart disease amounted to 154, 62, and 101 cases, respectively. We adjusted for sex, age, body mass index, MAP measured in the office (conventional PP and APWV) or by ambulatory monitoring (24-hour PP), smoking, and alcohol intake. With these adjustments, APWV maintained its prognostic significance in relation to each end point (PϽ0.05), whereas office and 24-hour PP lost their predictive value (PϾ0.19), except for office PP in relation to coronary heart disease (Pϭ0.02). For each 1-SD increment in APWV (3.4 m/s), the risk of an event increased by 16% to 20%. In sensitivity analyses, APWV still predicted all cardiovascular events after standardization to a heart rate of 60 beats per minute, after adjustment for 24-hour MAP instead of office MAP, and/or after additional adjustment for the ratio of total to HDL serum cholesterol and diabetes mellitus at baseline. Conclusions-In

AimsCarotid–femoral pulse wave velocity (PWV), a direct measure of aortic stiffness, has become increasingly important for total cardiovascular (CV) risk estimation. Its application as a routine tool for clinical patient evaluation has been hampered by the absence of reference values. The aim of the present study is to establish reference and normal values for PWV based on a large European population.Methods and resultsWe gathered data from 16 867 subjects and patients from 13 different centres across eight European countries, in which PWV and basic clinical parameters were measured. Of these, 11 092 individuals were free from overt CV disease, non-diabetic and untreated by either anti-hypertensive or lipid-lowering drugs and constituted the reference value population, of which the subset with optimal/normal blood pressures (BPs) (n = 1455) is the normal value population. Prior to data pooling, PWV values were converted to a common standard using established conversion formulae. Subjects were categorized by age decade and further subdivided according to BP categories. Pulse wave velocity increased with age and BP category; the increase with age being more pronounced for higher BP categories and the increase with BP being more important for older subjects. The distribution of PWV with age and BP category is described and reference values for PWV are established. Normal values are proposed based on the PWV values observed in the non-hypertensive subpopulation who had no additional CV risk factors.ConclusionThe present study is the first to establish reference and normal values for PWV, combining a sizeable European population after standardizing results for different methods of PWV measurement.

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Abstract-In previous studies, of which several were underpowered, the relation between cardiovascular outcome and blood pressure (BP) variability was inconsistent. We followed health outcomes in 8938 subjects (mean age: 53.0 years; 46.8% women) randomly recruited from 11 populations. At baseline, we assessed BP variability from the SD and average real variability in 24-hour ambulatory BP recordings. We computed standardized hazard ratios (HRs) while stratifying by cohort and adjusting for 24-hour BP and other risk factors. Over 11.3 years (median), 1242 deaths (487 cardiovascular) occurred, and 1049, 577, 421, and 457 participants experienced a fatal or nonfatal cardiovascular, cardiac, or coronary event or a stroke.Higher diastolic average real variability in 24-hour ambulatory BP recordings predicted (PՅ0.03) total (HR: 1.14) and cardiovascular (HR: 1.21) mortality and all types of fatal combined with nonfatal end points (HR: Ն1.07) with the exception of cardiac and coronary events (HR: Յ1.02; PՆ0.58). Higher systolic average real variability in 24-hour ambulatory BP recordings predicted (PϽ0.05) total (HR: 1.11) and cardiovascular (HR: 1.16) mortality and all fatal combined with nonfatal end points (HR: Ն1.07), with the exception of cardiac and coronary events (HR: Յ1.03; PՆ0.54). SD predicted only total and cardiovascular mortality. While accounting for the 24-hour BP level, average real variability in 24-hour ambulatory BP recordings added Ͻ1% to the prediction of a cardiovascular event. Sensitivity analyses considering ethnicity, sex, age, previous cardiovascular disease, antihypertensive treatment, number of BP readings per recording, or the night:day BP ratio were confirmatory. In conclusion, in a large population cohort, which provided sufficient statistical power, BP variability assessed from 24-hour ambulatory recordings did not contribute much to risk stratification over and beyond 24-hour BP. (Hypertension. 2010;55:1049-1057.)Key Words: blood pressure variability Ⅲ ambulatory blood pressure Ⅲ population science Ⅲ risk factors Ⅲ epidemiology A mbulatory blood pressure monitoring not only provides information on the blood pressure level but on the diurnal changes in blood pressure as well. Blood pressure variability includes both short-term and circadian components, which can be estimated by the SD of the blood pressure values over a defined period of the day or by the night:day blood pressure ratio, respectively. We recently reported in Ͼ7000 subjects recruited from 6 populations on the prognos- Although the aforementioned analyses shed light on the association between outcome and long-term blood pressure variability, the predictive value of short-term reading-toreading blood pressure variability remains uncertain. Possible limitations of previous studies were a lack of statistical power, 2-5 selection of specific groups of patients, 5-7 categorization of variability by arbitrary cutoff points, 2,4,7-9 and sole reliance on fatal end points. 10,11 Moreover, various parameters can capture short-term b...

ABP is superior to CBP in predicting cardiovascular events, but not total and noncardiovascular mortality. Cardiovascular risk gradually increases from normotension over white-coat and masked hypertension to sustained hypertension.

Ambulatory BP provided prognostic information about cardiovascular disease better than office BP. Isolated office hypertension was not a risk factor and isolated ambulatory hypertension tended to be associated with increased risk. A blunted BP decrease at night was a risk factor in subjects with daytime ambulatory hypertension.

We investigated the major products of proglucagon (PG) processing in plasma in the fasting state, after intravenous arginine and after an oral glucose load in noninsulin-dependent diabetics (NIDDM) and in weight matched controls using specific radioimmunoassays and analytical gel filtration. In the fasting state the glucagonlike peptide-1 (GLP-1) immunoreactivity was significantly elevated in the NIDDM group compared with the control group. Both after intravenous arginine and after an oral glucose load a rise in the plasma concentrations of all immunoreactive moieties measured was seen. All integrated incremental responses after intravenous arginine were identical in the two groups. After oral glucose the insulin concentrations in plasma were lower and the concentrations of all proglucagon products were higher in the NIDDM group compared to the control group. The gel filtration analysis showed that arginine stimulated the secretion of pancreatic glucagon (PG 33-61), major proglucagon fragment (PG 72-158) and probably GLP-1 (PG 72-107 amide) in both groups, whereas oral glucose stimulated the secretion of glicentin (PG 1-69) and intestinal GLP-1 (PG 78-107 amide), an insulinotropic hormone. The elevated levels of immunoreactive GLP-1 in diabetics in the fasting state were mainly due to an increased concentration of major proglucagon fragment. (J. Clin. Invest. 1991. 87:415-423.)

Abstract-The relationship between ambulatory blood pressure and mortality in a general Western population is unknown.Therefore, we conducted this prospective study of a random sample of 1700 Danish men and women, aged 41 to 72 years, without major cardiovascular diseases. At baseline, ambulatory blood pressure, office blood pressure, and other risk factors were recorded. After a mean period of 9.5 years, 174 had died: 63 were cardiovascular deaths. In multivariate proportional hazards models, adjusted for other risk factors of significance, the relative risk of cardiovascular mortality (95% confidence interval) associated with 10 mm Hg increments in systolic and 5 mm Hg increments in diastolic ambulatory blood pressure were 1.51 (1.28 to 1.77) and 1.43 (1.26 to 1.61). The corresponding figures for all cause mortality were 1.18 (1.06 to 1.31) and 1.18 (1.09 to 1.28). The relative risks of cardiovascular mortality were lower for office blood pressure, and office blood pressure did not predict all cause mortality. When ambulatory and office blood pressures were entered in the same multivariate models, only the ambulatory blood pressures were significant predictors of all cause mortality and cardiovascular mortality. The relationship between ambulatory blood pressures and risk of mortality was log-linear, with no indication of a threshold. The absolute risk of mortality was also dependent on age and smoking status, and an upper "acceptable" ambulatory blood pressure based on risk of mortality could only be defined when other risk factors were taken into account. In conclusion, ambulatory blood pressure provided prognostic information on mortality above and beyond that of office blood pressure.