M. De Buyzere

Night-day blood pressure ratio and dipping pattern as predictors of death and cardiovascular events in hypertension

Our objective was to assess the prognostic significance of the night-time dipping pattern and the night–day blood pressure (BP) ratio for mortality and cardiovascular events in hypertensive patients without major cardiovascular disease at baseline. We performed a meta-analysis on individual data of 3468 patients from four prospective studies performed in Europe. Age of the subjects averaged 61±13 years; 45% were men and 61% were under antihypertensive treatment at the time of ambulatory BP monitoring. The night–day BP ratio and 24-h BP averaged, respectively, 0.907±0.085/0.866±0.095 and 138.1±16.4/82.3±11.0 mm Hg. Total follow-up time amounted to 23 164 patient-years. We used multivariable Cox regression analysis to assess the outcome of reverse dippers, non-dippers and extreme dippers vs dippers, and to assess the hazard ratios associated with 1 standard deviation higher night–day BP ratio. In comparison with dippers, and with adjustment for confounders and 24-h BP, the incidence of cardiovascular events was worse in reverse dippers (P⩽0.05), whereas mortality was lower in extreme dippers (P⩽0.01); outcome was similar in non-dippers and dippers. The systolic night–day BP ratio independently predicted all-cause mortality and cardiovascular events (P⩽0.001), which persisted after additional adjustment for 24-h BP (P⩽0.05); appropriate interaction terms indicated that the results were similar in men and women, in younger and older patients and in treated and untreated patients. In conclusion, the dipping pattern and the night–day BP ratio significantly and independently predict mortality and cardiovascular events in hypertensive patients without history of major cardiovascular disease, even after adjustment for 24-h BP.

Determining carotid artery pressure from scaled diameter waveforms: comparison and validation of calibration techniques in 2026 subjects

Calibrated diameter distension waveforms could provide an alternative for local arterial pressure assessment more widely applicable than applanation tonometry. We compared linearly and exponentially calibrated carotid diameter waveforms to tonometry readings. Local carotid pressures measured by tonometry and diameter waveforms measured by ultrasound were obtained in 2026 subjects participating in the Asklepios study protocol. Diameter waveforms were calibrated using a linear and an exponential calibration scheme and compared to measured tonometry waveforms by examining the mean root-mean-squared error (RMSE), carotid systolic blood pressure (SBPcar) and augmentation index (AIx) of calibrated and measured pressures. Mean RMSE was 5.2(3.3) mmHg (mean(stdev)) for linear and 4.6(3.6) mmHg for exponential calibration. Linear calibration yielded an underestimation of SBPcar by 6.4(4.1) mmHg which was strongly correlated to values of brachial pulse pressure (PPbra) (R = 0.4, P < 0.05). Exponential calibration underestimated true SBPcar by 1.9(3.9) mmHg, independent of PPbra. AIx was overestimated by linear calibration by 1.9(10.1)%, the difference significantly increasing with increasing AIx (R = 0.25, P < 0.001) and by exponential calibration by 5.4(10.6)%, independently of the value of AIx. Properly calibrated diameter waveforms offer a viable alternative for local pressure estimation at the carotid artery. Compared to linear calibration, exponential calibration significantly improves the pressure estimation.

Small and large artery elasticity indices in peripheral arterial occlusive disease (PAOD)

In peripheral arterial occlusive disease (PAOD), arterial compliance of the central arteries has been reported to be reduced. It is, however, not clear whether, in PAOD, decreased arterial compliance is also accompanied by similar changes in the peripheral arteries. Therefore the aim of the study was to determine the large (C1) and small (C2) artery elasticity indices in PAOD and their relations to its well-accepted characteristics (ankle-brachial index, ABI; pulse pressure, PP; absolute claudication distance, ACD). A total of 43 patients with PAOD (mean age 68 ± 9 years; ABI of the limiting leg 0.65 ± 0.14; SBP (systolic blood pressure) 149 ± 20 mmHg, and ACD 488 ± 187 m) were enrolled as well as 16 control subjects of comparable age (69 ± 4 years) and blood pressure (SBP 147 ± 27 mmHg). All subjects underwent non-invasive pulse wave analysis in order to determine arterial compliance of the aorta and major side branches (C1) and of the distal circulation (C2), using a modified Windkessel model. In PAOD, both C1 (1.41 ± 0.56 ml/mmHg) and C2 (0.023 ± 0.012 ml/mmHg) were comparable to values in an age and blood pressure-matched control group (C1, 1.25 ± 0.66 ml/mmHg; C2, 0.027 ± 0.008 ml/mmHg). C1 was significantly correlated with ACD (r = 0.36, p = 0.02), PP (r =-0.33, p < 0.02) and only borderline with ABI (r = 0.28, p = 0.07). C2 was correlated with PP (r =-0.38, p < 0.01), ABI (r = 0.36, p < 0.02) but not with ACD. Large (C1) and small (C2) artery elasticity indices in PAOD were decreased but comparable to values in an elderly group with isolated systolic hypertension. Moreover, C1 and C2 correlated with markers (ABI and PP) of severity of vascular disease.

Anti-myosin humoral immune response following cardiac injury.

A sensitive and highly specific ELISA assay was developed to determine the anti-myosin humoral immune response (AMA) in various heart diseases: acute viral myocarditis, infective endocarditis, acute myocardial infarction, and valve and coronary bypass surgery. The mean study entry AMA titer of each patient group was already significantly increased compared with age matched controls. During further follow-up (90 d) all the groups except for endocarditis showed a significant increase of AMA titer compared with their entry titer. Anti-myosin antibody titer were higher after cardiac surgery than after myocardial infarction or inflammatory heart disease. These results suggest that anti-myosin immune response is not limited to infectious processes in which the pathogen induces antibodies which cross-react with heart constituents but is merely caused by direct cardiac injury. Myosin as a major compound of heart cellular proteins turned out to be a good candidate to trigger immune response after cardiac injury.

Three- and four-element Windkessel models: Assessment of their fitting performance in a large cohort of healthy middle-aged individuals

Lumped-parameter models are used to estimate the global arterial properties by fitting the model to measured (aortic) pressure and flow. Different model configurations coexist, and it is still an open question as to which model optimally reflects the arterial tree and leads to correct estimates of arterial properties. An assessment was made of the performance of (a) the three-element Windkessel model (WK3) consisting of vascular resistance R, total arterial compliance C, and characteristic impedance Zc; (b) a four-element model with an inertance element L placed in parallel with Zc (WK4-p); and (c) a four-element model with L placed in series with Zc (WK4-s). Models were fitted to data measured non-invasively in 2404 healthy subjects, aged between 35 and 55 years. It was found that model performance segregated into two groups. In a group containing 20 per cent of the dataset (characterized by low blood pressure and wave reflection) the WK4-p model outperformed the other models, with model behaviour as envisioned by its promoters. In these cases, the WK3 and WK4-s models led to increased overestimation of total arterial compliance and underestimation of characteristic impedance. However, in about 80 per cent of the cases, the WK4-p model showed a behaviour that was very similar to that of the WK3 and WK4-s models. Here, the WK4-s model yielded the best quality of fit, although model parameters reached physically impossible values for L in about 12 per cent of all cases. The debate about which lumped-parameter model is the better approximation of the arterial tree is therefore still not fully resolved.

Effect of polyunsaturated isocaloric fat diets on plasma lipids, apolipoproteins and fatty acids

The effect of an increased polyunsaturated fatty acid concentration in the diet on the plasma lipoproteins from a normal group of healthy persons and from a group of hypercholesterolemic patients, consuming an isoenergetic and an isocholesterolemic diet, was examined and the changes in the plasma phospholipids were measured. Nine normal and 10 hypercholesterolemic patients were treated with a polyunsaturated diet for 1 month. Controls and hypercholesterolemic patients were screened on their lipid and lipoprotein profiles and their P/S ratio in the diet was calculated and increased with a factor 4. In the control group the P/S ratio was increased from 0.35 to 1.38 and in the hypercholesterolemic group from 0.46 to 1.59. They received the diet for at least 4 weeks before a second analysis of lipids and lipoproteins. The most important results are a decrease of plasma cholesterol, followed by a significant increase of HDL cholesterol. The cholesterol-lowering effect results largely from the plasma LDL decrease, especially in the patient group. Apo A-I is decreased accompanied by a significant increase of the ratio HDL-C/apo A-I. The observed changes are most pronounced in the hypercholesterolemic group. There is no change in apo B but a significant change in the linoleic acid concentration especially in the HDL cholesterol esters. The major phospholipids in plasma are identical in both groups and there is an identical change under the PUFA diet, sphingomyelin is increased and phosphatidylcholine is decreased, which may be related to an increase of the HDL2/HDL3 ratio.

The relationship between diet and subclinical atherosclerosis: results from the Asklepios Study

Background/Objectives:Nutritional epidemiology shifted its focus from effects of single foods/nutrients toward the overall diet. Food-based dietary guidelines (FBDGs) are promoted worldwide to stimulate a healthy diet, including a variety of foods, to meet nutrient needs and to reduce the risk for non-communicable diseases. The objective of this study was to investigate whether adherence to the FBDG is associated with reduced femoral/carotid atherosclerosis and/or inflammation.Subjects/Methods:In October 2002, 2524 healthy men and women aged 35–55 years were recruited for the Belgian Asklepios cohort study. Subjects were extensively phenotyped, including echographic assessment of (carotid and femoral) atherosclerosis. A dietary index consisting of three subscores (dietary quality, diversity and equilibrium) was calculated to measure adherence to the Flemish FBDG, using data from a semi-quantitative food-frequency questionnaire. General linear models were used to investigate associations between these scores and cardiovascular (CV) risk factors and atherosclerosis and inflammation markers.Results:Women had better overall dietary scores than men (69 vs 59%). Participants with higher dietary scores showed better age-adjusted CV risk profiles (lower waist/hip ratio, blood pressure, non-high-density lipoprotein-cholesterol, blood triglycerides and homocystein), although most of these associations were only significant in men. Higher dietary scores were also inversely associated with inflammation makers (interleukin-6 and leukocyte count). Associations between diet and atherosclerosis were only found for femoral atherosclerosis and significance disappeared after adjustment for confounders.Conclusions:Better adherence to the Flemish FBDG is associated with a better CV risk profile and less inflammation, mainly among men. There was no direct effect on the presence of carotid or femoral atherosclerosis.

Validation of a new automated IMT measurement algorithm.

Several large-scale studies have confirmed that intima-media thickness (IMT) values can be used to accurately identify cardiovascular risk. 1-5 With the advent of more accurate ultrasonographic measurement applications, there has been a growing interest in validated, clinically applicable tools for performing automated IMT measurements. This study aims to validate a new semi-automated IMT detection algorithm, supplied by GE Vingmed Ultrasound, by comparing it with IMT measurements performed manually at the common carotid artery.

Cardiac involvement in pheochromocytoma.

We report the details of a 40-year-old farmer, a cigarette smoker, who was admitted with general malaise, nausea, vomiting, upper abdominal pain, with ST-elevation on ECG suggestive of an acute anterolateral myocardial infarction. He was treated with nitrates, heparin, beta-blockade and angiotensin-converting enzyme (ACE) inhibitors. Because of the presence of some blood while vomiting no thrombolysis was given and abdominal echography was performed. This revealed a nodular mass at the right adrenal gland. Urinary catecholamines and abdominal magnetic resonance imaging confirmed the suspected diagnosis of pheochromocytoma. Before adrenectomy, a coronary angiography under alpha blocker therapy was performed, which demonstrated no significant coronary artery disease, although the patient showed ST-elevations on ECG. Pathological examination of the adrenal tumor was compatible with a diagnosis of pheochromocytoma. Postoperatively urinary catecholamines dropped dramatically, and the ECG normalised slowly over time. After 8 months the patient is still well. Blood pressure is well controlled with no antihypertensive drugs and exercise testing shows no evidence of myocardial ischaemia.

Posttranslational heterogeneity of bone alkaline-phosphatase in metabolic bone-disease.

Bone alkaline phosphatase is a marker of osteoblast activity. In order to study the posttranscriptional modification (glycosylation) of bone alkaline phosphatase in bone disease, we investigated the relationship between mass and catalytic activity of bone alkaline phosphatase in patients with osteoporosis and hyperthyroidism. Serum bone alkaline phosphatase activity was measured after lectin precipitation using the Iso-ALP test kit. Mass concentration of bone alkaline phosphatase was determined with an immunoradiometric assay (Tandem-R Ostase). In general, serum bone alkaline phosphatase mass and activity concentration correlated well. The activity : mass ratio of bone alkaline phosphatase was low in hyperthyroidism. Activation energy of the reaction catalysed by bone alkaline phosphatase was high in osteoporosis and in hyperthyroidism. Experiments with neuraminidase digestion further demonstrated that the thermodynamic heterogeneity of bone alkaline phosphatase can be explained by a different glycosylation of the enzyme.