Yvonne Plantinga

Ramipril dose-dependently increases nitric oxide availability in the radial artery of essential hypertension patients.

Design and participants A double-blind, crossover, randomized study was designed to evaluate the effect of 3-month treatment with a lower versus a higher antihypertensive dosage of ramipril (5 or 10 mg/day) on nitric oxide (NO)-dependent vasodilation in 46 untreated patients with essential hypertension. Radial artery flow-mediated dilation (FMD), before and after the intra-arterial infusion of NG-monomethyl-L-arginine (L-NMMA), to block NO synthase, and the response to sublingual glyceril trinitrate (GTN, 25 μg) were measured at baseline and after the two treatment periods as a change in artery diameter (computerized system from ultrasound scans). Plasma angiotensin II and oxidative stress markers were also assessed. Results FMD was significantly (P < 0.01) lower in hypertensive patients (4.6 ± 1.8%) than in normotensive subjects (7.1 ± 2.6%), whereas the response to GTN was similar. L-NMMA significantly (P < 0.001) inhibited FMD in normotensive but not in hypertensive subjects. Mean 24-h ambulatory blood pressure, plasma angiotensin II and oxidative stress marker levels were similarly reduced at the end of the two treatment periods. Both dosages of ramipril significantly (P < 0.001) increased FMD (5 mg: 5.9 ± 2.1%; 10 mg: 6.3 ± 2.4%) without modifying the response to GTN. However, compared with baseline (11 ± 19%), the inhibiting effect of L-NMMA on FMD (NO-dependent FMD) was significantly (P < 0.01) greater with ramipril 10 mg (49 ± 12%) than 5 mg per day (38 ± 15%). The improvement in FMD and NO-dependent FMD was not related to changes in plasma levels of angiotensin II or markers of oxidative stress. Conclusion Treatment with ramipril at a higher dosage induced a greater improvement in NO-dependent vasodilation compared with the lower antihypertensive dosage in hypertensive patients.

Dietary supplementation with cis-9,trans-11 conjugated linoleic acid and aortic stiffness in overweight and obese adults

BACKGROUND Animal studies suggest that dietary cis-9,trans-11 (c9,t11) conjugated linoleic acid (CLA) may inhibit or regress the development of atherosclerosis. The effect of CLA on atherosclerosis has not been assessed in humans. OBJECTIVE We investigated the effect of c9,t11 CLA supplementation on aortic pulse wave velocity (a marker of atherosclerosis) and on cardiovascular risk factors in overweight and obese but otherwise apparently healthy subjects. DESIGN In a double-blind, randomized, placebo-controlled, parallel-group trial, we randomly assigned 401 subjects, aged 40-70 y and with a body mass index (in kg/m(2)) > or = 25, to receive either 4 g CLA/d (2.5 g c9,t11 CLA/d and 0.6 g trans-10,cis-12 CLA/d) or placebo supplements for 6 mo. Aortic pulse wave velocity, blood pressure, anthropometric characteristics, and concentrations of fasting lipid, glucose, insulin, and C-reactive protein were measured before and after supplementation. RESULTS During the intervention, mean (+/-SE) pulse wave velocity did not change in the c9,t11 CLA group (Delta0.00 +/- 0.07) compared with the placebo group (Delta0.09 +/- 0.06). There was no effect of c9,t11 CLA supplementation on blood pressure, body composition, insulin resistance, or concentrations of lipid, glucose, and C-reactive protein. CONCLUSION This study does not support an antiatherosclerotic effect or an effect on cardiovascular risk factors of c9,t11 CLA. This trial was registered at www.clinicaltrials.gov as NCT00706745.

Metabolic Syndrome and Vascular Alterations in Normotensive Subjects at Risk of Diabetes Mellitus

We evaluated the possible association between early vascular abnormalities and the metabolic syndrome (MS) in 77 normotensive subjects (mean age: 50 years) at risk of developing diabetes for family history of diabetes, obesity, or impaired fasting glucose. Fifty healthy subjects were recruited as controls. MS was defined according to the ATP III criteria. Brachial artery endothelium-dependent and -independent vasodilation were assessed as flow-mediated dilation (FMD) and response to glyceryl trinitrate (GTN, 25 &mgr;g sublingual), respectively, by automatic computerized edge detection system. Carotid-femoral pulse wave velocity (PWV) and radial augmentation index (AIx) were assessed by applanation tonometry. PWV was significantly (P<0.01) higher in subjects with MS (n=29, 9.0±1.9 m/s) as compared with those without MS (n=48, 7.7±1.2 m/s) and controls (7.2±1.5 m/s). FMD was significantly (P<0.05) reduced in both subjects with (5.8±2.7%) and without MS (6.1±3.7%) as compared with controls (6.9±2.5%). No significant differences were found for response to GTN and AIx. PWV and FMD were significantly (P<0.05) affected by increasing number of MS components. Among the components of the MS, only blood pressure significantly affected PWV, whereas blood pressure and fasting glucose influenced FMD. Logistic regression analysis showed that MS was associated with increased risk of altered PVW (odd ratio: 7.95, confidence limits: 1.06 to 69.11), whereas only blood pressure component was significantly related with increased risk of impaired FMD (odd ratio: 3.60, confidence limits: 1.01 to 12.78). In conclusion, in normotensive subjects at risk of developing diabetes mellitus, the presence of MS is associated with a selective alteration of central PWV.

Carotid intima-media thickness measurement in cardiovascular screening programmes:

Support for the notion that a carotid intima-media thickness (CIMT) measurement is useful in individual cardiovascular risk prediction in addition to a risk function may come from studies showing that for an individual a high or low CIMT measurement leads to a correct shift from one to another risk category and this shift is followed by different treatment consequences. We set out to systematically review the published evidence by performing a PubMed search (2 March 2009). Out of 50 publications on CIMT and future events, 31 reported on the relation in the correct domain, [i.e. those free from symptomatic vascular disease or diabetes mellitus in which assessment of risk using a risk function (e.g. Framingham or SCORE) to base initiation of drug treatment upon is recommended]. Most studies reported relative risks (or equivalents) for the entire population only, and no information on relative risks within certain risk categories that may be of use to reclassify individuals based on combination of absolute and relative risks. No data on potential shifts of participants was presented. Eight studies specifically focused on the added value of CIMT in risk prediction. In seven studies the area under the curve (AUC) of a receiver operating characteristic was used to assess improvements in risk prediction. These analyses showed that addition of a CIMT measurement to established risk factors led to small and sometimes significant improvements in the AUC. However, change in AUC should not be the only parameter to rely on to judge the appropriateness of CIMT in risk stratification. In one study (n = 242), evidence was presented in participants with an intermediate Framingham risk score, a CIMT measurement above the 60th (men) and 80th (women) percentile of age-specific normal CIMT values, shifted participants above the threshold for initiation of drug therapy. Yet, the study was based on 24 events, and no information was presented on the proportion of participants correctly shifted. At present it seems that the published evidence to quantitatively support the use of a CIMT measurement to help in risk stratification on top of a risk function is limited.

C-Reactive Protein and Hypertension: Is there A Causal Relationship?

There is a large body of evidence indicating that inflammation plays a crucial role in all steps characterizing the atherosclerotic process. C-Reactive Protein is a circulating marker of inflammation which recently emerged as a powerful independent determinant of cardiovascular events. Hypertension is closely linked to inflammation. Experimental data and results from cross-sectional studies in humans indicate a relationship between CRP levels and blood pressure. In particular, CRP seems to be related with markers of arterial stiffness, thus suggesting a specific interaction between CRP and systolic blood pressure. However, such observational studies cannot provide any direct evidence for a cause-effect relation. Prospective studies are likely candidates to better define the putative causal relationship on this association. Available results from longitudinal studies are scanty, and do not allow to draw definitive conclusions. Moreover, prospective, placebo-controlled intervention trials documenting that reduction of CRP levels by pharmacological treatment might lead to a reduced risk to develop hypertension are not yet available. Without such crucial information, at the present time the causal connection between inflammation and blood pressure, although regarded as an intriguing possibility, remains undiscovered.

Peripheral wave reflection and endothelial function in untreated essential hypertensive patients with and without the metabolic syndrome.

Objective Metabolic syndrome is associated with a high risk of cardiovascular disease in hypertension. We evaluated whether metabolic syndrome is associated with early vascular alterations, such as increased peripheral wave reflections and endothelial dysfunction, in untreated essential hypertensive patients. Methods Augmentation index and pulse wave velocity were determined with applanation tonometry in 391 untreated hypertensive patients and 166 controls. Endothelium-dependent response was assessed as flow-mediated dilation of the brachial artery. Metabolic syndrome was defined according to the latest National Cholesterol Education Program Adult Treatment panel III. Results Hypertensive patients showed significantly (P < 0.001) increased augmentation index and central pulse wave velocity, as well as reduced flow-mediated dilation, compared with controls. No further impairment in augmentation index or flow-mediated dilation was observed between patients with or without the metabolic syndrome components and with increasing number of metabolic syndrome. Age and systolic blood pressure, but no other single factor of the metabolic syndrome, resulted as significant predictors of augmentation index and flow-mediated dilation. Female gender was associated with increased augmentation index (P < 0.05) in the presence of the metabolic syndrome. Central pulse wave velocity was selectively impaired by metabolic syndrome in both genders. Finally, reactive hyperemia was reduced in patients with the metabolic syndrome and decreased significantly with the increasing number of metabolic syndrome. Conclusions In untreated hypertensive patients, the presence of metabolic syndrome, which selectively impairs central pulse wave velocity, does not account for a further deterioration of peripheral wave reflection and conduit artery endothelial function. Our results suggest that blood pressure, age and gender are important determinants of peripheral vascular structural and functional parameters in these subjects, irrespective of the metabolic syndrome.

Subclinical cardiac involvement in patients with facioscapulohumeral muscular dystrophy

Myocardial involvement is a common finding in certain myopathies, while it has not been extensively investigated in facioscapulohumeral muscular dystrophy (FSHD1A). Aim of this study was to assess in FSHD1A patients the electrical and functional properties of the myocardium. Twenty-four patients with FSHD1A (mean age 41.2+/-14.5 years) and 24 matched healthy subjects were studied. Standard- and signal-averaged electrocardiography were recorded to determine QT dispersion and the presence of ventricular late potentials (VLPs). Standard echocardiography with systo-diastolic variations of integrated backscatter signal (CV-IBS) were performed to assess functional properties of the myocardium. Compared with control subjects, patients with FSHD1A had significantly lower CV-IBS and higher QT dispersion. Nine patients had positive VLPs. QT and QTc dispersion were inversely related to CV-IBS at both septum and posterior wall levels. Moreover, septal CV-IBS was inversely related to the Kpnl-BinI4q fragment size. These results suggest a subclinical cardiac involvement in FSHD1A patients, which can represent a substrate for ventricular arrhythmias and heart failure.

Online measurement of the vasodilation of peripheral arteries on ultrasound images

The online measurement of the vasodilation of a peripheral artery is useful in many clinical applications. Moreover, ultrasound imaging is recommended because of the advantages of this technique such as non-invasivity and feasibility. However, an algorithm with a subpixel resolution is required to obtain a useful plot of the vasodilation when using ultrasound images since the temporal changes of the vascular diameter on these images are usually not greater than 1-2 pixels. The algorithm we propose in this paper is based on the first absolute central moment, a mathematical operator which is used as an edge detector. The performances of the algorithm are analysed both on test discontinuities and on the online analysis of the brachial artery in in-vivo studies