Modest opposite associations of endogenous testosterone and oestradiol with left ventricular remodelling and function in healthy middle-aged men.

In healthy middle-aged men, endogenous testosterone does not seem to increase risk for cardiovascular disease (CVD). One explanation might be a differential effect of testosterone, and another, interference with oestradiol with respect to specific cardiovascular functions. To investigate these possibilities, we evaluated in a cross-sectional population of 1223 healthy men, aged 46 (6) years, associations between endogenous testosterone, oestradiol and left ventricular structure and function (echocardiography). Testosterone was inversely associated with ejection fraction (EF) and with more sensitive systolic tissue Doppler imaging indices. Oestradiol was positively associated with EF. These associations were confirmed by linear regression analyses, and consistent for calculated free as well as for total sex steroid concentrations. Standardized regression coefficients were -0.13 for testosterone (P < 0.01) and 0.12 for oestradiol (P < 0.01) for the association with EF, in a model which included height, waist circumference, triglycerides, glucose, systolic blood pressure, drug-treated hypertension, heart rate, haematocrit, current smoking, serum sampling time, age and excessive alcohol use. The study suggests an opposite link, albeit modestly, of testosterone and oestradiol with left ventricle systolic function in healthy middle-aged men. The finding provides a partial explanation for the overall neutral effect on CVD of testosterone in healthy middle-aged men.

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.

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.

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.

Noninvasive assessment of left ventricular and myocardial contractility in middle-aged men and women: disparate evolution above the age of 50?

End-systolic elastance (E(es)) is a frequently used index of left ventricular (LV) contractility. However, because of its inherent dependence on LV geometry, E(es) cannot be used to compare myocardial contractile state between ventricles with different geometries, which is the case in any cross-sectional study. Various normalization methods for E(es) have been proposed in the literature, but a standardized method is still lacking. In this study, we introduced a novel alternative normalization technique and compared it with three previously suggested methods. We tested all normalization methods to assess the age- and sex-related differences in myocardial contractility in a large population sample of 2,184 middle-aged (ages, 35-55 yr) untreated subjects free from overt cardiovascular disease. Ventricular contractility E(es) was determined using a previously validated noninvasive single-beat method, based on two-dimensional echocardiographic and brachial blood pressure measurements. Myocardial contractility was estimated as 1) E(es).end-diastolic volume (EDV); 2) E(es).LV mass (LVM); 3) 0.433.E(es).LVM/relative wall thickness (RWT), based on a theoretical LV model; and 4) 0.0941.E(es).LVM(0.455).RWT(-0.159), a novel semiempirical expression derived in this study. Because of the difference in their underlying assumptions, the various myocardial contractility indexes do not provide consistent information with respect to sex differences. Despite these discrepancies, it was found that myocardial contractility in women appears to be better preserved after the age of 50 yr compared with that in men. The physiological mechanisms behind this potentially clinically important phenomenon at population level require further investigation.

A comparison between systolic and diastolic pulse contour analysis in the evaluation of arterial stiffness.

Several methodologically independent measures of arterial stiffness derived from either the systolic or diastolic segments of the arterial pulse have been proposed. The exact nature of the large and small artery elasticity indices (C1 and C2, respectively) derived from diastolic pulse contour analysis remains largely unexplored, although C2 has controversially been termed to be "oscillatory" and "reflective." We investigated the relation between C2 and, respectively, a prototype of arterial reflectivity (ie, the augmentation index, AIx) and a covariate of arterial reflectivity (body height). A validated transfer function is used to transform a tonometrically obtained radial pressure wave into an ascending aortic pressure wave, from which AIx is derived using systolic pulse contour analysis. Diastolic pulse contour analysis using a modified Windkessel model is used to derive C1 and C2. One hundred subjects, who were free from atherothrombotic disease and 19 to 77 years of age, with a wide pressure range (97 to 186/52 to 104 mm Hg) were studied. Mean values of C1, C2, AIx, and body height were, respectively, 13.8+/-4.3 mL/mm Hgx10, 5.9+/-3.1 mL/mm Hgx100, 128.5+/-24.9%, and 169+/-9 cm. Coefficients of variation were 32.8% for C1, 33.3% for C2, and 6.7% for AIx. C2 was significantly and inversely correlated to AIx (r=-0.707, P<0.001). Both AIx and C2 were correlated to body height (r=-0.487, P<0.001, and r=0.514, P<0.001). In conclusion, the results of this study provide the first clinical evidence that validates a probable biophysical equivalent of the C2 element of a third-order, 4-element modified Windkessel model. We suggest that C2 is, at least in part, a measure of arterial wave reflectance. However, although short-term reproducibility of AIx is excellent, C2 showed markedly increased variability with the devices used.

Interchangeability of carotid and femoral intima-media thickness in risk stratification.

BACKGROUND: Carotid intima-media thickness (c-IMT) is an intermediate phenotype not only for the local but also the global arteriosclerotic status, a concept which has been validated by its ability to act as a marker for future cardiovascular and cerebrovascular events. Whether the association between c-IMT and risk factors, distant atherosclerotic disease and prognosis are the sole prerogative of the carotid artery, or whether these findings can be extrapolated to other arterial sites is less well studied. In view of the concept of vascular heterogeneity, we measured the IMT in a muscular, lower extremity artery, the common femoral (f-IMT), and in elastic upper extremity artery, the common carotid, in apparently healthy individuals and explored the relationship with risk factors and the individuals 10-year cardiovascular (CV) risk, calculated using the Framingham systolic blood pressure equation. METHODS: A population of 156 apparently healthy normotensive Caucasian volunteers between 18 and 65 years was studied (mean age 43+/-13 years; 68 men, 88 women; mean arterial blood pressure 126 +/- 15/70 +/- 10 mmHg). The c-IMT and f-IMT were measured using a 10 MHz vascular linear array transducer at the far walls 1 to 2 centimetres proximal to the right common carotid and right common femoral artery bifurcations, respectively. Risk factors were assessed and the 10-year cardiovascular risk was calculated using the Framingham systolic blood pressure equation. RESULTS: The median c-IMT was 0.52 mm (interquartile range 0.45-0.62 mm) and f-INT was 0.52 mm (0.39-0.67). Both parameters were significantly correlated (r = 0.363; p < 0.01) and both were significantly correlated to the calculated 10-year CV risk (r = 0.579; p < 0.01 and r = 0.574; p < 0.01 for the carotid and c-IMT and f-IMT, respectively). Median risk was low: 2.11% (0.27-5.50). Although measures of agreement were higher for the f-IMT versus risk (0.47) than for the c-IMT versus risk (0.30), the former showed a significantly wider scatter with increasing age and with quartiles of CV risk. The c-IMT and f-IMT do not share determinant risk factors to the same extent and with only 20% of mutual variance explained, cannot be regarded as interchangeable. CONCLUSIONS: Although the c-IMT and f-IMT are significantly intercorrelated and correlate to the calculated 10-year CV risk, they are not interchangeable. While the f-IMT is less suited as a continuous variable for risk stratification in a low-risk population, our data suggest its possible use as a dichotomised risk marker.

Aldosterone and vascular damage.

Although the aldosterone escape mechanism is well known, aldosterone has often been neglected in the pathophysiologic consequences of the activated renin-angiotensin-aldosterone system in arterial hypertension and chronic heart failure. There is now evidence for vascular synthesis of aldosterone aside from its secretion by the adrenal cortex. Moreover, aldosterone is involved in vascular smooth muscle cell hypertrophy and hyperplasia, as well as in vascular matrix impairment and endothelial dysfunction. The mechanisms of action of aldosterone may be either delayed (genomic) or rapid (nongenomic). Deleterious effects of aldosterone leading to vascular target-organ damage include (besides salt and water retention) decreased arterial and venous compliance, increased peripheral vascular resistance, and impaired autonomic vascular control due to baroreflex dysfunction.

Inverse relationship between aldosterone and large artery compliance in chronically treated heart failure patients.

AIMS: The purpose of this study was to examine, in chronically treated heart failure patients vs control subjects, the influence of neurohumoral activation and aldosterone escape on arterial elastic behaviour, assessed by non-invasive mathematical lumped-parameter modelling of the compliance of the arterial system. METHODS AND RESULTS: Radial arterial pulse waves were recorded non-invasively for 30 s with an arterial tonometer sensor array in 13 chronic heart failure patients (mean age, 59 +/- 2.5 years) in New York Heart Association class II. The patients had been taking digoxin, furosemide, captopril and aspirin for more than 3 months. Thirteen healthy subjects (mean age, 50 +/- 4.0 years) acted as controls. Compliance of the proximal (aorta and major branches, C1) and distal parts (C2) of the circulation were derived from a third order four-element modified Windkessel model which can reproduce arterial pressure waveforms, including both exponential and oscillatory sections. Active renin, angiotensin II and aldosterone levels were determined on venous blood samples in the supine position and after 30 min active standing. There was decreased proximal (C1, 1.51 +/- 0.11 ml x mmHg(-1), P<0.01) and distal (C2, 0.050 +/- 0.011 ml x mmHg(-1)) arterial compliance in the chronic heart failure patients vs controls (C1, 1.71 +/- 0.16 ml x mmHg(-1); C2, 0.054 +/- 0.006 ml x mmHg(-1)). The chronic heart failure patients were characterized by an aldosterone escape phenomenon which was inversely correlated with the proximal arterial compliance in both supine (r= - 0.795, P=0.002) and standing (r= - 0.628, P=0.029) positions. CONCLUSIONS: In chronically treated heart failure patients with full angiotensin-converting enzyme-inhibition and diuretics, there is decreased compliance of the aorta and its major branches, which is inversely correlated with the aldosterone escape phenomenon.

Renin-angiotensin-aldosterone system, RR interval, and blood pressure variability during postural changes in borderline arterial hypertension.

This study aimed to examine the changes in RR interval and blood pressure (BP) variability and humoral factors during postural changes in borderline arterial hypertension. Twenty-nine patients (44 +/- 3 year; BP, 145 +/- 3/84 +/- 3 mm Hg) with borderline hypertension and a control group of 38 subjects (35 +/- 2 year; BP, 123 +/- 3/70 +/- 2 mm Hg) underwent power spectrum analysis of RR interval and BP (low frequency (LF), 0.05 to 0.15 Hz; high frequency (HF), 0.15 to 0.40 Hz) in the supine and standing positions. Concentrations of plasma renin activity, angiotensin II, and aldosterone in supine and standing positions had been determined in the hypertensive group. Borderline hypertensives are characterized by higher oscillations of systolic and diastolic BP, but not of RR interval in the supine position versus the control group. Low frequency and HF components of systolic and diastolic BP expressed as absolute data are also significantly higher in borderline hypertensives. Moreover, standing tended to increase the LF/HF ratio of both RR interval and BP variability compared to controls. The standing position was able to further activate the LF but not the HF component of BP variability. In borderline hypertension renin release during postural changes correlated well with the decrease in the power of the HF vagal component of RR interval variability (r = -0.70, P < .001) and with the increase of the LF component of diastolic blood pressure variability (r = 0.43, P = .03). In conclusion, our results indicate that in borderline arterial hypertension, LF and HF oscillations of BP are already significantly increased at rest.(ABSTRACT TRUNCATED AT 250 WORDS)