Bernd Eber

Arterial stiffness, wave reflections, and the risk of coronary artery disease.

Background—Increased arterial stiffness, determined invasively, has been shown to predict a higher risk of coronary atherosclerosis. However, invasive techniques are of limited value for screening and risk stratification in larger patient groups. Methods and Results—We prospectively enrolled 465 consecutive, symptomatic men undergoing coronary angiography for the assessment of suspected coronary artery disease. Arterial stiffness and wave reflections were quantified noninvasively using applanation tonometry of the radial artery with a validated transfer function to generate the corresponding ascending aortic pressure waveform. Augmented pressure (AP) was defined as the difference between the second and the first systolic peak, and augmentation index (AIx) was AP expressed as a percentage of the pulse pressure. In univariate analysis, a higher AIx was associated with an increased risk for coronary artery disease (OR, 4.06 for the difference between the first and the fourth quartile [1.72 to 9.57; P <0.01]). In multivariate analysis, after controlling for age, height, presence of hypertension, HDL cholesterol, and medications, the association with coronary artery disease risk remained significant (OR, 6.91; P <0.05). The results were exclusively driven by an increase in risk with premature vessel stiffening in the younger patient group (up to 60 years of age), with an unadjusted OR between AIx quartiles I and IV of 8.25 (P <0.01) and a multiple-adjusted OR between these quartiles of 16.81 (P <0.05). Conclusions—AIx and AP, noninvasively determined manifestations of arterial stiffening and increased wave reflections, are strong, independent risk markers for premature coronary artery disease.

Estrogen replacement therapy in older women: a neuropsychological and brain MRI study.

OBJECTIVE: To determine if postmenopausal women receiving estrogen perform better on demanding cognitive tests than women without estrogen replacement and if this beneficial effect on cognition is caused by estrogen‐related prevention of silent ischemic brain damage.

Validation of a Brachial Cuff-Based Method for Estimating Central Systolic Blood Pressure

The prognostic value of central systolic blood pressure has been established recently. At present, its noninvasive assessment is limited by the need of dedicated equipment and trained operators. Moreover, ambulatory and home blood pressure monitoring of central pressures are not feasible. An algorithm enabling conventional automated oscillometric blood pressure monitors to assess central systolic pressure could be of value. We compared central systolic pressure, calculated with a transfer-function like method (ARCSolver algorithm), using waveforms recorded with a regular oscillometric cuff suitable for ambulatory measurements, with simultaneous high-fidelity invasive recordings, and with noninvasive estimations using a validated device, operating with radial tonometry and a generalized transfer function. Both studies revealed a good agreement between the oscillometric cuff-based central systolic pressure and the comparator. In the invasive study, composed of 30 patients, mean difference between oscillometric cuff/ARCSolver-based and invasive central systolic pressures was 3.0 mm Hg (SD: 6.0 mm Hg) with invasive calibration of brachial waveforms and −3.0 mm Hg (SD: 9.5 mm Hg) with noninvasive calibration of brachial waveforms. Results were similar when the reference method (radial tonometry/transfer function) was compared with invasive measurements. In the noninvasive study, composed of 111 patients, mean difference between oscillometric cuff/ARCSolver–derived and radial tonometry/transfer function–derived central systolic pressures was −0.5 mm Hg (SD: 4.7 mm Hg). In conclusion, a novel transfer function-like algorithm, using brachial cuff-based waveform recordings, is suited to provide a realistic estimation of central systolic pressure.

Noninvasive determination of carotid-femoral pulse wave velocity depends critically on assessment of travel distance: a comparison with invasive measurement.

Objectives European Society of Hypertension guidelines recommend use of carotid– femoral pulse wave velocity (cfPWV) as a favored measure of aortic stiffness. However, there is no consensus on the measurement of distance travelled by the pulse wave along the aorta to the femoral artery. The aim of our study was to compare cfPWV, calculated with commonly used noninvasive methods for travel distance assessment, against aortic PWV measured invasively. Methods One hundred and thirty-five patients had aortic PWV measured invasively during cardiac catheterization, from the delay in wave foot and distance travelled as the catheter was withdrawn from the ascending aorta to the aortic bifurcation. On the following day, noninvasive cfPWV was assessed, using the SphygmoCor system, relating the delay between carotid and femoral wavefoot to travel distance, estimated with five different methods on body surface. Results Mean travel times were in good agreement [(travel time) TTinvasive was 63 ms, TTnoninvasive was 59.3 ms, Spearmans R: 0.8, P < 0.00001]. Mean PWVinvasive was 8.5 m/s. CfPWV, as assessed noninvasively, depended largely on the method used for travel distance estimation: 11.5, 9.9, 8.7, 11.9, and 9.6 m/s, using direct carotid–femoral distance, carotid–femoral minus carotid–suprasternal notch distances, suprasternal notch–femoral minus carotid–suprasternal notch distances, suprasternal notch–femoral plus carotid–suprasternal notch distances, and suprasternal notch–symphysis distance, respectively. There was acceptable correspondence between PWVinvasive and cfPWVnoninvasive (Spearmans R: 0.73–0.77, P < 0.0001). Conclusion For noninvasive assessment of cfPWV, estimation of pulse wave travel distance is critical. Best agreement with invasive measurements was found for the method of subtracting carotid–suprasternal notch distance from suprasternal notch–femoral distance.

The Mattis Dementia Rating Scale Normative data from 1,001 healthy volunteers

Article abstract We administered the Mattis Dementia Rating Scale (MDRS) to 1,001 healthy volunteers, aged 50 to 80 years, randomly selected from our community. Multivariate regression analysis revealed educational level (p = 0.000004) and age (p = 0.00001), but no other sociodemographic or risk factors for stroke, to be significantly associated with the MDRS score. The age- and education-specific lowest quintile cutoff scores ranged from 140 in subjects aged 50 to 59 years with at least college experience to 130 in subjects aged 70 to 80 years with only 4 to 9 years of schooling. These percentile distributions obtained for decades of age and different levels of education should be useful reference values for clinicians and investigators when applying the MDRS to assess cognitive functioning.

Increased Neopterin in Patients With Chronic and Acute Coronary Syndromes

OBJECTIVES The aim of our study was to determine neopterin levels in patients with chronic and acute coronary syndromes. BACKGROUND In chronic and acute coronary syndromes the release of different cytokines activates cellular defense. Infiltration of neutrophils and monocytes/macrophages is detected in the vessel wall as well as in the myocardium. Neopterin, which is a by-product of the guanosine triphosphate-biopterin pathway, is a marker for those activated macrophages. METHODS We studied 123 subjects: 1) 21 consecutive patients (17 men, 4 women; mean age +/- SD 66 +/- 15 years, range 31 to 87) with acute myocardial infarction (AMI); 2) 62 consecutive patients (50 men, 12 women; mean age 61 +/- 8 years, range 43 to 81) with signs and symptoms of clinically stable coronary artery disease (CAD); and 3) 40 healthy blood donors (28 men, 12 women; mean age 35 +/- 13 years). Neopterin levels were determined with a commercially available enzyme-linked immunosorbent assay method. RESULTS In patients with AMI before thrombolytic therapy, neopterin levels were significantly higher than levels in patients with CAD and control subjects (13.7 vs. 8.6 and vs. 6.8 nmol/liter, p < 0.0001). Values also differed significantly between patients with CAD and control subjects (p < 0.0001). Neopterin levels in patients with AMI were measured seven times during a 72-h period. Within-group comparison showed significant differences over this period (p < 0.00001). The lowest value (11.4 nmol/liter) was observed after 4 h and differed significantly from the initial value and values after 24 and 72 h (p < 0.05). After 72 h, neopterin increased to 14.9 nmol/liter, a value significantly different from all values other than the initial one. There was no correlation between neopterin and creatine kinase (CK); CK, MB isoenzyme; or lactate dehydrogenase as markers for the extent of the myocardial infarction during the observation period. CONCLUSIONS Our data support the hypothesis of an activation of monocytes and macrophages in patients with an acute or chronic coronary syndrome. Neopterin as a marker for macrophage activation is significantly increased in patients with chronic CAD and more pronounced in patients with AMI shortly after the onset of symptoms.

Wave Reflections, Assessed With a Novel Method for Pulse Wave Separation, Are Associated With End-Organ Damage and Clinical Outcomes

We recently developed a novel method for assessment of arterial wave reflections (ARCSolver method): based on adopted Windkessel methods, flow curves are estimated from pressure waveforms, and wave separation analysis is performed, yielding the amplitudes of the forward and backward waves. The aim of this study was to investigate their clinical correlates and prognostic impact. In 725 patients (417 men; mean age, 64 years) undergoing coronary angiography, we determined wave reflections from radial tonometry and transfer function-derived aortic waveforms using pulse wave analysis, as well as wave separation analysis. Measures of pulsatile arterial function were statistically significant, although moderately associated with markers of cardiac load and subclinic cardiac, renal, and aortic end-organ damage. After a median follow-up duration of 1399 days, 139 patients reached the combined cardiovascular end point (death, myocardial infarction, stroke, coronary, cerebrovascular, and peripheral revascularization). In univariate analysis, the relative risk of the combined end point increased with increasing levels of incident pressure wave height, augmented pressure, and forward and backward wave amplitude (hazard ratio for 1 SD was 1.302, 1.236, 1.226, and 1.276; P<0.01 for all, respectively). In multivariate analysis, backward wave amplitude was the most consistent predictor of the combined end point. Of note, its predictive value was independent of brachial systolic, diastolic, and mean blood pressures and was superior to brachial pulse pressure. In conclusion, the amplitude of the reflected wave, as assessed with a novel method for wave separation, is associated with hypertensive end organ damage and is an independent predictor of cardiovascular events in high-risk patients.

Oscillometric estimation of aortic pulse wave velocity: comparison with intra-aortic catheter measurements.

ObjectivesRecently, a novel method to estimate aortic pulse wave velocity (aPWV) noninvasively from an oscillometric single brachial cuff waveform reading has been introduced. We investigated whether this new approach provides acceptable estimates of aPWV compared with intra-aortic catheter measurements. MethodsEstimated values of aPWV obtained from brachial cuff readings were compared with those obtained using an intra-aortic catheter in 120 patients (mean age 61.8±10.8 years) suspected for coronary artery disease undergoing cardiac catheterization. Differences between aPWV values obtained from the test device and those obtained from catheter measurements were estimated using Bland–Altman analysis. ResultsThe mean difference±SD between brachial cuff-derived values and intra-aortic values was 0.43±1.24 m/s. Comparison of aPWV measured by the two methods showed a significant linear correlation (Pearson’s R=0.81, P<0.0001). The mean difference for repeated oscillometric measurements of aPWV was 0.05 m/s, with 95% confidence interval limits from −0.47 to 0.57 m/s. ConclusionaPWV can be obtained using an oscillometric device with brachial cuffs with acceptable accuracy compared with intra-aortic readings.

Risk factors for microangiopathy-related cerebral damage in the Austrian stroke prevention study

Microangiopathy-related cerebral damage (MARCD) represents a common incidental MRI observation in the elderly. The risk factors of such findings are widely unknown. We therefore performed MRI in 349 randomly selected volunteers (ages 50 to 70 years) without neuropsychiatric disease, and evaluated the association of MARCD with conventional and recently suggested cerebrovascular risk factors such as apolipoprotein E genotypes, plasma concentrations of essential antioxidants and anticardiolipin antibody titres. MARCD was defined as evidence of early confluent and confluent deep white matter hyperintensities and lacunes. It was present in 71 (20.3%) subjects. Individuals with MARCD were older than those without such findings (62.7 years vs 59.6 years; P=0.0001). They had a higher rate of arterial hypertension (45.1% vs 28.1%; P=0.006) and cardiac disease (50.7% vs 37.1%; P=0.04), higher systolic blood pressure readings at exam (144.4 mmHg vs 136.7 mmHg; P=0.004), and higher serum fibrinogen concentrations (327.1 mg/dl vs 292.5 mg/dl; P=0.001). Their levels of total cholesterol (217.6 mg/dl vs 231.2; P=0.009), apolipoprotein A-I (167.3 mg/dl vs 177.4 mg/dl, P=0.02), lycopene (0.17 micromol/l vs 0.24 micromol/l; P=0.003), retinol (1.91 micromol/l vs 2.10 micromol/l; P=0.02) and alpha-tocopherol (27.55 micromol/l vs 31.14 micromol/l; P=0.001) were significantly lower. Forward stepwise regression analysis created a model of independent predictors of MARCD with age entering first (odds ratio 2.01/10 years), fibrinogen second (odds ratio 2.45/100 mg/dl), alpha-tocopherol third (odds ratio 0.55/10 micromol/l), and arterial hypertension fourth (odds ratio 1.96). The association of MARCD with various treatable clinical conditions may have preventive implications.

Pulse waveform characteristics predict cardiovascular events and mortality in patients undergoing coronary angiography.

Objectives Pulse waveform characteristics (Augmentation Index – AIx and pulse wave transit time) are measures of the timing and extent of arterial wave reflections. Although previous studies reported an independent association with cardiovascular morbidity, it remains to be established that waveform characteristics, derived from noninvasive pulse waveform analysis, predict cardiovascular outcomes independent of and additional to brachial blood pressure. Methods We prospectively assessed AIx, heart-rate corrected AIx, and pulse wave transit time, using radial applanation tonometry and a validated transfer function to generate the aortic pressure curve, in 520 male patients undergoing coronary angiography. Primary endpoint was a composite of all-cause mortality, myocardial infarction, stroke, cardiac, cerebrovascular, and peripheral revascularization. Results During a follow-up of 49 months, 170 patients reached the primary endpoint. On the basis of Cox proportional hazards regression models, all pressure waveform characteristics predicted the primary endpoint. A 10% increase of AIx and heart-rate corrected AIx was associated with a 20.5% (95% confidence interval 6.5–36.4, P = 0.003) and 31.4% (95% confidence interval 13.2–52.6, P = 0.0004) increased risk of the primary endpoint, respectively. A 10-ms increase of pulse wave transit time was associated with a 20.8% (95% confidence interval 10.8–29.6, P = 0.0001) lower risk of the primary endpoint. In multiple adjusted models, AIx, heart-rate corrected AIx, and pulse wave transit time were independently associated with the combined endpoint even after adjustments for brachial blood pressure, age, extent of coronary artery disease, clinical characteristics, and medications. Conclusion The study provides evidence that pulse waveform characteristics consistently and independently predict cardiovascular events in coronary patients.