Martin Rammer

Thomas Weber; Siegfried Wassertheurer; Martin Rammer; Edwin Maurer; Bernhard Hametner; Christopher C. Mayer; Johannes Kropf; Bernd Eber

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.

Thomas Weber; Marcus Ammer; Martin Rammer; Audrey Adji; Siegfried Wassertheurer; Stefan Rosenkranz; Bernd Eber

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.

Thomas Weber; Siegfried Wassertheurer; Martin Rammer; Anton Haiden; Bernhard Hametner; Bernd Eber

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.

Thomas Weber; Elisabeth Lassnig; Michael Porodko; Marcus Ammer; Martin Rammer; Bernd Eber

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.

Johann Auer; Martin Rammer; Robert Berent; Thomas Weber; Elisabeth Lassnig; Bernd Eber

BACKGROUND Findings from previous studies relating lipoprotein(a) [Lp(a)] as an independent risk factor for coronary atherosclerosis and the presence of angiographically detectable coronary atherosclerotic lesions are not consistent. This study was performed to determine whether the plasma concentration of Lp(a) is associated with coronary atherosclerosis asessed by coronary angiography. METHODS We studied a total of 100 men and women (41 women, 59 men, age 63.7 +/- 11.0 years) who were referred for coronary angiography. Base-line data collection comprised conventional risk factors for coronary artery disease, lipids, fasting total homocysteine, and clinical characteristics. The relation between plasma Lp(a) levels and the presence or absence of coronary lesions was studied. The coronary angiograms were evaluated in a blinded manner. Any coronary stenosis was considered as coronary artery disease (CAD). RESULTS From the 100 patients, 40 were found to have no CAD and 60 had CAD assessed by coronary angiography. Estimates of the relative risk of coronary heart disease for the fifth quintile of plasma Lp(a) as compared with the first quintile were 0.87 (95 percent confidence interval, 0.66 to 1.34). After adjustment for age, sex, lipoproteins, and homocysteine levels, estimates of the relative risk of coronary heart disease for the fifth quintile of plasma Lp(a) as compared with the first quintile were 1.06 (95 percent confidence interval, 0.81 to 1.39). The presence of angiographic CAD was associated with patient age (p=0.048), male sex (p<0.01), high LDL-cholesterol levels (p=0.02), low HDL-cholesterol levels (p=0.02), high plasma fibrinogen levels (p<0.01) and high fasting total homocysteine levels (p=0.04). CONCLUSION These results suggest that the plasma concentration of Lp(a) is not associated with the presence of coronary artery disease in patients referred for coronary angiography.Background — Findings from previous studies relating lipoprotein(a) [Lp(a)] as an independent risk factor for coronary atherosclerosis and the presence of angiographically detectable coronary atherosclerotic lesions are not consistent.This study was performed to determine whether the plasma concentration of Lp(a) is associated with coronary atherosclerosis asessed by coronary angiography. Methods — We studied a total of 100 men and women (41 women, 59 men, age 63.7±11.0 years) who were referred for coronary angiography. Base-line data collection comprised conventional risk factors for coronary artery disease, lipids, fasting total homocysteine, and clinical characteristics.The relation between plasma Lp(a) levels and the presence or absence of coronary lesions was studied. The coronary angiograms were evaluated in a blinded manner. Any coronary stenosis was considered as coronary artery disease (CAD). Results — From the 100 patients, 40 were found to have no CAD and 60 had CAD assessed by coronary angiography. Estimates of the relative risk of coronary heart disease for the fifth quintile of plasma Lp(a) as compared with the first quintile were 0.87 (95 percent confidence interval, 0.66 to 1.34). After adjustment for age, sex, lipoproteins, and homocysteine levels, estimates of the relative risk of coronary heart disease for the fifth quintile of plasma Lp(a) as compared with the first quintile were 1.06 (95 percent confidence interval, 0.81 to 1.39).The presence of angiographic CAD was associated with patient age (p=0.048), male sex (p<0.01), high LDL-cholesterol levels (p=0.02), low HDL-cholesterol levels (p=0.02), high plasma fibrinogen levels (p<0.01) and high fasting total homocysteine levels (p=0.04). Conclusion — These results suggest that the plasma concentration of Lp(a) is not associated with the presence of coronary artery disease in patients referred for coronary angiography.

Thomas Weber; Martin Rammer; Bernd Eber

To the Editor: Carotid-femoral pulse wave velocity (cfPWV) is currently considered the gold-standard measurement for arterial stiffness.1 In clinical routine, noninvasive assessment is the only feasible method, whereas, for research purposes, catheter-based invasive determination, as well as MRI, may play a role. Precise determination of the distance traveled by the pulse wave is easily feasible with the latter 2 methods but has been a …

Thomas Weber; Marcus Ammer; Martin Rammer; M. F. OʼRourke; Bernd Eber

Background: Although carotid-femoral pulse wave velocity (cfPWV) is commonly equated with aortic stiffness and, thus, aortic PWV, this may not be completely accurate. Methods, patients: We measured strictly aortic PWV (from ascending aorta to bifurcation) invasively in 378 patients undergoing coronary angiography as well as cfPWV non-invasively, using the SphygmoCor system. Patients were divided into age groups (from < 45 years to > 75 years), and age-dependent changes in aortic PWV, cfPWV, their determinants (travel distance - TD, travel time - TT) and differences between them were assessed. Results: Body height significantly decreased with increasing age, and this was paralleled by a decrease in TD, as assessed non-invasively. In contrast, TD, as assessed invasively (catheter length), tended to increase with age, probably due to an increase in ascending aortic length or increased aortic kinking. As a result, the difference (TD aortic minus cf) showed a significant increase with age (p = 0.001). TT (aortic as well as cf) shortened significantly with increasing age, but the shortening was more pronounced for aortic TT, resulting in a significant decrease of the difference (TT aortic minus cf) from roughly 10 msec in younger patients to -4 msec in elderly patients (p < 0.0001). This may be due to an increase in stiffening of the ascending aorta. Finally, aortic as well as cfPWV significantly increased with increasing age. The increase was more pronounced for aortic PWV, resulting in a net difference (PWV aortic minus cf) of -0.7 m/sec in the youngest patients, increasing up to 1 m/sec in the oldest patients (p < 0.0001) – Figure. Conclusion: Aortic and cf PWV cannot be easily equated. With age > 70 years, the effect of the more pronounced decrease of aortic TT on PWV is combined with a more pronounced increase of aortic TD, leading to a higher aortic PWV as compared with cfPWV. In younger age (< 56 years), the opposite is true. Figure 1. No caption available.

Thomas Weber; Marcus Ammer; C Biber; M Windpessl; Siegfried Wassertheurer; Bernhard Hametner; C. Mayer; J. Kropf; Martin Rammer; Elisabeth Lassnig; Bernd Eber

Background: Whereas the predictive value of wave reflection (pressure augmentation-AP) and arterial stiffness (pulse wave velocity-PWV) on cardiovascular events has been shown in different populations, only very few studies investigated their independent prognostic impact. Methods, patients: In 654 patients (372 men, mean age 62.8 years) with preserved systolic function undergoing coronary angiography for suspected coronary artery disease (CAD), we measured aortic PWV invasively. Wave reflections were determined from non-invasive radial tonometry and transfer-function derived aortic waveforms, using pulse wave analysis (AP) as well as pulse wave separation (amplitude of forward – Pf – and backward – Pb – wave). Wave separation technique was based on mechanistic flow models and validated against combined ECHO-doppler and pressure measurements in 131 patients. A combined cardiovascular endpoint (death, myocardial infarction, stroke, coronary, cerebrovascular and peripheral revascularization) served as outcome variable in uni- and multivariate Cox proportional hazards regression models. Results: After a mean follow-up of 1110 days, 87 patients reached the combined endpoint. In univariate analysis, the relative risk of the combined endpoint increased with increasing levels of AP (for 1 SD, i.e. 8.0 mm Hg, relative risk 1.23; 95% CI 1.04–1.46; p = 0.017), Pf (for 1 SD, i.e. 9.4 mm Hg, relative risk 1.34; 95% CI 1.11–1.55; p = 0.001), Pb (for 1 SD, i.e. 6.9 mm Hg, relative risk 1.34; 95% CI 1.13–1.59; p = 0.0008), and aortic PWV (for 1 SD, i.e. 2.4 m/sec, relative risk 1.36; 95% CI 1.17–1.58; p < 0.0001), respectively. In multivariate analysis, Pb (relative risk for 1 SD 1.32; 95% CI 1.05–1.66; p = 0.017) or Pf (relative risk for 1 SD 1.27; 95% CI 1.02–1.57; p = 0.03) and aortic PWV (relative risk for 1 SD 1.26 and 1.27 and p = 0.03 with models including Pb and Pf, respectively) remained significantly associated with the occurrence of the combined endpoint after adjustment for gender, age, smoking status, extent of CAD, presence of peripheral arterial disease, diastolic function, and mean blood pressure. Conclusion: Arterial stiffness as well as wave reflections are important and independent predictors of cardiovascular risk.

Thomas Weber; Marcus Ammer; Martin Rammer; Bernd Eber

Background: Pulse waveform analysis (PWA) facilitates non-invasive determination of central blood pressures (central systolic blood pressure – CSBP and central pulse pressure – CPP) and waveform characteristics (Augmentation Index – AIx; AIx normalized for heart rate 75 – AIx 75; Pressure Augmentation – AP). Both have been shown to improve risk prediction, but their potential impact on management of hypertension in clinical practice has not been clarified. Methods: We performed PWA in 108 patients (58 men, 50.9 +/- 12.7 years) undergoing routine examinations including ambulatory blood pressure measurement (ABPM) for suspected or treated hypertension. CSBP, CPP, AIx, and AP > mean + 1 SD (based on published cohorts) were categorized as elevated. The relationships between office and ABPM blood pressures and PWA measures were compared, using t-test or CHI square test. Results: Mean office blood pressure was 149 / 92 mm Hg, mean day / night / 24 hour ABPM was 143/91, 129/79, and 140/88 mm Hg, respectively. Based on office blood pressure or ABPM, 81.5 or 86.1 % of patients were hypertensive. With respect to CSBP, CPP, AIX, and AP, 77.8, 50, 23.1, and 33.3 % were categorized as elevated. Patients with hypertension (office BP) had significantly (p < 0.05) higher values for CSBP, CPP, AIx 75, and AP, although overlap of categories was incomplete. E.g., 53.3 / 20 / 16.7 % of patients with office normotension and 87.2 / 61.5 / 39.7 % of patients with office hypertension had elevated CSBP / CPP / AP. Considering ABPM, patients with hypertension had significantly higher values of CSBP and AIx 75, although PWA categories did not differ. CSBP, CPP, AIx, AIx 75, and AP were not different across daytime ABPM categories, but patients with nighttime hypertension had significantly (p < 0.05) higher values of CSBP, CPP, AIx, AIx 75, and AP. ROC curve analysis revealed an AUC for detecting systolic nighttime hypertension with CSBP of 0.79 (p < 0.0001). Dipping pattern was associated with CSBP, CPP, and AP. Conclusion: Taking PWA characteristics into account would alter labelling of patients as normotensive or hypertensive and, thus, change management. The association between nighttime blood pressure and waveform characteristics is remarkable and deserves further study.

Thomas Weber; Johann Auer; Erich Kvas; Elisabeth Lassnig; Gudrun Lamm; Nina Stark; Martin Rammer; Bernd Eber