Sphygmocor software

In all individuals, blood pressure was recorded after 15 minutes of seated rest using a validated osillometric device (HEM 750CP; Omron Corporation, Japan). Radial artery waveforms were then recorded using a high fidelity micromanometer (SPC-301; Millar Instruments) and SphygmoCor software (AtCor Medical, Australia), which generated a corresponding central (ascending aortic) pressure waveform, using a validated transfer function.^{13 (link)} From this, the AIx, a measure of wave reflections, was calculated. After a further period of supine rest, blood pressure was reassessed and then carotid–femoral aPWV, a measure of aortic stiffness, calculated using the SphygmoCor device by sequential recording of ECG-gated pressure waveforms at the carotid and femoral sites, as previously described, with surface distances measured using a tape measure.^{14 (link)}High-resolution B-mode ultrasound was used to determine CIMT of the common carotid arteries, measured 1 cm from the bulb. Image analysis was performed using Vascular Tools 5 software (Medical Imaging Application PLC), with the larger of the 2 values (left or right) used in analysis. CIMT measurement was available for only a limited number of controls (n=279). Further information on assessments is provided in the online-only Data Supplement.

We recorded carotid, femoral and radial arterial waveforms using a SPC-301 micromanometer (Millar Instruments Inc., USA) linked to a computer running SphygmoCor software (AtCor Medical Pty. Ltd., Australia). Pulse waves were calibrated by the supine brachial BP measured immediately before tonometry. From radial signals, SphygmoCor software constructed the aortic (central) pulse wave using a validated generalized transfer function. Central pulse pressure (PP) was central systolic minus diastolic pressure. Augmentation pressure (AP) was the pressure difference between the first and second shoulder of the central waveform. In 157 men and 117 women, we measured aortic pulse wave velocity (PWV), the non-invasive gold standard of arterial stiffness, as the carotid-femoral distance divided by the carotid-femoral pressure transit time [16 (link)].

Assessments were performed pre- and post-treatment. After a 15-minute rest, seated brachial blood pressure was recorded (OMRON-750CP, Omron Corp, Japan). Radial artery waveforms were then obtained using a high-fidelity micromanometer (SPC-301, Millar Instruments, Texas, USA) and recorded using Sphygmocor software (AtCor Medical, Sydney, Australia), which generated a corresponding central waveform and aortic augmentation index using the software’s validated transfer function. Augmentation index is a composite measure of arterial wave reflections. Supine carotid-femoral aortic pulse wave velocity (aPWV), which is a measure of aortic stiffness, was also measured using the same device, as previously described [21 (link)].

We measured brachial artery vasoreactivity using Hitachi Prosound Alpha 7 (Hitachi Aloka Medical America, Wallingford, CT, USA) [18 (link)]. First, the ultrasonography probe was positioned 1–3 cm proximal to the ante-cubital fossa with a 60-degree tilt. A blood pressure measuring cuff was inflated to 220 mmHg around the mid-forearm for five minutes. A video was recorded for the baseline (BSL) arterial diameter (60 s before cuff inflation) and 300 s after cuff deflation (reactive hyperemia (RH)). The Automated Edge Detection software system was used to capture images for subsequent analysis. As previously reported, relative FMD was computed using the highest brachial artery diameter at BSL minus the largest mean measures recorded after cuff deflation [percent FMD = (RH diameter in mm − BSL diameter in mm/BSL diameter in mm × 100)] [18 (link),21 (link),24 (link),25 (link),26 (link)]. Applanation tonometry (Millar Instruments, Houston, TX, USA) was used to measure central pulse wave velocity from the waveform at the carotid and femoral (central) site using the SphygmoCor software (AtCor Medical, Sydney, Australia).

The parameters for central hemodynamics, namely central SBP, central DBP, central pulse pressure, central mean arterial pressure (MAP), augmentation pressure, and AIx, were determined noninvasively by applying a proprietary digital signal processing and transfer function using the cuff-based SphygmoCor System (AtCor Medical, Sydney, Australia). After a 5-min rest, a cuff was placed on the participant’s dominant upper arm. Brachial blood pressure and wave form were automatically determined and converted into the aortic pressure wave form using the generalized transfer function provided by the SphygmoCor software (AtCor Medical). AIx@75 was computed to standardize for a heart rate of 75 beats per minute.

c-fPWV was measured using applanation tonometry with a Millar transducer and SphygmoCor software (AtCor Medical, Sydney, Australia). The c-fPWV measurement was performed by placing the transducer at the femoral and then the carotid artery. Distance was measured on the body surface from the suprasternal notch to femoral and carotid artery sites, and the subtraction distance method was used to determine cfPWV from the foot-to-foot pulse transit time between the carotid and femoral pulses in reference to the R wave of the electrocardiogram.