Abstract
Arterial stiffening is a hallmark of the aging process and atherosclerosis, including peripheral arterial disease (PAD). We investigated the associations between carotid‐femoral pulse wave velocity (c‐fPWV), augmentation index corrected for heart rate (Aix@HR75), ankle brachial index (ABI), and subendocardial viability ratio (SEVR), an indicator of cardiac perfusion. The c‐fPWV, Aix@HR75, and SEVR was estimated using applanation tonometry. The ankle systolic pressure measurements for the calculation of the ABI were obtained using an 8‐mHz Doppler probe. The study group included 555 subjects, mean age 63 ± 11 years (248 PAD (ABI < 1.0), and 307 non‐PAD (ABI ≥ 1.0 ≤ 1.3). After the stepwise selection process in both PAD and non‐PAD patients SEVR was not related to c‐fPWV and ABI (P = .154; P = .156) and (P = .101; P = .402), respectively. In PAD patients, SEVR was negatively related to Aix@HR75 (P < .0001) and aortic PP (P = .0005). In conclusion, arterial stiffness is associated with non‐invasive indices of myocardial perfusion in PAD patients, suggesting a potential pathophysiological link for increased cardiovascular events.
Keywords: arterial stiffness, peripheral arterial disease, subendocardial viability
1. INTRODUCTION
A series of epidemiological studies have shown that peripheral arterial disease (PAD) is prevalent particularly in elderly and in the presence of type 2 diabetes, smoking history, and hypertension.1 In clinical practice, PAD can be detected by the measurement of ankle‐brachial index (ABI), a non‐invasive, objective, easy, and reproducible test.2 In several populations, the presence of an ABI < 0.9 (PAD) confers an independent risk for cardiovascular events and total mortality,3 however, the pathophysiological basis of this independent association remains incompletely characterized. The increase of arterial stiffness observed in PAD patients4, 5 may have a major role.6 Increased arterial stiffness increases the velocity of both forward and reflected pulse waves. This increase in PWV causes arrival of reflected waves at the aorta during systole, and not during diastole, as it occurs under conditions of normal aortic elastic properties. The early arrival of the reflected waves causes (1) augmentation of the systolic aortic pressure, and thus, an increase of left ventricular afterload, wall stress, and cardiac workload leading to increased left ventricular mass and myocardial oxygen demands; and (2) reduction in the diastolic aortic pressure resulting in reduced myocardial perfusion.7, 8 Buckberg et al9 confirmed the extreme susceptibility of the subendocardium to factors that increase myocardial oxygen demand and/or restrict blood supply. They have coined the term “subendocardial viability ratio” and have demonstrated that the ratio of the area of the diastolic phase to that of the systolic phase in the central aortic profile has a close correlation with the blood supply to the subendocardium. By analogy with the invasively measured subendocardial viability index pulse wave analysis (PWA) can provide information about subendocardial viability ratio (SEVR), an indicator of the degree of myocardial perfusion relative to left‐ventricular workload9, 10 and hemodynamic parameters, including augmentation index (Aix), determined by the relative height of the first and second systolic peaks of the aortic pressure profile. Even though in older PAD patients, an increase of arterial stiffness tend to coexist,11, 12 the relationship with SEVR is less well documented. The aim of this study is to evaluate the association between c‐fPWV and Aix@HR75, ABI, and SEVR in PAD and non‐PAD patients.
2. METHODS
2.1. Study population
A total of 711 subjects referred to the Angiology Unit of the Research Center on Vascular Diseases at the University of Milan L. Sacco Hospital were evaluated for non‐invasive tests (pulse wave analysis, c‐fPWV). The ankle‐brachial index (ABI) was performed to diagnose PAD (ABI < 0.90) and borderline PAD, defined as subjects with an ABI value of between 0.91 and 0.99.2 We excluded patients with atrial fibrillation, pacemakers, and frequent extra systole; if clinical examinations (non‐palpable femoral pulses) suggested the presence of bilateral iliac disease, which could cause inaccurate cfPWV measurements;13 and subjects with high ABI (>1.3), suggesting poorly compressible, calcified arteries. Patients with critical limb ischemia (CLI; limb pain that occurs at rest that may be accompanied by tissue loss [ischemic ulcer or gangrene]) and those younger than 39 years old were also excluded. The study group included a total of 555 subjects age range (40‐95 years), divided into 2 groups. The first was composed of 248 patients with PAD and borderline PAD and the second was composed of 307 non‐PAD (ABI ≥ 1.0 ≤ 1.3). All participants had been informed about the study protocol and gave their informed consent to participate in the study.
2.2. Risk factors CAD and CVD definitions
Cardiovascular risk factors were ascertained through direct examination and an interview carried out by trained research assistants. Hypertension was defined as systolic blood pressure (SBP) ≥ 140 mm Hg or diastolic blood pressure (DBP) ≥ 90 mm Hg at the time of the visit (2 readings average) or a history of hypertension or use of antihypertensive medications (Calcium‐channel‐blockers, angiotensin converting enzyme inhibitors (ACE‐I) diuretics, β‐blockers, Angiotensin II receptor blockers (ARBs) or, α‐blockers). Type 2 diabetes mellitus was defined as fasting blood glucose ≥ 126 mg/dL or a history of diabetes or the use of antidiabetic medications (insulin or oral hypoglycemic agents). Hypercholesterolemia was defined as total serum cholesterol >200 mg/dL or the use of lipid‐lowering treatment. Coronary artery disease (CAD) and Cerebrovascular disease (CVD) were assessed by clinical history (myocardial infarction, stroke) or interventions. Patients with asymptomatic carotid stenosis were not classified as CVD. Height and weight were measured and body mass index was calculated as weight to height squared (kg/h²).
2.3. Hemodynamic assessment and definitions
Pharmacologic treatment was suspended (when possible) 12 hours before the measurements. Patients rested in a supine position for 5‐10 minutes in a quiet room in a comfortable environment at a temperature of 22 ± 1°C. The protocol of sequential measurements in the laboratory included: brachial blood pressure measurement in the dominant arm using a standard mercury sphygmomanometer. Three readings were taken, separated by 2‐minute intervals, and the average was used for analysis. Peripheral pulse pressure (PP) was calculated as the difference between SBP and DBP. Arterial tonometry was performed using the SphygmoCor device (AtCor Medical) in radial, carotid, and femoral arteries.8 Radial pressure waveform was calibrated to brachial SBP and DBP measurements (obtained with the sphygmomanometer). The mean arterial pressure (MAP) was calculated integrating the calibrated radial pressure wave. Central pressure was determined using a transfer function from the radial artery pressure waveform.14 Augmentation pressure (AP) was defined as the difference between the second and the first systolic peak of the derived aortic pressure waveform. The augmentation index (Aix) was defined as the difference between the second and first systolic peaks of the central arterial waveform, expressed as a percentage of the central pulse pressure. In addition, as Aix is influenced by heart rate, it was normalized for a standard heart rate of 75 bpm (Aix@75) in accordance with Wilkinson et al15 Furthermore, the pulse pressure amplification (PPa) was calculated as the ratio of brachial PP over central PP.16 The subendocardial viability ratio (SEVR) (also known as the Buckberg index), an index of myocardial oxygen supply and demand and an indicator of coronary microvascular function, was calculated with pulse wave analysis and expressed as the ratio of the diastolic pressure time index (DPTI) and systolic pressure time index (SPTI).10 Carotid‐femoral pulse wave velocity (c‐fPWV) was measured by sequentially recording electrocardiography (ECG)‐gated carotid and femoral artery waveforms. Wave transit time was calculated by software using the R wave of a simultaneously recorded ECG as a reference frame. The distance between the carotid and the femoral sampling sites was measured above the surface of the body with a tape. aPWV was determined by dividing the distance between the 2 recording sites by the wave transit time.11 All measurements were made by 1 investigator (GS) in duplicate and mean values were used for the final analysis. Immediately after measurement of the arterial stiffness variables, the ankle systolic BP measurements for ABI calculation was obtained by 2 operators using an 8‐mHz Doppler probe and a BP cuff after 10 minutes of rest with the patient in a supine position. The systolic pressure was measured on either the posterior tibial or dorsalis pedis artery. ABI was calculated by dividing the higher of the 2 ankle systolic blood pressures in each leg by the higher of the 2 brachial systolic blood pressures. The higher of the 2 brachial pressures was used as the denominator to account for the possibility of subclavian artery stenosis, which can decrease the blood pressure in the upper extremity. Peripheral arterial disease was defined as ABI < 0.9 at rest or after treadmill test performed on the borderline group to confirm PAD. Patients with a history of lower limb revascularization (arterial bypass, angioplasty, or stenting) were also considered as having PAD.2 Asymptomatic PAD was defined as a resting ABI < 0.90 with an absence of prior lower‐extremity peripheral vascular events or clinical symptoms indicative of intermittent claudication (IC). The lowest ABI values were used for statistical analysis.
2.4. Statistical analysis
Statistical analyses were performed using JMP software version 10.0. Continuous variables were reported as mean ± SD and categorical variables as percentages for all patients. The statistical assessment of data was performed by Student t‐test for numeric data and Pearson χ² for categorical data. To identify specific determinants of SEVR in PAD and non‐PAD patients, the SEVR were considered as dependent variables while demographic, CVD risk factors (BMI, hypertension, dyslipidemia, type 2 diabetes, smoking history), ABI, blood pressure parameters, AP, Aix, Aix@HR75, c‐f PWV, statins, and antihypertensive medications were entered as independent variables. The effects were examined by multiple stepwise regression model and BIC index (minimum Bayesian information criterion) to choose the best model. P values < .05 were considered significant.
3. RESULTS
3.1. Characteristics of the study population
The clinical characteristics of the participants are summarized in Table 1. The study group was composed of 555 subjects: 248 PAD patients (73% male) aged 68 ± 10 years and 307 non‐PAD (56% male) aged 59 ± 10 years (P < .0001). In comparison to non‐PAD patients, PAD patients showed a higher prevalence of common risk factors (smoking history, hypertension, type 2 diabetes mellitus, dyslipidemia), CAD and CVD history and relative treatment (antiplatelet, ACE‐I, ARBs, calcium channel blockers, Statins, Antidiabetics). There were no significant differences in height and weight between the 2 groups (P = .189) and (P = .545). In the PAD group, 35 (14%) patients showed borderline PAD, 73 (29%) intermittent claudication, 18 (7%) with a history of lower limb revascularization. Hemodynamic parameters are summarized in Table 2. In comparison to non‐PAD, PAD patients showed a higher mean arterial pressure, brachial and aortic SBP, PP, and AP, Aix, Aix @75HR, c‐f PWV and lower brachial and aortic DBP, time reflected wave, PP amplification, SEVR, and ABI. There was no significant difference in HR between the 2 groups.
Table 1.
Clinical and demographic characteristics of study population
| Parameters | Overall (n = 555) | PAD (n = 248) | Non‐PAD (n = 307) | P‐value |
|---|---|---|---|---|
| Age, mean ± SD, y | 63 ± 11 | 68 ± 10 | 59 ± 10 | <.0001 |
| Sex male, n (%) | 354 (62) | 181 (73) | 173 (56) | <.0001 |
| Height, mean ± SD, cm | 164 ± 9 | 164 ± 9 | 165 ± 9 | .189 |
| Weight, mean ± SD, kg | 73 ± 13 | 74 ± 12 | 73 ± 13 | .545 |
| BMI, mean ± SD, kg/m2 | 27 ± 4 | 28 ± 4 | 27 ± 4 | .039 |
| Hypertension, n (%) | 310 (63) | 196 (79) | 114 (37) | <.0001 |
| Type 2 diabetes, n (%) | 166 (28) | 97 (39) | 69 (23) | <.0001 |
| Dyslipidaemia, n (%) | 349 (63) | 174 (70) | 175 (57) | .0014 |
| Smoking history, n (%) | 295 (53) | 198 (80) | 97 (32) | <.0001 |
| CAD history, n (%) | 103 (119) | 75 (30) | 28 (9) | <.0001 |
| CVD history, n (%) | 17 (3) | 13 (5) | 4 (1) | .0074 |
| Anti‐Platelets, n (%) | 207 (37) | 157 (63) | 50 (16) | <.0001 |
| Calcium‐channel‐blockers, n (%) | 78 (14) | 50 (20) | 28 (9) | .0007 |
| ACE‐I, n (%) | 88 (16) | 81 (33) | 7 (2) | <.0001 |
| β‐blockers, n (%) | 92 (17) | 63 (25) | 29 (9) | <.0001 |
| ARBs, n (%) | 92 (17) | 65 (26) | 27 (9) | <.0001 |
| Diuretics, n (%) | 40 (7) | 25 (10) | 15 (5) | .0186 |
| Nitrates, n (%) | 24 (4) | 18 (7) | 6 (2) | .006 |
| Statins, n (%) | 165 (30) | 121 (49) | 44 (14) | <.0001 |
| Antidiabetics, n (%) | 136 (25) | 95 (38) | 41 (13) | <.0001 |
| Insulin, n (%) | 19 (3) | 15 (6) | 4 (1) | .002 |
| α‐blockers, n (%) | 8 (1) | 7 (3) | 1 (0.3) | .014 |
ACE‐I, Angiotensin‐converting enzyme inhibitors; ARBs, Angiotensin II receptor blockers; BMI, body mass index; CAD, coronary artery disease; CVD, cerebrovascular disease.
Table 2.
Hemodynamic parameters
| Parameters‐Mean (SD) | Overall (n = 555) | PAD (n = 248) | Non‐PAD (n = 307) | P‐value |
|---|---|---|---|---|
| SBP‐brachial artery, mm Hg | 133 ± 21 | 140 ± 20 | 128 ± 20 | <.0001 |
| DBP‐brachial artery, mm Hg | 80 ± 10 | 79 ± 10 | 81 ± 10 | .0061 |
| PP‐brachial artery, mm Hg | 53 ± 19 | 61 ± 19 | 46 ± 15 | <.0001 |
| SBP‐aortic, mm Hg | 124 ± 20 | 130 ± 20 | 119 ± 19 | <.0001 |
| DBP‐aortic, mm Hg | 81 ± 10 | 80 ± 10 | 82 ± 10 | .0036 |
| PP‐aortic, mm Hg | 43 ± 17 | 51 ± 17 | 37 ± 14 | <.0001 |
| Mean arterial pressure, mm Hg | 99 ± 13 | 100 ± 12 | 98 ± 14 | .0153 |
| Heart rate, bpm | 69 ± 11 | 68 ± 11 | 70 ± 11 | .085 |
| Augmentation pressure, mm Hg | 14 ± 8 | 17 ± 9 | 11 ± 7 | <.0001 |
| Augmentation index, % | 31 ± 10 | 33 ± 9 | 29 ± 10 | <.0001 |
| Aix @75HR, % | 28 ± 9 | 29 ± 9 | 26 ± 9 | <.0001 |
| Time reflected wave, ms | 137 ± 12 | 133 ± 12 | 140 ± 11 | <.0001 |
| Pulse pressure amplification | 1.25 ± 0.13 | 1.23 ± 0.14 | 1.27 ± 0.11 | .0002 |
| SEVR | 149 ± 30 | 145 ± 31 | 152 ± 28 | .0037 |
| c‐f PWV, m/s | 9.8 ± 2.7 | 10.6 ± 2.8 | 8.9 ± 2.2 | <.0001 |
| Ankle brachial index | 0.92 ± 0.2 | 0.71 ± 0.2 | 1.09 ± 0.1 | <.0001 |
Aix @75HR, aortic augmentation index corrected for heart rate 75; c‐fPWV, carotid‐femoral Pulse wave velocity; DBP, diastolic blood pressure, PP, pulse pressure; SBP, systolic blood pressure; SEVR, subendocardial viability ratio. c‐fPWV, carotid‐femoral pulse wave velocity.
3.2. Variables associated to SEVR in PAD patients
Table 3 shows the effects of the variables for the SEVR, after the stepwise selection process. In PAD patients SEVR was negatively related to females (P = .020), aortic pulse pressure (P = .0005), and augmentation pressure (P < .0001), Aix@HR75 (P < .0001) and positively to brachial SBP (P = .0001) and Aix (P = .0001). The c‐f PWV and ABI were not related to SEVR (P = .154) and (P = .156), respectively. In this group of patients, antihypertensive medications and statins were not related to SEVR.
Table 3.
Current estimates table using SEVR as the dependent variable in PAD patients
| Parameters | PAD | |
|---|---|---|
| Estimate | P | |
| Aix @75HR | −4.058 | <.0001 |
| c‐fPWV | .154 | |
| AP | −1.671 | <.0001 |
| Aix | 4.719 | <.0001 |
| ABI | .156 | |
| Sex, F | −6.39 | .020 |
| BMI | 0.798 | .009 |
| SBP, brachial artery | 0.458 | .0001 |
| PP aortic | −0.683 | .0005 |
| HR | −0.262 | .515 |
| Age | .466 | |
| Height | .431 | |
| Hypertension (Y/N) | .110 | |
| Type 2 diabetes (Y/N) | .688 | |
| Dyslipidaemia (Y/N) | .623 | |
| Smoking history (Y/N) | .714 | |
| DBP‐brachial artery | .454 | |
| PP‐brachial artery | .402 | |
| SBP‐aortic | .680 | |
| DBP‐aortic | .687 | |
| Calcium‐channel‐blockers | .743 | |
| β‐blockers | .713 | |
| Statins | .861 | |
| ACE‐I | .899 | |
| Nitrates | .238 | |
ABI, Ankle brachial index; Aix, augmentation index; Aix @75HR, corrected for a heart rate of 75 beats/min; BMI, body mass index; c‐fPWV, carotid‐femoral Pulse Wave Velocity; DBP, Diastolic blood pressure; HR, heart rate; PP, Peripheral pulse pressure; SBP, Systolic blood pressure.
3.3. Variables associated to SEVR in non‐PAD group
Table 4 shows the effects of the variables for the SEVR after the stepwise selection process. In the non‐PAD group, SEVR was negatively related to females (P < .0001), height (P = .014), aortic SBP (P = .0005), heart rate (P < .0001), and augmentation pressure (P = .0004) and positively to DBP (P < .0001). The c‐f PWV, Aix, Aix@HR75, aortic PP, and ABI were not related to SEVR (P = .101), (P = .377), (P = .436), (P = .969), (P = .402), respectively. Also, in this group antihypertensive medications and statins were not related to SEVR.
Table 4.
Current estimates table using SEVR as the dependent variable in non‐PAD patients
| Parameters | Non‐PAD | |
|---|---|---|
| Estimate | P | |
| Aix @75HR | .436 | |
| c‐fPWV | .101 | |
| AP | −0.849 | .0004 |
| Aix | .377 | |
| ABI | .402 | |
| Sex, F | −14.96 | <.0001 |
| Height | −0.375 | .014 |
| HR | −2.037 | <.0001 |
| SBP‐aortic | −0.834 | .0005 |
| DBP‐aortic | 1.083 | <.0001 |
| Age | .805 | |
| BMI | .472 | |
| Hypertension (Y/N) | .811 | |
| Type 2 diabetes (Y/N) | .887 | |
| Dyslipidaemia (Y/N) | .398 | |
| Smoking history (Y/N) | .995 | |
| SBP, brachial artery | .809 | |
| DBP‐brachial artery | .445 | |
| PP‐brachial artery | .317 | |
| PP aortic | .969 | |
| Calcium‐channel‐blockers | .277 | |
| β‐blockers, | .604 | |
| Statins | .966 | |
| ACE‐I | .197 | |
| Nitrates | .921 | |
ABI, ankle brachial index; Aix, augmentation index; Aix @75HR, corrected for a heart rate of 75 beats/min; AP, augmentation pressure; BMI, body mass index; c‐fPWV, carotid‐femoral pulse wave velocity; DBP, diastolic blood pressure; HR, heart rate; PP, peripheral pulse pressure; SBP, systolic blood pressure.
4. DISCUSSION
Previous studies have demonstrated that in older PAD patients an increase of aortic stiffness and wave reflections tend to coexist.4, 5, 11, 12 This study examined the relationship between arterial stiffness (cfPWV, Aix@HR75), ABI, and SEVR in PAD and non‐PAD patients. The results revealed that in the PAD group c‐fPWV and ABI were not related to SEVR, while Aix@HR75 and aortic PP were negatively related to SEVR (Table 3), suggesting that arterial stiffness is associated with non‐invasive indices of myocardial perfusion. Several studies have shown that arterial stiffness has a strong link with the mechanisms of coronary blood flow. In experimental studies, a reduction in coronary reserve flow in the presence of coronary stenosis after mechanical induction of a decrease in aortic compliance has been described.17, 18 Other authors have reported that PWV is independently related with the impairment of coronary microcirculation as assessed by coronary flow reserve (CFR) in patients with CAD as well as hypertensive patients.19, 20 An association between aortic stiffness and increased predisposition to ischemia was reported in the Rotterdarm study.21 In recent years, it has been widely admitted that the tonometric subendocardial viability ratio (SEVR) is a valuable estimate of myocardial perfusion relative to cardiac workload,10, 22 and it is also a predictor of coronary flow reserve.23 Arterial stiffness is often determined by measuring the c‐fPWV. However, other methods are also used, including the assessment of PP and the augmentation index (Aix), an index of wave reflection.8 Our finding, that arterial stiffness is associated with indices of myocardial perfusion, is consistent with the above mentioned studies. However, our multiple regression analysis showed that the Aix@HR75 and aortic PP were significantly related to SEVR, whereas c‐fPWV was not. The reasons for these differences are unclear, but it is possible that different average values of PWV may be involved. Guelen et al report that the cardiac oxygen supply demand ratio DPTI/SPTI decreased with increasing PWV. Aix and/or PP are often presented as stiffness parameters, however, they are the result of several factors, including, but not limited to, arterial stiffness (ie, heart rate).15 This could explain why when the reflection wave is expressed as Aix the relationship with SEVR is direct, but inverse when expressed as Aix and corrected for heart rate (Aix@HR75). The mechanism of association between Aix@HR75 aortic PP and SEVR remains unknown; however, in PAD patients arterial stiffening may lead to systemic hemodynamics changes (ie, increased aortic SBP and decreased aortic DBP; Table 2). This results in an increased left ventricle (LV) systolic afterload, and thus, increased oxygen demand, decreased diastolic coronary perfusion pressure, and reduced oxygen delivery that leads to subendocardial ischemia.6, 7
Our results are in line with a recent study by Tritakis et al24 The same authors using Arteriograph reported that in patients with angiographically documented CAD, a decreasing coronary flow reserve (CFR) measured non‐invasively (using Doppler echocardiography) is inversely related to Aix, but not to PWV in multivariate analysis, suggesting that stiffening of the smaller muscular arteries contributes to a reduced CFR. Finally, in the present study the result of a low SEVR in PAD patients is in accord with previous studies that reported the effects of various clinical conditions on SEVR.25, 26 Prince et al27in 144 patients with type 1 diabetes, reported che SEVR was associated with low ABI in multivariable models (P = .02), but only 16 participants (11.1%) had a low ABI (< 0.9). In 65 PAD patients, Mosimann et al28 reported that a lower ABI was directly related to SEVR (P = .036). The results of our analysis however, suggest that a lower ABI is not related to SEVR (Table 3).
4.1. Potential implications
What would be the clinical implications of our results? The PAD is not just a disease of the peripheral arteries, but in addition, it is an indication of a high probability of generalized vascular atherosclerosis.29 Our findings are a further evidence that the association between arterial disease, arterial stiffness, and myocardial perfusion indices beyond generalized atherosclerosis might be a potential hemodynamic link for cardiac events in PAD through plaque vulnerability and/or oxygen supply dysbalance.6, 30, 31, 32 In this context, the observation by Jacomella et al33 that the procedure of balloon angioplasty (percutaneous transluminal angioplasty, PTA) may be associated with an improvement of Aix when compared to a control group without revascularisation procedures, may have therapeutic implications.
4.2. Study limitations
The present study has some limitations. First, this was an observational study that did not reveal causal relationships. In this study, we used arterial tonometry to determine the subendocardial oxygen supply‐demand ratio since this approach seems to provide a relatively reliable surrogate assessment of the real subendocardial oxygen supply‐demand ratio. However, the assessment of DPTI:SPTI ratio based only on pulse waveforms is affected by several factors, including left ventricular mass, left ventricular diastolic pressure,29 and data that were not available in our study. Finally, in a recent study SEVR presented a moderate correlation (r = .651) with the invasive coronary flow reserve (calculated by a 0.014‐inch Doppler guidewire).23 Further studies are thus needed in order to improve this noninvasive approach by combining the use of arterial tonometry with a cardiac ultrasound assessment.
5. CONCLUSIONS
In conclusion, our results suggest that in PAD patients higher Aix@HR75 and aortic PP were associated with non‐invasive indices of myocardial perfusion in PAD, indicating a potential pathophysiological link for increased cardiovascular events. PAD is linked with cardiovascular morbidity and mortality, but the basis of the independent association remains poorly understood in detail. Noninvasive estimation of central hemodynamic parameters (Aix@HR75, SEVR, c‐fPWV) could provide more information concerning the pathophysiology of cardiovascular complications in these high‐risk patients.
CONFLICT OF INTEREST
The authors declare no conflict of interest.
ACKNOWLEDGMENTS
The authors are indebted to Ms. Sara Foletto for the linguistic revision of the text.
Scandale G, Dimitrov G, Recchia M, et al. Arterial stiffness and subendocardial viability ratio in patients with peripheral arterial disease. J Clin Hypertens. 2018;20:478–484. 10.1111/jch.13213
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