CAVI (Cardio-Ankle Vascular Index) as an independent predictor of hypertensive response to exercise.

OBJECTIVES: Hypertensive response to exercise (HRE) is related to the development of future hypertension, cardiovascular morbidity, and mortality, independent of resting blood pressure. We hypothesized that arterial stiffness as measured by cardio-ankle vascular index (CAVI) could be an independent predictor of HRE. MATERIALS AND METHODS: Retrospective chart review of patients participated in the preventive health program at the Bangkok Heart Hospital who underwent both CAVI and treadmill stress testing on the same day between June and December 2018 were performed. Variables for the prediction of HRE were analyzed using univariate analysis, and significant variables were entered into multiple logistic regression. An ROC curve was created to test the sensitivity and specificity of CAVI as a predictor of HRE. RESULTS: A total of 285 participants (55.1% female) were enrolled in this study. There were 58 patients (20.4%) who met the HRE definition (SBP > 210 mmHg in males, SBP > 190 mmHg in females, or DBP > 110 mmHg in both males and females), with a mean age of 46.4 12.8 years. In univariate analysis, age, systolic blood pressure at rest, diastolic blood pressure at rest, pulse pressure at rest, diabetes mellitus, hypertension, dyslipidemia, history of beta-blocker, and CAVI results were statistically significant. Multiple logistic regression revealed that CAVI and systolic blood pressure were statistically significant predictors of HRE with OR of 5.8, 95%CI: 2.9-11.7, P < 0.001 and OR 1.07, 95%CI: 1.03-1.10, P = 0.001 respectively. ROC curve analysis of the CAVI revealed an AUC of 0.827 (95%CI: 0.76-0.89, p < 0.001), and the sensitivity and specificity of cut-point CAVI > 8 were 53% and 92%, respectively. CONCLUSION: This study demonstrated that CAVI is an independent predictor of hypertensive response to exercise. Additionally, the findings suggest that CAVI > 8 can be a valuable tool in identifying individuals at risk for hypertensive responses during exercise.

Validity of Atherosclerotic Calcified Lesions Observed on Low-Dose Computed Tomography and Cardio-Ankle Vascular Index as Surrogate Markers of Atherosclerosis Progression.

The significance of atherosclerotic calcified lesions observed on low-dose computed tomography (LDCT) performed during general checkups was investigated. The coronary arteries (CA), ascending aorta and aortic arch (AAAA), descending thoracic aorta (DTA), and abdominal aorta (AA) were examined. Semiquantitative calcified index analysis of the DTA and AA in terms of atherosclerosis risk factors and cardio-ankle vascular index (CAVI) measurements was also performed. We included 1594 participants (mean age: 59.2 years; range: 31-91 years). The prevalence of calcified lesions was 71.0%, 66.6%, 57.2%, and 37.9% in the AA, CA, AAAA, and DTA, respectively. Age-related advances in calcification among participants with no major risk factors, revealed that calcification appeared earliest in the AA, followed by the CA, AAAA, and DTA. Participants with calcified lesions in all arteries had a significantly greater CAVI than those without calcification. The CAVI was negatively correlated with low-density lipoprotein cholesterol levels, particularly in participants without calcified lesions in the DTA. Calcified lesions on LDCT could indicate the end stage of atherosclerotic lesions. The CAVI can be used to assess atherosclerotic changes at all stages of disease progression. A combination of LDCT and CAVI could be used as a routine non-invasive assessment of atherosclerosis.

Cardiovascular risk prediction with cardio-ankle vascular index in the malaysian cohort study.

The cardio-ankle vascular index (CAVI) is an important parameter assessing arterial function. It reflects arterial stiffness from the origin of the aorta to the ankle, and the algorithm is blood pressure independent. Recent data have suggested that a high CAVI score can predict future cardiovascular disease (CVD) events; however, to date, no study has been done in Malaysia. We conducted a prospective study on 2,168 The Malaysian Cohort (TMC) CVD-free participants (971 men and 1,197 women; mean age 51.64 ± 8.38 years old) recruited from November 2011 to March 2012. This participants were followed-up until the emergence of CVD incidence and mortality (endpoint between May to September 2019; duration of 7.5 years). Eligible participants were assessed based on CAVI baseline measurement which categorised them into low (CAVI <9.0) and high (CAVI ≥ 9.0) scores. The CVD events in the group with high CAVI (6.5 %) were significantly higher than in the low CAVI (2.6 %) group (p < 0.05). CAVI with cut-off point ≥ 9.0 was a significant independent predictor for CVD event even after adjustment for male, ethnicity, age, and intermediate atherogenic index of plasma (AIP). Those who have higher CAVI have 78 % significantly higher risk of developing CVD compared to those with the low CAVI (adjusted OR [95 % CI] = 1.78 [1.04 - 3.05], p =0.035). In addition, the participants with higher CAVI have significantly lower survival probability than those who have lower CAVI values. Thus, this study indicated that the CAVI can predict CVD event independently among the TMC participants.

Ongoing Effects of SARS-CoV-2 Infection on Arterial Stiffness in Healthy Adults.

There are limited data on the arterial stiffness changes after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The present study evaluated the changes in arterial stiffness in completely healthy patients who had a SARS-CoV-2 infection using the cardio-ankle vascular index (CAVI). The study included 70 patients with SARS-CoV-2 infection between December 2020 and June 2021. A cardiac evaluation was carried out, including chest X-ray, electrocardiography (ECG), and echocardiography in all patients. Within the 1st month and 7th month CAVI was measured. Mean age was 37.8 ± 10.0 years, and 41/70 were female. Mean height was 168.6 ± 9.5 cm, mean weight 73.2 ± 15.1 kg, and mean body mass index (BMI) of the group was 25.6 ± 4.2, respectively. CAVI results from the right arm were 6.45 ± .95 at 1-month follow-up and 6.68 ± 1.05 at 7 months follow-up (P = .016) and from the left arm were 6.43 ± 1.0 at 1-month follow-up, 6.70 ± 1.05 at 7-month follow-up (P = .005). Our results showed an ongoing injury in the arterial system after healthy SARS-COV-2 patients during 7 months, as represented by CAVI measurements.

The effects of severe periodontitis on arterial stiffness using cardio-ankle vascular index in patients with type 2 diabetes.

BACKGROUND AND OBJECTIVE: Arterial stiffness, which is a measure of the elasticity of the arteries, is also a risk factor for the development of cardiovascular diseases and its measurement is important for evaluating the atherosclerosis process. The purpose of this cross-sectional study to investigate whether severe periodontitis in short-term type 2 diabetes may be associated with increased cardio-ankle vascular index (CAVI) values specified for subclinical atherosclerosis risk. METHODS: A total of 136 subjects, including 69 subjects with short-term type 2 diabetes (35 with severe periodontitis and 34 with periodontally healthy) and 67 systemically healthy subjects (32 with severe periodontitis and 35 with periodontally healthy) were enrolled to this study. Assessment of all participants included in this study in terms of arterial stiffness was determined by CAVI. Serum fasting plasma glucose (FPG), glycated haemoglobin (HbA1c), triglyceride (TRG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), total cholesterol (TC) and C-reactive protein (CRP) levels were calculated using standard methods. Full mouth periodontal measurements were recorded. Multiple linear regression analysis was performed to evaluate the relationship between periodontal parameters and mean CAVI values of the groups. RESULTS: Mean CAVI levels were significantly higher in diabetic and periodontitis group compared to the other study groups (p < .05). In diabetes and periodontitis group, CAVI was showed positive correlations with CRP (r = .337, p = .048) and HbA1c (r = .442, p = .008). Also, positive significant correlations were found with probing depth (PD) and clinical attachment level (CAL) in the periodontitis groups. Multiple regression analysis revealed that CAL independently predicted CAVI levels in periodontitis groups (ß = .433, p = .019 in diabetes and periodontitis groups and ß = .57, p = .001 in systemically healthy and periodontitis group respectively). CONCLUSION: This is the first study investigating the association between severe periodontitis and CAVI in patients with short-term diabetes. Our findings suggest that severe periodontitis may be an intermediate factor in the pathway between type 2 diabetes and cardiovascular disease by increasing the arterial stiffness.

Percentage of mean arterial pressure as a marker of atherosclerosis for detecting patients with coronary artery disease.

The percentage of mean arterial pressure (%MAP) is the height of the mean arterial waveform divided by the peak amplitude of the waveform of pulse volume recording. The purpose of this study was to determine whether the cutoff value of 45% for %MAP at the ankle, which is recommended for the diagnosis of lower extremity artery disease, in combination with ankle-brachial index (ABI) is useful for detecting patients with clinical coronary artery disease (CAD) and investigate the optimal cutoff value of %MAP to diagnose patients with CAD.　We measured ABI and %MAP in 2213 subjects　(mean age: 61.2 ± 15.5 years). Multivariate analysis revealed that %MAP ≥ 45% was significantly associated with a higher risk of CAD after adjusting for traditional cardiovascular risk factors (odds ratio [OR], 2.14; 95% confidence interval [CI], 1.43-3.21; p < 0.001). However, the association was no longer significant after adjusting for ABI (OR, 1.39; 95% CI, 0.83-2.33; p = 0.21), whereas ABI was significantly associated with CAD (OR, 0.98; 95% CI, 0.97-0.99; p = 0.005). The optimal cutoff value of %MAP derived from a receiver operating characteristic curve to diagnose CAD was 40.3%. Multivariate analysis revealed that %MAP ≥ 40.3% was significantly associated with a higher risk of CAD (OR, 1.63; 95% CI, 1.19-2.24; p = 0.002) independent of ABI (OR, 0.98; 95% CI, 0.97-0.99; p = 0.002). The cutoff value of 40.3%, but not 45%, for %MAP may be useful for detecting patients with advanced atherosclerosis and for cardiovascular risk assessment independent of ABI. REGISTRATION INFORMATION: http://www.umin.ac.jp (University Hospital Medical Information Network Clinical Trials Registry) (UMIN000039512).

[Association between cardio-ankle vascular index and markers of thrombosis in hospitalized patients COVID-19].

AIM: To evaluate the relationship between the cardio-ankle vascular index (CAVI) and the marker of procoagulant state - D-dimer in hospitalized patients with coronavirus disease 2019 (COVID-19). MATERIALS AND METHODS: This cross-sectional study involved adult patients admitted to the University hospital with clinically diagnosed or laboratory-confirmed COVID-19. We compared groups of patients with normal and elevated CAVI. Univariate and multivariate logistic regression analyses were performed to assess the association between risk factors and elevated D-dimer levels; odds ratios (ORs) with 95% confidence intervals (95% CI) were calculated to determine the strength of association. A p<0.05 was considered statistically significant. RESULTS: The study included 152 patients [64 (42.1%) men and 88 (57.9%) women], mean age 59.10±12.74 years. 45 (29.6%) had elevated CAVI. Patients with elevated CAVI were older, had more comorbid diseases, a higher Charlson comorbidity index and D-dimer levels. Age, the comorbidity index, and CAVI above 9.5 were associated with elevated D-dimer levels in patients with COVID-19. In a multivariate logistic regression, CAVI above 9.5 was an independent predictor of increased D-dimer in patients with COVID-19 (OR 2.513, 95% CI 1.050-6.012; p=0.038). CONCLUSION: In this study, for the first time, the association between a vascular stiffness marker, elevated CAVI, and increased D-dimer levels in COVID-19 patients was shown. This relationship may be a consequence of endothelial dysfunction and can be used as an additional marker of coagulopathy developing as part of COVID-19.

Reference-range of arterial stiffness by cardio-ankle vascular index in normal pregnancy.

OBJECTIVE: To establish the arterial stiffness, represented by the cardio-ankle vascular index (CAVI) at various gestational ages among low-risk pregnant women. The second objective is to construct the reference range of mean arterial pressure and maternal heart rate during pregnancy. METHODS: This cross-sectional study was conducted on low risk pregnant Thai women, meeting the following inclusion criteria: 1) singleton pregnant women aged 18 years old or over; 2) gestational age between 11 and 40 weeks; 3) low-risk pregnancy without any underlying medical diseases; and 4) known final pregnancy outcomes. Pregnancy-induced hypertension, gestational diabetes and fetal growth restriction were excluded. The mean CAVI, mean arterial pressure (MAP), and heart rate were measured at each gestational age. RESULTS: A total of 329 measurements for each parameter were available for analysis. CAVI was significantly correlated with gestational age with the best fitted model: CAVI = 6.952 - 0.076(GA) + 0.001(GA)2; SD = 0.742 (R2 = 0.049; p-value < 0.001). The maternal age and pre-pregnancy BMI were correlated with CAVI. CAVI gradually increased with maternal age and decreased with increasing body mass index (BMI). The MAP and heart rate of normal pregnancy in each gestation were conducted. CONCLUSION: The reference range of CAVI in normal pregnancies as a function of gestational age and the model for predicting CAVI based on multiple regression analysis are constructed and presented. These reference ranges may be useful in predicting risk of cardiovascular disorders during pregnancy.

Novel Peripheral Perfusion Dynamics Indices for Detecting and Grading Arterial Stenosis.

PURPOSE: Peripheral artery disease causes severe morbidity, especially in diabetics and the elderly. There is a need for accurate noninvasive detection of peripheral arterial stenosis. The study has tested the hypothesis that arterial stenosis and the associated adaptation of the downstream circulation yield characteristic changes in the leg perfusion dynamics that enable early diagnosis, utilizing impedance plethysmography. METHODS: The arterial perfusion dynamic was derived from impedance plethysmography (IPG). Two degrees of arterial stenosis were emulated by inflating a blood-pressure cuff around the thigh to 45 and 90 mmHg, in healthy volunteers (n = 30). IPG signals were acquired continuously throughout the experiment. Ankle and brachial blood pressures were measured at the beginning of each experiment and at the end of each emulated stenosis phase. RESULTS: Thigh compressions did not affect the pulse-transit time, but prolonged the time to the peak perfusion wave. Segmentation of the perfusion upstroke into two phases, at the time point of maximum acceleration (MAT), revealed that arterial compression prolonged only the initial slow phase duration (SPd). The MAT and SPd were proportional to the emulated stenosis severity and detected the arterial stenosis with high sensitivity (> 93%) and specificity (100%). The SPd increased from 46.4 ± 21.2 ms at baseline to 75.4 ± 38.5 ms and 145 ± 39 ms under 45 mmHg and 90 mmHg compressions (p < 0.001), without affecting the pulse-transit time. CONCLUSIONS: The novel method and indices can identify and grade the emulated arterial stenosis with high accuracy and may assist in differentiating between focal arterial stenosis and widespread arterial hardening.

Association between blood glucose levels and arterial stiffness marker: comparing the second derivative of photoplethysmogram and cardio-ankle vascular index scores.

Objective: This study aimed to compare the association between fasting plasma glucose (FPG) and glycosylated hemoglobin A1c (HbA1c) levels using the second derivative of photoplethysmogram (SDPTG) index and the cardio-ankle vascular index (CAVI). Methods: Electronic medical records of 276 participants (160 men, 116 women) who visited the health promotion center of a university hospital were examined. Age, sex, body mass index (BMI), blood pressure, and lipid profile were considered as risk factors for arterial stiffness, together with the FPG, HbA1c, CAVI, and SDPTG indices. Hierarchical regression models were constructed, and all participants were divided into low-normal, high-normal, prediabetic, and diabetic groups to examine the group-based differences in CAVI and SDPTG indices. Results: FPG and HbA1c were independently predictive of increased CAVI, and their predictive powers for CAVI were equivalent (ß = 0.214 and 0.200, respectively). Risk factors, including age, BMI, and male sex, were also predictive of CAVI (ß= 0.593-0.630, -0.256 - -0.280, and 0.142-0.178, respectively). None of the FPG and HbA1c values were predictive of the SDPTG indices. The CAVI was higher in the diabetes group than in the other three groups according to HbA1c level, while the d/a index of the SDPTG decreased in the prediabetes group and increased in the diabetes group. Conclusions: CAVI may not be substituted for SDPTG indices when evaluating arterial stiffness based on the glucose level. Moreover, the progression rate of arterial stiffness may differ between the diabetic and nondiabetic stages.

Association between ankle-brachial blood pressure index with all-cause and cardiovascular mortality in adults without arterial stiffness.

PURPOSE: To explore the relationship between ankle-brachial blood pressure index (ABPI) and all-cause or cardiovascular mortality in adults without arterial stiffness. METHODS: A total of 6784 participants without arterial stiffness were enrolled from National Health and Nutrition Examination Survey 1999-2004. The hazard ratio (HR) and 95% confidence interval (CI) of ABPI associating with the risk of all-cause and cardiovascular mortality was calculated by Cox proportional regression models adjusted for demographic and traditional risk factors. Dose-response relationship was explored with restricted cubic spines. RESULTS: After an average follow-up of 12.1 years, 1844 all-cause deaths and 299 cardiovascular deaths occurred. Compared with the lowest ABPI quartile, the second quartile was associated with the lowest risk of all-cause mortality (HR 0.89, 95%CI 0.79-0.98; p = 0.036) and cardiovascular mortality (HR 0.75, 95%CI 0.56-0.98; p = 0.048). Besides, dose-response analysis revealed that ABPI was nonlinearly correlated to all-cause mortality (p for nonlinearity < 0.001) and linearly correlated to cardiovascular mortality (p for nonlinearity = 0.459). CONCLUSIONS: The relationship between ABPI and all-cause and cardiovascular mortality followed a L-shape curve. A lower ABPI was independently associated with an increased risk of all-cause and cardiovascular mortality in adults without arterial stiffness.

Reimagining the Value of Brachial-Ankle Pulse Wave Velocity as a Biomarker of Cardiovascular Disease Risk-A Call to Action on Behalf of VascAgeNet.

This review critiques the literature supporting clinical assessment and management of cardiovascular disease and cardiovascular disease risk stratification with brachial-ankle pulse wave velocity (baPWV). First, we outline what baPWV actually measures-arterial stiffness of both large central elastic arteries and medium-sized muscular peripheral arteries of the lower limb. Second, we argue that baPWV is not a surrogate for carotid-femoral pulse wave velocity. While both measures are dependent on the properties of the aorta, baPWV is also strongly dependent on the muscular arteries of the lower extremities. Increased lower-extremity arterial stiffness amplifies and hastens wave reflections at the level of the aorta, widens pulse pressure, increases afterload, and reduces coronary perfusion. Third, we used an established evaluation framework to identify the value of baPWV as an independent vascular biomarker. There is sufficient evidence to support (1) proof of concept; (2) prospective validation; (3) incremental value; and (4) clinical utility. However, there is limited or no evidence to support (5) clinical outcomes; (6) cost-effectiveness; (8) methodological consensus; or (9) reference values. Fourth, we address future research requirements. The majority of the evaluation criteria, (1) proof of concept, (2) prospective validation, (3) incremental value, (4) clinical utility and (9) reference values, can be supported using existing cohort datasets, whereas the (5) clinical outcomes and (6) cost-effectiveness criteria require prospective investigation. The (8) methodological consensus criteria will require an expert consensus statement. Finally, we finish this review by providing an example of a future clinical practice model.

Pulse Wave Morphology Changes in Aortic Valve Stenosis Detected with Cardio-Ankle Vascular Index.

Background: Cardio-ankle vascular index (CAV) is a measure of systemic arterial stiffness and has been shown to increase after aortic valve surgery. However, change in CAVI-derived pulse wave morphology has not previously been addressed. Case Study: A 72-year-old female was transferred to a large center for heart valve interventions for evaluation of her aortic stenosis. Few co-morbidities were detected on medical history, other than previous radiation treatment for breast cancer, and no signs of other concomitant cardiovascular disease. The patient was accepted for surgical aortic valve replacement due to severe aortic valve stenosis and arterial stiffness was assessed with CAVI, as part of an ongoing clinical study. The pre-operative CAVI was 4.7 which after surgery increased almost 100% to 9.35. In tandem, the slope of systolic upstroke pulse morphology captured from brachial cuffs was changed from a prolonged flattened pattern to a steeper. Conclusion: After aortic valve replacement surgery due to aortic valve stenosis, in addition to increased CAVI-derived measures of arterial stiffness, the slope of the CAVI-derived upstroke pulse wave morphology changes to a steeper slope. This finding could have implications in the future of aortic valve stenosis screening and utilization of CAVI.

Foot Dorsal and Plantar Flexion to Enhance Crossing of Tortuous Highly-Calcific Ankle Vessels During Lower Limb Revascularization Procedures: A Technical Note.

PURPOSE: To describe a crossing technique of stenotic/occluded and tortuous highly calcific ankle vessels during complex percutaneous limb salvage intervention in diabetic patients with ischaemic foot ulcers (Rutherford 5 and 6). TECHNIQUE: We propose a simple technique to achieve "straightening" of the tortuous vessel and allow safe devices passage into the foot arteries, Patients were asked to hold their foot in plantar or dorsal flexion, accordingly to the treated artery. If unable to do so, an equipe member executed the manoeuvre on their behalf. RESULTS: The technique was applied in 148 cases, with a success rate of 81% (120/148). No complications related to the manoeuvre were observed. CONCLUSION: Crossing of tortuous distal crural vessels can be challenging in diabetic patients; in our experience, this technique can be a useful tool to obtain a successful recanalization in complex procedures with high risk of failure.

Possible Clinical Benefits of Cardio-Ankle Vascular Index Measurement in Urological Diseases.

Many factors are considered to affect vascular physiology. It is known that one of the reasons for many diseases is a pathology at the microvascular level. Therefore, the relationship between endothelial dysfunction and many diseases is currently being investigated. The clinical evaluations of arterial stiffness have made it possible to perform necessary risk assessment regarding cardiovascular diseases. In this way, protective measures can be taken against microvascular pathologies in many organs. In this paper, we present a review of studies investigating the relationship between urological conditions and the cardio-ankle vascular index (CAVI), a marker of arterial stiffness. As with erectile dysfunction, some studies have shown that conditions such as lower urinary tract symptoms, overactive bladder, and chronic kidney disease are also associated with an elevated CAVI. The association of erectile dysfunction and chronic kidney disease with vascular pathologies has been clearly demonstrated. In addition, lower urinary tract symptoms may be the first sign of silent vascular dysfunction. Assessing arterial stiffness with CAVI can help prevent future cardiovascular events in these patients.

Cutoff Values of Brachial-Ankle Pulse Wave Velocity for Atherosclerotic Risks by Age and Sex in the Japanese General Population.

AIM: In this study, we aim to analyze the correlation between brachial-ankle pulse wave velocity (baPWV) and Suita score or Framingham risk score and obtain the cutoff value of baPWV by sex and age for cardiovascular risk, as assessed by these scores in the large Japanese annual health checkup data. METHODS: In total, 25,602 participants (14,539 men and 11,063 women), who had their annual health checkups, were included in this study. Cutoff values of baPWV for the moderate- and high-risk groups stratified by sex and age were obtained using a receiver operating characteristic (ROC) curve analysis. RESULTS: As per our findings, the Suita score demonstrated better correlations with baPWV than the Framingham risk score in both sexes (men, Suita score R2=0.41 and Framingham risk score R2=0.37; women, Suita score R2=0.54 and Framingham risk score R2=0.33). The ROC curve analysis demonstrated the cutoff values of baPWV for moderate- and high-risk groups estimated using the Suita score, and they are as follows: in men, the baPWV cutoff values were 1,350 cm/s in the 40s, 1,430 cm/s in the 50s, 1,520 cm/s in the 60s, and 1,880 cm/s in the 70s. In women, the baPWV cutoff values were 1,350 cm/s in the 40s, 1,430 cm/s in the 50s, 1,570 cm/s in the 60s, and 1,800 cm/s in the 70s. CONCLUSIONS: We demonstrated that baPWV significantly correlated with the Suita score or Framingham risk score in both men and women, with the former presenting a stronger correlation than the latter. We propose the cutoff values of baPWV for moderate- and high-risk groups estimated using the Suita score.