An Increase in Vascular Stiffness Is Positively Associated With Mitochondrial Bioenergetics Impairment of Peripheral Blood Mononuclear Cells in the Older Adults.

The cardio-ankle vascular index (CAVI) is a noninvasive parameter reflecting vascular stiffness. CAVI correlates with the burden of atherosclerosis and future cardiovascular events. Mitochondria of peripheral blood mononuclear cells (PBMCs) have been identified as a noninvasive source for assessing systemic mitochondrial bioenergetics. This study aimed to investigate the relationship between CAVI values and mitochondrial bioenergetics of PBMCs in the older adults.. This cross-sectional study enrolled participants from the Electricity Generating Authority of Thailand between 2017 and 2018. A total of 1 640 participants with an ankle-brachial index greater than 0.9 were included in this study. All participants were stratified into 3 groups based on their CAVI values as high (CAVI ≥ 9), moderate (9 > CAVI ≥ 8), and low (CAVI < 8), in which each group comprised 702, 507, and 431 participants, respectively. The extracellular flux analyzer was used to measure mitochondrial respiration of isolated PBMCs. The mean age of the participants was 67.9 years, and 69.6% of them were male. After adjusted with potential confounders including age, sex, smoking status, body mass index, diabetes, dyslipidemia, hypertension, and creatinine clearance, participants with high CAVI values were independently associated with impaired mitochondrial bioenergetics, including decreased basal respiration, maximal respiration, and spare respiratory capacity, as well as increased mitochondrial reactive oxygen species. This study demonstrated that CAVI measurement reflects the underlying impairment of cellular mitochondrial bioenergetics in PBMCs. Further longitudinal studies are necessary to establish both a causal relationship between CAVI measurement and underlying cellular dysfunction.

Association between Atherosclerosis and High-Risk Colorectal Adenomas based on Cardio-Ankle Vascular Index and Ankle-Brachial Index.

Background/Aims: Colorectal adenomas are precancerous lesions that may lead to colorectal cancer. Recent studies have shown that colorectal adenomas are associated with atherosclerosis. The cardio-ankle vascular index (CAVI) and ankle-brachial index (ABI) are noninvasive methods for evaluating atherosclerosis. This study examined the association between atherosclerosis and high-risk colorectal adenomas based on the CAVI and ABI. Methods: The data of patients aged ≥50 years who had a colonoscopy and CAVI and ABI measurements from August 2015 to December 2021 at the Kangwon National University Hospital were analyzed retrospectively. After the colonoscopy, subjects were divided into no, overall, and high-risk (size ≥1 cm, high-grade dysplasia or villous adenoma, three or more adenomas) adenoma groups based on the pathology findings. The data were subjected to univariate and multivariate logistic regression analyses. Results: Among the 1,164 subjects, adenomas and high-risk adenomas were found in 613 (52.6%) and 118 (10.1%) patients, respectively. The rate of positive ABI (<0.9) and positive CAVI (≥9.0) were significantly higher in the high-risk adenoma group (22.0% and 55.9%) than in the no adenoma (12.3% and 39.6%) and the overall adenoma group (15.7% and 44.0%) (p=0.008 and p=0.006, respectively). Multivariate analysis revealed a positive CAVI and smoking status to be significantly associated with high-risk adenoma with an odds ratio of 1.595 (95% confidence interval 1.055-2.410, p=0.027) and 1.579 (1.072-2.324, p=0.021), respectively. Conclusions: In this study, a significant correlation between positive CAVI and high-risk adenomas was observed. Therefore, CAVI may be a significant predictor for high-risk colorectal adenoma.

Relationship between Lipoprotein Lipase Derived from Subcutaneous Adipose Tissue and Cardio-Ankle Vascular Index in Japanese Patients with Severe Obesity.

INTRODUCTION: Cardio-ankle vascular index (CAVI) is an arterial stiffness index that correlates inversely with body mass index (BMI) and subcutaneous fat area. Lipoprotein lipase (LPL) that catalyzes the hydrolysis of serum triglycerides is produced mainly in adipocytes. Serum LPL mass reflects LPL expression in adipose tissue, and its changes correlate inversely with changes in CAVI. We hypothesized that LPL derived from subcutaneous adipose tissue (SAT) suppresses the progression of arteriosclerosis and examined the relationship of LPL gene expression in different adipose tissues and serum LPL mass with CAVI in Japanese patients with severe obesity undergoing laparoscopic sleeve gastrectomy (LSG). METHODS: This study was a single-center retrospective database analysis. Fifty Japanese patients who underwent LSG and had 1-year postoperative follow-up data were enrolled (mean age 47.5 years, baseline BMI 46.6 kg/m2, baseline HbA1c 6.7%). SAT and visceral adipose tissue (VAT) samples were obtained during LSG surgery. LPL gene expression was analyzed by real-time PCR. Serum LPL mass was measured by ELISA using a specific monoclonal antibody against LPL. RESULTS: At baseline, LPL mRNA expression in SAT correlated positively with serum LPL mass, but LPL mRNA expression in VAT did not. LPL mRNA expression in SAT was correlated, and serum LPL mass tended to correlate inversely with the number of metabolic syndrome symptoms, but LPL mRNA expression in VAT did not. LPL mRNA expression in SAT and CAVI tended to correlate inversely in the group with visceral-to-subcutaneous fat ratio of 0.4 or higher, which is considered metabolically severe. Serum LPL mass increased 1 year after LSG. Change in serum LPL mass at 1 year after LSG tended to be an independent factor inversely associated with change in CAVI. CONCLUSIONS: Serum LPL mass reflected LPL mRNA expression in SAT in Japanese patients with severe obesity, and LPL mRNA expression in SAT was associated with CAVI in patients with visceral obesity. The change in serum LPL mass after LSG tended to independently contribute inversely to the change in CAVI. This study suggests that LPL derived from SAT may suppress the progression of arteriosclerosis.

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.

Insufficient blood pressure control is independently associated with increased arterial stiffness.

Hypertension is a risk factor for atherosclerosis. Achieving the therapeutic target value of blood pressure (BP) prevents the onset of cardiovascular events; however, it is not clear how antihypertensive drug use and BP control status relate to arterial stiffness. The purpose of this study is to investigate the relationship between BP control status with or without antihypertensive drugs and arterial stiffness. Nine hundred eighty individuals (mean age: 68 ± 11 years) who participated in a community-based cohort study were enrolled. Arterial stiffness was evaluated using the cardio-ankle vascular index (CAVI). Higher BP was defined as a systolic BP ≥ 140 mmHg or diastolic BP ≥ 90 mmHg. Participants were divided into four groups: normal, non higher BP without antihypertensive drugs (n = 421); untreated, higher BP without antihypertensive drugs (n = 174); good control, non higher BP with antihypertensive drugs (n = 209); and poor control, higher BP with antihypertensive drugs (n = 176). In multivariable logistic analysis adjusted for age, sex, dyslipidemia and diabetes mellitus medication use, obesity, smoking, alcohol drinking, and heart rate at the CAVI measurement for a high CAVI-using a borderline cutoff value of 8.0-the other three groups were significantly associated with a high CAVI when compared with the normal group. By contrast, multivariable logistic analysis of a high CAVI using an abnormal cutoff value of 9.0 demonstrated that the poor control and untreated groups were significantly associated with a high CAVI, whereas the good control group was not. In conclusion, even with antihypertensive drugs, poor BP control is independently associated with a high CAVI.

Association of Sleep Duration and Cardio-Ankle Vascular Index in Community-Dwelling Older Adults.

AIM: This study aims to investigate the association of the Cardio-Ankle Vascular Index (CAVI) with self-reported sleep duration and sleep quality in community-dwelling older adults aged ≥ 65 years. METHODS: The Tarumizu Study was a cohort of community-based health checkups conducted in the Tarumizu City, Japan, in 2018 and 2019. In total, 997 participants aged ≥ 65 years (median age, 74 years) were examined. We obtained the average sleep duration and sleep quality using self-reported questionnaires and classified them into three separate groups according to sleep duration (＜6 h, 6-8 h, and ≥ 8 h) and sleep quality (good, medium, and poor). The arterial stiffness was measured using the CAVI. RESULTS: As per our findings, the CAVI was significantly higher in the ≥ 8 h sleep group (CAVI=9.6±1.3) than in the ＜6 h (CAVI=9.1±1.1) or 6-8 h (CAVI=9.1±1.2) groups (p＜0.001). After adjustment for age, sex, systolic blood pressure, current smoking status, body mass index, frequency of exercise, educational background, frailty, sleep medication, sleep quality, and nap duration, multivariable regression analysis demonstrated that the CAVI was significantly higher in the ≥ 8 h group than in the 6-8 h group (p=0.016). In contrast, multivariable regression analysis showed that there was no significant association between sleep quality and CAVI. CONCLUSIONS: A significant association was noted between long sleep duration (≥ 8 h) and elevated CAVI in community-dwelling older adults aged ≥ 65 years. We, therefore, suggest that long sleep duration, not sleep quality, is correlated with arterial stiffness in older adults.

Analysis of effects of acute hypovolemia on arterial stiffness in rabbits monitored with cardio-ankle vascular index.

Although elasticity of the conduit arteries is known to be contribute effective peripheral circulation via Windkessel effects, the relationship between changes in intra-aortic blood volume and conduit artery elasticity remains unknown. Here we assessed the effects of change in intra-aortic blood volume induced by blood removal and subsequent blood transfusion on arterial stiffness and the involvement of autonomic nervous activity using our established rabbit model in the presence or absence of the ganglion blocker hexamethonium (100 mg/kg). Blood removal at a rate of 1 mL/min gradually decreased the blood pressure and blood flow of the common carotid artery but increased a stiffness indicator the cardio-ankle vascular index, which was equally observed in the presence of hexamethonium. These results suggest that arterial stiffness acutely responds to changes in intra-aortic blood volume independent of autonomic nervous system modification.

Determining the Relationship between Triglycerides and Arterial Stiffness in Cardiovascular Risk Patients Without Low-Density Lipoprotein Cholesterol-Lowering Therapy.

Data examining the relationship between arterial stiffness and triglyceride (TG) and other cardiovascular risk factors have remained to be sparse.Of the 5,109 patients with any cardiovascular risk factors in the Cardiovascular Prognostic Coupling Study in Japan (the Coupling Registry), the data of 1,534 patients who had no history of cardiovascular disease and were without low-density lipoprotein cholesterol (LDL-C) -lowering therapy (average age 67.9 ± 12.0 years, 55% males) were analyzed. Arterial stiffness was evaluated using the cardio-ankle vascular index (CAVI). Among the clinical and behavioral cardiovascular risk factors, the significant factors that constituted the CAVI value were smoking, diabetes, lower high-density lipoprotein cholesterol, and higher TG. After adjustment for age, sex, and body mass index (BMI), only TG (odds ratio [OR] per 1 standard deviation, 1.26 [95% confidence interval, 1.12-1.44]) and diabetes (OR, 1.52 [1.22-1.90]) were found to be associated with a risk of higher CAVI (≥ 9.0). TG (C-statistic, 0.80 [0.78-0.82]; P = 0.040) and diabetes (C-statistic, 0.80 [0.78-0.82]; P = 0.038) significantly improved the discrimination of the risk of a higher CAVI beyond the model that included age, sex, and BMI.TG was associated with a risk of arterial stiffness, and its contribution was slight but almost the same as that of diabetes among patients who had cardiovascular risk without a history of cardiovascular disease and LDL-C-lowering therapy.

Assessment of cardio-ankle vascular index in patients with abdominal aortic aneurysm: An observational study.

OBJECTIVES: Arterial stiffness is associated with major adverse cardiovascular events. The aim of this study is to investigate arterial stiffness by cardio-ankle vascular index (CAVI) in patients with abdominal aortic aneurysm (AAA). METHODS: This observational and cross-sectional study involved 59 subjects with AAA and 32 healthy subjects. All subjects underwent ultrasonography examination. CAVI was measured by VaSera-1000 CAVI instrument. RESULTS: Mean abdominal aortic diameter of AAA patients and controls were 43.88 ± 9.28 mm and 20.43 ± 3.14 mm, consecutively. Baseline clinical characteristics of the patients and controls were similar for age, presence of hypertension, diabetes, dyslipidemia, coronary artery disease and smoking. Left ventricle ejection fraction and Left ventricle mass index (LVMI) were similar between groups. CAVI was significantly higher in patients with AAA than controls (9.74 ± 1.50 vs. 7.60 ± 1.07, p < 0.001). CAVI was positively correlated with AAA diameter (r = 0.461, p < 0.001) and negatively correlated with left ventricle ejection fraction (r= -0.254, p = 0.015). CAVI >8.3 had a sensitivity 89.8% and a specificity of 78.1% for predicting the presence of AAA in ROC analysis (area under curve = 0.897, 95%CI = 0.816-0.951, p < 0.001). CONCLUSION: CAVI is increased in patients with AAA. Increased arterial stiffness may be a mechanical link between AAA, coronary artery disease and peripheral artery disease or a common mechanism effects the arterial stiffness, coronary artery disease, peripheral artery disease and AAA. Therefore, CAVI may be used as a valuable marker for risk stratification for the development of AAA in susceptible patients.

Arterial stiffness measured by cardio-ankle vascular index in Korean women with polycystic ovary syndrome.

Many studies have reported an increased arterial stiffness using pulse wave velocity (PWV) in women with polycystic ovary syndrome (PCOS). However, PWV is essentially dependent on blood pressure (BP) at the time of measurement. The cardio-ankle vascular index (CAVI) is a relatively new index for measuring arterial stiffness, and its conspicuous feature is its independency from the BP at the time of measurement. The aim of this study was to evaluate arterial stiffness by CAVI in PCOS patients (n = 26) and in the age-matched controls (n = 59). The CAVI was measured by a single medical professional. The mean age of the women with PCOS was 33.3 (±6.6) years, and that of the matched controls was 33.1 (±5.9) years (p = .861). The mean CAVIs were similar between the patients and controls (6.49 ± 0.41 and 6.39 ± 0.65, respectively, p = .452). The CAVI increased linearly with age in both groups, but in the women with PCOS, CAVI showed relatively strong negative correlations with body mass index (BMI) in both the unadjusted (r = -0.537, p = .005) and adjusted models (r = -0.474, p = .003 after age and BMI adjustment and r = -0.604, p = .033 after age, BMI, sitting auscultatory systolic BP and square root hs-CRP adjustment). In conclusion, relatively young women with PCOS may not have increased arterial stiffness. A negative correlation between CAVI and BMI in women with PCOS requires further study to determine whether vascular adaptation to adiposity occurred in these women. Impact Statement What is already known on this subject? Increased arterial stiffness is one of the earliest adverse structural and functional alterations in blood vessels, potentially leading to later cardiovascular disease. Many studies have reported an increased arterial stiffness using pulse wave velocity (PWV) in women with polycystic ovary syndrome (PCOS). However, PWV is essentially dependent on blood pressure (BP) at the time of measurement. The cardio-ankle vascular index (CAVI) is a relatively new index for measuring arterial stiffness, and its conspicuous feature is its independency from the BP at the time of measurement. What do the results of this study add? The CAVIs were similar between the women with PCOS and the age-matched controls. The CAVI increased linearly with age in both groups, but in women with PCOS, CAVI showed a relatively strong negative correlation with the body mass index (BMI). What are the implications of these findings for clinical practice and/or further research? Relatively young women with PCOS may not have increased arterial stiffness. However, CAVI showed a negative correlation with BMI only in the women with PCOS, suggesting that adiposity itself is associated with the decreased arterial stiffness in these women. This finding requires a replication, and whether adaptation to the hemodynamic consequences of adiposity occurred in the PCOS patients remains to be established. Further longitudinal studies are needed to verify the relationships among vascular stiffness, adiposity and PCOS.