The Process of Plaque Rupture: The Role of Vasa Vasorum and Medial Smooth Muscle Contraction Monitored by the Cardio-Ankle Vascular Index.

A warning sign for impending cardiovascular events is not fully established. In the process of plaque rupture, the formation of vulnerable plaque is important, and oxidized cholesterols play an important role in its progression. Furthermore, the significance of vasa vasorum penetrating the medial smooth muscle layer and being rich in atheromatous lesions should be noted. The cardio-ankle vascular index (CAVI) is a new arterial stiffness index of the arterial tree from the origin of the aorta to the ankle. The CAVI reflects functional stiffness, in addition to structural stiffness. The rapid rise in the CAVI means medial smooth muscle cell contraction and strangling vasa vasorum. A rapid rise in the CAVI in people after a big earthquake, following a high frequency of cardiovascular events has been reported. There are several cases that showed a rapid rise in the CAVI a few weeks or months before suffering cardiovascular events. To explain these sequences of events, we proposed a hypothesis: a rapid rise in the CAVI means medial smooth muscle contraction, strangling vasa vasorum, leading to ischemia and the necrosis of vulnerable plaque, and then the plaque ruptures. In individuals having a high CAVI, further rapid rise in the CAVI might be a warning sign for impending cardiovascular events. In such cases, treatments to decrease the CAVI better be taken soon.

Rapid Rise in Cardio-Ankle Vascular Index as a Predictor of Impending Cardiovascular Events -Smooth Muscle Cell Contraction Hypothesis for Plaque Rupture.

Predictive factors for vascular events have not been established. The vasculature of the atheroma is supplied by penetration of the vasa vasorum through the smooth muscle cell layer from the adventitia. Smooth muscle cell contraction induces compression of the vasa vasorum, resulting in ischemia in intimal atheromatous lesions. Cardio-ankle vascular index (CAVI) has become known as an index of arterial stiffness of the arterial tree from the origin of the aorta to the ankle. CAVI reflects the progress of arteriosclerosis, and a rapid rise in CAVI indicates arterial smooth muscle cell contraction. We hypothesized that rapidly increased arterial stiffness evaluated by CAVI may be a predictor of impending cardiovascular events.

Relationships Between Arterial Pressure-Volume Index and Cardiovascular Disease Biomarkers in Patients With Hypertension.

Background: The arterial pressure-volume index (API), which is obtained by conventional blood pressure measurement, is a new marker for arterial stiffness. The aim of this study was to clarify the relationships between the API and various clinical parameters, including cardiovascular disease (CVD) biomarkers, in patients with hypertension for the prevention of CVD. Methods: This cross-sectional study enrolled 288 patients with hypertension receiving pharmacological treatment, without a history of CVD (males/females: 115/173; age: 63 ± 11 years (mean ± standard deviation)). The API was automatically calculated using a commercial device. Results: The API was significantly correlated with important CVD biomarkers, such as the concentration of urinary albumin (r = 0.42, P < 0.001), high-sensitivity troponin T (r = 0.39, P < 0.001), and skin autofluorescence (marker of advanced glycation end products in tissues) (r = 0.41, P < 0.001). Multiple regression analyses demonstrated that when the API was used as a subordinate factor, these biomarkers were independent variables. According to the receiver operating characteristic curve analysis, an API of > 26 is the optimal cut-off point for determining albuminuria as ≥ 30 mg/g Cr, high high-sensitivity cardiac troponin T concentration as ≥ 0.014 ng/mL, or high skin autofluorescence as ≥ 3.0 arbitrary unit (area under the curve = 0.703, 0.702, and 0.704; and P < 0.001, respectively). Conclusion: This investigation demonstrates that API had an independent relationship with relevant CVD biomarkers, such as urinary albumin, high-sensitivity troponin T, and skin autofluorescence. Additionally, the outcomes of receiver operating characteristic curve analysis are presented as values that an API > 26 defines for these biomarkers linked with the formation of CVD.

Clinical Significance of the Cardio-Ankle Vascular Index in Postmenopausal Women With Hypercholesterolemia.

BACKGROUND: The cardio-ankle vascular index (CAVI) is a physiological indicator of arterial elasticity. However, limited information regarding the clinical significance of the CAVI in patients with hypercholesterolemia is available. This cross-sectional study aimed to elucidate the clinical significance of the CAVI for the primary prevention of cardiovascular disease (CVD) among postmenopausal women with hypercholesterolemia. METHODS: A total of 168 untreated postmenopausal hypercholesterolemic women (low-density lipoprotein cholesterol levels ≥ 140 mg/dL, mean age ± standard deviation, 63 ± 10 years) with no history of CVD events were enrolled. The CAVI was measured using commercial devices, after which, its relationships with various clinical parameters, such as carotid artery ultrasonography findings and CVD biomarkers, were examined. RESULTS: A significant positive correlation was observed between the CAVI and maximum intima-media thickness of the common carotid artery (max-C-IMT), which was evaluated using carotid artery ultrasonography (r = 0.49, P < 0.001). Regarding CVD biomarkers, the CAVI was significantly correlated with estimated glomerular filtration rate (r = -0.18, P < 0.001), high-sensitivity C-reactive protein (r = 0.36, P < 0.001), whole blood passage time as a marker of blood rheology (r = 0.41, P < 0.001), and skin autofluorescence as a marker of advanced glycation end products in tissues (r = 0.46, P < 0.001), although no significant correlation was noted between serum lipid parameters and the CAVI. Multiple regression analysis identified max-C-IMT (ß = 0.35, P < 0.001), whole blood passage time (ß = 0.18, P = 0.007), skin autofluorescence (ß = 0.17, P = 0.011), and age (ß = 0.16, P = 0.018) as variables independently associated with CAVI. CONCLUSION: The present study indicated that the CAVI is an essential CVD risk factor among postmenopausal women with hypercholesterolemia. Moreover, impaired blood rheology and increase of skin autofluorescence were associated with elevated CAVI in such patients.

Skin Autofluorescence as a Predictor of First Heart Failure Hospitalization in Patients With Heart Failure With Preserved Ejection Fraction.

BACKGROUND: An autofluorescence (AF) reader can be used to diagnose skin AF non-invasively by measuring local accumulation of advanced glycation end-products. A number of studies have investigated the relationships between skin AF and cardiovascular disease. However, data regarding the usefulness of skin AF as a predictor of chronic heart failure remain limited. This prospective study aimed to elucidate the usefulness of skin AF as a predictor of first heart failure (HF) hospitalization in patients with HF with preserved ejection fraction (HFpEF). METHODS: A total of 412 outpatients with HFpEF with no history of HF hospitalization were enrolled. Patients were assigned to either the low (group L; skin AF ≤ 2.9 arbitrary units (AU); n = 303) or the high (group H; skin AF ≥ 3.0 AU; n = 109) group according to optimal skin AF cut-off levels determined using receiver operating characteristic curves. Clinical parameters and the usefulness of skin AF as a predictor of first HF hospitalization were evaluated. RESULTS: The E/e' ratio as a marker of left ventricular diastolic function was significantly higher in group H patients than in group L patients at baseline (group H, 11.8 ± 3.8; group L, 10.6 ± 3.3; P = 0.002). During the 72.7-month follow-up period, 43 HF cases were hospitalized (group L, 15 cases; group H, 28 cases; P < 0.001, log-rank test). Multivariate Cox regression analyses revealed that group H exhibited a significantly higher risk of first HF hospitalization than did group L (hazard ratio, 2.26; 95% confidence interval, 1.21 - 3.52; P = 0.014). CONCLUSIONS: The present study demonstrated that skin AF can predict the risk of first HF hospitalization in patients with HFpEF. Prospective studies, including intervention therapies, are required to validate our observations.

Correlation Between the Cardio-Ankle Vascular Index and Renal Resistive Index in Patients With Essential Hypertension.

BACKGROUND: Renal resistive index (RRI) is a parameter determined by Doppler sonography that reflects renal hemodynamics. Significant relationships connecting increases in the RRI with cardiovascular risk factors and the incidence of cardiovascular disease in hypertensive patients have been reported. This cross-sectional study aimed to clarify the relationship between cardio-ankle vascular index (CAVI), a novel marker of arterial stiffness, and the RRI in patients with essential hypertension with the goal of primary prevention of cardiovascular disease. METHODS: The study included 245 patients undergoing treatment for essential hypertension (95 men and 150 women; mean age ± standard deviation, 65 ± 13 years) with no history of cardiovascular disease. The CAVI and RRI were measured using commercial devices, and their relationships to various clinical parameters were examined. RESULTS: A significant positive correlation was observed between the CAVI and RRI (r = 0.43, P < 0.001). Multiple regression analyses revealed a value of ß of 0.28 (P < 0.001) when CAVI was evaluated as the independent and RRI as the dependent variable. Receiver-operating characteristic curve analysis indicated that the CAVI cutoff point for high RRI (> 0.70) was 9.0 with area under the curve of 0.700 (P < 0.001). CONCLUSION: The results from this study indicate that the CAVI varies directly with measures of renal vascular hemodynamics (RRI) in patients with essential hypertension. These findings identified a cardiovascular risk value of the CAVI from the perspective of renal hemodynamics as 9.0 in this patient population.

Relationships Between the Cardio-Ankle Vascular Index and Pulsatility Index of the Common Carotid Artery in Patients With Cardiovascular Risk Factors.

BACKGROUND: Pulsatility index (PI) is a hemodynamic parameter determined using Doppler sonography; it reflects the degree of peripheral vascular resistance. Moreover, researchers have reported significant relationships between an increase in the PI of the common carotid artery (CCA) and ischemic stroke. This cross-sectional study aimed to clarify the relationships between cardio-ankle vascular index (CAVI) as a marker of arterial stiffness and the PI of the CCA in patients with cardiovascular risk factors for the primary prevention of ischemic stroke. METHODS: A total of 405 outpatients undergoing treatment for cardiovascular risk factors (152 men and 253 women; mean age ± standard deviation, 64 ± 9 years) with no history of cardiovascular events, including ischemic stroke, were enrolled. The CAVI and the PI of the CCA were measured using commercial devices, and their relationships to various clinical parameters were examined. RESULTS: A significant positive correlation was observed between the CAVI and the PI of the CCA (r = 0.44, P < 0.001). Further, multiple regression analysis revealed that the CAVI (ß = 0.19, P < 0.001) was selected as independent factor for PI of the CCA as a subordinate factor. Meanwhile, high-sensitivity C-reactive protein, as an inflammation marker, and skin autofluorescence, as a marker of advanced glycation end products in the tissues, were selected as independent variables for either the CAVI or the PI of the CCA as a subordinate factor. The receiver-operating characteristic curve analysis indicated that the cut-off point of the CAVI for high PI of the CCA (> 1.60) as a risk value of stroke incidence by previous report was 9.1 (area under the curve = 0.750, P < 0.001). CONCLUSION: The present results indicate that the CAVI reflects cerebrovascular resistance in patients with cardiovascular risk factors. Moreover, the risk value of the CAVI for ischemic stroke incidence was considered to be 9.1 in these patients.

Clinical Significance of Arterial Velocity Pulse Index in Patients With Stage B Heart Failure With Preserved Ejection Fraction.

BACKGROUND: In clinical settings, the arterial velocity pulse index (AVI) is explored as a novel marker of atherosclerosis using pulse wave analysis; however, data regarding the correlations between AVI and heart failure (HF) are limited. This study aimed to elucidate the clinical significance of AVI in patients with stage B HF with preserved ejection fraction (HFpEF). METHODS: In this cross-sectional study, 345 patients with stage B HFpEF (no symptoms despite evidence of cardiac structural or functional impairment, and left ventricular ejection fraction which is estimated by echocardiography ≥ 50%) were enrolled. Patients with a history of HF hospitalization were excluded. The AVI was measured using a commercial device, and associations between AVI and various clinical parameters were examined. RESULTS: Significant correlations between AVI and various clinical parameters, such as E/e' as a maker of left ventricular diastolic function (r = 0.35; P < 0.001), high-sensitivity cardiac troponin T levels as a marker of myocardial injury (r = 0.47; P < 0.001), reactive oxygen metabolite levels as an oxidative stress marker (r = 0.31; P < 0.001), urinary albumin concentration as a marker of kidney function (r = 0.34; P < 0.001) and calf circumference as a marker of muscle mass volume (r = -0.42; P < 0.001) were observed. Furthermore, multiple regression analyses revealed that these clinical parameters were selected as independent variables when AVI was used as a subordinate factor. CONCLUSIONS: This study shows that AVI might be a determining factor for prognosis in patients with stage B HFpEF. Nevertheless, further comprehensive prospective studies, including intervention therapies, are warranted to validate the findings of this study.

Relationships Between Skin Autofluorescence and Cardio-Ankle Vascular Index in Japanese Male Patients With Metabolic Syndrome.

BACKGROUND: An autofluorescence (AF) reader can be used to noninvasively measure tissues that accumulated advanced glycation end-products to diagnose skin AF. This study aimed to clarify the clinical significance of skin AF as a risk factor for cardiovascular disease in Japanese male patients with metabolic syndrome using the cardio-ankle vascular index (CAVI) as a marker of arterial function. METHODS: This cross-sectional study enrolled 261 Japanese male patients with metabolic syndrome without history of cardiovascular disease (mean age, 58 ± 7 years (mean ± standard deviation)). Associations between skin AF and various clinical parameters including CAVI were examined. RESULTS: Skin AF was significantly positively correlated with CAVI (r = 0.40, P < 0.001). Furthermore, multiple regression analyses revealed that skin AF (ß = 0.18, P = 0.002) was selected as an independent subordinate factor for CAVI. Meanwhile, homeostatic model assessment of insulin resistance (HOMA-IR) as a marker of insulin resistance, smoking habits and high-sensitivity C-reactive protein as an inflammation marker were independent variables for either CAVI or skin AF as a subordinate factor. According to the receiver-operating characteristic curve analysis and results of previous reports that determined CAVI of ≥ 9.0 as a diagnostic criterion for vascular failure, skin AF of > 2.7 arbitrary unit is the optimal cut-off point for discriminating high CAVI (area under the curve = 0.718, P < 0.001). CONCLUSION: Findings in this study indicate that skin AF may be an important risk factor of cardiovascular disease in Japanese male patients with metabolic syndrome. In addition, the risk value of skin AF was considered as higher than 2.7 arbitrary unit. Further investigations in a large number of prospective studies, including intervention therapies, are required to validate the results in this study.

Clinical Significance of Skin Autofluorescence in Elderly Patients With Long-Standing Persistent Atrial Fibrillation.

BACKGROUND: Recent clinical studies have demonstrated the importance of skin autofluorescence as a cardiovascular risk factor. However, data regarding the relationship between skin autofluorescence and atrial fibrillation are limited. The aim of this study was to clarify the clinical significance of skin autofluorescence in elderly patients with long-standing persistent atrial fibrillation. METHODS: This cross-sectional study enrolled 112 elderly patients with long-standing persistent atrial fibrillation who were treated medically (46 men and 66 women; mean age, 81 ± 9 years). The association between skin autofluorescence and various clinical parameters was examined. RESULTS: Significant relationships were observed between skin autofluorescence and CHADS2 score (r = 0.53, P < 0.001), high-sensitivity cardiac troponin T level (r = 0.43, P < 0.001), reactive oxygen metabolite levels (r = 0.52, P < 0.001), and whole blood passage time (r = 0.45, P < 0.001). Furthermore, multiple regression analyses showed that these clinical parameters were independent variables when skin autofluorescence was used as a subordinate factor. Receiver-operating characteristic curve analysis indicated that the risk values of skin autofluorescence for high CHADS2 scores (≥ 2) or elevated high-sensitivity cardiac troponin T levels (> 0.014ng/mL) were 2.6 arbitrary units (AU) and 2.7 AU, respectively. CONCLUSIONS: The findings of this study indicated that skin autofluorescence may be a prognostic factor in elderly patients with long-standing persistent atrial fibrillation. The risk value of skin autofluorescence was considered as 2.6 AU or 2.7 AU.

Clinical Significance of Low Blood Testosterone Concentration in Men as a Cardiovascular Risk Factor From the Perspective of Blood Rheology.

BACKGROUND: Recent clinical studies have indicated the importance of low blood testosterone concentration or whole blood passage time (WBPT) which reflects blood rheology as a cardiovascular risk factor. On the contrary, there are no reports regarding the association of blood testosterone concentrations and WBPT. This cross-sectional study aimed to elucidate the clinical significance of low blood testosterone concentration in men as a cardiovascular risk factor from the perspective of blood rheology using WBPT. METHODS: In total, 382 male patients with traditional cardiovascular risk factor and no history of cardiovascular disease (age (mean ± standard deviation (SD)), 64 ± 10 years) were enrolled. Serum total testosterone concentration (T-T) was measured as a marker of testosterone level in vivo, and WBPT was also measured using microchannel array flow analyzer as a commercial device. The relationship between T-T and WBPT was evaluated. RESULTS: There was a significantly negative correlation between T-T and WBPT (r = -0.45; P < 0.001). Furthermore, multiple regression analysis revealed that T-T (ß = -0.25; P < 0.001) could be selected as an independent variable when WBPT was used as a subordinate factor. According to receiver operating characteristic curve analysis and the result of the previous report that determined WBPT of > 72.4 s as a risk for incidence of primary cardiovascular disease, T-T of < 551.4 ng/dL is the optimal cut-off point for discriminating high WBPT. CONCLUSIONS: The study results showed that T-T is independently and inversely associated with WBPT in male patients with traditional cardiovascular risk factor and no history of cardiovascular disease. In addition, this study suggests that the incidence of primary cardiovascular events can be prevented by maintaining T-T at approximately ≥ 550 ng/dL from the perspective of blood rheology.

Clinical Impact of Blood Testosterone Concentration on Cardio-Ankle Vascular Index in Female Patients With Type 2 Diabetes Mellitus.

BACKGROUND: Information regarding testosterone as a significant risk factor of cardiovascular disease (CVD) in female patients with type 2 diabetes mellitus (DM) is limited. However, some clinical studies reported the importance of cardio-ankle vascular index (CAVI) as a novel physiological marker of arterial function in type 2 DM. This cross-sectional study aimed to elucidate the clinical effects of blood testosterone concentration on CAVI in female patients with type 2 DM. METHODS: A total of 238 postmenopausal patients including 97 with a history of CVD with type 2 DM (age (mean ± standard deviation (SD)), 73 ± 9 years) were enrolled. CAVI was measured according to the standard technique, and serum total testosterone concentration (T-T) was also measured as a testosterone level marker in vivo. The relationship between CAVI and T-T was evaluated. RESULTS: CAVI is significantly higher (CVD vs. non-CVD: 10.2 ± 1.2 vs. 9.2 ± 1.0, P < 0.001), and log-T-T significantly lower (CVD vs. non-CVD: 1.2 ± 0.2 ng/dL vs. 1.5 ± 0.2 ng/dL, P < 0.001) in patients with CVD than those without CVD. CAVI was significantly negatively correlated with log-T-T (r = -0.41; P < 0.001). Furthermore, multiple regression analysis indicated that CVD (ß = 0.23; P < 0.001) and log-T-T (ß = -0.18; P < 0.01) were selected as independent subordinate variables for CAVI. CONCLUSIONS: This study showed that T-T was independently inversely associated with CAVI, indicating that low testosterone concentration is a considerable risk factor for the progression of arterial dysfunction in female patients with type 2 DM.

Clinical Usefulness of the Cardio-Ankle Vascular Index as a Predictor of Primary Cardiovascular Events in Patients With Chronic Kidney Disease.

BACKGROUND: The cardio-ankle vascular index (CAVI) is a physiologic marker reflecting arterial function. There have been no prospective studies investigating the relationship between CAVI and cardiovascular events in patients with chronic kidney disease (CKD). The aim of this prospective study was to assess the clinical usefulness of CAVI as a predictor of primary cardiovascular events in patients with CKD. METHODS: The study enrolled 460 outpatients with CKD but no history of cardiovascular disease (152 men and 308 women; mean ± standard deviation age, 74 ± 12 years). Patients were assigned to one of three groups: low (L, CAVI < 9; n = 100), medium (M, CAVI 9 - 10; n = 199), or high (H, CAVI > 10; n = 161). The utility of the CAVI as a predictor of primary cardiovascular events was evaluated. RESULTS: During the follow-up period (median 60.1 months), major adverse cardiovascular events (MACE) occurred in 91 cases (L, 8 (8.0%); M, 31 (15.6%); H, 52 (32.3%); P < 0.001, log-rank test). On multivariate Cox regression analysis, the risk for a MACE was significantly higher in group H than in non-group H (hazard ratio, 2.04; 95% confidence interval, 1.31 - 3.02; P < 0.01). A CAVI cut-off of 9.7 yielded the largest area under the curve, 0.701 (95% confidence interval: 0.657 - 0.743, P < 0.001), indicating a sensitivity of 74.0% and a specificity of 59.6% for discriminating between those who did and did not experience a MACE during follow-up. CONCLUSIONS: The results of this study showed that a high CAVI is a predictor of primary cardiovascular events in patients with CKD.

Clinical Impact of Hemorheology on Subclinical Myocardial Injury in Patients with Hypertension.

BACKGROUND: The blood concentration of high-sensitivity cardiac troponin T (hs-cTnT) is a useful biomarker for myocardial injury or the pathogenesis of hypertension. Little is known about the relationship between hemorheology and myocardial injury in patients with hypertension. This cross-sectional study aimed to clarify the clinical impact of hemorheology on subclinical myocardial injury assessed with a microchannel array flow analyzer (MC-FAN) and its impact on hs-cTnT in patients with hypertension. METHODS: A total of 447 outpatients (men: 181; women: 266; mean age: 65 ± 13 years), with no history of cardiovascular disease, including admission for heart failure, who were undergoing treatment for hypertension, were enrolled. Whole blood passage time (WBPT) as a marker of hemorheology was measured with a MC-FAN, and the relationship between hs-cTnT levels and various clinical parameters, including WBPT, was examined. RESULTS: hs-cTnT levels were detected in 400 patients (89.5%). WBPT was significantly higher in patients with detectable hs-cTnT levels than in those with undetectable hs-cTnT levels (60.5 ± 16.8 s versus 50.2 ± 14.2 s, P < 0.001). In patients with detectable hs-cTnT levels, there was a significant positive correlation between WBPT and hs-cTnT level (r = 0.33; P < 0.001). Multiple regression analysis revealed that WBPT was an independent variable when hs-cTnT was a subordinate factor (ß = 0.15; P < 0.01). Receiver-operating characteristic curve analysis indicated that a cutoff value for WBPT of 55.6 s yielded the largest area under the curve (0.744; P < 0.001) for discriminating high hs-cTnT levels as ≥ 0.014 ng/mL. CONCLUSION: The results indicate that WBPT is independently associated with hs-cTnT in hypertensive patients with no history of cardiovascular events, suggesting that impairment of hemorheology in small cardiac vessels causes subclinical myocardial injury. In addition, the study suggests that progression of myocardial injury can be prevented by maintaining WBPT at approximately ≤ 55 s.

Usefulness of the Whole Blood Passage Time as a Predictor of Primary Cardiovascular Events in Patients With Traditional Cardiovascular Risk Factors.

BACKGROUND: Recent clinical studies have reported that impaired hemorheology is a significant cardiovascular risk factor, but there has been no prospective study of its relationship with cardiovascular events. The aim of this prospective study was to assess the efficacy of whole blood passage time (WBPT), measured by a microchannel array flow analyzer (MC-FAN), as a predictor of primary cardiovascular events in patients with traditional cardiovascular risk factors. METHODS: The study enrolled 1,134 outpatients with traditional cardiovascular risk factors but no history of cardiovascular events (438 men and 696 women; mean ± standard deviation age, 67 ± 11 years). Based on the value of WBPT, the patients were assigned to one of three groups: L (low, WBPT < 50 s; n = 499), M (medium, WBPT 50 - 70 s; n = 295), or H (high, WBPT > 70 s; n = 340). The utility of the WBPT as a predictor of primary cardiovascular events was evaluated. RESULTS: During the follow-up period (median 81.9 months), major adverse cardiovascular events (MACE) occurred in 95 cases (L, 21 cases (4.2%); M, 24 cases (8.1%); H, 50 cases (14.7%); P < 0.001, log-rank test). In multivariate Cox regression analyses, the risk for MACE was significantly higher in group H than in group L (hazard ratio, 2.32; 95% confidence interval, 1.31 - 3.20; P < 0.01). A WBPT cut-off of 72.4 s yielded the largest area under the curve of 0.705 (95% confidence interval: 0.678 - 0.732), with a sensitivity of 51.7% and specificity of 85.4% for discriminating between those who did and did not experience MACE during the follow-up period. CONCLUSION: This study showed that WBPT evaluated by a MC-FAN was a predictor of primary cardiovascular events in patients with traditional cardiovascular risk factors.

Efficacy of the Reactive Oxygen Metabolite Test as a Predictor of Initial Heart Failure Hospitalization in Elderly Patients With Chronic Heart Failure.

BACKGROUND: The reactive oxygen metabolites (d-ROMs) test has recently been explored as a novel marker of oxidative stress in vivo and used in clinical settings. Conversely, data regarding the utility of the d-ROMs test as a predictor of patients with chronic heart failure (CHF) are limited. This prospective study aims to elucidate the efficacy of the d-ROMs test as a predictor of initial heart failure (HF) hospitalization in elderly patients with CHF. METHODS: A total of 428 elderly outpatients with CHF with no history of HF hospitalization (108 males, 320 females; mean age, 75 ± 7 years) were enrolled. Based on the median value of d-ROMs test levels (303 U.CARR), the patients were divided into the following two groups: group L (low d-ROMs test levels) and group H (high d-ROMs test levels). The utility of the d-ROMs test as a predictor of initial HF hospitalization was evaluated. RESULTS: During the 88.1-month follow-up period, 58 HF cases were hospitalized (group L, 17 cases; group H, 41 cases; P < 0.001, log-rank test). Multivariate Cox regression analyses revealed that group H exhibited a significantly higher risk for HF hospitalization than did group L (hazard ratio (HR), 2.35; 95% confidence interval (CI), 1.37 - 4.43; P < 0.01). Furthermore, the HR (vs. group L with low brain natriuretic peptide (BNP) levels (< 200 pg/mL), HR, 9.18; 95% CI, 4.78 - 22.94; P < 0.001) for the incidence of HF hospitalization increased in group H with high BNP levels (≥ 200 pg/mL). CONCLUSIONS: The present study demonstrates that high d-ROMs test levels predict initial HF hospitalization in elderly patients with CHF. In addition, the predictive value for the incidence of HF hospitalization increases by using a combination of two biomarkers as d-ROMs test and BNP levels.

Clinical Significance of Skin Autofluorescence in Patients With Type 2 Diabetes Mellitus With Chronic Heart Failure.

BACKGROUND: Recent clinical studies have shown that skin autofluorescence (AF) levels are significantly associated with diabetic complications. In contrast, data regarding the relationships between skin AF and chronic heart failure (CHF) are limited. The aim of this study was to clarify the clinical significance of skin AF in patients with type 2 diabetes mellitus (DM) with CHF. METHODS: This cross-sectional study enrolled 257 outpatients with type 2 DM with CHF who were treated medically (96 men and 161 women; mean age, 79 ± 7 years). Associations between skin AF and various clinical parameters were examined. RESULTS: Incidence of skin AF in patients with a history of hospitalization due to HF was significantly higher than in those without a history of hospitalization due to HF (3.0 ± 0.5 AU vs. 2.7 ± 0.5 AU, respectively, P < 0.001). Significant positive correlations were found between skin AF and various clinical parameters, such as E/e' as a maker of left ventricular diastolic function (r = 0.30, P < 0.001), high-sensitivity cardiac troponin T levels as a marker of myocardial injury (r = 0.45, P < 0.001), reactive oxygen metabolite levels as an oxidative stress marker (r = 0.31, P < 0.001), and cardio-ankle vascular index as a marker of arterial function (r = 0.38, P < 0.001). Furthermore, multiple regression analyses showed that these clinical parameters (E/e' (ß = 0.25, P < 0.001)), high-sensitivity cardiac troponin T levels (ß = 0.30, P < 0.001), cardio-ankle vascular index (ß = 0.21, P < 0.001), reactive oxygen metabolite levels (ß = 0.15, P < 0.01), and a history of hospitalization due to HF (ß = 0.23, P < 0.001) were independent variables when skin AF was used as a subordinate factor. CONCLUSION: The findings of this study showed that skin AF may be a determining factor for prognosis in patients with type 2 DM with CHF. Further investigations in a large prospective study, including intervention therapies, are required to validate the results of this study.

Clinical Significance of Cardio-Ankle Vascular Index as a Cardiovascular Risk Factor in Elderly Patients With Type 2 Diabetes Mellitus.

BACKGROUND: The cardio-ankle vascular index (CAVI) is a novel physiological marker of atherosclerosis that reflects systemic arterial stiffness. The aim of this study was to clarify the clinical significance of CAVI as a risk factor for cardiovascular diseases (CVDs) in elderly patients with type 2 diabetes mellitus. METHODS: This cross-sectional study enrolled 216 elderly (≥ 65 years) outpatients with type 2 diabetes mellitus who were undergoing antidiabetic treatment (96 males and 120 females; mean age, 75 ± 7 years (mean ± standard deviation)). Associations between CAVI and various clinical parameters were examined. RESULTS: CAVI was significantly higher in patients with a history of CVD than in those without a history of CVD (10.4 ± 1.4 vs. 9.5 ± 1.0, respectively, P < 0.001). There were significantly positive correlations between CAVI and various clinical parameters, such as skin autofluorescence (r = 0.47, P < 0.001), high-sensitivity cardiac troponin T levels (r = 0.39, P < 0.001), and reactive oxygen metabolite levels (r = 0.28, P < 0.001). Furthermore, multiple regression analyses revealed that these clinical parameters ((skin autofluorescence (ß = 0.30, P < 0.001), high-sensitivity cardiac troponin T levels (ß = 0.18, P < 0.001), reactive oxygen metabolite levels (ß = 0.15, P < 0.01), and a history of CVD (ß = 0.19, P < 0.001)) were independent variables when CAVI was used as a subordinate factor. CONCLUSION: Findings of this study indicate that CAVI may be an important CVD risk factor in elderly patients with type 2 diabetes mellitus. Further investigations in a large number of prospective studies, including intervention therapies, are required to validate our results.

Relationships between the arterial velocity pulse index as a novel marker of atherosclerosis and biomarkers of cardiac or renal condition in patients with type 2 diabetes mellitus.

BACKGROUND: The arterial velocity pulse index (AVI) has been explored as a novel marker of atherosclerosis using pulse wave analysis in the clinical setting. The aim of this study was to clarify the relationships between the AVI and biomarkers of cardiac or renal condition in patients with type 2 diabetes mellitus. METHODS: In total, 301 outpatients with type 2 diabetes mellitus (116 males and 185 females; mean age ± standard deviation: 63 ± 12 years) without a history of cardiovascular events were enrolled in this study. The AVI and biomarkers of cardiac or renal condition were measured using a commercial device, and the relationships between the AVI and the biomarkers were examined. RESULTS: The AVI was significantly associated with biomarkers of cardiac condition such as the blood levels of brain natriuretic peptide (r = 0.29, P < 0.001) and high-sensitivity cardiac troponin T (hs-cTnT) (r = 0.48, P < 0.001). The AVI was also significantly associated with biomarkers of renal condition such as the estimated glomerular filtration rate (r = -0.22, P < 0.001) and urinary albumin excretion (r = 0.42, P < 0.001). Multiple regression analysis revealed that hs-cTnT and urinary albumin excretion were independent variables that were correlated with the AVI when it was used as a subordinate factor. CONCLUSION: The results of this study indicate that the AVI is significantly associated with hs-cTnT and urinary albumin excretion in patients with type 2 diabetes mellitus.

Clinical impact of skin autofluorescence on high-sensitivity troponin T in hypertensive patients.

BACKGROUND: Recent studies have reported the importance of high-sensitivity troponin T (hs-cTnT) or skin autofluorescence (AF) as a cardiovascular risk factor. However, little is known about the relationship between these two markers. The aim of this study was to clarify the clinical impact of skin AF on hs-cTnT in hypertensive patients, from the perspective of primary prevention of cardiovascular events. METHODS: In total, 457 outpatients on treatment for hypertension [182 men and 275 women; mean (± SD) age, 67 ± 13 y] and with no history of cardiovascular events were enrolled. Hs-cTnT levels and skin AF were measured using commercial devices, and relationships between hs-cTnT levels and various clinical parameters including skin AF were examined. RESULTS: Hs-cTnT was detected in 405 (88.6%) patients. Skin AF was significantly higher in patients with detectable hs-cTnT than in those without detectable hs-cTnT [2.6 ± 0.5 arbitrary units (AU) vs. 2.2 ± 0.5 AU, respectively, p < 0.001]. In patients with detectable hs-cTnT, there was a significantly positive correlation between skin AF and Log-hs-cTnT (r = 0.41, p < 0.001). Furthermore, multiple regression analysis revealed that skin AF was the strongest variable associated with Log-hs-cTnT as a subordinate factor (ß = 0.30, p < 0.001). CONCLUSIONS: The results of this study indicate that skin AF is an important determining factor for hs-cTnT elevation in hypertensive patients with no history of cardiovascular events.