Akira Yamashina

Comparison between carotid-femoral and brachial-ankle pulse wave velocity as measures of arterial stiffness

Background Arterial stiffness is an important risk factor for cardiovascular disease. Carotid-femoral pulse wave velocity (cfPWV) is the most recognized and established index of arterial stiffness. An emerging automatic measure of PWV primarily used in the Asian countries is brachial-ankle PWV (baPWV). Method To systematically compare these two methodologies, we conducted a multicenter study involving a total of 2287 patients. Results There was a significant positive relation between baPWV and cfPWV (r = 0.73). Average baPWV was approximately 20% higher than cfPWV. Both cfPWV and baPWV were significantly and positively associated with age (r = 0.56 and 0.64), systolic blood pressure (r = 0.49 and 0.61), and the Framingham risk score (r = 0.48 and 0.63). The areas under the receiver operating curves (ROCs) of PWV to predict the presence of both stroke and coronary artery disease were comparable between cfPWV and baPWV. Conclusion Collectively, these results indicate that cfPWV and baPWV are indices of arterial stiffness that exhibit similar extent of associations with cardiovascular disease risk factors and clinical events.

The role of vascular biomarkers for primary and secondary prevention. A position paper from the European Society of Cardiology Working Group on peripheral circulation: Endorsed by the Association for Research into Arterial Structure and Physiology (ARTERY) Society

While risk scores are invaluable tools for adapted preventive strategies, a significant gap exists between predicted and actual event rates. Additional tools to further stratify the risk of patients at an individual level are biomarkers. A surrogate endpoint is a biomarker that is intended as a substitute for a clinical endpoint. In order to be considered as a surrogate endpoint of cardiovascular events, a biomarker should satisfy several criteria, such as proof of concept, prospective validation, incremental value, clinical utility, clinical outcomes, cost-effectiveness, ease of use, methodological consensus, and reference values. We scrutinized the role of peripheral (i.e. not related to coronary circulation) noninvasive vascular biomarkers for primary and secondary cardiovascular disease prevention. Most of the biomarkers examined fit within the concept of early vascular aging. Biomarkers that fulfill most of the criteria and, therefore, are close to being considered a clinical surrogate endpoint are carotid ultrasonography, ankle-brachial index and carotid-femoral pulse wave velocity; biomarkers that fulfill some, but not all of the criteria are brachial ankle pulse wave velocity, central haemodynamics/wave reflections and C-reactive protein; biomarkers that do no not at present fulfill essential criteria are flow-mediated dilation, endothelial peripheral arterial tonometry, oxidized LDL and dysfunctional HDL. Nevertheless, it is still unclear whether a specific vascular biomarker is overly superior. A prospective study in which all vascular biomarkers are measured is still lacking. In selected cases, the combined assessment of more than one biomarker may be required.

Relationship between Radial and Central Arterial Pulse Wave and Evaluation of Central Aortic Pressure Using the Radial Arterial Pulse Wave

Since a decrease of central aortic pressure contributes to the prevention of cardiovascular events, simple measurement of not only brachial blood pressure but also central aortic pressure may be useful in the prevention and treatment of cardiovascular diseases. In this study, we simultaneously measured radial artery pulse waves non-invasively and ascending aortic pressure invasively, before and after the administration of nicorandil. We then compared changes in central aortic pressure and radial arterial blood pressure calibrated with brachial blood pressure in addition to calculating the augmentation index (AI) at the aorta and radial artery. After nicorandil administration, the reduction in maximal systolic blood pressure in the aorta (Δa-SBP) was −14±15 mmHg, significantly larger than that in early systolic pressure in the radial artery (Δr-SBP) (−9±12 mmHg). The reduction in late systolic blood pressure in the radial artery (Δr-SBP2) was −15±14 mmHg, significantly larger than Δr-SBP, but not significantly different from Δa-SBP. There were significant relationships between Δa-SBP and Δr-SBP (r=0.81, p<0.001), and between Δa-SBP and Δr-SBP2 (r=0.91, p<0.001). The slope of the correlation regression line with Δr-SBP2 (0.83) was larger and closer to 1 than that with Δr-SBP (0.63), showing that the relationship was close to 1:1. Significant correlations were obtained between aortic AI (a-AI) and radial AI (r-AI) (before nicorandil administration: r=0.91, p<0.001; after administration: r=0.70, p<0.001). These data suggest that the measurement of radial artery pulse wave and observation of changes in the late systolic blood pressure in the radial artery (r-SBP2) in addition to the ordinary measurement of brachial blood pressure may enable a more accurate evaluation of changes in maximal systolic blood pressure in the aorta (a-SBP).

Delayed contrast enhancement of MRI in hypertrophic cardiomyopathy

Fibrotic lesions in the myocardium exhibit delayed contrast enhancement (DCE) on MR images. On the other hand, plexiform fibrosis is observed in hypertrophic cardiomyopathy (HCM), indicating an association of this condition with the pathogenesis of heart failure and arrhythmia. To examine the occurrence and extent of DCE and its relation to cardiac function and arrhythmia in HCM, we studied 59 patients with HCM who had undergone MRI. The relationship of DCE to cardiac function and arrhythmia was further investigated. DCE occurred in 45 (76.3%) of the 59 patients with HCM, with a high frequency of localization in regions, where the right ventricle is attached. As for the relationship of DCE to cardiac function, a significant decrease (P=0.007) in cardiac function was observed in the group in which 4 or more segments exhibited DCE, compared with the group in which DCE was observed in 3 or less segments. Regarding the relationship of DCE to arrhythmia, both the occurrence of DCE and the extent of DCE were significantly larger (p<0.05, p=0.026, respectively) in the group with VT. These results indicate that DCE may save to identify severe cases of HCM on the basis of cardiac function, arrhythmia, and pathophysiological aspects.

Effect of Flow-Triggered Adaptive Servo-Ventilation Compared With Continuous Positive Airway Pressure in Patients With Chronic Heart Failure With Coexisting Obstructive Sleep Apnea and Cheyne-Stokes Respiration

Background—In patients with chronic heart failure (CHF), the presence of sleep-disordered breathing, including either obstructive sleep apnea or Cheyne-Stokes respiration-central sleep apnea, is associated with a poor prognosis. A large-scale clinical trial showed that continuous positive airway pressure (CPAP) did not improve the prognosis of such patients with CHF, probably because of insufficient sleep-disordered breathing suppression. Recently, it was reported that adaptive servo-ventilation (ASV) can effectively treat sleep-disordered breathing. However, there are no specific data about the efficacy of flow-triggered ASV for cardiac function in patients with CHF with sleep-disordered breathing. The aim of this study was to compare the efficacy of flow-triggered ASV to CPAP in patients with CHF with coexisting obstructive sleep apnea and Cheyne-Stokes respiration-central sleep apnea. Methods and Results—Thirty-one patients with CHF, defined as left ventricular ejection fraction <50% and New York Heart Association class ≥II, with coexisting obstructive sleep apnea and Cheyne-Stokes respiration-central sleep apnea, were randomly assigned to either CPAP or flow-triggered ASV. The suppression of respiratory events, changes in cardiac function, and compliance with the devices during the 3-month study period were compared. Although both devices decreased respiratory events, ASV more effectively suppressed respiratory events (&Dgr;AHI [apnea-hypopnea index], −35.4±19.5 with ASV; −23.2±12.0 with CPAP, P<0.05). Compliance was significantly greater with ASV than with CPAP (5.2±0.9 versus 4.4±1.1 h/night, P<0.05). The improvements in quality-of-life and left ventricular ejection fraction were greater in the ASV group (&Dgr;LVEF [left ventricular ejection fraction], +9.1±4.7% versus +1.9±10.9%). Conclusions—These results suggest that patients with coexisting obstructive sleep apnea and Cheyne-Stokes respiration-central sleep apnea may receive greater benefit from treatment with ASV than with CPAP.

Effect of Flow-triggered Adaptive Servo-ventilation Compared with Continuous Positive Airway Pressure in Chronic Heart Failure Patients with Coexisting Obstructive Sleep Apnea and Cheyne-Stokes Respiration

Background—In patients with chronic heart failure (CHF), the presence of sleep-disordered breathing, including either obstructive sleep apnea or Cheyne-Stokes respiration-central sleep apnea, is associated with a poor prognosis. A large-scale clinical trial showed that continuous positive airway pressure (CPAP) did not improve the prognosis of such patients with CHF, probably because of insufficient sleep-disordered breathing suppression. Recently, it was reported that adaptive servo-ventilation (ASV) can effectively treat sleep-disordered breathing. However, there are no specific data about the efficacy of flow-triggered ASV for cardiac function in patients with CHF with sleep-disordered breathing. The aim of this study was to compare the efficacy of flow-triggered ASV to CPAP in patients with CHF with coexisting obstructive sleep apnea and Cheyne-Stokes respiration-central sleep apnea. Methods and Results—Thirty-one patients with CHF, defined as left ventricular ejection fraction <50% and New York Heart Association class ≥II, with coexisting obstructive sleep apnea and Cheyne-Stokes respiration-central sleep apnea, were randomly assigned to either CPAP or flow-triggered ASV. The suppression of respiratory events, changes in cardiac function, and compliance with the devices during the 3-month study period were compared. Although both devices decreased respiratory events, ASV more effectively suppressed respiratory events (&Dgr;AHI [apnea-hypopnea index], −35.4±19.5 with ASV; −23.2±12.0 with CPAP, P<0.05). Compliance was significantly greater with ASV than with CPAP (5.2±0.9 versus 4.4±1.1 h/night, P<0.05). The improvements in quality-of-life and left ventricular ejection fraction were greater in the ASV group (&Dgr;LVEF [left ventricular ejection fraction], +9.1±4.7% versus +1.9±10.9%). Conclusions—These results suggest that patients with coexisting obstructive sleep apnea and Cheyne-Stokes respiration-central sleep apnea may receive greater benefit from treatment with ASV than with CPAP.

Comparative value of brain perfusion SPECT and [123I]MIBG myocardial scintigraphy in distinguishing between dementia with Lewy bodies and Alzheimer’s disease

PurposeBoth decreased occipital perfusion on brain single-photon emission computed tomography (SPECT) and reduction in cardiac 123I-metaiodobenzylguanidine (MIBG) uptake are characteristic features of dementia with Lewy bodies (DLB), and potentially support the clinical diagnosis of DLB. The aim of this study was to compare the diagnostic value of these two methods for differentiation of DLB from Alzheimer’s disease (AD).MethodsThe study population comprised 19 patients with probable DLB and 39 patients with probable AD who underwent both SPECT with N-isopropyl-p-[123I]iodoamphetamine and MIBG myocardial scintigraphy. Objective and quantitative measurement of perfusion in the medial occipital lobe, including the cuneus and lingual gyrus, was performed by the use of three-dimensional stereotactic surface projections.ResultsMedial occipital perfusion was significantly decreased in the DLB group compared with the AD group. The mean heart/mediastinum ratios of MIBG uptake were significantly lower in the DLB group than in the AD group. Although SPECT failed to demonstrate significant hypoperfusion in the medial occipital lobe in five patients with DLB, marked reduction of MIBG uptake was found in all patients with DLB. Receiver operating characteristic analysis revealed that MIBG myocardial scintigraphy enabled more accurate discrimination between DLB and AD than was possible with perfusion SPECT.ConclusionMIBG myocardial scintigraphy may improve the sensitivity in the detection of DLB. In particular, this method may provide a powerful differential diagnostic tool when it is difficult to distinguish cases of DLB from AD using brain perfusion SPECT.

Elevated C-Reactive Protein Augments Increased Arterial Stiffness in Subjects With the Metabolic Syndrome

We examined whether the presence of an increasing number of metabolic syndrome “disorders” was associated with an increasing pulse wave velocity, which is recognized as a marker of cardiovascular risk, and evaluated whether an elevated plasma C-reactive protein level augments this increasing pulse wave velocity. Using a cross-sectional study design, C-reactive protein, metabolic syndrome–related anthropometric parameters, and pulse wave velocity were measured in 5752 middle-aged Japanese men (44±10 years old). In linear regression analyses, all of the metabolic “disorders” and the logarithm of the C-reactive protein significantly correlated with pulse wave velocity. Multiple linear regression analysis demonstrated that triglycerides, HDL cholesterol, mean blood pressure, fasting glucose, and the logarithm of the C-reactive protein were significant independent positive predictors of pulse wave velocity (R-square=0.38). The presence of an increasing number of metabolic “disorders” in the subjects was associated with an increasing pulse wave velocity (no disorders 1228±139 cm/s ≥3 disorders 1437±250 cm/s; P<0.01). Among subjects with the metabolic syndrome, pulse wave velocity was higher in cases with (1508±278 cm/s) than in those without an elevated C-reactive protein (1427±243 cm/s; P<0.01). In conclusion, an increase in arterial stiffness may constitute a pathophysiological basis for the increased risk of cardiovascular disease in patients with the metabolic syndrome and that an elevated C-reactive protein level may aggravate this cardiovascular risk.

Continuous smoking and progression of arterial stiffening: a prospective study.

OBJECTIVES We prospectively and longitudinally determined the effects of smoking on the progression of arterial stiffening as well as the involvement of inflammation in this process. BACKGROUND Smoking is an important avoidable risk factor for cardiovascular disease, and arterial stiffness might be involved in the pathophysiology. No prospective study has examined the effect of continuous smoking on the age-associated progression of arterial stiffening. METHODS In 2,054 Japanese subjects (40 +/- 8 years of age), brachial-ankle pulse wave velocity (baPWV) and serum C-reactive protein (CRP) levels were measured at the baseline and the end of a 5- to 6-year follow-up period. RESULTS The annual rate of change of the baPWV during the study period was significantly greater in the continuous heavy smokers (11.0 +/- 1.9 cm/s/year, n = 181) than in the never-smokers (5.5 +/- 0.6 cm/s/year, n = 1,018). This difference remained significant even after adjustments for covariates, including age (p < 0.05). In continuous smokers (n = 493), the mean number of cigarettes smoked/day during the study period showed a significant relationship with the changes in baPWV. No significant relationship was found between the change in baPWV and serum CRP levels. CONCLUSIONS Continuous smoking might accelerate the age-associated progression of structural stiffening of the large- to middle-size arteries. We also found a dose-response relationship between cigarette consumption and accelerated arterial stiffening. However, we failed to confirm any significant association between the rate of arterial stiffening and the serum CRP levels in the smokers.

Arterial stiffness and declines in individuals with normal renal function/early chronic kidney disease

OBJECTIVE We evaluated the temporal association between arterial stiffening and the early stage of renal functional decline. METHODS In 2053 Japanese employees with an estimated glomerular filtration rate (GFR) of > or = 60 ml/min/1.73 m(2) plus no proteinuria (40+/-8 years old) at the start, brachial-ankle pulse wave velocity (baPWV) and serum C-reactive protein (CRP) were measured before and after a 5-6-year follow-up period. RESULTS After adjusting for confounding variables including serum CRP levels, higher baseline baPWV was associated with lower follow-up GFR (value expressed as per doubling: -16; 95% confidence interval: -24 to -9; P<0.01) and with higher annual rate of decline in GFR (value expressed as per doubling: -3; 95% confidence interval: -4 to -2; P<0.01). Every m/s higher baPWV was associated with a 36% increased odds (95% CI 1.09-1.70; P<0.01) for a development of a GFR <60 ml/min/1.73 m(2) at follow-up. In contrast, baseline GFR was not associated with follow-up baPWV (P=0.08) or the annual rate of change in baPWV (P=0.11). CONCLUSION In a Japanese occupational cohort with normal renal function/early chronic kidney disease, elevated arterial stiffness was an independent risk factor for the decline in renal function. CRP did not appear to exert any significant influence on this association.