Simultaneous occurrence of accelerated nodulosis in lungs, liver, and kidneys, and acute exacerbation of interstitial pneumonia in a patient with rheumatoid arthritis: an autopsy case report.

BACKGROUND: Accelerated nodulosis (ARN) is a rare variant of rheumatoid nodules (RNs) that is characterized by a rapid onset or the worsening of RNs. It generally develops at the fingers in patients with rheumatoid arthritis (RA) receiving methotrexate (MTX). Few case reports have described ARN at an extracutaneous location. CASE PRESENTATION: An elderly patient with long-standing RA was admitted to our hospital with acute respiratory failure. Computed tomography upon admission showed diffuse ground-glass opacities superimposed with subpleural reticular shadowing and honeycombing and multiple nodules in the lungs and liver. Despite the discontinuation of MTX and introduction of an immunosuppressive regimen with pulse methylprednisolone followed by a tapering dose of prednisolone and intravenous cyclophosphamide, the patient died due to the acute exacerbation (AE) of RA-related interstitial lung disease (ILD) following the parallel waxing and waning of a diffuse interstitial shadow and pulmonary and liver nodules. At autopsy, RNs were scattered throughout both lung fields in addition to extensive interstitial changes. RNs were also detected in the liver and kidneys. The foci of cryptococcosis were mainly identified in alveolar spaces. Based on the clinical and pathological findings, these nodules were most consistent with ARN because of acute increases in the size and number of previously detected pulmonary nodules. CONCLUSION: The present case is noteworthy because ARN was concurrently detected in multiple internal organs and may be associated with the AE of RA-related ILD.

Paraneoplastic dermatomyositis appearing after nivolumab therapy for gastric cancer: a case report.

BACKGROUND: While dermatomyositis is often associated with malignancy, several autoimmune diseases like myositis can be caused by immune checkpoint inhibitors. Differentially diagnosing malignancy-associated dermatomyositis or myositis caused by immune checkpoint inhibitors is sometimes difficult, particularly when a patient with malignancy shows the symptoms of myositis after checkpoint inhibitor administration. We experienced such a case in which we had difficulties in diagnosing paraneoplastic dermatomyositis or drug-associated myositis. In this case, all of our team initially assumed that the diagnosis was myositis caused by immune checkpoint inhibitors. However, it turned out finally that the diagnosis was paraneoplastic dermatomyositis. Because the diagnosis was unexpected, we report here. CASE PRESENTATION: We report the case of a 71-year-old Japanese man who developed clinical symptoms of myositis, such as muscle aches and weakness, after initiation of nivolumab therapy for his gastric cancer. He was initially diagnosed with nivolumab-induced myositis, because the myositis symptoms appeared after nivolumab administration, and nivolumab is known to trigger various drug-associated autoimmune diseases. However, according to his characteristic skin lesions, the type of muscle weakness, his serum marker profiles, electromyography of his deltoid muscle, and magnetic resonance imaging, he was finally diagnosed as having paraneoplastic dermatomyositis. Accordingly, treatment with intravenously administered corticosteroid pulse treatment, immunoglobulin injection, and tacrolimus was applied; his symptoms subsequently improved. However, to our regret, at day 142 after administration, he died due to rapid worsening of his gastric cancer. CONCLUSION: Differentially diagnosing paraneoplastic dermatomyositis or drug-associated myositis caused by immune checkpoint inhibitors is difficult in some cases. The differential diagnosis is crucial because it influences the decision regarding the appropriateness of the use of immunosuppressive treatment against the autoimmune diseases as well as the decision regarding the appropriateness of the continuous use of immune checkpoint inhibitors against the primary cancers. Because subclinical autoimmune disease may become overt after administering immune checkpoint inhibitors, non-apparent autoimmune diseases, which have already existed, should also be considered to avoid the delay of appropriate treatment, when symptoms of autoimmune diseases are recognized.

Autonomic nervous activation triggered during induction of reactive hyperemia exerts a greater influence on the measured reactive hyperemia index by peripheral arterial tonometry than on flow-mediated vasodilatation of the brachial artery in patients with hypertension.

Flow-mediated vasodilatation of the brachial artery (FMD) and reactive hyperemia index (RHI) measured by peripheral arterial tonometry are known to be weakly associated with one another, but the mechanisms underlying this weak association remain to be clarified. We examined whether the autonomic nervous activation induced by the 5 min forearm clamping used to induce reactive hyperemia might exert any influence on the FMD and RHI in subjects with hypertension. In 115 subjects with hypertension (age 61±1 years), the FMD and RHI were measured simultaneously, and the heart rate variability (HRV) parameters (low-frequency component (LF), high-frequency component (HF), and the ratio (LF/HF) between the two) were calculated from the electrocardiographic recordings obtained before and after the start of forearm clamping. A multivariate linear regression analysis with adjustments for confounding variables demonstrated that the RHI, but not the FMD, was significantly associated with the percent change of the LF/HF associated with forearm clamping (beta=-0.204, P=0.043). In conclusion, autonomic nervous system activation, especially sympathetic activation, induced by 5-min forearm clamping utilized to provoke reactive hyperemia may significantly affect the RHI rather than FMD in subjects with hypertension.

Arterial stiffness/central hemodynamics, renal function, and development of hypertension over the short term.

OBJECTIVES: We examined the following: whether the estimated glomerular filtration rate calculated from the serum cystatin C levels (eGFRcys) and the brachial-ankle pulse wave velocity (baPWV) might be independent predictors of the development of hypertension over the short term, without any interaction; whether the baPWV may be directly associated with the development of hypertension without the mediation of the arterial stiffness-related acceleration of renal functional decline; whether the second peak of the radial pressure waveform (SP2) might also be a significant independent predictor of the development of hypertension. METHODS: In 1229 middle-aged normotensive Japanese men with preserved renal function, the baPWV, SP2 and eGFRcys were measured at the baseline and at the end of the 3-year study period. RESULTS: Hypertension was detected at the end of the 3-year study period in 127 men. The logistic regression analysis with adjustments demonstrated significant independent odds ratios of the baPWV and eGFRcys for the presence of hypertension at the end of the 3-year study period, without any interaction. When entered simultaneously in this model, the SP2 also showed a significant odds ratio. General linear model analysis revealed that none of the baPWV or SP2 measured at the baseline was related to the renal function assessed at the end of the 3-year study period. CONCLUSIONS: The mechanisms underlying the association between arterial stiffness/central hemodynamics and the short-term development of hypertension appear to differ from those underlying the association between kidney function and the short-term development of hypertension.

Central blood pressure: a powerful predictor of the development of hypertension.

We examined whether the central aortic systolic blood pressure, a marker of the function of the systemic arterial tree, might be a more powerful predictor of the development of hypertension than the brachial-ankle pulse wave velocity, a marker of the stiffness of the large- to middle-sized arteries, independent of the conventional risk factors for the development of hypertension. In 1268 Japanese men without hypertension (43±8 years old), the relationships between three variables (the second peak of the radial pressure waveform (SP2), brachial-ankle pulse wave velocity and conventional risk factors measured at the first examination) with the presence of hypertension at the second examination (after 3 years' follow-up) were examined. Hypertension was detected at the second examination in 154 men. The best cutoff points of the brachial-ankle pulse wave velocity and SP2, for predicting the development of hypertension, were 12.7 m/s and 109 mm Hg, respectively. The results of a logistic regression analysis confirmed that an SP2 of ≥109 mm Hg (odds ratio=8.493, P<0.001) was a more powerful predictor of the development of hypertension than a brachial-ankle pulse wave velocity of ≥12.7 m/s, independent of the conventional risk factors. The net reclassification index of SP2 (at the best cutoff point) to brachial-ankle pulse wave velocity was 0.211 (P<0.001), indicating that SP2 is a better predictor of the development of hypertension than brachial-ankle pulse wave velocity. In middle-aged Japanese men without hypertension, SP2 may be a more powerful predictor of the development of hypertension than the assessment of stiffness in large to middle-sized arteries independent of the conventional risk factors.

Overlap syndrome: additive effects of COPD on the cardiovascular damages in patients with OSA.

The chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA) have been recently much focused as independent risks for cardiovascular disease. Furthermore, the complication of both has a worse prognosis compared with patients with only one of these diseases. However, the details of the underlying mechanisms of this worsened prognosis have not been clear. The cross-sectional study was conducted to examine whether the overlap of COPD augment the increase in arterial stiffness in subjects with OSA. If so, we examined the exaggeration of nocturnal hypoxemia and its related inflammation are related to this augmentation of increased arterial stiffness. In 524 male subjects with OSA diagnosed by polysomnography (apnea-hypopnea index >5/h) (52 ± 14 years old), the forced expiratory volume at 1 s/the forced vital capacity (FEV(1)/FVC) ratio, brachial-ankle pulse wave velocity (baPWV), blood C-reactive protein (CRP) and B-natriuretic peptide (BNP) levels were measured. The prevalence rate of COPD was 12% in this study subjects. Plasma BNP levels and the crude (median value, 17.2 vs. 14.1 m/s, p < 0.01) and adjusted value of baPWV were significantly higher in subjects with overlap syndrome than in those with OSA alone. However, parameters of nocturnal hypoxemia and serum CRP levels were similar between both groups. Thus, the overlap of COPD in patients with OSA augments increase in arterial stiffness without the exaggeration of nocturnal hypoxemia and inflammation. Even so, this augmentation may partially contribute to the increased cardiovascular risk in the overlap syndrome.

Strength of relationships of the pulse wave velocity and central hemodynamic indices with the serum N-terminal fragment B-type natriuretic peptide levels in men: a worksite cohort study.

BACKGROUND: It has not been fully clarified as to which marker related to arterial stiffness or central hemodynamics might be most closely associated with the blood natriuretic peptide levels. The present cross-sectional study was conducted to examine the strength of the relationships of the arterial stiffness and central hemodynamic indices with the serum N-terminal fragment B-type natriuretic peptide (NT-pro BNP) levels. METHODS AND RESULTS: In a total of 2,657 male employees of a company (46±9 years old), the first and second peaks of the radial systolic pressure waveform (SBP1 and SBP2, respectively), the radial augmentation index (rAI), the PP2 (SBP2 minus the diastolic blood pressure), the brachial-ankle pulse wave velocity (baPWV), and the serum NT-pro BNP levels were measured. Even after adjustments for confounding variables, the SBP1, SBP2, PP2, rAI and baPWV showed a significant positive association with the serum NT-pro BNP levels. A stepwise multivariate linear regression analysis demonstrated that among these variables, only PP2 contributed significantly to the serum NT-pro BNP levels (ß=0.176, partial R-square=0.017, P<0.001). CONCLUSIONS: In middle-aged Japanese men, among the parameters related to arterial stiffness and central hemodynamics, PP2 showed the closest relationship with the serum NT-pro BNP levels. Therefore, elevation of the serum NT-pro BNP levels appears to reflect, at least in part, the pathophysiological abnormalities related to increased central pulse pressure.

[Bone and calcium update; diagnosis and therapy of bone metabolism disease update. Clinical assessment of atherosclerosis in aorta].

The purpose of clinical assessment of atherosclerosis in aorta is to detect early lesions that are associated with a substantial risk of cardiovascular disease, such as stroke, aortic aneurysm and dissection, and to develop a treatment strategy for reduction of the cardiovascular risk. The pulse wave velocity (PWV) and pulse wave analysis (augmentation index : AI) can reveal atherosclerotic functional vascular abnormalities. On the contrary, plain X-rays, ultrasound examination, computed tomography (CT) , and magnetic resonance imaging (MRI) can be employed to easily assess the severity of atherosclerotic vascular damage morphologically. In these examinations, only PWV, as an index of arterial stiffness, can detect early atherosclerotic change in aorta before organic change. So, considering the importance of detecting early lesion, PWV is the most useful examination of atherosclerosis in aorta.

Arterial-cardiac destiffening following long-term antihypertensive treatment.

BACKGROUND: We examined whether in addition to producing a greater degree of improvement of the arterial stiffness, long-term angiotensin II receptor blocker (ARB) treatment might also have a more beneficial effect on the cardiac diastolic dysfunction than long-term calcium-channel blocker (CCB) treatment; we also evaluated the association between the improvements of the two variables brought about by ARB treatment in subjects with stage I or II hypertension. METHODS: One hundred and thirteen patients were randomly allocated to treatment with an ARB (candesartan) or a CCB (amlodipine). Echocardiography and measurement of the brachial-ankle pulse wave velocity (PWV) were conducted in both groups at the start of the treatment and at the end of 2-3-years' treatment. RESULTS: After adjustments for covariates, the extent of reduction of the brachial-ankle PWV (-200 ± 18 cm/s vs. -141 ± 18 cm/s, P = 0.03) and that of the increase of the E/A ratio (0.08 ± 0.03 vs. 0.01 ± 0.03, P = 0.04) were significantly greater in the candesartan group than in the amlodipine group. A significant relationship was identified between the delta changes of the brachial-ankle PWV and delta changes of the E/A ratio observed following long-term candesartan treatment. CONCLUSION: Long-term candesartan treatment may have a more beneficial effect on the stiffness of the large- to- middle-sized arteries than long-term amlodipine treatment, and this treatment may also concomitantly improve the cardiac diastolic dysfunction; a significant association appeared to exist between the improvements of the two variables observed following long-term candesartan treatment.

Relationships among the serum omega fatty acid levels, serum C-reactive protein levels and arterial stiffness/wave reflection in Japanese men.

OBJECTIVE: We examined the relationship among the serum omega-3 and omega-6 fatty acid (O3FA and O6FA) levels, serum C-reactive protein (CRP) levels, and arterial stiffness/wave reflection (AS/WR) in healthy Japanese men. METHODS: In 2206 Japanese healthy men, parameters related to the AS/WR (i.e., brachial-ankle pulse wave velocity and radial arterial pulse wave analysis) were measured. RESULTS: No significant inverse relationships were observed between the serum O3FA levels and the AS/WR-related parameters. Adjusted values of the AS/WR-related parameters and serum CRP levels were higher in the subjects with serum O6FA levels in the highest tertile than in those with serum O6FA levels in the lowest tertile. CONCLUSIONS: In healthy Japanese men with known high dietary intakes of O3FAs, the serum O3FA levels may not reflect the pathophysiological abnormalities related to AS/WR. Increased serum O6FA levels appeared to be independently associated with the unfavorable conditions related to AS/WR and inflammation.

Effects of aging and persistent prehypertension on arterial stiffening.

An age-related association of blood pressure in the non-hypertensive range (non-hypertensive blood pressure) to the cardiovascular mortality has been demonstrated. This prospective study was conducted to examine the effects of age, persistence of pre-hypertension (preHYP) during the study period, and the interaction between these factors on the rate of progression of arterial stiffening. Among 1563 healthy Japanese subjects without hypertension (age range: 29-95 years), the brachial-ankle pulse wave velocity (baPWV) was measured twice (i.e., at baseline and 5-6 years later). The adjusted (including for blood pressure) value of the annual rate of increase of the baPWV during the study period (delPWV) increased in a linear manner along with the age category (categorized into 29-39 years, 40-59 years, and 60 years or older for this study) and the evolutional category of non-hypertensive blood pressure during the study period (categorized into persistence of normal blood pressure, borderline evolution, and persistence of preHYP), and a significant interaction between the two in relation to the delPWV was also noted (non-standardization coefficient=5.08 [95% confidence interval=3.24-6.92], F-value=29.40, P<0.01). In conclusion, the present study suggests that persistence of preHYP is associated with accelerated structural stiffening of the large- to middle-sized arteries, and that age may exert a synergistic effect on this acceleration of arterial stiffening. Thus, persistence of preHYP also appears, like hypertension, to be associated with progressive vascular damage, and this progression may be more pronounced in middle-aged and elderly subjects.

Increased arterial stiffness weakens the relationship between wave reflection and the central pressure indexes in men younger than 60 years of age.

BACKGROUND: Interactions among age, arterial stiffness, and pressure wave reflection affect the central blood pressure (CBP). We evaluated our hypothesis that the contribution of the wave reflection to the CBP indexes is reduced at higher levels of arterial stiffness, independent of the effect of age. METHODS: In 2,691 Japanese men aged <60 years old who are not suffering from cardiovascular disease or receiving medications for cardiovascular risk factors, the brachial-ankle pulse wave velocity (PWV), radial augmentation index (AI), and second peak of the radial pressure waveform (SBP2), a marker of CBP, were measured. RESULTS: The increase in the radial AI associated with increase of the brachial-ankle PWV became attenuated at brachial-ankle PWV values of ≥15 m/s. Stepwise multivariate linear regression analysis demonstrated that 33.6% of the total variation in the value of SBP2 and 54.0% of the total variation in the value of the SBP2 minus the diastolic blood pressure, a marker of the central pulse pressure (CPP), were accounted for by the change of the radial AI in the group with brachial-ankle PWV values of <15 m/s, with the corresponding percentages of 16.2 and 38.0% in the group with brachial-ankle PWV values of ≥15 m/s (P < 0.01). CONCLUSIONS: In non-elderly Japanese men, the contribution of the wave reflection to the CBP indexes may be reduced in subjects with higher levels of arterial stiffness, independent of the effect of age. Notwithstanding, the wave reflection may still be the major determinant of the CPP at any given level of arterial stiffness.

Effects of Moderate-to-Severe Impairment of the Estimated Glomerular Filtration Rate and of Proteinuria on the Central Hemodynamics and Arterial Stiffness in Middle-Aged Healthy Japanese Men.

We evaluated the effects of moderate-to-severe impairment of the estimated glomerular filtration rate (eGFR: 15 to 59 mL/min per 1.73 m(2)) and of proteinuria on the central hemodynamics and the pulse wave velocity (PWV) in 2244 middle-aged healthy Japanese men who were not receiving any medications for cardiovascular diseases or cardiovascular risk factors. The adjusted value of the radial augmentation index was higher in the subjects with proteinuria than in those without proteinuria. On the other hand, this value was similar between the subjects with and without moderate-to-severe impairment of the eGFR. Not only proteinuria but also moderate-to-severe impairment of the eGFR was associated with increase in the adjusted value of the brachial-ankle PWV. Thus, proteinuria was found to be an independent risk factor for abnormal central hemodynamics and increased stiffness of the large- to middle-sized arteries, while moderate-to-severe impairment of the eGFR was associated with an increase of the arterial stiffness, but not with abnormality of the central hemodynamics.

[Noninvasive diagnostic imaging technique for arteriosclerotic lesion].

The purpose of noninvasive examination of arteriosclerotic lesions is to detect early lesions that are associated with a substantial risk of cardiovascular disease, such as coronary artery disease, stroke, obstructive arteriosclerosis, aneurysm and arterial dissection, and to develop a treatment strategy for reducing the risk of arteriosclerotic lesions. The spread of the noninvasive diagnostic imaging techniques, such as vascular ultrasound, MDCT and MRI has brought about a significant improvement in the morphological assessment of arteriosclerotic lesions in routine clinical practice. In particular, the development of equipment for MDCT and MRI is remarkable, both techniques having the potential to become the gold standard for the assessment of arteriosclerotic lesions in the future. In this article, we shall review the current status of noninvasive diagnostic imaging of arteriosclerotic lesions showing rapid progression.

[Vascular calcification and serum markers].

Recently, the multidetector computed tomography (CT) is available to measure quantitative analysis of coronary vascular calcification (coronary calcification score [CACscore]). Vascular calcification is recognized not only in the end stage of atherosclerosis but also in the early stage of atherosclerosis. Recent data suggested that bone- related factors are closely related to coronary artery disease and vascular calcification. In this review, we discuss for regulatory mechanisms of vascular calcification.

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.

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.

Association of serum cystatin C with pulse wave velocity, but not pressure wave reflection, in subjects with normal renal function or mild chronic kidney disease.

BACKGROUND: This prospective cross-sectional study was conducted to clarify whether serum cystatin C levels might be associated with not only arterial stiffness, but also the pressure wave reflection, in middle-aged Japanese subjects with normal renal function or mild chronic kidney disease (CKD) (stage 1 or 2 CKD) (i.e., creatinine-based estimate of the glomerular filtration rate (eGFRcr) > or =60 ml/min/1.73 m(2) plus a result of the urine dipstick test for proteinuria of <1+). METHODS: In 2,904 Japanese subjects (45 +/- 9 years old), the brachial-ankle pulse wave velocity (baPWV), radial augmentation index adjusted to a heart rate of 75 beats/min (rAI75), and serum cystatin C levels were measured. RESULTS: Multivariate linear regression analysis demonstrated that the serum cystatin C levels were significantly correlated with the baPWV (standardized coefficient = 0.04, P < 0.01) even after adjustments for confounding variables, but not with the AI75 (standardized coefficient = 0.01, P = 0.71). adjusted values of the baPWV, but not those of rAI75, were higher in subjects with serum cystatin C levels in the highest tertile than in those with serum cystatin levels in the intermediate or lowest tertile. CONCLUSION: In middle-aged Japanese subjects with normal renal function or mild CKD (stage 1 or 2 CKD) (eGFRcr >60 ml/min/1.73 m(2) plus a result of the urine dipstick test for proteinuria of <1+), the serum cystatin C levels may reflect facet of cardiovascular risk associated with arterial stiffness, but not that associated with the pressure wave reflection.

Effects of CPAP therapy on the sympathovagal balance and arterial stiffness in obstructive sleep apnea.

OBJECTIVE: Increased arterial stiffness and sympathovagal imbalance are noted in patients with obstructive sleep apnea (OSA). It has been thought that continuous positive airway pressure (CPAP) therapy can have beneficial effects on the vascular function in such cases. However, it is not yet clear whether the improvement of sympathovagal balance by CPAP might be related to reduction of the arterial stiffness, independent of changes in the blood pressure. METHODS: In 50 consecutive eligible patients with OSA (apnea-hypopnea index>/=20/hour) receiving CPAP therapy, the brachial-ankle pulse wave velocity (baPWV), heart rate variability (LF, HF and LF/HF ratio), baroreceptor sensitivity (BRS), plasma levels of C-reactive protein (CRP), and endothelial function as assessed by changes in the forearm blood flow before and after reactive hyperemia (END) were measured before and after 3-months' CPAP therapy. RESULTS: Significant decrease of the LF/HF ratio, plasma levels of CRP, baPWV and heart rate were observed after 3 months' CPAP therapy. The change in the baPWV following 3-months' CPAP therapy was significantly correlated with the change in the LF/HF ratio and mean blood pressure (MBP), but not with that of the BRS, CRP or END after the therapy. Multivariate linear regression analysis demonstrated a significant correlation between the change in the LF/HF ratio and that in the baPWV (beta=0.305, p=0.041), independent of the changes in the MBP, plasma CRP levels and heart rate. CONCLUSIONS: Improvement of the sympathovagal balance by CPAP therapy may be significantly related to decreased stiffness of the central to middle-sized arteries, independent of the changes in the blood pressure and vascular endothelial status.