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.

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.

[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.

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.

Overweight body mass index classification modifies arterial stiffening associated with weight gain in healthy middle-aged Japanese men.

The present study was conducted to clarify whether body mass index (BMI [kg/m(2)]) classifications (i.e., without excess weight, overweight, and obese) modify the rate of progression of arterial stiffening, a cardiovascular risk factor associated with weight gain. A 3-year observational study was conducted in 2,080 healthy middle-aged Japanese men (aged 42+/-10 years). Brachial-ankle pulse wave velocity (baPWV) was measured at the beginning and end of the study period. In overweight subjects (30>BMI>or=25), the estimated annual rate of increase of baPWV (ARbaPWV) in subjects with weight gain (>or=5% weight gain; ARbaPWV, 21.8+/-4.4 cm/s/year) was significantly higher than in those without weight gain (<5% weight gain; ARbaPWV, 12.5+/-1.6 cm/s/year), after adjustments for changes in blood pressure and other variables (p<0.05). This change was not observed in subjects without excess weight (BMI<25) or in obese subjects (BMI>or=30). The increase in the ARbaPWV associated with weight gain in the overweight group was also higher than that in the without excess body weight or obese groups. Our study revealed that the BMI classifications modified the annual rate of increase in arterial stiffening associated with weight gain. Weight gain seemed to accelerate arterial stiffening in overweight subjects, but not in subjects without excess weight. The weight gain in overweight subjects seemed to worsen the cardiovascular risk related to arterial stiffness in middle-aged healthy Japanese men. Thus, the prevention of weight gain should be emphasized in overweight subjects.

Different progression of tumor xenografts between mucin-producing and mucin-non-producing mammary adenocarcinoma-bearing mice.

Previously, we found that MUC2 mucins could activate monocytes/macrophages through a scavenger receptor leading to cyclooxygenase (COX) 2 induction and overproduction of prostaglandin E2 (PGE2). To investigate the role of mucins in the tumor-bearing state, we compared s.c. tumor formation by using mucin-producing (TA3-Ha) and mucin-non-producing (TA3-St) cloned variants of mouse mammary adenocarcinomas. Expression of COX2 mRNA and protein and production of PGE2 were elevated in peritoneal macrophages stimulated with epiglycanin, which is a mucin-like glycoprotein produced by TA3-Ha cells. S.c. tumor tissues comprising TA3-Ha cells grew much faster than tissues comprising TA3-St cells. COX2 protein and vascular endothelial growth factor in TA3-Ha tumor tissues were elevated compared with the TA3-St tumor tissues. Although similar numbers of macrophages were observed immunochemically in the two types of tumor tissues, COX2 was induced prominently in the infiltrating macrophages in TA3-Ha tumor tissues but only faintly in TA3-St tumor tissues. Furthermore, angiogenesis progressed remarkably in TA3-Ha tumor tissues but only slightly in TA3-St tumor tissues. Epiglycanin-induced overproduction of PGE2 down-regulated interleukin-12 production by macrophages. IFN-gamma-producing CD4 T cells in spleens obtained from TA3-Ha tumor-bearing mice were significantly reduced compared with TA3-St tumor-bearing mice, suggesting that mucins cause PGE2-mediated immune suppression. Actually, the tumor growth of a TA3-Ha cell xenograft was suppressed effectively by oral administration of a COX2 inhibitor but that of a TA3-St cell one was not. These results suggest that mucins play an important role in tumor progression through overproduction of PGE2.

Discrepancy between improvement of insulin sensitivity and that of arterial endothelial function in patients receiving antihypertensive medication.

OBJECTIVES: We evaluated whether the changes in the insulin sensitivity observed in hypertensive patients following treatment with an angiotensin II receptor blocker (candesartan) or calcium-channel antagonist (amlodipine) might be related to improvement of the endothelial function (END) and/or plasma level of high-sensitive C-reactive protein (CRP) following such treatment. METHODS AND RESULTS: Seventy-one hypertensive patients (age: 58 +/- 10 years) without obvious target organ damage were allocated randomly to treatment with either candesartan at the dose of 8 mg/day or amlodipine at the dose of 5 mg/day. At the start and end of the 8-month treatment period, the homeostasis model assessment index of insulin resistance (HOMA-IR index), plasma CRP and END, as assessed by changes in the forearm blood flow in reactive hyperemia, were determined. While significant improvement of END was observed in patients receiving either drug, only candesartan, but not amlodipine, also reduced the plasma CRP and HOMA-IR index (2.13 +/- 1.92 --> 1.53 +/- 1.47, P < 0.05). In the patients receiving treatment with candesartan, stepwise multivariate linear regression analysis revealed that the percent change in the HOMA-IR index was significantly and independently correlated with that in the plasma CRP (beta = 0.38, P < 0.05), but not with that in END: CONCLUSION: Improvement of the END alone by the antihypertensive medication might not entirely explain the improvement of the insulin sensitivity observed in these patients. Additional mechanisms may be involved, and the anti-inflammatory effects of the medication observed in patients treated with candesartan may also be related, at least in part, to the observed improvement of insulin sensitivity.

Effect of telmisartan on forearm postischemic hyperemia and serum asymmetric dimethylarginine levels.

BACKGROUND: Although telmisartan may be more beneficial for glucose metabolism than other angiotensin II receptor blockers (ARBs), it has not been determined whether telmisartan exerts more favorable effects on biological and functional parameters related to endothelial function than other ARBs. METHODS: A study with a crossover design was conducted in 40 hypertensive patients (61 +/- 10 years old, mean +/- SD) who had previously been treated with ARBs other than telmisartan or valsartan (ie, ARBs were switched to either telmisartan 40 mg/day or valsartan 80 mg/day, administered alternately for 12 weeks each). Blood examinations were conducted, and the mean reactive hyperemia ratio (mRHR) was measured by plethysmography for each treatment regimen. RESULTS: There were no significant differences in either blood pressure or plasma levels of monocyte chemoattractant protein-1, C-reactive protein, 3-nitrotyrosine, or vascular cell adhesion molecule-1 between the two treatment regimens. The mRHR (2.7 +/- 1.0 v 2.4 +/- 1.0, mean +/- SD) was larger (P < .05), and the plasma levels of asymmetric dimethylarginine (ADMA) (0.45 +/- 0.08 v 0.50 +/- 0.17 micromol/L, mean +/- SD) and the homeostasis model assessment index of insulin resistance (HOMA-IR) (2.3 +/- 1.6 v 2.8 +/- 2.1, mean +/- SD) were lower (P < .05) in telmisartan-treated patients than in valsartan treated patients. The percent change in ADMA, but not in HOMA-IR, correlated significantly with that in the mRHR (beta = -0.33, t value = -2.00, P = .04). CONCLUSIONS: At doses producing equivalent hypotensive effects, telmisartan apparently had a more favorable effect on functional parameters related to endothelial function than did valsartan. The reduction in plasma ADMA levels may contribute to this more favorable effect of telmisartan.

N-terminal mutational analysis of the interaction between growth-blocking peptide (GBP) and receptor of insect immune cells.

GBP, a small insect cytokine isolated from lepidopterans, has a variety of functions. We constructed a series of mutants focusing on the unstructured N-terminal residues of GBP by acetylation, deletion, and elongation in order to investigate the interaction between GBP and its receptor in plasmatocytes. The 1H NMR spectra showed no significant changes in the tertiary structures of these peptides, which indicated that all the mutants maintained their core beta-sheet structures. The deletion and acetylated mutants, 2-25GBP, Ac2-25GBP, and AcGBP, lost their activity. 2-25GBP was the strongest antagonist, while Ac2-25GBP and AcGBP were moderate. In contrast, the elongated mutants, (-1R)GBP, (-1A)GBP, and (-2G,-1R)GBP maintained their plasmatocyte-spreading activity. These results demonstrate the importance of the GBP N-terminal charged amine and length of N-terminal GBP-peptide backbone for plasmatocyte-spreading activity. Next, we analyzed other mutant peptides, 1-25(N2A)GBP and 2-25(N2A)GBP, focusing on Asn2. Surprisingly, 2-25(N2A)GBP had slight plasmatocyte-spreading activity, whereas 2-25GBP lost its activity. Finally, substituted mutant, F3AGBP, had neither plasmatocyte-spreading activity nor antagonistic activity. These results demonstrate the function of each N-terminal residue in the interaction between GBP and its receptor in plasmatocytes.

Peptide mimics of epidermal growth factor (EGF) with antagonistic activity.

Epidermal growth factor is a potent growth-promoting factor for a variety of tissue cells in vivo and in vitro. Epidermal growth factor binds, phosphorylates, and activates epidermal growth factor receptors on the cell surface. In this study, we attempted to design functional peptide mimics by panning a phage display library on the anti-epidermal growth factor monoclonal antibody. By using anti-epidermal growth factor monoclonal antibody as a mold of the structure of the binding site of epidermal growth factor, high-efficiency probing was expected. From a random peptide phage display library, phage clones that bind to the anti-epidermal growth factor monoclonal antibody were isolated. One of the phage clones also exhibited binding activity to the epidermal growth factor receptor. The amino acid sequence of this phage clone showed slight similarity to the primary sequence of epidermal growth factor. We synthesized this motif to a 9-amino-acid intramolecularly disulfide-linked peptide. This synthetic peptide inhibited mitogenesis as well as epidermal growth factor receptor tyrosine phosphorylation, which is induced by epidermal growth factor. The present results suggest that the peptide synthesized in this study may mimic the epidermal growth factor receptor-binding region in epidermal growth factor.

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.

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.

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.