Obstructive Sleep Apnea as Possible Causal Factor for Visit-to-Visit Blood Pressure Variability.

BACKGROUND: Recent studies have shown that visit-to-visit blood pressure variability (BPV) is an independent risk factor for cardiovascular disease. However, it has not been clarified whether obstructive sleep apnea (OSA) is associated with visit-to-visit BPV. METHODS AND RESULTS: The 56 subjects with OSA and 26 control subjects without OSA were examined. Office BP was measured on 5 separate consecutive occasions prior to a polysomnography examination. The visit-to-visit BPV was expressed as the standard deviation and the coefficient of variation of the 5 systolic BP measurements. In subjects with an apnea-hypopnea index (AHI) of more than 20 episodes per hour, the visit-to-visit BPV was also measured after the start of continuous positive airway pressure (CPAP) therapy. Overall, the AHI positively correlated with the standard deviation and the coefficient of variation of systolic BP. In a multivariate analysis, the plasma noradrenaline level and the AHI were independently and positively correlated with the standard deviation and the coefficient of variation of the systolic BP. Among the patients who underwent CPAP therapy, good adherence with CPAP therapy significantly reduced the visit-to-visit BPV. CONCLUSIONS: OSA is associated with abnormal visit-to-visit BPV and sympathetic activation seems to be related in some way. (Circ J 2016; 80: 1787-1794).

Pathophysiological contribution of vascular function to baroreflex regulation in hypertension.

BACKGROUND: We examined which pathophysiological abnormalities of vascular function might be closely associated with abnormal baroreflex regulation in subjects with hypertension. METHODS AND RESULTS: In the cross-sectional assessment, 280 subjects with hypertension were enrolled for measurement of brachial-ankle pulse wave velocity (baPWV), radial augmentation index (rAI), flow-mediated vasodilatation (FMD) of the brachial artery and baroreceptor sensitivity (BRS). These parameters were measured again as prospective assessment in some of these subjects. In the cross-sectional assessment, after adjustment for confounding variables including anti-hypertensive medication, the baPWV, but not the rAI or FMD, was found to have a significant independent relationship with BRS (standardization coefficient, -0.149, P<0.043). In the subjects who were newly started on anti-hypertensive medication (n=40), regression of baPWV before and 1 year after the start of medication was significantly associated with change in BRS during the same period. In subjects already on anti-hypertensive medication (n=92) also, the evolutional change of baPWV over a follow-up period >1.5 years was significantly associated with change in BRS during the same period. CONCLUSIONS: Increased stiffness of the large- to middle-sized arteries, rather than abnormal central hemodynamics or endothelial dysfunction, appears to contribute to abnormal baroreflex regulation in patients with hypertension.

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.

Longitudinal changes in late systolic cardiac load and serum NT-proBNP levels in healthy middle-aged Japanese men.

BACKGROUND: We determined whether any significant association exists between change in late systolic cardiac load with time, estimated by radial pressure waveform analysis, and development of cardiac hemodynamic stress in individuals with preserved cardiac function. METHODS: Brachial-ankle pulse wave velocity, radial augmentation index (rAI), first peak of the radial pressure waveform (SP1), systolic and pulse pressure at the second peak of the radial pressure waveform (SP2 and PP2), and serum levels of N-terminal fragment B-type natriuretic peptide (NT-proBNP) were measured at the start (first examination) and at the end (second examination) of this 3-year study in healthy Japanese men (n = 1,851). RESULTS: A stepwise multivariate linear regression analysis demonstrated that among the parameters of radial pressure waveform analysis and markers of arterial stiffness analyzed, only PP2 was significantly associated with serum NT-proBNP levels in study participants at both the first and second examinations. Furthermore, among the parameters analyzed, only change in PP2 was significantly correlated with the change in serum NT-proBNP levels during the study period (beta = 0.131, P < 0.001). CONCLUSIONS: Sustained late systolic cardiac load might be a more significant determinant of the development of cardiac hemodynamic stress than sustained early systolic cardiac load or arterial stiffening in individuals with preserved cardiac function.

Correlations of arterial stiffness/central hemodynamics with serum cardiac troponin T and natriuretic peptide levels in a middle-aged male worksite cohort.

BACKGROUND: Elevated serum levels of cardiac troponin T (cTnT) and N-terminal fragment of B-type natriuretic peptide (NT-proBNP), and also increased arterial stiffness/abnormal central hemodynamics, are well-known risk factors for future cardiovascular events. The present study was conducted to clarify which of the two - the serum level of cTnT or that of NT-proBNP - might be more closely associated with the arterial stiffness/central hemodynamics. METHODS: In 2374 male employees of a company (46±9 years), the following parameters were measured: second peak of the radial systolic pressure waveform (SP2), radial augmentation index (rAI), PP2 (SP2 minus the diastolic blood pressure), brachial-ankle pulse wave velocity (baPWV), and serum levels of cTnT and NT-pro BNP. RESULTS: After adjustments for confounding variables, binary logistic regression analyses demonstrated that baPWV was associated with a significant odds ratio for serum NT-proBNP ≥125pg/mL (1.690; 95% confidence interval=1.136-2.514, p=0.002) and rAI was associated with a significant odds ratio for serum NT-proBNP ≥55pg/mL (1.205; 95% confidence interval=1.012-1.435, p=0.036). The baPWV, rAI, SP2, and PP2 were not associated with significant odds ratios for elevated serum cTnT levels (≥0.014ng/mL and ≥0.010ng/mL). CONCLUSIONS: In the middle-aged male worksite cohort studied, increased arterial stiffness/abnormal central hemodynamics appeared to be associated with elevated serum NT-proBNP levels, rather than with minimally elevated serum cTnT levels. This difference may be one of the plausible explanations for the independency of the predictive values of the two serum markers for future cardiovascular events.

Longitudinal changes of the serum calcium levels and accelerated progression of arterial stiffness with age.

BACKGROUND AND AIMS: The progression of arterial stiffness is accelerated by aging, although the underlying mechanisms have not yet been clarified. This prospective observational study was conducted to clarify whether longitudinal changes in the serum calcium/phosphate levels are associated with the accelerated progression of arterial stiffness with age. METHODS: In a cohort of employees at a construction company (1507 middle-aged Japanese men), the serum calcium/phosphate levels and brachial-ankle pulse wave velocity (baPWV) were measured at the start and at the end of a 3-year study period. RESULTS: A general linear model multivariate analysis revealed a significant interaction of the 2 factors {age and longitudinal changes of the serum calcium levels (delCa) during the follow-up period} on the longitudinal changes of the baPWV during the study period (delPWV). The delCa was significantly correlated with the delPWV even after adjustments for covariates in subjects aged ≥48 years. The delPWV in subjects aged ≥48 years with the delCa in the upper tertile (69 ± 137 cm/s) was significantly larger than that in the other groups even after adjustments for covariates (e.g., del PWV in subjects aged <48 years with the delCa in the lower tertile = 1 ± 94 cm/s) (p < 0.01). CONCLUSIONS: The association between the arterial stiffness and serum calcium levels differed with age. Pathophysiological abnormalities related to increased serum calcium levels appeared to be associated with accelerated progression of arterial stiffness with age.

Differences in effects of age and blood pressure on augmentation index.

BACKGROUND: The effect of age on the augmentation index (AI) differs between young adults and the elderly, and the AI reaches a plateau after the age of 60 years. We examined whether the effects of age and an elevation in blood pressure on the AI differ between young adults and the elderly, between subjects with and without high blood pressure, or between subjects with and without a high AI. METHODS: The radial AI was measured in 10,190 subjects who were either healthy or had hypertension (n = 5,477 men and 4,743 women). RESULTS: In both sexes, a phased increase in the radial AI with age could only be confirmed up to an age of 60 years. A phased increase in the radial AI with the systolic blood pressure (SBP) could be confirmed up to an SBP of >170 mm Hg. Among subjects categorized within the highest age tertile, the highest SBP tertile, or the highest radial AI tertile, stepwise multivariable analyses demonstrated that SBP, but not age, was a significant independent factor influencing the radial AI. CONCLUSIONS: The effect of age and blood pressure on AI differ not only between young adults and the elderly but also between those with and those without high blood pressure or between those with and those without a high AI. The effect of an elevation in blood pressure, but not aging, on the AI is significant in the elderly, in subjects with high blood pressure, or in those with a high AI.

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.

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 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.

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 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.

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.

Relationship of insulin resistance to macro- and microvasculature reactivity in hypertension.

BACKGROUND: Although insulin resistance (IR) is thought to be related to vascular dysfunction, the difference in the relationship of IR to microvasculature and macrovasculature reactivity has not yet been clarified. The present study was conducted to clarify whether the IR is more closely related to the macrovasculature reactivity (flow-mediated vasodilatation of the brachial artery induced by reactive hyperemia: FMD) or microvasculature reactivity (skin reactive hyperemia as assessed by laser Doppler flowmetry: SRH) in patients with hypertension. METHODS: In 75 consecutive hypertensive patients (61 +/- 11 years of age) without obvious cardiovascular (CV) disease and/or risk factors for CV disease other than hypertension, FMD, SRH, and homeostasis model assessment index of IR (HOMA(IR)) were measured. RESULTS: No significant relationship was observed between FMD with the parameters of SRH. In the univariate linear regression analysis, HOMA(IR) showed a significant correlation with the FMD (R(2) = 0.05, P < 0.05), but not with the parameters of SRH. Multivariate linear regression analysis demonstrated a significant association between HOMA(IR) and FMD, even after adjustments for covariates, including the use of medication for hypertension. (R(2) = 0.32, beta = -0.29, P = 0.02). CONCLUSIONS: The complication of IR in hypertensive patients without obvious CV disease/risk factors may be related to impaired macrovasculature rather than microvasculature reactivity, apart from the influence of antihypertensive medication on the reactivity of the vasculature and insulin sensitivity.

Synergistic relationship between changes in the pulse wave velocity and changes in the heart rate in middle-aged Japanese adults: a prospective study.

OBJECTIVES: Temporal associations between rates of increases in pulse wave velocity (PWV), a marker of arterial stiffness, and heart rate (HR) indices (baseline HR and changes in HR) as well as inflammatory markers were examined. METHODS: In 1795 apparently healthy Japanese individuals (mean age 39 +/- 8 years old), brachial-ankle PWV (baPWV) and serum C-reactive protein (CRP) levels were measured at the baseline and at the end of a 5-6-year follow-up period. RESULTS: Heart rate at the baseline examination and changes in HR during the follow-up period were significantly associated with the corresponding changes in baPWV during the study period (nonstandardized co-efficient = 0.14, 95% confidential interval = 8.14 x 10-0.19, P < 0.01) even after the adjustment for atherogenic risk factors. When individuals were divided into four groups categorized by baseline HR (higher or lower than median HR) and increase/decrease in HR during the study period, serum CRP levels and atherogenic risk factors were significantly worse in the individuals with high baseline HR accompanied by increased HR during the study period. There was no significant relationship between the changes in the baPWV and the changes in the serum CRP levels. Even after the adjustment for confounding factors, changes in baPWV were significantly higher in this group than the other three groups (P < 0.01). CONCLUSIONS: The study results suggest a synergistic role of high baseline HR and increase in HR during the study period in accelerating age-associated increases in PWV. Inflammation might not be a major factor for this relationship.

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.

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.