Mari Odaira

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.

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 × 10−2–0.19, 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.

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.

Predictors of Progression From Prehypertension to Hypertension in Japanese Men

BACKGROUND This 3-year prospective study in middle-aged Japanese men with prehypertension examined the usefulness of the plasma levels of C-reactive protein (CRP) and the brachial-ankle pulse wave velocity (baPWV) as predictors of the development to hypertension as compared with other previously proposed markers, such as the age, initial blood pressure, heart rate, obesity, smoking, and alcohol intake. METHODS AND RESULTS Among 777 men with prehypertension (42 +/- 8 years old), hypertension developed in 58 men during the observation period. Significant elevation of blood pressure during this 3-year follow-up was not observed in some, but not all, subjects. Univariate linear regression analysis demonstrated that baPWV, body mass index (BMI), age, and alcohol intake, but not plasma levels of CRP, heart rate, and smoking, on the first examination were significant variables related to the changes in systolic blood pressure from the first examination to the second examination. Multivariate linear regression analysis confirmed that baPWV and BMI were weak but significant independent variables related to the changes in systolic blood pressure (R(2) = 0.03). The logistic regression analysis demonstrated that baPWV >13.5 m/s (adjusted odds ratio = 3.32 (1.79-6.15)) and BMI >25.0 (adjusted odds ratio = 2.27 (1.25 - 4.13)) were significant predictors of future hypertension independent of blood pressure on the first examination. CONCLUSION This 3-year prospective study suggested that the baPWV and BMI, but not plasma CRP levels, are not powerful but significant independent markers to identify middle-aged Japanese men with prehypertension at high risk for 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.

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.

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.

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. METHODSANDRESULTS 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).