Jiko Yamada

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.

Arterial stiffness and progression to hypertension in japanese male subjects with high normal blood pressure

Objectives This observational study was conducted to compare the significance of the relationship between arterial stiffness and progression to higher blood pressure categories among middle-aged Japanese men with high normal blood pressure (HNP), normal blood pressure (NRP) and optimal blood pressure (OPP). Methods and results During the 3-year observational period, 100 subjects with HNP developed hypertension (n = 475; 42 ± 9 years), and 175 of those with normal NRP (n = 581; 41 ± 8 years) and 249 of those with OPP (n = 702; 39 ± 8 years) showed progression to higher blood pressure categories. A binary logistic regression analysis adjusted for known risk factors revealed that values of the brachial-ankle pulse wave velocity, a surrogate marker of arterial stiffness, in the highest quartile, as compared with those in the lowest quartile, obtained at the start of the study were significantly predictive of the progression to hypertension [adjusted odds ratio = 9.4 (95% confidence interval, 3.0–29.8), P < 0.01]. The predictive value of this parameter for progression to higher blood pressure categories in subjects with HNP was more significant than that in those with NRP or OPP. Conclusions Increased arterial stiffness and elevated blood pressure may be mutually causally related, and it appears that the significance of this relationship may increase with increasing blood pressure, even in subjects without hypertension. Assessment of arterial stiffness may be more reliable for predicting the progression to hypertension in cases of HNP than in cases with NRP or OPP.

The relationships of cardiovascular disease risk factors to flow-mediated dilatation in Japanese subjects free of cardiovascular disease.

We examined the relationship of several cardiovascular disease (CVD) risk factors to flow-mediated vasodilatation of the brachial artery (FMD) and the clustering effect of risk factors on FMD in Japanese subjects free of CVD. In 819 Japanese subjects free of CVD (age 45±10 years, 611 men and 208 women), FMD correlated significantly with the Framingham risk points score (FRS) (r=−0.27, p<0.01). FMD was higher in subjects in the 1st tertile of the FRS range than in patients in either the 2nd or 3rd tertiles of the FRS range, but it was similar between the subjects in the 2nd and 3rd tertiles. FMD was found to have a significant independent negative correlation with age (β=−0.19, p < 0.01), gender (β=−0.024, p < 0.01) and smoking habit (β=−0.08, p = 0.02). In subjects ≥ 50 years of age, the FMD in men with one CVD risk factor, excluding smoking, was similar to that in men with no CVD risk factors. CVD risk factors did not attenuate FMD in women. Thus, in Japanese subjects free of CVD, FMD may be a useful marker of CVD risk, but it may not be a robust marker for endothelial damage related to clusters of CVD risk factors. Age, gender and smoking were independent variables related to the impairment of FMD, which therefore appears to be less applicable in subjects aged 50 or more, and especially in women.

Synergistic Acceleration of Arterial Stiffening in the Presence of Raised Blood Pressure and Raised Plasma Glucose

Arterial stiffness is recognized as a marker of arterial damage and an indicator of cardiovascular risk. This observational study was conducted to examine the synergistic effect of raised blood pressure (RBP; ≥130/85 mm Hg) and raised plasma glucose (RPG; ≥110 mg/dL) even at levels below those conventionally used to define hypertension and diabetes on the rate of increase of the pulse wave velocity (PWV) over a 3-year period in 2080 Japanese men (age 42±9 years). First, the subjects were classified into 4 groups based on the presence at the first examination of RBP, RPG, both abnormalities, or neither abnormality. The estimated annual rate of increase of the PWV was higher in subjects with both the abnormalities than in those with either abnormality alone or neither of the 2 abnormalities. Second, the subjects were also classified based on the evolutional status of these abnormalities during the study period; persistence of both of the abnormalities synergistically accelerated the rate of increase of the PWV (68.3±7.1 cm/s per year), as compared with the persistence of either abnormality alone (persistence of RBP alone: 18.2±1.6 cm/s per year; persistence of RPG alone: 21.2±7.4 cm/s per year) or persistence of neither abnormality (11.1±0.8 cm/s per year; P<0.01). Thus, blood pressure and fasting plasma glucose levels even below those defining hypertension and diabetes may synergistically lead to progression of arteriosclerotic arterial damage. This synergistic progression may contribute to the additive increases in the risk of cardiovascular events, at least in part.

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.

The effects of changes in the metabolic syndrome detection status on arterial stiffening: a prospective study.

We conducted a prospective study to examine the effects of alterations of the metabolic syndrome detection status on the rate of progression of arterial stiffness, which is recognized as a marker of arterial damage and an indicator of cardiovascular risk. Brachial-ankle pulse wave velocity as an index of arterial stiffening was recorded twice over a 3-year period in 2,080 Japanese men (age, 42±9 years). At the start of the prospective study, pulse wave velocity was higher in the subjects with metabolic syndrome (n=125) than in those without metabolic syndrome (n=1,955) even after adjusting for mean blood pressure. The annual rate of increase of the pulse wave velocity was higher in the group with persistent metabolic syndrome (27±51 cm/s/year, n=71) than in the group with regression of metabolic syndrome (6±39 cm/s/year, n=54) or the group in which metabolic syndrome was absent (13±37 cm/s/year, n=1,843; p<0.05) after adjustment for changes in blood pressure. In conclusion, the changes in the metabolic syndrome detection status of the subjects during the study period affected the annual rate of progression of arterial stiffening, and persistent metabolic syndrome during the study period was associated with acceleration of arterial stiffening in middle-aged Japanese men. On the other hand, resolution of metabolic syndrome may be associated with attenuation of the progression of arterial damage. Therefore, the increased cardiovascular risk associated with the presence of metabolic syndrome may be at least partly mediated by acceleration of the progression of arterial stiffening.

Heart rate elevation precedes the development of metabolic syndrome in Japanese men: a prospective study.

This observational study of Japanese men without metabolic syndrome (MetS) (age: 41±8 years) was conducted to clarify whether or not heart rate elevation precedes the development of full-blown MetS. MetS was defined based on two modifications of the criteria of the Japanese Expert Committee on the Diagnosis and Classification of Metabolic Syndrome. Premetabolic syndrome subjects were defined as those having one component of MetS with increased body mass index (BMI). Among the subjects without MetS (n=1,859 when the BMI criterion was ≥25 and n=2,020 when the BMI criterion was ≥27.5), the incidence of progression to full-blown MetS by the time of the second examination at the end of the 3-year study period was higher in the subjects with premetabolic syndrome than in those without it. The receiver-operator characteristic curve analysis and binary logistic regression analysis revealed that the odds ratio (OR) of a heart rate ≥69 beats/min at the first examination for progression to full-blown MetS by the time of the second examination was significant in subjects with premetabolic syndrome (BMI≥25: OR=3.64 [1.22–10.88]; BMI≥27.5: OR=3.67 [1.28–10.55]; p<0.05). Thus, heart rate elevation appears to precede the development of full-blown MetS in subjects with premetabolic syndrome. Heart rate seems to be a simple and useful marker for predicting the progression to full-blown MetS of middle-aged Japanese men with premetabolic syndrome.

Relationship between arterial stiffness and the risk of coronary artery disease in subjects with and without metabolic syndrome

We examined the influence of metabolic syndrome (MetS) on the relationship between arterial stiffness and the risk of coronary artery disease (CAD). In 396 subjects (age, 63±11 years) who underwent coronary angiography, multiple linear regression analysis demonstrated that the brachial-ankle pulse wave velocity (PWV), but not the presence of MetS, was a significant determinant of the number of diseased coronary arteries (β=0.10, p<0.05), even though both the brachial-ankle PWV and the number of diseased coronary arteries were higher in subjects with MetS (n=100) than in those without MetS (n=296). However, in subjects with MetS, multiple linear regression analysis demonstrated that the brachial-ankle PWV was not a significant determinant of the number of diseased coronary arteries. The brachial-ankle PWV values were classified into tertile ranges in subjects with and without MetS. The number of diseased coronary arteries increased significantly with an increase in the tertile number of the brachial-ankle PWV in the subjects without MetS (tertile 1=1.00±0.86, tertile 2=1.29±1.01, and tertile 3=1.45±1.05), but not in those with MetS. In conclusion, the results of this study suggest that arterial stiffness is a marker of the risk of CAD in subjects without MetS, whereas in subjects with MetS, the syndrome may directly produce clinically significant atherosclerotic stenosis of the coronary arteries independent of its significant promotion of the development of coronary atherosclerosis via an increase of arterial stiffness.

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.