Yusuke Ohya

An association between uric acid levels and renal arteriolopathy in chronic kidney disease : a biopsy-based study

Uric acid (UA) can induce renal arteriolopathy in animal models. Whether there is an association between UA and renal arteriolopathy in patients with chronic kidney disease (CKD) is unknown. Here, we examined the cross-sectional association of serum UA levels with renal arteriolar hyalinosis and wall thickening. Arteriolar parameters were assessed by semiquantitative grading (max: grade 3) of arterioles in 167 patients with CKD (mean age, 42.4 years; 86 men and 81 women) who underwent renal biopsy. The mean serum UA level was 6.4u2009mgu2009dl−1. We observed hyalinosis in 94 patients (56%) and wall thickening in 119 patients (71%). As the UA level tertile increased, the proportion of higher-grade (grade 2 and 3) hyalinosis and wall thickening increased (hyalinosis, P<0.0001 and wall thickening, P=0.0002, for trend). Multiple logistic analysis adjusted for age ⩾40 years, sex, hypertension status, diabetes mellitus status and estimated glomerular filtration rate <60u2009mlu2009min−1 per 1.73u2009m2 showed that hyperuricemia (UA ⩾7u2009mgu2009dl−1) was significantly associated with a higher risk of hyalinosis (adjusted odds ratio: 3.13; 95% confidence interval: 1.23–7.94; P=0.02) and higher-grade (equal to or higher than the mean value) wall thickening (adjusted odds ratio: 2.66; 95% confidence interval: 1.11–6.38; P=0.03). Hence, these results suggest that hyperuricemia may be related to renal arteriolar damage in patients with CKD.

Metabolic Syndrome and Cognitive Decline Among the Oldest Old in Okinawa: In Search of a Mechanism. The KOCOA Project

The study aim was to test whether the metabolic syndrome or its components predicted cognitive decline among persons aged 80 years and older (mean 85.0 years). Participants were members of the Keys to Optimal Cognitive Aging Project, a prospective cohort study in Okinawa, Japan. Metabolic syndrome was assessed at baseline. Cognitive functions were assessed annually for up to 3 years. One hundred and forty-eight participants completed at least one follow-up with 101 participating in all three assessments and 47 participating in two of the three assessments. The mean and median duration of follow-up were 1.8 and 2 years, respectively. Metabolic syndrome and four components were not associated with decline in global and executive cognitive functions. However, high glycosylated hemoglobin was associated with decline in memory function at the second follow-up. Our study supports accumulating evidence that the positive association between metabolic syndrome and cognitive function might not hold for the oldest old.

Hyperuricemia predicts future metabolic syndrome: a 4-year follow-up study of a large screened cohort in Okinawa, Japan

The aim of this study was to determine whether hyperuricemia could predict future metabolic syndrome (MetS) in a large screened cohort of Japanese male and female subjects. We evaluated 5936 subjects (3144 male subjects, 2792 female subjects; mean age 48.7 years) who underwent health checkup programs in 2006 and 2010, who were MetS free in 2006. At baseline, hyperuricemia was detected in 927 male subjects (29.5%) and 276 female subjects (9.9%). Subjects with baseline hyperuricemia had significantly higher MetS prevalence in 2010 than those without (male subjects: 34.8 vs. 20.6%, P<0.0001; female subjects: 15.6 vs. 4.8%, P<0.0001). Compared with subjects in the first quintile of uric acid levels at baseline, the age-adjusted odds ratios (ORs) for MetS cumulative incidence among subjects in the third, fourth and fifth quintiles were, 1.8 (95% confidence interval (CI): 1.4–2.4: P<0.0001), 2.1 (95% CI: 1.6–2.8: P<0.0001) and 3.2 (95% CI: 2.4–4.1: P<0.0001), respectively, for male subjects and 2.4 (95% CI: 1.3–4.7: P=0.0075), 3.0 (95% CI: 1.6–5.7: P=0.0010) and 4.8 (95% CI: 2.6–8.8: P<0.0001), respectively for female subjects. Multivariable logistic analysis revealed that hyperuricemia was significantly associated with MetS cumulative incidence in male subjects (OR 1.5: 95% CI: 1.3–1.8, P<0.0001) and female (OR 2.0, 95% CI: 1.3–3.0, P<0.0001). In conclusion, hyperuricemia is a significant and independent predictor of MetS in Japanese male and female subjects. For both genders, MetS risk increases with increased serum uric acid levels.

Age- and sex-related effects on ankle–brachial index in a screened cohort of Japanese: the Okinawa Peripheral Arterial Disease Study (OPADS)

Aims Age-related change of ankle–brachial index (ABI) within the general population, especially <40 years, has not been determined in large population studies. We evaluated the value of the ABI by age- and sex-related differences in a screened cohort. Methods and results The ABI was examined in 13,211 participants (aged 21–89 years) in a health evaluation programme. The mean ABI was lower in women than in men at all ages. The ABI was lowest at <40 years, and increased with age; the maximum was at 60–69 years in both sexes. In participants <40 years, 186 (22%) of women and 108 (9.8%) of men had a borderline ABI (0.9–1.0). The prevalence of an ABI ≤0.9 in men increased with age, and sharply rose to 3.3% at ≥70 years. Conversely, women demonstrated a J-curve relationship, where the prevalence of an ABI ≤0.9 was lowest at 60–69 years (0.2%), and increased at <40 (0.9%) and ≥70 years (1.6%). The prevalence of atherosclerotic risk factors was higher in participants with an ABI ≤0.9 than those with an ABI >0.9 in men, both ≤60 and >60 years, and in women >60 years. In women ≤60 years, however, the prevalence of atherosclerotic risk factors in participants with an ABI >0.9 was as small as those with an ABI ≤0.9. Conclusion The ABI increased with age until 60–69 years, and was lower in women than in men. It is unlikely that a low ABI in younger healthy women always indicate that existence of arterial stenosis.

Trends in the Incidence of Stroke and Cardiovascular Risk Factors on the Isolated Island of Okinawa: The Miyakojima Study

BACKGROUNDnRapid deterioration of cardiovascular risk control, especially obesity, has occurred in Okinawa; this may affect cardiovascular disease incidence, including stroke.nnnMETHODSnCross-sectional field studies were conducted in 2 periods, 1988-1991 as the first period, and 2002-2005 as the second period, in the isolated island of Okinawa, Miyakojima. To evaluate population backgrounds related to cardiovascular risk factors, data from the health checkup programs conducted in 1987 and 2001 were surveyed.nnnRESULTSnTotal of 257 patients in the first period and 370 in the second were diagnosed with first-time stroke. The age-adjusted annual incidence rate of first-time stroke of the first and second periods was 124 and 144 per 100,000 standard population of Japan. The age-adjusted annual incidence rate showed an upward trend for brain infarction (50 to 73) and downward trend for brain hemorrhage (61 to 54); however, those trends were not significant. The health checkup surveys illustrated that blood pressure decreased in all age groups during the second survey period. However, the body mass index increased in patients aged 50 years or more. Fasting blood glucose levels of patients aged 30-79 years and non-HDL cholesterol levels of patients aged 50-79 years significantly increased.nnnCONCLUSIONSnIn Miyakojima, the incidence of first-time stroke and all of its subtypes did not change significantly between two periods, even though blood pressure decreased significantly in the second period. Metabolic deterioration may be associated with the upward trend in incidence of brain infarction.

Heart rate as a possible therapeutic guide for the prevention of cardiovascular disease

Epidemiologic evidence indicates that an elevated heart rate (HR) is an independent predictor of all-cause and cardiovascular (CV) mortality. Ivabradine, a pure HR-lowering agent, reduces CV events in patients with coronary artery disease (CAD) and chronic heart failure, and indicate that an HR greater than 70 b.p.m. is hazardous. These findings demonstrate not only that an elevated HR is an epiphenomenon of CV risk status but also that an elevated HR itself should be a therapeutic target. In addition, recent epidemiologic evidence demonstrates that the in-treatment HR or HR change predicts subsequent all-cause and CV mortality, independent of the HR-lowering strategy. Characteristics of the in-treatment HR or HR change are also important as possible therapeutic guides for risk management. However, there have been concerns regarding deleterious effects on CV event prevention owing to β-blocker-derived pharmacologic HR reduction. The potential role of HR and its modulation should be considered in future guidance documents.

Interrelationship between brachial artery function and renal small artery sclerosis in chronic kidney disease

Chronic kidney disease (CKD), characterized by senile inflammation, is a risk factor for cardiovascular disease. Conduit artery function and small artery structure relate to cardiovascular disease. We examined the correlations, determinants and interrelationships of arterial indices in association with CKD in a cross-sectional study of 139 patients (60% male; mean age 44 years) with CKD (stages 3–5, 39%) who underwent a renal biopsy. Conduit artery function and small artery sclerosis were assessed by brachial artery flow-mediated dilatation (FMD) and semiquantitative evaluation of small artery intimal thickening (SA-IT), respectively. The estimated glomerular filtration rate correlated with FMD (r=0.31, P=0.0002) and inversely correlated with SA-IT (r=−0.54, P<0.0001). Multiple regression analysis showed that FMD was inversely correlated with SA-IT and vice versa. In addition, high-sensitivity C-reactive protein (hs-CRP) was significantly correlated with SA-IT, but not FMD. Multiple logistic analysis revealed that higher hs-CRP concomitant with decreased FMD was further associated with the risk of severe SA-IT compared with their individual effects. These findings suggest that both conduit artery and small artery disease develop with mutual interaction in parallel with decreased kidney function. Coexistence of inflammation and conduit artery dysfunction may be closely related to renal small artery sclerosis in patients with CKD.

Beneficial Effect of Switching from a Combination of Angiotensin II Receptor Blockers other than Losartan and Thiazides to a Fixed Dose of Losartan/Hydrochlorothiazide on Uric Acid Metabolism in Hypertensive Patients

Among the angiotensin II receptor blockers (ARBs), losartan (LOS) has uricosuric action. The clinical benefits of LOS compared with those of other ARBs may be apparent when it is combined with diuretics, which have an unfavorable influence on serum uric acid (SUA). The effects of switching from combinations of ARBs other than LOS and thiazides to a fixed-dose combination comprising 50 mg LOS and 12.5 mg hydrochlorothiazide on blood pressure (BP), SUA, percent fractional excretion of UA (FEUA), and urine pH were assessed in 57 hypertensive outpatients. A significant reduction in BP was observed after 6 months (P < .01). The switching therapy significantly decreased SUA level (6.0 ± 1.3 vs. 5.7 ± 1.3 mg/dL, P < .01), which was accompanied by increases in FEUA (P < .01) and urine pH (P < .01). The change in SUA was negatively correlated with the changes in FEUA (P < .004) and estimated glomerular filtration rate (P < .05). The change in FEUA was positively correlated with the changes in urine pH (P < .05) but not with BP or estimated glomerular filtration rate. In a separate group of patients treated with ARBs other than LOS (n = 82), a significant BP reduction was observed, but no change in SUA or FEUA was observed. In conclusion, switching therapy decreased SUA level, which was accompanied by an increase in FEUA. This result may depend on the balance between LOS-induced inhibitory action of urate transporter 1 and hydrochlorothiazide-induced plasma volume reduction. The increase in urine pH plays a role in UA urinary excretion.

Very old adults with better memory function have higher low-density lipoprotein cholesterol levels and lower triglyceride to high-density lipoprotein cholesterol ratios: KOCOA Project.

We cross-sectionally examined which lipid profiles are associated with better cognitive function among those aged 80 and older, free of dementia (Clinical Dementia Rating ≤0.5), functionally independent, and community-dwelling. Our cohort consisted of 193 participants from the Keys to Optimal Cognitive Aging (KOCOA) Project, a prospective cohort study in Okinawa, Japan. Higher low-density lipoprotein cholesterol levels and lower triglyceride/high-density lipoprotein cholesterol (TG/HDL-C) ratios were associated with higher scores in memory performance after controlling for confounders. Further research is required to clarify the associations among LDL-C levels, TG/HDL-C ratios, and healthy cognitive aging.

Association between the intima-media thickness of the brachiocephalic trunk and white matter hyperintensity in brain MRI

The intima-media thickness (IMT) of the brachiocephalic trunk (BCT) can be measured using duplex carotid ultrasonography, which is used for imaging the common carotid artery (CCA). However, the clinical significance of the BCT-IMT has not been studied. We reviewed 1109 stroke-free participants in the registry of the Okinawa General Health Maintenance Association. We compared the association between the BCT-IMT or the CCA-IMT with deep and subcortical white matter hyperintensity (DSWMH). The BCT-IMT was correlated with the CCA-IMT, and like CCA-IMT, it increased with advancing age. The increase in both the BCT-IMT and the CCA-IMT quartiles was correlated with the development of DSWMH. The multivariate logistic regression analysis indicated that, as observed for the CCA-IMT, the increase in the BCT-IMT was associated with a higher prevalence of significant DSWMH (Fazekas grade 2 or 3 per 0.1u2009mm increase in IMT; OR 1.02, 95% confidence interval 1–1.04; P=0.04). The increase in quartiles of the BCT-IMT was only associated with a higher prevalence of significant DSWMH in subjects with lower CCA-IMT (1st and 2nd quartiles, R2=0.18, P<0.05) but not in subjects with higher CCA-IMT (3rd and 4th quartiles). Combinations of the CCA-IMT and BCT-IMT quartiles failed to have an additive effect on the prevalence of significant DSWMH. The BCT-IMT has a similar clinical profile to the CCA-IMT in terms of its association with DSWMH. However, the CCA-IMT and the BCT-IMT did not predict DSWMH in an additive manner, and distinct mechanisms might underlie the observed thickening of the IMT in the CCA and BCT.