[Show abstract][Hide abstract] ABSTRACT: Tissue inhibitors of metalloproteinases (TIMPs) regulate matrix metalloproteinase activity and maintain extracellular matrix homeostasis. Although TIMP-3 has multiple functions (e.g., apoptosis, inhibition of VEGF binding to VEGF receptor, and inhibition of TNFα converting enzyme), its roles in thermogenesis and metabolism, which influence energy expenditure and can lead to the development of metabolic disorders when dysregulated, are poorly understood. This study aimed to determine whether TIMP-3 is implicated in metabolism by analyzing TIMP-3 knockout (KO) mice. TIMP-3 KO mice had higher body temperature, oxygen consumption, and carbon dioxide production than wild-type (WT) mice, although there were no differences in food intake and locomotor activity. These results suggest that metabolism is enhanced in TIMP-3 KO mice. Real-time PCR analysis showed that the expression of PPAR-δ, UCP-2, NRF-1 and NRF-2 in soleus muscle, and PGC-1α and UCP-2 in gastrocnemius muscle, was higher in TIMP-3 KO mice than in WT mice, suggesting that TIMP-3 deficiency may increase mitochondrial activity. When exposed to cold for 8 hours to induce thermogenesis, TIMP-3 KO mice had a higher body temperature than WT mice. In the treadmill test, oxygen consumption and carbon dioxide production were higher in TIMP-3 KO mice both before and after starting exercise, and the difference was more pronounced after starting exercise. Our findings suggest that TIMP-3 KO mice exhibit enhanced metabolism, as reflected by a higher body temperature than WT mice, possibly due to increased mitochondrial activity. Given that TIMP-3 deficiency increases energy expenditure, TIMP-3 may present a novel therapeutic target for preventing metabolic disorders.
PLoS ONE 04/2014; 9(4):e94930. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Many reports have shown that brachial-ankle pulse wave velocity (baPWV) and carotid-femoral PWV are prognostic factors for cardiovascular diseases. We evaluated heart-carotid PWV, heart-femoral PWV (hfPWV), and femoral-ankle PWV (faPWV) using carotid and femoral sensors. Our objectives were to reveal correlations among PWVs and to determine the clinical importance of the respective PWVs in predicting the cardiovascular events. This prospective cohort study included 338 patients with essential hypertension (mean age 61.3 ± 0.7, mean follow-up period 6.5 ± 0.1 years) whose regional PWVs were measured. Primary end points were stroke, cardiovascular diseases (CVD), and death. Kaplan-Meier analysis showed that subjects with higher faPWV and baPWV had a significantly higher incidence of stroke (p = 0.0288 and 0.0277, respectively), subjects with higher hfPWV had a significantly higher incidence of CVD (p = 0.0212), subjects with higher baPWV and hfPWV had a significantly higher incidence of stroke + CVD (p = 0.0070 and 0.0463, respectively), and subjects with higher baPWV had a significantly higher mortality rate (p = 0.0367). Cox proportional hazard model revealed that baPWV was a significant risk factor for stroke + CVD after adjustment for traditional risk factors (relative risk: 14.50, p = 0.0288). Higher baPWV may be a risk factor for stroke and CVD, but the prognostic impact of regional PWVs is still unclear in patients with hypertension.
[Show abstract][Hide abstract] ABSTRACT: Background: Patients with mild-to-moderate essential hypertension in the HOMED-BP trial were randomly allocated to first-line treatment with a calcium channel blocker (CCB), angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB). Methods: We recruited 265 (93 for CCB, 71 for ACEI and 101 for ARB) patients who completed the genomic study. Home blood pressure was measured for 5 days off-treatment before randomization and for 5 days after 2-4 weeks of randomized drug treatment. Genotyping was performed by 500K DNA microarray chips. The blood pressure responses to the three drugs were analyzed separately as a quantitative trait. For replication of SNPs with p < 10(-4), we used the multicenter GEANE study, in which patients were randomized to valsartan or amlodipine. Results: SNPs in PICALM, TANC2, NUMA1 and APCDD1 were found to be associated with CCB responses and those in ABCC9 and YIPF1 were found to be associated with ARB response with replication. Conclusion: Our approach, the first based on high-fidelity phenotyping by home blood pressure measurement, might be a step in moving towards the personalized treatment of hypertension. Original submitted 29 April 2013; Revision submitted 14 August 2013.
[Show abstract][Hide abstract] ABSTRACT: The mean intima media thickness (IMT) and plaque score from carotid ultrasonography are both widely used to evaluate macrovascular atherosclerotic change. The present study sought to examine which parameter more effectively predicts patient prognosis. This hospital-based cohort study included 356 patients with essential hypertension (mean age: 62.4±0.6). We investigated how the mean IMT and plaque score correlated with various parameters, including pulse wave velocity (PWV), and we assessed the ability of the mean IMT and plaque score to predict cardiovascular events and total mortality. The mean IMT and plaque score significantly correlated with systemic atherosclerotic change, target organ damage, age and PWV. Subjects with a higher mean IMT and subjects with higher plaque scores showed higher frequencies of stroke and total mortality. In addition, subjects with marginal thickening of the intima media (mean0.7) showed a significantly higher frequency of stroke than subjects with a mean IMT of <0.7. After adjustment for traditional risk factors, plaque score was significantly and independently predictive of stroke, and the predictive ability of the plaque score for the onset of stroke was equivalent to that of PWV. The mean IMT and plaque score showed a nonsignificant trend of higher risk of mortality after adjustment for traditional risk factors. The mean IMT and plaque score were significantly correlated with systemic atherosclerotic change. We revealed that plaque score predicted the onset of stroke more accurately than the mean IMT, and the accuracy of this prediction was equivalent to that from PWV in hypertensive patients. We also showed that marginal thickening of the intima media (as measured by mean IMT) may be a predictor of stroke.Hypertension Research advance online publication, 4 July 2013; doi:10.1038/hr.2013.61.
Hypertension Research 07/2013; · 2.94 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To assess how visit-to-visit variability of SBP correlates with systemic atherosclerotic change and various prognoses.
Visit-to-visit SBP variability correlates with cardiovascular events. However, the mechanisms underlying the impact of visit-to-visit SBP variability on prognoses are poorly understood.
A total of 485 patients with essential hypertension from the Non-Invasive Atherosclerotic Evaluation in Hypertension (NOAH) study cohort were included. We analyzed the correlation between visit-to-visit SBP variability and multiple clinical parameters. Next, we prospectively examined the correlation of SBP variability and frequency of cardiovascular disease (CVD) and total mortality. Patients with higher SBP variability exhibited significantly higher rates of statin use, as well as higher pulse wave velocity (PWV), left-ventricular mass index (LVMI), plaque score, and resistive index of the common carotid artery; these patients also exhibited lower estimated glomerular filtration rate. Kaplan-Meier analysis demonstrated that patients with higher SBP variability have a significantly higher incidence of CVD and mortality rate. The hazard ratio of SBP variability for incidence of CVD was greatly diminished after adjustment for intima-media thickness, plaque score, and resistive index, and was slightly diminished after adjustment for PWV and LVMI. Visit-to-visit SBP variability remained an independent risk factor for mortality after adjustment.
Visit-to-visit SBP variability correlates significantly with systemic atherosclerotic change, incidence of CVD, and mortality rate. Altered arterial functions, such as macrovascular atherosclerosis and vascular resistance, are responsible for the correlations between visit-to-visit SBP variability and incidence of CVD.
[Show abstract][Hide abstract] ABSTRACT: Fixed-dose combination (FDC) therapy with telmisartan 40 mg+amlodipine 5 mg (T40/A5) is expected to achieve tight blood pressure (BP) control because of the strong efficacy and long half-life of each drug. The aims of this study were to evaluate the 24-h antihypertensive efficacy of T40/A5 FDC therapy and to explore differences that may arise owing to different administration times in Japanese patients whose hypertension was not controlled by 5 mg of amlodipine per day. In this randomized clinical trial, 44 patients who had been taking amlodipine 5 mg per day and did not achieve their optimal BP target were enrolled (mean age: 67.8±10.2 years). The subjects were then randomly assigned to a T40/A5 morning or evening administration group (22 patients per group). At baseline and 8 weeks after randomization, we evaluated clinical BP and various laboratory values and performed ambulatory BP monitoring (ABPM). Clinical and mean BP evaluated with ABPM at 8 weeks (24 h, daytime, nighttime and early morning) were significantly decreased compared with BP at baseline. There were no significant differences in the diurnal BP profile change from baseline to 8 weeks between subjects in the morning and evening administration groups. There were also no significant differences in the diurnal BP profile change from baseline to 8 weeks between subjects with or without metabolic syndrome. We conclude that T40/A5 FDC therapy significantly decreased the 24-h mean and clinical BP, independent of administration time, in patients whose hypertension was not controlled by 5 mg of amlodipine.Hypertension Research advance online publication, 21 February 2013; doi:10.1038/hr.2013.10.
Hypertension Research 02/2013; · 2.94 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: AIM: Several studies using experimental non-alcoholic fatty liver disease (NAFLD) models have shown that ezetimibe, an inhibitor of cholesterol absorption mainly in the intestine, not only protects against diet-induced hyperlipidemia, but also attenuates liver steatosis. The aim of this study was to clarify whether ezetimibe inhibits the development of NAFLD and to elaborate the mechanism of ezetimibe to inhibit the development of NAFLD using Fatty Liver Shionogi (FLS) mice, a spontaneous model of NAFLD/non-alcoholic steatohepatitis. METHODS: Male FLS mice at 20 weeks of age were divided into two groups (n = 7 in each group). Mice fed a normal laboratory chow, CRF-1 or CRF-1 containing 0.005% w/w ezetimibe (7 mg/kg per day) for 4 weeks. After 4-week treatment with ezetimibe, the livers of each group of mice were subjected to histological as well as molecular evaluation. RESULTS: Ezetimibe administration for 4 weeks was associated with improvement of steatosis and fibrosis of the liver in normal diet-fed FLS mice. Ezetimibe reduced hepatic reactive oxygen species generation and prevented ubiquitination and protein degradation of microsomal triglyceride transfer protein (MTP), a key molecule for very low-density lipoprotein assembly and export, via downregulation of the protein expression of Skp2 and CDC20. CONCLUSION: Ezetimibe not only reduced lipid synthesis in the liver, but also promoted lipid discharge from the liver by preventing post-translational degradation of MTP via a reduction of hepatic reactive oxygen species generation, leading to inhibition of the development of NAFLD.
[Show abstract][Hide abstract] ABSTRACT: ANRIL is a recently discovered long non-coding RNA encoded in the chromosome 9p21 region. This locus is a hotspot for disease-associated polymorphisms, and it has been consistently associated with cardiovascular disease, and more recently with several cancers, diabetes, glaucoma, endometriosis among other conditions. ANRIL has been shown to regulate its neighbor tumor suppressors CDKN2A/B by epigenetic mechanisms and thereby regulate cell proliferation and senescence. However, the clear role of ANRIL in the pathogenesis of these conditions is yet to be understood. Here, we review the recent findings on ANRIL molecular characterization and function, with a particular focus on its implications in human disease.
International Journal of Molecular Sciences 01/2013; 14(1):1278-92. · 2.34 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Aim: Arterial stiffness has been reported to correlate with cardiovascular disease (CVD). Brachial-ankle pulse wave velocity (baPWV) is easy to measure and has been used as a marker to evaluate arterial stiffness. The objective of the present study was to determine the cut-off value of baPWV for predicting cardiovascular prognosis in a prospective cohort study.Methods: Four hundred forty patients with essential hypertension were analyzed in study 1 with a mean follow-up of 6.3±0.1 years. Four hundred patients from study 1 who did not have a past history of CVD and/or stroke were analyzed in study 2 with a mean follow-up of 6.4±0.1 years. Stroke, CVD, and death were the primary endpoints.Results: Receiver operating characteristic (ROC) curve analysis revealed that 1750.0 cm/sec is an appropriate cut-off value for baPWV to predict the onset of stroke, CVD, stroke+CVD, and total mortality (area under curve: 0.576-0.719). A baPWV higher than 1750.0 may also be a significant and independent risk factor for the onset of CVD+stroke (relative risk: 2.048 (1.176-3.616), p= 0.0113 in study 1; relative risk: 1.920 (1.028-3.634), p=0.0408 in study 2).Conclusions: The present study indicates that 1750.0 cm/sec could be a useful cut-off value for baPWV to predict cardiovascular prognosis.
Journal of atherosclerosis and thrombosis 12/2012; · 2.93 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The development of atherosclerosis is associated with disturbances in mitochondrial function that impair effective adenosine triphosphate (ATP) production, increase generation of superoxide and induce subsequent apoptosis in vascular smooth muscle cells (VSMCs). As peroxisome proliferator-activated receptor gamma (PPARγ) has a potentially important role in the regulation of mitochondrial metabolism, we studied effects of the partial PPARγ agonist and angiotensin receptor blocker telmisartan, on mitochondria-related cellular responses in VSMC. In human VSMC, telmisartan increased ATP levels and activation of mitochondrial complex II, succinate dehydrogenase, reduced the release of H(2)O(2) and attenuated H(2)O(2)-induced increases in caspase 3/7 activity, a marker of cellular apoptosis. Eprosartan, an angiotensin II receptor blocker that lacks the ability to activate PPARγ, had no effect on these mitochondria-related cellular responses in VSMC. Studies in PPARγ-deficient VSMC revealed that the effects of telmisartan on mitochondrial function were largely independent of PPARγ although the presence of PPARγ modulated effects of telmisartan on H(2)O(2) levels. These findings demonstrate that telmisartan can have significant effects on mitochondrial metabolism in VSMC that are potentially relevant to the pathogenesis of cardiovascular disease and that involve more than just angiotensin receptor blockade and activation of PPARγ.Hypertension Research advance online publication, 20 December 2012; doi:10.1038/hr.2012.199.
Hypertension Research 12/2012; · 2.94 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In the classical renin angiotensin system (RAS), angiotensin II (Ang II) plays many important roles in cardiovascular disease and in kidney, brain, and other organs via the Ang II type 1 receptor (AT1). The RAS consists of many angiotensin peptides, including Ang (1-7), Ang (1-9), Ang (2-8), and Ang IV. Ang (1-7), produced by angiotensin-converting enzyme 2 (ACE2), has received attention because ACE2-deficient mice have heart failure. In addition, the proto-oncogene mas and insulin regulatory aminopeptidase (IRAP) have been identified as receptors for Ang (1-7) and Ang IV, respectively, accelerating investigations into both peptides. Many groups have suggested that the ACE2/Ang (1-7)/mas axis results in beneficial effects in cardiovascular disease, renal damage, and glucose intolerance and plays an independent role in kidney disease and glucose metabolism. On the other hand, Ang IV/IRAP strongly influences memory disturbance and protects against brain ischemia. Finally, the classical RASACE/Ang II/AT1 axis blockade yields beneficial effects in the context of organ damage, and additional modulation of ACE2/Ang (1-7)/mas or angiotensin IV/IRAP with this blockade results in even greater improvement. In the near future, new treatments targeting RAS and using new angiotensin peptide players might be developed for managing lifestyle-related disease.
Current pharmaceutical design 11/2012; · 4.41 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Recently, new parameters related to hypertension, such as variability in blood pressure and ambulatory arterial stiffness index (AASI), were demonstrated to correlate with arteriosclerotic change. In this study, we investigated the correlation between circadian variability in blood pressure/AASI and renal function. We also investigated differences in the clinical impact of 24 h, daytime and nighttime blood pressure variability on renal and systemic atherosclerotic changes. We analyzed data from 120 patients who underwent renal Doppler ultrasonography (RDU) and ambulatory blood pressure monitoring (ABPM) at our hospital ward, and investigated the correlation between circadian variability in blood pressure/AASI and renal function, including resistive index (RI) evaluated with RDU, which is thought to be a good indicator of renal vascular resistance. Subjects with higher circadian variability in systolic blood pressure (SBP) had significantly higher RI. Daytime variability in SBP correlated more strongly with RI than nighttime variability. Meanwhile, only nighttime variability, but not daytime variability, in SBP was related to carotid atherosclerosis. Similarly, AASI was significantly correlated with RI. Circadian variability in SBP and AASI were both significantly correlated with renal function. Daytime SBP s.d. was especially more strongly correlated with renal vascular resistance, and nighttime SBP s.d. was significantly correlated with intima-media thickness (IMT) and plaque score. These results indicate that evaluating both daytime and nighttime blood pressure variability enables an assessment of pathological conditions in hypertensive patients to prevent cardiovascular diseases.Hypertension Research advance online publication, 18 October 2012; doi:10.1038/hr.2012.162.
Hypertension Research 10/2012; · 2.94 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Aim: Adiponectin is a key molecule involved in metabolic syndrome. Single nucleotide polymorphisms (SNPs) in the ADIPOQ gene encoding adiponectin correlate with various diseases, such as diabetes mellitus; however, there is insufficient information about ADIPOQ SNPs and the onset of cardiovascular events.Methods: This hospital-based cohort study included 353 patients with essential hypertension (mean age, 62.9±0.6; mean follow-up period. 7.9±0.2 years) in whom ADIPOQ SNPs encoding G276T, I164T, A349G, and/or G967A amino acid changes were detected. We analyzed the correlation between ADIPOQ SNPs and various parameters, including pulse wave velocity (PWV), and assessed whether these SNPs could be risk factors for the onset of stroke, cardiovascular disease, and mortality.Results: Subjects with the T allele of G276T showed significantly lower HDL cholesterol, and significantly higher HbA1c and brachial-ankle PWV (baPWV). Kaplan-Meier analysis revealed that subjects with the T allele of G276T had a significantly higher frequency of stroke (p= 0.0489). The Cox proportional hazard model showed that the T allele of G276T was an independent and significant risk factor for stroke after adjusting for traditional risk factors (relative risk: 1.879, p= 0.0479); however, when adjusted for traditional risk factors and baPWV, the relative risk was significantly diminished (relative risk: 0.710, p= 0.4937). G276T was significantly correlated with dyslipidemia and glucose metabolism.Conclusion: The T allele of G276T was a significant and independent risk for the onset of stroke, and mediated the incidence of stroke through increased arterial stiffness.
Journal of atherosclerosis and thrombosis 10/2012; · 2.93 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Receptor of advanced glycation end products (RAGE) is reportedly linked with chronic inflammatory diseases due to aging or diabetes. The aim of this study was to show how -374 T/A RAGE has an impact on systemic vascular damage and renal function. The study subjects were a total of 468 essential hypertension patients from the Non-Invasive Atherosclerotic Evaluation in Hypertension (NOAH) study cohort. We prospectively examined the association of -374 T/A RAGE with their prognoses and investigated the correlation between -374 T/A RAGE and multiple clinical parameters. Kaplan-Meier analysis did not show a significant association of -374 T/A RAGE with total mortality or the prevalence of cardiovascular events. Carriers of the A allele showed a significantly higher prevalence of diabetes mellitus (DM) and lower estimated glomerular filtration rate (eGFR) than subjects without this allele. In subjects with DM, carriers of the A allele showed a significantly lower eGFR. These significant correlations were only seen in male subjects. Carriers of the A allele of -374 T/A RAGE show an independent risk of atherosclerosis and reduced renal function in male hypertensive patients with DM.
Clinical and Experimental Hypertension 09/2012; · 1.46 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background
Visit-to-visit blood pressure (BP) variability has been reported to be a major risk for cardiovascular events. Renin angiotensin system (RAS) gene polymorphisms are reportedly genetic risk factors for cardiovascular diseases and arterial stiffness. In this study, we aimed to reveal the relationship between visit-to-visit BP variability and RAS gene polymorphisms.Methods
Study subjects included 427 essential hypertension patients from the Non-Invasive Atherosclerotic Evaluation in Hypertension study cohort, whose BP was measured during at least six outpatient visits. We analyzed the correlation between visit-to-visit variability in systolic BP (SBP) and RAS gene polymorphisms.ResultsWe identified angiotensinogen M235T, angiotensin II type 1 receptor A1166C, and angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphisms. Only ACE I/D polymorphisms were correlated with variability in diastolic BP; no gene polymorphisms were correlated with variability in SBP.ConclusionsRAS gene polymorphisms, especially ACE I/D polymorphisms, might genetically influence the visit-to-visit BP variability in hypertensive patients.American Journal of Hypertension, 2012; doi:10.1038/ajh.2012.118American Journal of Hypertension (2012); doi:10.1038/ajh.2012.118.
American Journal of Hypertension 08/2012; · 3.67 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: ACE type 2 (ACE2) functions as a negative regulator of the renin-angiotensin system by cleaving angiotensin II (AII) into angiotensin 1-7 (A1-7). This study assessed the role of endogenous ACE2 in maintaining insulin sensitivity. Twelve-week-old male ACE2 knockout (ACE2KO) mice had normal insulin sensitivities when fed a standard diet. AII infusion or a high-fat high-sucrose (HFHS) diet impaired glucose tolerance and insulin sensitivity more severely in ACE2KO mice than in their wild-type (WT) littermates. The strain difference in glucose tolerance was not eliminated by an AII receptor type 1 (AT1) blocker but was eradicated by A1-7 or an AT1 blocker combined with the A1-7 inhibitor (A779). The expression of GLUT4 and a transcriptional factor, myocyte enhancer factor (MEF) 2A, was dramatically reduced in the skeletal muscles of the standard diet-fed ACE2KO mice. The expression of GLUT4 and MEF2A was increased by A1-7 in ACE2KO mice and decreased by A779 in WT mice. A1-7 enhanced upregulation of MEF2A and GLUT4 during differentiation of myoblast cells. In conclusion, ACE2 protects against high-calorie diet-induced insulin resistance in mice. This mechanism may involve the transcriptional regulation of GLUT4 via an A1-7-dependent pathway.
[Show abstract][Hide abstract] ABSTRACT: The purpose of the study was to investigate the association of serum uric acid (UA) levels in hypertensive patients with the prognosis for cardiovascular disease (CVD) and mortality. This hospital-based cohort study included 669 patients with essential hypertension. A questionnaire was used to identify patients in whom hypertensive complications had occurred, as well as causes of death. The primary end point of this study was new onset of stroke or CVD (new onset of angina pectoris, myocardial infarction or heart failure). We evaluated the baseline characteristics of patients, including UA levels, and assessed whether UA levels could be used to predict stroke and CVD. We also classified subjects into four groups according to the serum UA levels. During a mean follow-up period of 7.1±0.1 years, 71 strokes, 58 cases of CVD and 64 deaths were recorded. Kaplan-Meier analysis revealed that subjects in the high UA group had a higher frequency of stroke and CVD (P=0.0120) and total mortality (P=0.0021). A Cox proportional hazard model determined that, after adjusting for traditional risk factors, serum UA levels were predictive of CVD (relative risk=1.30; P=0.0073), stroke and CVD (relative risk=1.19; P=0.0141), mortality (relative risk=1.23; P=0.0353) and stroke CVD and mortality (relative risk=1.19; P=0.0083), but not stroke (P=0.4268). The significant correlations were particularly marked in women. Serum UA levels may be an independent risk factor for stroke and CVD in patients with essential hypertension, particularly women.Hypertension Research advance online publication, 28 June 2012; doi:10.1038/hr.2012.99.
Hypertension Research 06/2012; · 2.94 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Aging is well known as one of the major causes of a reduced glomerular filtration rate (GFR). The resistive index (RI) measured by renal Doppler ultrasonography (RDU) is thought to be a good indicator of renal vascular resistance induced by arteriosclerosis. In this study, we investigated whether RI could be used to evaluate the pathogenesis of renal damage or the mechanisms of reduction of renal function by aging.
We investigated the correlation between RI and multiple clinical parameters and the influence of aging on the renal hemodynamic status of 194 in-patients (mean age 66.2 years) who underwent RDU at our hospital between February 2009 and July 2010.
RI was significantly correlated with the age, estimated GFR (eGFR), diastolic blood pressure, pulse pressure, and degree of albuminuria. Subjects aged ≥75 years showed a significantly higher correlation coefficient between eGFR and RI. RI showed a stronger correlation with age in subjects aged ≥75 years compared to eGFR.
The present study showed that renal vascular resistance and intra-renal arteriosclerosis had a greater impact on renal function in older than younger subjects, reflecting the possible mechanisms of renal function reduction due to aging.
Clinical and Experimental Nephrology 04/2012; 16(5):786-91. · 1.71 Impact Factor