Association between pre-treatment with statin and its inhibitory effect on the onset of coronary artery disease at the time of coronary computed tomography angiography: a new look at an old medication.

Coronary artery stenosis is often advanced by the time coronary computed tomography angiography (CCTA). Statins are the most important anti-lipidemic medication for improving the prognosis of coronary artery disease (CAD) patients. Although lipid-lowering therapy using statins appears to have been established as a method for preventing CAD, there remains the problem that CAD cannot be completely suppressed. In this study, we investigated whether pre-treatment with statin could significantly inhibit the onset of CAD when patients received CCTA for screening of CAD. The subjects were 1164 patients who underwent CCTA as screening for CAD. CAD was diagnosed when 50% or more coronary stenosis was present in the coronary arteries. Patient backgrounds were investigated by age, gender, body mass index, coronary risk factors [family history of cardiovascular diseases, smoking history, hypertension (HTN), diabetes mellitus (DM), dyslipidemia, chronic kidney disease (CKD) or metabolic sydrome] and medications. Patients were classified into two groups according to the presence or absence of statin pre-administration during CCTA [statin (-) group (n = 804) and (+) group (n = 360)]. Compared with the statin (-) group, the statin (+) group was significantly older and had higher rates of family history, HTN, and DM. The statin (+) group had a significantly higher % CAD than the statin (-) group. Serum levels of low-density lipoprotein cholesterol (LDL-C) were significantly lower in the statin (+) group than in the statin (-) group. There was no significant difference in either high-density lipoprotein cholesterol levels or triglyceride levels between the two groups. Age, male gender, HTN, DM and pre-treatment with statin were all associated with CAD (+) in all patients. In addition, factors that contributed to CAD (+) in the statin (-) group were age, male gender, and DM, and factors that contributed to CAD (+) in the statin (+) group were age, smoking, HTN and % maximum dose of statin. At the time of CCTA, the statin (+) group had a high rate of CAD and coronary artery stenosis progressed despite a reduction of LDL-C levels. To prevent the onset of CAD, in addition to strict control of other coronary risk factors (HTN etc.), further LDL cholesterol-lowering therapy may be necessary.

Endothelial lipase mediates efficient lipolysis of triglyceride-rich lipoproteins.

Triglyceride-rich lipoproteins (TRLs) are circulating reservoirs of fatty acids used as vital energy sources for peripheral tissues. Lipoprotein lipase (LPL) is a predominant enzyme mediating triglyceride (TG) lipolysis and TRL clearance to provide fatty acids to tissues in animals. Physiological and human genetic evidence support a primary role for LPL in hydrolyzing TRL TGs. We hypothesized that endothelial lipase (EL), another extracellular lipase that primarily hydrolyzes lipoprotein phospholipids may also contribute to TRL metabolism. To explore this, we studied the impact of genetic EL loss-of-function on TRL metabolism in humans and mice. Humans carrying a loss-of-function missense variant in LIPG, p.Asn396Ser (rs77960347), demonstrated elevated plasma TGs and elevated phospholipids in TRLs, among other lipoprotein classes. Mice with germline EL deficiency challenged with excess dietary TG through refeeding or a high-fat diet exhibited elevated TGs, delayed dietary TRL clearance, and impaired TRL TG lipolysis in vivo that was rescued by EL reconstitution in the liver. Lipidomic analyses of postprandial plasma from high-fat fed Lipg-/- mice demonstrated accumulation of phospholipids and TGs harboring long-chain polyunsaturated fatty acids (PUFAs), known substrates for EL lipolysis. In vitro and in vivo, EL and LPL together promoted greater TG lipolysis than either extracellular lipase alone. Our data positions EL as a key collaborator of LPL to mediate efficient lipolysis of TRLs in humans and mice.

Association between major adverse cardiovascular events and pentraxin-3 in patients who have undergone coronary computed tomography angiography: from the FU-CCTA registry.

Chronic vasculitis is considered to be associated with future cardiovascular events. Here, we present major cardiovascular events (MACEs) in patients who underwent coronary computed tomography angiography (CCTA) for screening for coronary artery disease (CAD), and the association between MACEs and the inflammation marker pentraxin (PTX)-3 or highly sensitive C-reactive protein (hsCRP). The patients who underwent CCTA for the purpose of screening for CAD at Fukuoka University Hospital (FU-CCTA registry), 456 patients with suspected CAD or at least one cardiovascular risk factor were followed for up to 5 years. The levels of PTX-3 and hsCRP in blood were measured at the time of CCTA, and the patients were divided into two groups according to the presence (MACEs group) or absence (non-MACEs group) of MACEs. There were no differences in PTX-3 or hsCRP between the MACEs (-) and MACEs ( +) groups in all patients. A multivariate analysis related to the presence or absence of MACEs by logistic regression analysis of inflammation factors (PTX-3 and hsCRP) in addition to conventional risk factors as independent variables was performed. PTX-3 was a predictor of MACEs in males, whereas smoking, but not PTX-3, was a predictor of MACEs in females. PTX-3 could be a predictor of MACEs in males, but not females.

ILRUN, a Human Plasma Lipid GWAS Locus, Regulates Lipoprotein Metabolism in Mice.

RATIONALE: Single-nucleotide polymorphisms near the ILRUN (inflammation and lipid regulator with ubiquitin-associated-like and NBR1 [next to BRCA1 gene 1 protein]-like domains) gene are genome-wide significantly associated with plasma lipid traits and coronary artery disease (CAD), but the biological basis of this association is unknown. OBJECTIVE: To investigate the role of ILRUN in plasma lipid and lipoprotein metabolism. METHODS AND RESULTS: ILRUN encodes a protein that contains a ubiquitin-associated-like domain, suggesting that it may interact with ubiquitinylated proteins. We generated mice globally deficient for Ilrun and found they had significantly lower plasma cholesterol levels resulting from reduced liver lipoprotein production. Liver transcriptome analysis uncovered altered transcription of genes downstream of lipid-related transcription factors, particularly PPARα (peroxisome proliferator-activated receptor alpha), and livers from Ilrun-deficient mice had increased PPARα protein. Human ILRUN was shown to bind to ubiquitinylated proteins including PPARα, and the ubiquitin-associated-like domain of ILRUN was found to be required for its interaction with PPARα. CONCLUSIONS: These findings establish ILRUN as a novel regulator of lipid metabolism that promotes hepatic lipoprotein production. Our results also provide functional evidence that ILRUN may be the casual gene underlying the observed genetic associations with plasma lipids at 6p21 in human.

Associations between smoking habits and major adverse cardiovascular events in patients who underwent coronary computed tomography angiography as screening for coronary artery disease.

We analyzed whether smoking was associated with major adverse cardiovascular events (MACE) and the progression of coronary atherosclerosis as assessed by coronary computed tomography angiography (CCTA) as screening for coronary artery disease (CAD). We enrolled 443 patients who had all undergone CCTA and either were clinically suspected of having CAD or had at least one cardiovascular risk factor. We divided the patients into smoking (past and current smoker) and non-smoking groups and into males and females, and evaluated the presence of CAD, severity of coronary atherosclerosis and MACE (cardiovascular death, ischemic stroke, acute myocardial infarction and coronary revascularization) with a follow-up of up to 5 years. %CAD and the severity of coronary atherosclerosis in the smoking group were significantly higher than those in the non-smoking group. %MACE in males and smokers were significantly higher than those in females and non-smokers, respectively. Interestingly, Kaplan-Meier curves also showed that female non-smokers enjoyed significantly greater freedom from MACE than female smokers (p = 0.007), whereas there was no significant difference in freedom from MACE between male non-smokers and male smokers (p = 0.984). Although there were no significant predictors of MACE in all patients according to a multiple logistic regression analysis, smoking was useful for predicting MACE in females, but not males. In conclusion, smoking was significantly associated with MACE in females, but not males, who underwent CCTA as screening for CAD.

Differences in lesion characteristics and patient background associated with the medium-term clinical outcomes of bare-metal and first-, second- and third-generation drug-eluting stents.

We investigated the lesion characteristics and patient background factors associated with the medium-term incidence of major adverse cardiac events (MACEs) for bare-metal stents (BMS) and 1st-, 2nd- and 3rd-generation drug-eluting stents (DES) using the PCI-Registry (FU-Registry). Between January 2003 and March 2016, 2967 cases/3508 lesions for which percutaneous coronary intervention was performed at Fukuoka University Hospital and related facilities were enrolled. Patients were divided into BMS and 1st-, 2nd- and 3rd-generation drug-eluting stent (DES) groups. The incidence of MACEs in the BMS group (26.2%) was significantly higher than those in the 1st, 2nd and 3rd DES groups (18.0%, 12.5%, and 11.0%, respectively). The incidence of MACEs in the BMS group was strongly associated with insulin use, hemodialysis, low high-density lipoprotein cholesterol, stent minimum lesion diameter, stent length, severe calcification and a small vessel diameter of less than 2.5 mm. Some of these factors showed no association with MACEs among the drug-elution groups, and only hemodialysis, arteriosclerosis obliterans and severe calcification showed a strong correlation in the 2nd DES group. In the 3rd DES group, none of the factors considered were associated with MACEs. In conclusion, in stent implantation, the number of factors associated with MACEs has gradually decreased as the stent generation increased.

Association between high-density lipoprotein cholesterol levels and major adverse cardiovascular events in patients who underwent coronary computed tomography angiography: FU-CCTA registry.

It is unclear whether higher levels of serum high-density lipoprotein cholesterol (HDL-C) prevent major adverse cardiovascular events (MACE). We prospectively evaluated 501 patients who had undergone coronary computed tomography angiography at Fukuoka University Hospital and either were clinically suspected of having coronary artery disease (CAD) or had at least one cardiovascular risk factor with a follow-up of up to 5 years. The primary endpoint was MACE (cardiovascular death, ischemic stroke, acute myocardial infarction and coronary revascularization). The patients were divided into tertiles according to the HDL-C level: 47 mg/dl ≥ HDL-C level [n = 167, lower HDL-C level (L-HDL)], 58 mg/dl ≥ HDL-C level ≥ 48 mg/dl [n = 167, middle HDL-C level (M-HDL)] and HDL-C level ≥ 59 mg/dl [n = 167, higher HDL-C level (H-HDL)] groups. There were significant differences in %CAD among the L-HDL, M-HDL and H-HDL groups. Unexpectedly, there was no difference in %MACE between M-HDL and H-HDL, although %MACE in M-HDL was significantly lower than that in L-HDL (p < 0.05). By a multivariate logistic regression analysis, MACE in H-HDL-C was independently associated with diabetes mellitus (DM) (p = 0.03). A Kaplan-Meier curve according to the HDL subgroup indicated that M-HDL, not H-HDL, enjoyed the greatest freedom from MACE among the 3 groups (log-rank test p = 0.047). Finally, the results of a Cox regression model indicated that L-HDL and H-HDL had significantly higher risk of MACE than M-HDL. In conclusions, patients with middle HDL-C levels, not higher HDL-C levels, showed the greatest freedom from MACE. Patients with higher HDL-C levels need to be strictly managed for DM to prevent MACE.

Association between lipid profile and endothelial dysfunction as assessed by the reactive hyperemia index.

INTRODUCTION: We investigated the associations between endothelial dysfunction (ED) as evaluated by the reactive hyperemia index (RHI) obtained using Endo-PAT2000® and atherosclerotic risk factors in patients who underwent coronary artery angiography (CAG). METHODS: The subjects consisted of 191 patients who were clinically suspected to have CAD and underwent CAG, and in whom we could perform Endo-PAT2000®. We divided the patients into ED (RHI<1.67, n = 71) and non-ED (RHI≥1.67, n = 120) groups. RESULTS: The ED group was significantly older and showed a higher ratio of low-density lipoprotein cholesterol (LDL-C) to high-density lipoprotein cholesterol (HDL-C) (L/H) than the non-ED group. A multivariate logistic regression analysis was performed to examine the associations between the presence of ED and age, gender, and BMI in addition to L/H. Age [odds ratio (OR) = 1.03, p = .02] and L/H (OR = 1.64, p = .01) were identified as significant independent markers of the presence of ED. Next, we divided 122 patients with statin treatment into ED (n = 40) and non-ED (n = 82) groups. The ED group tended to have higher L/H and lower HDL-C than the non-ED group. HDL-C (OR = 0.95, p = .01) and age (OR = 1.05, p = .04) were identified as independent markers of the presence of ED. CONCLUSIONS: L/H was an independent marker of the presence of ED in patients without dyslipidemia. In addition, among patients with statin treatment, HDL-C was an independent marker of the presence of ED.

Impact of visit-to-visit variability in blood pressure on coronary plaque as assessed by integrated backscatter intravascular ultrasound.

INTRODUCTION: Visit-to-visit variability (VVV) in blood pressure (BP) has been reported to be a strong predictor of cardiovascular disease. However, the association between VVV in BP and coronary plaque composition has not been fully elucidated. METHODS: One hundred-two consecutive patients with coronary artery disease (CAD) who underwent percutaneous coronary intervention (PCI) using integrated backscatter (IB) intravascular ultrasound (IVUS), and who had at least six clinic visits a year before PCI were included. We measured systolic and diastolic BP (SBP and DBP) at each visit and determined VVV in BP expressed as the standard deviation of the average BP. Grayscale and IB IVUS examinations were performed for the culprit lesion of a coronary artery just before PCI. RESULTS: There were no significant associations between the average SBP or DBP and various IVUS parameters. However, VVV in SBP was positively correlated with both the percentage (%) of atheroma volume (ß = 0.23, p = .02) and % lipid volume (ß = 0.53, p < .0001). VVV in DBP was positively correlated with % lipid volume (ß = 0.24, p = .01), while there was no significant correlation between VVV in DBP and % atheroma volume. A  multivariable linear regression analysis showed that VVV in SBP was independently associated with % atheroma volume (p = .04) and % lipid volume (p < .001). CONCLUSIONS: Larger VVV in SBP was significantly associated with an increased plaque burden and lipid composition at the culprit lesion of a coronary artery in CAD patients. The improvement of VVV in SBP may contribute to the regression and stabilization of coronary plaques.

Changes in the function of angiotensin II type 1 receptor due to cholesterol depletion from cell membrane.

Blockers of G-protein coupled receptors (GPCRs), angiotensin II (Ang II) type 1 (AT1) receptor and ß1-adrenergic (Ad) receptor, have been shown to improve the prognosis of cardiovascular disease. Cholesterol molecules in the cell membrane are needed to stabilize GPCRs as well as the cell membrane itself. We determined whether the functions of AT1 and ß1-Ad receptors were changed by cholesterol depletion from cardiovascular cell membranes. Ang II-induced inositol phosphate production through AT1 receptor was suppressed by cholesterol depletion from cell membranes using rosuvastatin or methyl-ß-cyclodextrin (MßCD), whereas isoproterenol-induced cyclic AMP production through ß1-Ad receptor did not change after cholesterol depletion. In addition, the binding affinities of Ang II and AT1 receptor blocker after cholesterol depletion were significantly lower than those before depletion. Although AT1 receptor expression levels did not change after cholesterol depletion, the expression levels of AT1 receptor that could bind to Ang II significantly decreased after depletion. The changes in the structure of AT1 receptor due to depletion were confirmed by substituted-cysteine accessibility mapping. In conclusion, Ang II-induced activation of AT1 receptor is reduced without affecting the function of ß1-Ad receptor after cholesterol depletion from cardiovascular cell membranes.

Correction to: Association between plasma levels of PCSK9 and the presence of coronary artery disease in Japanese.

In the original publication of the article, Tables 1, 2 and 3 was published incorrectly. Unnecessary inequality symbols were added to all the numbers in the 'p value' of Tables 1, 2 and 3. The correct tables should be as follows.

Importance of measurement of the diameter of the distal radial artery in a distal radial approach from the anatomical snuffbox before coronary catheterization.

Coronary catheterization by a distal radial approach at the site of the anatomical snuffbox has recently been reported to be both safe and useful. No data are available on the diameter of the distal radial artery (DRA) in Japan, and it is unclear whether the DRA is large enough to withstand the insertion of a conventional sheath by a traditional radial approach. We enrolled 142 patients who underwent coronary catheterization and evaluated the vessel diameter of the DRA using ultrasound. The vessel diameter of the DRA in the anatomical snuffbox (2.6 ± 0.5 mm) was significantly smaller than that of the proximal radial artery (PRA) at the conventional puncture site (3.1 ± 0.4 mm). The difference in vessel diameter between the DRA and PRA was 0.5 ± 0.4 mm, and the DRA/PRA ratio was 0.8 ± 0.1. Although the vessel diameter of the DRA was positively correlated with that of the PRA (r = 0.66, p < 0.0001), in some cases the DRA was extremely small compared to the PRA. When the vessel diameter of the DRA is smaller than the outer diameter of the sheath scheduled for use, we should puncture the PRA at the outset. We could perform coronary catheterization by a distal radial approach without major bleeding or adverse events, and there was no radial artery occlusion at the site of the anatomical snuffbox or the forearm. For coronary catheterization by a distal radial approach, we should evaluate whether there is sufficient vessel diameter using ultrasound before the procedure. In addition, this approach can be an effective option from the viewpoint of radial artery preservation.

Association between plasma levels of PCSK9 and the presence of coronary artery disease in Japanese.

The ability of pro-protein convertase subtilisin/kexin type 9 (PCSK9) levels to predict the presence or severity of coronary artery disease (CAD) remains controversial. The purpose of this study was to investigate these associations. We enrolled 393 patients who were clinically suspected to have CAD or who had at least one cardiac risk factor and underwent multidetector-row computed tomography coronary angiography. The presence of CAD (≥50% coronary stenosis), the number of significantly stenosed coronary vessels, and plasma levels of PCSK9 by ELISA were analyzed. Plasma PCSK9 levels (log-transformed data) were significantly associated with the presence of CAD. Next, we divided the patients into two groups (non-statin and statin groups) according to statin treatment. PCSK9 levels in the non-statin group were significantly lower than those in the statin group. There were no significant differences in PCSK9 levels between the absence and presence of CAD in the statin group. However, in the non-statin group, PCSK9 levels in patients with CAD were significantly higher than those in patients without CAD. PCSK9 levels, in addition to age, gender, BMI, DM and HDL-C, were independently associated with the presence of CAD by a multivariable analysis. In conclusion, our results demonstrated that plasma PCSK9 levels may be a marker for evaluating the presence of CAD.

Correction to: Association between discordance of LDL-C and non-HDL-C and clinical outcomes in patients with stent implantation: from the FU-Registry.

Unfortunately, the Fig. 1 was published incorrectly in the original publication of the article. The correct figure is as below.

Influence of chronic kidney disease on coronary plaque components in coronary artery disease patients with both diabetes mellitus and hypertension.

Chronic kidney disease (CKD) is well known to be associated with an increased incidence of coronary artery disease (CAD). Diabetes mellitus (DM) and hypertension (HTN), both of which are traditional risk factors for CAD, are the two most common causes of CKD. However, the influence of CKD on coronary atherosclerosis in CAD patients who have both DM and HTN remains uncertain. In these patients, we examined the relationship between CKD and coronary plaque using integrated backscatter intravascular ultrasound (IB IVUS). Two hundred two CAD patients with both DM and HTN who underwent percutaneous coronary intervention using IB IVUS were included. The patients were divided into two groups: CKD group (n = 106) and non-CKD group (n = 96). Gray-scale and IB IVUS examinations were conducted for the non-culprit segment of a coronary artery. As a result, although there was no significant difference in the percentage of plaque volume, the percentage of lipid volume was significantly higher in the CKD group than in the non-CKD group [median (IQR): 56.7% (45.4-67.0%) vs. 52.0% (38.3-60.2%), p = 0.03]. In all of the patients, estimated glomerular filtration rate levels were negatively correlated with the percentage of lipid volume (r = - 0.15, p = 0.03) and positively correlated with the percentage of fibrosis volume (r = 0.15, p = 0.04). A multivariate regression analysis showed that CKD was an independent predictor associated with the increased lipid volume (ß = 0.15, p = 0.047) and decreased fibrosis volume (ß = - 0.16, p = 0.03) in coronary plaques. In conclusion, among CAD patients who had both DM and HTN, CKD was associated with lipid-rich coronary plaques. CKD may contribute to the vulnerability of coronary plaque in these very high-risk patients.

Unique mode of binding between angiotensin II type 1 receptor and its blockers.

BACKGROUND: We hypothesized that the 5-oxo-1,2,4-oxadiazole moiety of azilsartan (AZL), which represents a small difference in the molecular structures of AZL and candesartan (CAN) [angiotensin II type 1 receptor (AT1R) blockers], may be responsible for the molecular effects of AZL. METHODS: We examined the binding affinities of AZL and CAN to AT1R, along with their ability to block receptor activity. A competition binding study, inositol phosphate (IP) production assay and extracellular signal-regulated kinase (ERK) assay were performed using wild-type (WT) and mutants AT1R-transfected cells. RESULTS: The binding affinities of CAN and AZL were reduced by > 5-fold for Y35F, W84F, R167K, K199Q and I288A compared with WT. In addition, AZL showed a > 5-fold reduction in its binding affinity to V108A. CAN and AZL exhibited > 20-fold and > 100-fold reductions in binding affinity to R167K, respectively. The loss of binding affinity of AZL to R167K was greater than that of CAN. CAN-7H exhibited a > 10-fold reduction in binding affinity to R167K compared with CAN. On the other hand, the binding affinity of AZL-7H to R167K was comparable to that of AZL. While 10-6M CAN and CAN-7H partly blocked Ang II-induced IP production in R167K, 10-6M AZL and AZL-7H did not. In addition, 10-6M CAN, but not 10-6M AZL, partly blocked Ang II-induced ERK activation in R167K. CONCLUSIONS: The interaction between 5-oxo-1,2,4-oxadiazole in AZL and Arg167 in the AT1R appears to be more important than the interaction between the tetrazole ring in CAN and Arg167.

Impact of the triglyceride level on coronary plaque components in female patients with coronary artery disease treated with statins.

Several studies have reported that elevated triglyceride (TG) levels may be more strongly associated with an increased risk of coronary artery disease (CAD) in females than in males. We examined gender differences in the relationship between TG levels and coronary atherosclerosis using integrated backscatter intravascular ultrasound (IB IVUS) in CAD patients treated with statins. Three hundred seventy-eight CAD patients (105 females and 273 males) who underwent percutaneous coronary intervention using IB IVUS, and who were already receiving statin treatment, were included. Gray-scale and IB IVUS examinations were performed for the non-culprit segment of a coronary artery and fasting serum TG concentrations were measured. We found that TG levels were significantly correlated with increased lipid (r = 0.40, p < 0.001) and decreased fibrous (r = - 0.37, p < 0.001) plaque components in females, but not in males. Low-density lipoprotein cholesterol and high-density lipoprotein cholesterol levels were not related to either the gray-scale or IB IVUS parameters in both genders. After adjustment for conventional coronary risk factors by a multivariate stepwise regression analysis, higher TG levels in females were independently associated with increased lipid (ß = 0.31, p< 0.001) contents in coronary plaques. In conclusion, among CAD patients treated with statins, TG levels were associated with lipid-rich coronary plaques in females, but not in males. TG levels may be more important indicators of residual risk after statin treatment in females than in males.

Association between discordance of LDL-C and non-HDL-C and clinical outcomes in patients with stent implantation: from the FU-Registry.

It is not yet clear whether the discordance of low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C) predicts the follow-up clinical outcome (major adverse cardiovascular events: MACEs) in patients with coronary stent implantation. Among 2015 patients with coronary stent implantation (Fukuoka University [FU]-Registry), excluding those with acute coronary syndrome or hemodialysis, we selected 801 patients who had undergone successful stent implantation with a follow-up until 18 months, and classified them into 3 groups according to baseline LDL-C and non-HDL-C levels [percentile(P)non-HDL-C more than (P)LDL-C, (P)non-HDL-C equal to (P)LDL-C, and (P)non-HDL-C less than (P) LDL-C]. We found that the discordance of (P)LDL-C and (P)non-HDL-C was not a significant predictor of MACEs. Higher LDL-C level was consistently and independently associated with higher incidences of MACEs after controlling for conventional risk factors and the type of stent used by multivariate Cox regression analyses. In conclusion, LDL-C levels are more important than non-HDL-C levels and the discordance of LDL-C and non-HDL-C levels as predictors of MACEs in patients with stable angina after stent implantation.

Associations between microalbuminuria and parameters of flow-mediated vasodilatation obtained by continuous measurement approaches.

The associations between microalbuminuria and various parameters of flow-mediated vasodilatation (FMD) are not completely understood. We retrospectively analyzed 265 consecutive patients who underwent coronary angiography and in whom we could measure FMD and the urine albumin-creatinine ratio (UACR). Using 15 continuous measurement approaches, we measured FMD as the magnitude of the percentage change in the brachial artery diameter from baseline to peak (bFMD), the maximum FMD rate calculated as the maximal slope of dilation (FMD-MDR), and the integrated FMD response calculated as the area under the dilation curve during the 60- and 120-s dilation periods (FMD-AUC60 and FMD-AUC120). We divided the patients into two groups according to UACR: normoalbuminuria (NOR, n = 211) and microalbuminuria (MIC, n = 54). The MIC group showed a significantly higher percentage of coronary artery disease than the NOR group. FMD-AUC60 and FMD-AUC120, but not FMD-MDR, in the MIC group were significantly lower than those in the NOR group. On the other hand, bFMD in the MIC group tended to be lower than that in the NOR group, but this difference was not significant. A multiple regression analysis indicated that FMD-AUC120 and diabetes mellitus were predictors of MIC. Finally, we defined the cut-off value of FMD-AUC120 for the presence of MIC in all patients as 8.4 mm x second (sensitivity 0.640, specificity 0.588) by a receiver-operating characteristic curve analysis. In conclusion, this study provides more definitive evidence for the association of microalbuminuria with endothelial dysfunction. FMD-AUC120 may be a superior marker for MIC.

Association Between the Presence or Severity of Coronary Artery Disease and Pericardial Fat, Paracardial Fat, Epicardial Fat, Visceral Fat, and Subcutaneous Fat as Assessed by Multi-Detector Row Computed Tomography.

The associations between the presence or severity of coronary artery disease (CAD) and measurements of various kinds of fat as assessed by multidetector row computed tomography (MDCT) are unclear. We enrolled 300 patients who were clinically suspected to have CAD or who had at least one cardiac risk factor and had undergone MDCT. The number of significantly stenosed coronary vessels (VD), and measurements of pericardial fat index, paracardial fat index, epicardial fat index, visceral fat index, and subcutaneous fat index were quantified using MDCT. Plasma levels of adiponectin, pentaxin-3, and high-sensitivity C-reactive protein factors were also measured. Pericardial fat index, paracardial fat index, and visceral fat index in a CAD group were significantly greater than those in a non-CAD group. In addition, the levels of these fat indices tended to increase as the number of VD increased and were positively correlated with the Gensini score. The area-under-the-curve for paracardial fat index was significantly greater than those for the other parameters of fat index measured by a receiver-operating characteristic curve analysis. The cut-off level of paracardial fat index that gave the greatest sensitivity and specificity for the diagnosis of CAD was 54.9 cm3/m2 (sensitivity 0.710, specificity 0.552). The presence of CAD was independently associated with paracardial fat index, in addition to age and diabetes mellitus, by a multiple logistic regression analysis. In conclusion, paracardial fat index may be a marker for evaluating the presence or severity of CAD.