Predictive value of serum dihomo-γ-linolenic acid level and estimated Δ-5 desaturase activity in patients with hepatic steatosis.

BACKGROUND: Hepatic steatosis is considered one of the features of metabolic syndrome (MetS). Polyunsaturated fatty acid (PUFA) metabolism is modulated in obesity. However, it has yet to be fully elucidated whether a serum PUFA profile is associated with hepatic steatosis. OBJECTIVE: We aimed to clarify the relationship between a serum PUFA profile and liver lipid content. METHODS: A cross-sectional study was conducted on 288 patients with dyslipidemia, diabetes, or coronary artery disease on statin therapy. Several PUFAs were measured, including eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), dihomo-γ-linolenic acid (DGLA) and arachidonic acid (AA) in serum lipids, and Δ-5 desaturase (D5D) activity was estimated by AA to DGLA ratio. Abdominal computed tomography (CT) measured visceral fat area (VFA) and the ratio of CT attenuation for liver to spleen (L/S). RESULTS: The L/S ratio showed significant correlations with serum DGLA level and D5D activity (p<0.0001 for both). Serum DGLA level and D5D activity were significantly correlated with body mass index (BMI) or VFA, and with Homeostasis Model Assessment-Insulin Resistance (HOMA-IR) (p<0.0001 for all). Multivariate logistic analysis revealed that a high DGLA level or low D5D activity was a significant determinant for hepatic steatosis (p<0.0001 for both) independent of BMI and HOMA-IR. ROC analysis revealed that they significantly enhanced the value of MetS-related factors in predicting hepatic steatosis (p<0.05 for both). CONCLUSIONS: A high DGLA level and low D5D activity in serum lipids may be useful markers predicting hepatic steatosis incrementally to MetS-related conventional factors.

Impact of dyslipidemic components of metabolic syndrome, adiponectin levels, and anti-diabetes medications on malondialdehyde-modified low-density lipoprotein levels in statin-treated diabetes patients with coronary artery disease.

BACKGROUND: A residual risk of cardiovascular disease tends to persist despite standard prevention therapy with statins. This may stem partly from increased oxidized low-density lipoprotein (LDL) levels. However, how oxidized LDL can be further reduced beyond statin therapy in high-risk diabetes patients remains unclear. We aimed to clarify the clinical factors associated with oxidized LDL levels in statin-treated high-risk diabetes patients. METHODS: This cross-sectional observational study included 210 diabetes patients with coronary artery diseases (CAD) who were treated with statins. We determined serum malondialdehyde-modified LDL (MDA-LDL), LDL cholesterol, high-density lipoprotein (HDL) cholesterol, triglyceride (TG), remnant lipoprotein cholesterol, hemoglobin (Hb) A1c, adiponectin, and C-reactive protein (CRP) levels and investigated the factors influencing the MDA-LDL level. RESULTS: In univariate analysis, the MDA-LDL level was significantly correlated with LDL cholesterol (p < 0.0001), TG (p < 0.0001), HDL cholesterol (p = 0.017), and adiponectin (p = 0.001) levels but not with age, body mass index, waist circumference, blood pressure, or HbA1c levels. Even after adjusting for the LDL cholesterol level, the correlations between the MDA-LDL level and the TG, HDL cholesterol, and adiponectin levels were still significant. Among these significant factors, multivariate analysis revealed that the MDA-LDL level was independently associated with the LDL cholesterol, TG, and HDL cholesterol but not with adiponectin levels. The MDA-LDL level was also significantly associated with the CRP level (p = 0.014) and the remnant lipoprotein cholesterol level (p < 0.0001) independently of the LDL cholesterol level. The number of metabolic syndrome (MS) components was significantly associated with the MDA-LDL/LDL cholesterol ratio (p < 0.0001). Furthermore, the use of metformin and α-glucosidase inhibitors was inversely associated with high MDA-LDL levels (p = 0.033 and 0.018, respectively). CONCLUSION: In statin-treated diabetes patients with CAD, the MDA-LDL level was significantly correlated with TG and HDL cholesterol levels. Adiponectin level was also significantly associated with the MDA-LDL level, but not independent of the above-mentioned factors. The management of dyslipidemic MS components, including the use of metformin or α-glucosidase inhibitors, may be important for reducing the oxidized LDL levels beyond statin therapy in high-risk diabetes patients.

Predictive value of adiponectin in patients with multivessel coronary atherosclerosis detected on computed tomography angiography.

AIM: Multislice computed tomography coronary angiography (CTCA) can be used to detect coronary plaques that predict the risk of cardiovascular events. This study aimed to identify the risk factors associated with the extent of coronary plaques detected using CTCA and to determine the value of adiponectin measurement for identifying high-risk patients with multivessel coronary atherosclerosis. METHODS: The study included 298 patients who underwent CTCA for coronary artery disease (CAD) screening between July 2008 and October 2011. We investigated the relationship between the extent of coronary atherosclerosis in terms of the number of diseased vessels and various risk factors, including the serum adiponectin level. RESULTS: The adiponectin level was found to be significantly associated with multivessel coronary atherosclerosis in a univariate analysis (p=0.001). A multivariate analysis revealed the adiponectin level to also be significantly associated with multivessel coronary atherosclerosis (p=0.01), independent of other significant risk factors, including an advanced age, male gender, diabetes mellitus (DM) and hypertension (HT). A receiver operating characteristic curve analysis revealed that a combination of these factors significantly predicted multivessel coronary atherosclerosis (area under the curve, 0.73;95% confidence interval, 0.67-0.78). As the number of these factors increased, the proportion of patients with multivessel coronary atherosclerosis increased, while the proportion of patients with normal coronary arteries decreased (p < 0.0001). CONCLUSIONS: A low adiponectin level combined with an advanced age, male gender, DM, and HT is independently and incrementally associated with multivessel coronary atherosclerosis. The number of factors may predict the extent of coronary atherosclerosis in patients without documented CAD.

A case of a young, healthy woman with spontaneous coronary artery dissection associated with oral contraceptive use: Long-term residual dissection of the coronary artery.

Spontaneous coronary artery dissection (SCAD) is a rare cause of acute coronary syndrome, typically affecting young, healthy women, particularly during the peripartum period. Oral contraceptive use is also recognized as a risk factor for SCAD. In the present report, we describe a case of a young woman with an anterior wall myocardial infarction caused by SCAD of the left anterior descending artery (LAD). The event was probably associated with the patient's oral contraceptive use. The patient underwent percutaneous coronary intervention, and she did not experience any recurrent chest pain or other cardiac symptoms. Although the coronary angiography revealed good LAD flow and no symptoms after 6 months, cardiac computed tomography and intravascular ultrasound revealed that LAD dissection was still present. We continued to closely follow-up the patient without initiating any additional intervention, and the patient has had no cardiac event for up to 4 years of follow-up. .

Correlation of fasting serum apolipoprotein B-48 with coronary artery disease prevalence.

BACKGROUND: Postprandial hyperlipidemia partially refers to the postprandial accumulation of chylomicrons and chylomicron remnants (CM-R). Many in vitro studies have shown that CM-R has highly atherogenic properties, but consensus is lacking on whether CM-R accumulation correlates with the development of atherosclerotic cardiovascular diseases. We investigated the correlation between CM-R accumulation and the prevalence of coronary artery disease (CAD). DESIGN: Subjects who received a coronary angiography and did not take any lipid-lowering drugs (n = 189) were enrolled. Subjects with coronary artery stenosis (≥ 75%) were diagnosed as CAD. Biochemical markers for glucose and lipid metabolism including fasting apolipoprotein (apo) B-48 concentration were compared between CAD patients (n = 96) and age-, sex-, and body mass index (BMI)-matched non-CAD subjects without overt coronary stenosis (< 75%) (n = 67). We tried to determine which metabolic parameters were correlated with the prevalence of CAD by multiple logistic regression analysis, and whether or not the combination of high apo B-48 and other coronary risk factors (high triglyceride, low HDL-C, high HbA1c or low adiponectin levels) increased the prevalence of CAD. RESULTS: Fasting serum apo B-48 levels were significantly higher in CAD patients than in non-CAD subjects (3·9 ± 2·4 vs. 6·9 ± 2·6 µg/mL, P < 0·0001) and had the most significant correlation with the existence of CAD. The clustering of high fasting apo B-48 levels (> 4·34 µg/mL, the cut-off value) and other coronary risk factors were found to be associated with a stronger risk of CAD compared with single high fasting apo B-48 levels. CONCLUSION: Fasting serum apo B-48 levels significantly correlated with the prevalence of CAD.

Cardiovascular risk management with liaison critical path in Japan: its effects on implementation of evidence-based prevention in practice.

BACKGROUND: Liaison critical paths (LCPs) for coronary artery disease (CAD) were developed to support collaborative care for CAD patients between cardiologists in emergency hospitals and referring physicians through sharing of medical information, including cardioprotective medications and cardiovascular risk factors. However, little is known about the effects of LCPs in practice. METHODS: We conducted an observational study of CAD patients undergoing percutaneous coronary intervention in our hospital between September 2007 and June 2010; these patients were managed with an LCP by referring physicians after discharge. We surveyed implementation of scheduled hospital visits, prescription of cardioprotective medicines, and risk factor measurements 6 and 12 months after discharge. RESULTS: Implementation rate of hospital visits was significantly elevated from 50.7% to 89.3% after establishing LCPs. At the 12-month visit, prescription rates for anti-platelet drugs, statins, ß-blockers, and angiotensin-converting enzyme inhibitors or angiotensin II type I receptor blockers were 99.7%, 95.0%, 77.1%, and 74.3%, respectively. Target achievement rates for low-density lipoprotein cholesterol (LDL-C; < 100 mg/dL) and high-density lipoprotein cholesterol (HDL-C; ≥ 40 mg/dL) significantly increased from 48.6% to 64.5% and 62.0% to 82.7%, respectively, while those for body mass index (BMI; < 25 kg/m(2)), blood pressure (< 130/80 mmHg), triglycerides (< 150 mg/dL), and HbA1c (< 7.0 %) were unchanged. BMI, triglycerides, HDL-C, LDL-C, and HbA1c levels significantly improved in patients who implemented all visits. Moreover, risk factor management did not differ significantly between cardiologists and non-cardiologists using LCPs. CONCLUSIONS: LCPs for CAD may facilitate implementation of optimal medical therapy and target achievement of risk factors in practice. KEYWORDS: Liaison critical path; Coronary artery disease; Cardiovascular prevention; Risk factors; Clinical practice.

Peripartum cardiomyopathy presenting with syncope due to Torsades de pointes: a case of long QT syndrome with a novel KCNH2 mutation.

Peripartum cardiomyopathy (PPCM) is a cardiomyopathy of unknown cause that occurs in the peripartum period. We report a case of PPCM presenting with syncope 1 month after an uncomplicated delivery. Electrocardiography showed Torsades de pointes (TdP) and QT interval prolongation. Echocardiography showed left ventricular systolic dysfunction and endomyocardial biopsy showed myocyte degeneration and fibrosis. Administration of magnesium sulfate and temporary pacing eliminated recurrent TdP. Genetic analyses revealed that recurrent TdP occurred via electrolyte disturbance and cardiac failure due to PPCM on the basis of a novel mutation in KCNH2, a gene responsible for inherited type 2 long QT syndrome.

Patients with CD36 deficiency are associated with enhanced atherosclerotic cardiovascular diseases.

AIM: The clustering of dyslipidemia, impaired glucose tolerance and hypertension increases the morbidity and mortality from cardiovascular events. A class B scavenger receptor, CD36, is a receptor for oxidized LDL and a transporter of long-chain fatty acids. Because of the impaired uptake of oxidized LDL in CD36-deficient macrophages and from the results of CD36 knockout mice, CD36 deficiency (CD36-D) was supposed to be associated with reduced risks for coronary artery disease (CAD); however, CD36-D patients are often accompanied by a clustering of coronary risk factors. The current study aimed to investigate the morbidity and severity of cardiovascular diseases in CD36-D patients. METHODS: By screening for CD36 antigen on platelets and monocytes using FACS or the absent myocardial accumulation of 123I-BMIPP by scintigraphy, 40 patients with type I CD36-D were collected, the morbidity of CAD and their features of atherosclerotic cardiovascular diseases were observed. Screening for CD36-D in both CAD patients (n = 319) and healthy subjects (n = 1,239) were underwent. RESULTS: The morbidity of CAD was significantly higher in CD36-D patients than in the general population; 50% of patients (20 out of 40) had CAD identified by BMIPP scintigraphy and 37.5% (3 out of 8) by FACS screening, respectively. Three representative CD36-D cases demonstrated severe CAD and atherosclerosis. The frequency of CD36-D was three times higher in CAD patients than in healthy subjects (0.9% vs 0.3%, p < 0.0001). CONCLUSION: The morbidity of CAD is significantly higher in CD36-D patients suffering from severe atherosclerosis, implying that the status of CD36-D might be atherogenic.

Combination of serum adiponectin level and metabolic syndrome is closely associated with coronary artery disease in Japanese subjects with good glycemic control.

OBJECTIVE: Metabolic syndrome (MetS) and decreased adiponectin level have been reported to be clinically associated with type 2 diabetes mellitus and coronary artery disease (CAD). However, it has not been fully defined whether they are associated with the severity of CAD, independent of hyperglycemia. In the current study, we investigated the clinical relationship between serum adiponectin level and MetS, and its association with the severity of CAD in patients with good glycemic control. PATIENTS AND METHODS: In this study, we enrolled 97 subjects with an HbA1c concentration of < 7.0% (5.5+/-0.6%), who underwent coronary angiography. We measured serum adiponectin levels and various metabolic variables, and assessed the severity of CAD by angiography. RESULTS: Multivariate analysis revealed that the number of MetS components was not correlated with adiponectin level, despite their significant correlation in the univariate analysis. Low adiponectin levels (< 4.5 microg/mL) or > or = 3 of 5 MetS components showed significant association with the severity of CAD (adiponectin, p=0.002; MetS, p=0.049). The correlation of adiponectin levels (divided by tertiles or quartiles) with the severity of CAD was not significant after adjustment for age and gender. On the other hand, two models of combined scores from adiponectin levels and the number of MetS components showed a significant correlation with the severity of CAD even after adjustment for age and gender (model 1, p=0.023; model 2, p=0.018). CONCLUSION: Our findings suggest that the combination of adiponectin levels and the number of MetS components is linked to the severity of CAD in subjects with good glycemic control.

Chylomicron remnants are increased in the postprandial state in CD36 deficiency.

The clustering of risk factors including dyslipidemia, hyperglycemia, and hypertension is highly atherogenic along with the excess of remnants from triglyceride (TG)-rich lipoproteins. CD36 is involved in the uptake of long-chain fatty acids (LCFAs) in muscles and small intestines. Patients with CD36 deficiency (CD36-D) have postprandial hypertriglyceridemia, insulin resistance, and hypertension. To investigate the underlying mechanism of postprandial hypertriglyceridemia in CD36-D, we analyzed lipoprotein profiles of CD36-D patients and CD36-knockout (CD36-KO) mice after oral fat loading (OFL). In CD36-D patients, plasma triglycerides, apolipoprotein B-48 (apoB-48), free fatty acids (FFAs), and free glycerol levels were much higher after OFL than those of controls, along with increases in chylomicron (CM) remnants and small dense low-density lipoprotein (sdLDL) particles. In CD36-KO mice, lipoproteins smaller than CM in size in plasma and intestinal lymph were markedly increased after OFL and mRNA levels of genes involved in FFA biosynthesis, such as fatty acid binding protein (FABP)-1 and FAS, were significantly increased. These results suggest that CD36-D might increase atherosclerotic risk by enhancing plasma level of CM remnants due to the increased synthesis of lipoproteins smaller than CM in size in the intestine.

Clinical significance of high-molecular weight form of adiponectin in male patients with coronary artery disease.

BACKGROUND: It has been reported previously that the measurement of plasma total adiponectin level is clinically useful to estimate the risk of coronary artery disease (CAD). Here, the relevance of high molecular weight (HMW) adiponectin with risk factors for atherosclerosis is investigated METHODS AND RESULTS: A total of 186 consecutive male CAD patients participated in the study and were categorized into quartiles based on their total adiponectin level. The interquartile cut-off points were 4.0, 5.5 and 7.0 microg/ml. The HMW adiponectin levels were significantly lower in the quartile of lower total adiponectin levels both in non-diabetic and diabetic patients. In contrast, low molecular weight adiponectin levels (which were calculated as the Total - HMW) were constant. In univariate analysis, total adiponectin correlated negatively with body mass index and hemoglobin (Hb) A1c, and HMW adiponectin correlated negatively with HbA1c in non-diabetic patients. On the other hand, total and HMW adiponectin correlated positively with high-density lipoprotein-cholesterol (HDL-C) in diabetic patients. Multiple regression analysis revealed that HMW adiponectin correlated negatively with HbA1c in non-diabetic patients, and total and HMW adiponectin correlated positively with HDL-C in diabetic patients. CONCLUSIONS: Change in the HMW isoform reflects a change in total adiponectin level. Measurement of total and HMW adiponectin were equally useful in assessing metabolic risk in CAD patients.

Relationship between hemostatic markers and platelet indices in patients with aortic aneurysm.

The purpose of this study was to investigate whether platelet indices [platelet count, mean platelet volume (MPV), platelet-large cell ratio (P-LCR) and platelet distribution width (PDW)] could serve as diagnostic tools to evaluate the potential significance of platelet heterogeneity on thrombus formation in patients with aortic aneurysm (AA). Blood samples were obtained from 54 patients with AA (mean age 73 years; 40 males and 14 females), and from 120 age-matched controls (AC; mean age 74 years; 61 males and 59 females). Blood platelet indices were measured using an automated counter for all AC (n = 120) and AA (n = 54). Plasma thrombin-antithrombin III complex (TAT), alpha(2)-plasmin inhibitor-plasmin complex (PIC), D-dimer, von Willebrand factor antigen (vWF:Ag) and interleukin-6 (IL-6) were also measured in part of AC and AA. In AA patients, TAT, PIC, D-dimer, vWF:Ag and IL-6 levels were significantly (p < or =0.0005) higher than in AC. In the patients, TAT was significantly inversely correlated with platelet count (rho = -0.302, p = 0.038, n = 48), and significantly positively correlated with MPV (rho = 0.329, p = 0.0373, n = 48), P-LCR (rho = 0.361, p = 0.0134, n = 48) and PDW (rho = 0.315, p = 0.0466, n = 48). PIC was negatively correlated with platelet count and inversely correlated with MPV, P-LCR and PDW. vWF:Ag was not correlated with platelet count, and inversely correlated with MPV, P-LCR and PDW in the patients. IL-6 was positively correlated with platelet count, and significantly inversely correlated with MPV, P-LCR and PDW in the patients. In AC, vWF:Ag was inversely correlated with platelet count and significantly positively correlated with MPV, P-LCR and PDW. However, PIC, TAT and IL-6 were not correlated with platelet indices in AC. D-dimer was not at all correlated with platelet indices both in AA and AC. In conclusion, the correlation between platelet indices and plasma hemostatic factor levels, e.g. TAT, PIC, D-dimer, vWF:Ag and IL-6, will be important factors for the understanding of platelet heterogeneity in patients with AA.

Relationship between platelet indexes and coronary angiographic findings in patients with ischemic heart disease.

To understand the mechanisms linking platelets to the risk of coronary artery disease, we investigated the relation between coronary angiographic morphology and platelet indexes--platelet count, mean platelet volume (MPV), platelet-large cell ratio (P-LCR) and platelet distribution width (PDW)--in patients with ischemic heart disease. Eighty-four patients with ischemic heart disease and 120 aged controls (AC) were enrolled in the study. The patients without any signs of acute myocardial infarction and acute coronary syndromes who underwent coronary angiography were divided into two groups, an 'angiographically negative group' (group 0) and an 'angiographically positive group' (group 1), with positive coronary obstruction depending on the diagnostic criteria in our hospital. Platelet indexes were measured in peripheral venous blood. The mean platelet counts were significantly lower in groups 1 and 0 than in AC (p = 0.0128 and p = 0.0041, respectively). MPV, P-LCR and the PDW were significantly higher in group 0 than in group 1 and AC (p = 0.0352 and 0.0433, p = 0.0059 and 0.0052, p = 0.00461 and 0.0146, respectively). The indexes of group 1 were almost the same compared with AC with respect to MPV, P-LCR and PDW. In conclusion, these findings suggest that the measurement of platelet indexes may reflect the underlying pathophysiological state and subsequent clinical events in the patients. In particular, lower P-LCR seems to identify patients with positive coronary angiography.

Relationship between hemostatic factors and the platelet index in patients with ischemic heart disease.

To understand the heterogeneity of platelets, we investigated the correlation between hemostatic factors and the platelet index [platelet count, mean platelet volume (MPV), platelet-large cell ratio (P-LCR) and platelet distribution width (PDW)] in patients with ischemic heart disease (IHD). Ninety-seven patients with IHD and 120 aged controls (AC) were enrolled in the study. D-dimer, thrombin-antithrombin III complex (TAT), von Willebrand factor antigen (VWF:Ag) and platelet indexes were measured in the peripheral venous blood. The D-dimer and TAT levels in the patients were significantly elevated compared to the AC. VWF:Ag was also elevated, but not significantly so. However, no differences were observed in the platelet index between the patients and the AC. In the patients, the level of VWF:Ag was significantly inversely correlated with the platelet count, but such correlations were not observed in the D-dimer and TAT. TAT was significantly positively correlated with MPV, P-LCR and PDW. VWF:Ag was also correlated, though not significantly, with MPV, P-LCR and PDW. The D-dimer was not correlated with the platelet index. In the AC, the platelet count was inversely correlated with VWF:Ag, but not significantly so. VWF:Ag showed significant positive correlations with MPV, P-LCR and PDW. However, the D-dimer and TAT were not correlated with the platelet index in AC. These findings suggest that VWF:Ag and TAT seem to be profoundly related to platelet volume.

Evaluation of platelet indexes in patients with aortic aneurysm.

The purpose of this study was to investigate whether platelet indexes [platelet count, mean platelet volume (MPV), platelet-large cell ratio (P-LCR), and platelet distribution width (PDW)] could serve as diagnostic tools to evaluate the potential significance of platelet heterogeneity on thrombus formation. Blood samples were obtained from 54 patients with aortic aneurysm (AA; mean age 73 years; 40 males, 14 females), from 120 age-matched controls (AC; mean age 74 years; 61 males, 59 females), and from 38 young controls (YC; mean age 30 years; 20 males, 18 females). We measured the blood platelet indexes using an automated counter, as well as plasma D-dimer and thrombin-antithrombin III complex (TAT) using ELISA. The AA patients were divided into two groups, group A (platelet count more than 150 x 10(9)/l, n = 36) and group B (platelet count below 150 x 10(9)/l, n = 18). There was no difference in the platelet count between AC and YC. However, P-LCR was significantly higher (p = 0.0113) in AC. MPV and PDW were also higher, but not significantly so. The platelet count was not different between group A and AC. MPV (p = 0.0024 and <0.0001, respectively), P-LCR (p < 0.0012 and <0.0001, respectively) and PDW (p = 0.0006 and 0.0005, respectively) were significantly lower in group A than in group B and AC. The platelet indexes were significantly lower in the 54 AA patients than in the AC. There were significant inverse relationships between the platelet count and other indexes in the AC and 54 AA patients; however, no relationships were observed in group A, B and YC. The D-dimer and TAT levels were significantly higher in group B than in groups A and YC. In conclusion, these findings suggest that large platelets decrease rather than increase in patients with AA.

Adiponectin I164T mutation is associated with the metabolic syndrome and coronary artery disease.

OBJECTIVES: This study examined the association of mutations in adiponectin gene with the prevalence of coronary artery disease (CAD). BACKGROUND: Coronary artery disease is a major cause of mortality in the industrial countries. Adiponectin gene locus, chromosome 3q27, is the candidate site for CAD. We have reported that adiponectin has antiatherogenic and antidiabetic properties, and that the plasma levels negatively correlated with body mass index (BMI) are significantly low in patients with CAD or type 2 diabetes. METHODS: The study subjects were 383 consecutive patients with angiographically confirmed CAD and 368 non-CAD subjects adjusted for age and BMI in the Japanese population. Single nucleotide polymorphisms (SNPs) in the adiponectin gene were determined by Taqman polymerase chain reaction (PCR) method or a PCR-based assay for the analysis of restriction fragment length polymorphism. The plasma adiponectin concentration was measured by enzyme-linked immunosorbent assay. RESULTS: Among SNPs, the frequency of I164T mutation was significantly higher in CAD subjects (2.9%) than in the control (0.8%, p < 0.05). The plasma adiponectin levels in subjects carrying the I164T mutation were significantly lower than in those without the mutation, and were independent of BMI. In contrast, SNP94 and SNP276, which are reported to be associated with an increased risk of type 2 diabetes, were associated neither with CAD prevalence nor with plasma adiponectin level. Subjects with I164T mutation exhibited a clinical phenotype of the metabolic syndrome. CONCLUSIONS: The I164T mutation in the adiponectin gene was a common genetic background associated with the metabolic syndrome and CAD in the Japanese population.

Association of hypoadiponectinemia with coronary artery disease in men.

BACKGROUND: Adiponectin is an adipocyte-derived plasma protein that accumulates in the injured artery and has potential antiatherogenic properties. This study was designed to determine whether a decreased plasma adiponectin level (hypoadiponectinemia) can be independently associated with the prevalence of coronary artery disease (CAD). METHODS AND RESULTS: The consecutive 225 male patients were enrolled from inpatients who underwent coronary angiography. Voluntary blood donors (n=225) matched for age served as controls. Plasma adiponectin levels in the CAD patients were significantly lower than those in the control subjects. Multiple logistic regression analysis including plasma adiponectin level, diabetes mellitus, dyslipidemia, hypertension, smoking habits, and body mass index revealed that hypoadiponectinemia was significantly and independently correlated with CAD (P<0.0088). The entire study population was categorized in quartiles based on the distribution of plasma adiponectin levels. The interquartile cutoff points were 4.0, 5.5, and 7.0 microg/mL. The multivariate-adjusted odds ratios for CAD in the first, second, and third quartiles were 2.051 (95% confidence interval [CI], 1.288 to 4.951), 1.221 (95% CI, 0.684 to 2.186), and 0.749 (95%CI, 0.392 to 1.418), respectively. CONCLUSIONS: Male patients with hypoadiponectinemia (<4.0 microg/mL) had a significant 2-fold increase in CAD prevalence, independent of well-known CAD risk factors.

Relationship between hemostatic markers and circulating biochemical markers of collagen metabolism in patients with aortic aneurysm.

Our objective was to determine the relationship between plasma levels of hemostatic molecular markers--D-dimer and thrombin-antithrombin III complex (TAT)--and circulating biochemical markers of collagen metabolism--aminoterminal propeptide of type III procollagen (PIIIP) and carboxyterminal propeptide of type I procollagen (PICP)--in patients with aortic aneurysm. The subjects were 43 patients with aortic aneurysm (AA; mean age 71 years) and 26 age-matched controls (mean age 75 years). The mean D-dimer, TAT and PIIIP levels were higher in the patients than in the controls (p < 0.0001, 0.0001 and 0.012, respectively), while the mean PICP level was similar to that in the controls. Increased D-dimer had a significant correlation with PIIIP (r = 0.412, p = 0.006) and PICP (r = 0.342, p = 0.0246), while TAT correlated with PIIIP (r = 0.3194, p = 0.0374), but not with PICP. There was also a significant correlation (r = 0.306, p = 0.0463) between PIIIP and PICP. As shown by the significant positive correlations among D-dimer, TAT and PIIIP, accelerated fibrinolysis and thrombogenesis induce an increase of collagen degradation and procollagen synthesis in atherosclerotic lesions. These findings show that D-dimer and TAT, especially the former, may be useful markers to monitor the progression and predict the prognosis of AA.

Association of adiponectin mutation with type 2 diabetes: a candidate gene for the insulin resistance syndrome.

Adiponectin, also referred to as AdipoQ or ACRP30, is a plasma protein produced and secreted exclusively from adipose tissue. The protein contains a collagen-like domain and a C1q-like globular domain. A protease-generated globular segment enhances fatty acid oxidation in muscles, thereby modulating lipid and glucose metabolism. Plasma adiponectin levels are inversely correlated with the severity of insulin resistance. A recent genome-wide scan study mapped a susceptibility locus for type 2 diabetes and the metabolic syndrome to chromosome 3q27, where the adiponectin gene is located. Here, we screened Japanese patients with type 2 diabetes and age- and BMI-matched nondiabetic control subjects for mutations in adiponectin gene. We identified four missense mutations (R112C, I164T, R221S, and H241P) in the globular domain. Among these mutations, the frequency of I164T mutation was significantly higher in type 2 diabetic patients than in age- and BMI- matched control subjects (P < 0.01). Furthermore, plasma adiponectin concentrations of subjects carrying I164T mutation were lower than those of subjects without the mutation. All the subjects carrying I164T mutation showed some feature of metabolic syndrome, including hypertension, hyperlipidemia, diabetes, and atherosclerosis. Our findings suggest that I164T mutation is associated with low plasma adiponectin concentration and type 2 diabetes.