Should We Intensify Statin Management in ACS Patients with Very Low LDL Cholesterol Levels?

No abstract available.

Functional Implications of HMG-CoA Reductase Inhibition on Glucose Metabolism

HMG-CoA reductase inhibitors, i.e. statins, are effective in reducing cardiovascular disease events but also in cardiac-related and overall mortality. Statins are in general well-tolerated, but currently the concerns are raised if statins may increase the risk of new-onset diabetes mellitus (NOD). In this review, the possible effects of statins on organs/tissues being involved in glucose metabolism, i.e. liver, pancreas, adipose tissue, and muscles, had been discussed. The net outcome seems to be inconsistent and often contradictory, which may be largely affected by in vitro experimental settings or/and in vivo animal conditions. The majority of studies point out statin-induced changes of regulations of isoprenoid metabolites and cell-associated cholesterol contents as predisposing factors related to the statin-induced NOD. On the other hand, it should be considered that dysfunctions of isoprenoid pathway and mitochondrial ATP production and the cholesterol homeostasis are already developed under (pre)diabetic and hypercholesterolemic conditions. In order to connect the basic findings with the clinical manifestation more clearly, further research efforts are needed.

Functional Implications of HMG-CoA Reductase Inhibition on Glucose Metabolism

HMG-CoA reductase inhibitors, i.e. statins, are effective in reducing cardiovascular disease events but also in cardiac-related and overall mortality. Statins are in general well-tolerated, but currently the concerns are raised if statins may increase the risk of new-onset diabetes mellitus (NOD). In this review, the possible effects of statins on organs/tissues being involved in glucose metabolism, i.e. liver, pancreas, adipose tissue, and muscles, had been discussed. The net outcome seems to be inconsistent and often contradictory, which may be largely affected by in vitro experimental settings or/and in vivo animal conditions. The majority of studies point out statin-induced changes of regulations of isoprenoid metabolites and cell-associated cholesterol contents as predisposing factors related to the statin-induced NOD. On the other hand, it should be considered that dysfunctions of isoprenoid pathway and mitochondrial ATP production and the cholesterol homeostasis are already developed under (pre)diabetic and hypercholesterolemic conditions. In order to connect the basic findings with the clinical manifestation more clearly, further research efforts are needed.

Metabolic Syndrome Causes Cardiovascular Disease under Stable Statin Medication

OBJECTIVE: Statins are known to prevent only 30–50% of cardiovascular disease(CVD) by reducing low-density lipoprotein cholesterol (LDL-C). There is a controversy about whether metabolic syndrome(MS) can increase the risk of CVD. The aim of this study is to investigate whether MS can increase the risk of CVD, even after LDL-C is ideally controlled by taking statins. METHODS: As a retrospective observational study, we investigated CVD events of 909 patients (61.3±10.2 years old) by reviewing medical records for at least 1 year before and after taking statins respectively, from June 2005 to February 2008, and analyzed the risk factors of CVD. RESULTS: During the study period (881.4±232.8 days), 46 cases of CVD events occurred in patients with a very high risk of CVD and in patients with a high risk of CVD. In patients with a very high risk of CVD, 56.8% (21 cases over 37) of CVD events occurred in patients who achieved LDL-C goal (< 70 mg/dL). A total of 9 events developed among high risk patients who reached LDL-C goal (< 100 mg/dL). The patients with MS revealed significantly higher rates of CVD events [p=0.015; hazard ratio (HR) 3.033; 95% confidence interval (CI) 1.184–7.768]. Significantly higher rates of CVD events were also found in subgroup analysis of the patient with a past history of CVD events [p=0.017; HR 3.431; 95% CI 1.183–9.956]. Similar pattern was demonstrated in patients with diabetes [p=0.049; HR 2.738; 95% CI 0.963–7.782]. Cox regression analysis identified metabolic syndrome [p=0.025; HR 5.237; 95% CI 1.235–22.204], a past history of CVD events [p=0.000; HR 5.349; 95% CI 2.321–12.327], basal LDL-C level [p=0.024; HR 1.013; 95% CI 1.002–1.025] and total cholesterol level after statin therapy [p=0.024; HR 0.978; 95% CI 0.959–0.997] as independent predictors of CVD among LDL-C goal achieved patients. CONCLUSION: Metabolic syndrome is the independent risk factor of CVD events in high risk patients with or without a past history of CVD events or diabetes. In these patients, statins could not prevent CVD events effectively.

Prevalence, Treatment Pattern and Resource Use in Patients with Mixed Dyslipidemia Using Lipid Modifying Agents in Korea (PRIMULA): An Observational Study

OBJECTIVE: Limited information is available on the effectiveness of lipid-modifying therapy (LMT) for low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG) in the Korean population. The objective of this study was to describe the prevalence of different types of lipid disorders in Korean patients using LMT. METHODS: Eight hundred seventy-one dyslipidemia patients, who were LMT-naive for >1 year prior to retrospective enrollment, were included for analysis. Serum levels of LDL-C, HDL-C, TG and total cholesterol (TC) were assessed after >1 year of LMT. We also analyzed the therapeutic effects of LMT in the subjects with high cardiovascular risk factors (n=629), atherosclerotic cardiovascular disease (ASCVD) (n=296) or diabetes without ASCVD (n=316). RESULTS: The rates of elevated LDL-C without other abnormal lipids levels, elevated TG or decreased HDL-C (with normal LDL-C levels) and high LDL-C combined with elevated TG and/or decreased HDL-C were 33.4%, 13.0% and 53.6%, respectively. After at least one year on LMT (statin alone: 81%, statin and cholesterol absorption inhibitor: 10%, fibrates alone: 3%, others: 3%), 61% of patients had at least one lipid abnormality, with 3.4% failing to reach the therapeutic LDL-C target level or a normal level of HDL-C and TG. After LMT, 64.9% of patients with high cardiovascular risk factors, 64.5% of those with ASCVD or and 64.2% of those with diabetes without ASCVD also had at least one lipid abnormality. CONCLUSION: Approximately two-thirds of patients did not reach the target or normal lipid profile after taking LMT, irrespective of combining disease and high cardiovascular risk factors. Tight lipid control is required, especially in patients with dyslipidemia and high cardiovascular risk factors or comorbid diseases.

Dyslipidemia and Lipid-Lowering in Patients with High Risk of Cardiovascular Diseases and Their Cardiovascular Outcomes in Korea (ENSURE study): Secondary Prevention in Chronic Stable Angina

BACKGROUND AND OBJECTIVES: The aim of this study was to investigate the status of LDL-cholesterol level and its relationship with subsequent cardiovascular events in Korean patients with chronic stable angina. METHODS: The patients with stable angina were retrospectively and consecutively enrolled from out-patients clinic during 2007-2009. Mean follow-up duration was 3 years. Occurrences of major adverse cardio-cerebrovascular event (MACCE: a composite of death, myocardial infarction, unstable angina, coronary revascularization, cerebrovascular events, peripheral artery disease and aortic disease requiring hospital admission.) were compared by initial LDL-cholesterol levels using Cox proportional-hazards model. RESULTS: 1,683 subjects were enrolled from 9 hospitals. Initial median LDL-cholesterol by tertile was 62.2, 90.2, and 124.0mg/dL respectively, however, the differences in LDL-cholesterol level among initial 3 tertile groups became narrow at 3rd year (67.8, 85.0, and 91.6mg/dL, respectively). MACCE occurred in 138 (8.2%) subjects, including 127 coronary events, 9 cerebrovascular events and 2 peripheral artery disease during the 3-year follow-up. The adjusted hazard ratio for MACCE was 1.02 (95% confidence interval 0.64-1.64) in the middle tertile of LDL-cholesterol, 1.53 (p=0.063, 95% Confidence Interval 0.98-2.40) in the highest tertile of LDL-cholesterol. The newly diagnosed diabetes mellitus was more frequent in subjects with statin treatment than subjects without statin during the 3-year follow-up (1.5% vs 0.6%). CONCLUSION: Increased cardiovascular risk was observed in angina patients with higher initial LDL-cholesterol levels during the 3-year follow-up, although the differences were statistically insignificant.

The ideal management of blood cholesterol: a review of the updated 2013 ACC/AHA cholesterol guideline for reducing cardiovascular risk

Atherosclerotic cardiovascular disease (ASCVD) is the most important public health problem worldwide in terms of the size of expenditures in most healthcare budgets. In November 2013, the American College of Cardiology and American Heart Association (ACC/AHA) released a clinical practice guideline on the treatment of blood cholesterol to reduce ASCVD risk in adults. Based on the design and results of the randomized clinical trials and meta-analyses published through July 2013, four groups of individuals were identified for whom an extensive body of randomized clinical tria evidence demonstrated a clear reduction in ASCVD events from statin therapy with a good margin of safety. Together with ASCVD, in severe hypercholesterolemic (low-density lipoprotein cholesterol > or =190 mg/dL) or diabetic subjects, the guideline recommends the use of statins if the newly-developed Pooled Cohort Equations estimate a 10-year ASCVD risk of equal to or higher than 7.5%. The guideline recommendations represent a new paradigm for treating cholesterol focused on using the appropriate intensity of statin therapy for those most likely to benefit, while the guideline has eliminated low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol targets. Non-statin therapies were discouraged due to the lack of evidence for their production of acceptable ASCVD risk reduction benefits. This radical shift away from the set of previous guidelines has created controversy and confusion. This article reviews the 2013 ACC/AHA guideline for the treatment of blood cholesterol to reduce ASCVD risk in adults and the optimal strategies for using this guideline in clinical practice.

Familial Hypercholesterolemia and the Atherosclerotic Disease

Familial hypercholesterolemia (FH) is associated with premature atherosclerotic cardiovascular diseases, and is inherited as an autosomal dominant trait. The prevalence of heterozygous FH is one in five hundred people. Owing to dysfunctional low density lipoprotein (LDL) receptors due to genetic mutations, serum low density lipoprotein-cholesterol (LDL-C) levels are considerably increased from birth. FH is clinically diagnosed by confirmation of family history and characteristic findings such as tendon xanthoma or xanthelasma. Thus, clinical concern and suspicion are important for early diagnosis of the disease. Current guidelines recommend lowering LDL-C concentration to at least 50% from baseline. Statins are shown to lower LDL-C levels with high safety, and thus, have been the drug of choice. However, it is difficult to achieve an ideal level of LDL-C with a single statin therapy in the majority of FH patients. Alternatively, lipid lowering combination therapy with the recently-introduced ezetimibe has shown more encouraging results.

Omega-3-Fatty Acid and Triglyceride / 대한내과학회지

No abstract available.

Possible Regulation of Platelets by Native and Modified Low Density Lipoprotein-Cholesterol Particles

No abstract available.

Cost-effectiveness of the Use of Statins in the Korean Population

OBJECTIVE: Statins reduce risk of cardiovascular disease through lowering of LDL-C (Low Density Lipoprotein cholesterol). We analyzed cost-effectiveness of statins in the reduction of serum LDL-C level among Korean population at high cardiovascular risk. METHODS: Rosuvastatin (5, 10, and 20 mg), atorvastatin (10, 20, 40, and 80 mg) and simvastatin (20, 40, and 80 mg) were included for the analysis, because those statins and doses were mostly prescribed in Korea. We determined effectiveness as % reduction of LDL cholesterol (LDL-C) levels per mg dose and % population reached to the ideal LDL-C level (<100 mg/dL), which is the target goal of LDL-C level for the high cardiovascular risk group as recommended by NCEP-ATP III guideline. The annual cost, which included overall cost for the drug price and management during follow up, was calculated. Average cost-effectiveness ratio (ACER) was calculated and used as the parameter representing cost-effectiveness of each statins. RESULTS: The lowest dose of each statins showed that achieving LDL-C target level was not high even in subjects showing relatively low basal LDL-C levels (<160 mg/dL). Also in case basal LDL-C level was over 160 mg/dL, the majority of statins were not sufficient to control LDL-C levels except atorvastatin 80 mg. In case of basal LDL-C level was lower than 160 mg/dl, atorvastatin 20 mg was the most cost-effective statin for LDL-C reduction regardless of considering basal LDL-C level. Simvastatin 40 mg was also cost-effective if basal LDL-C levels were between 100-129 mg/dL. CONCLUSIONS: For the reduction of LDL-C level in high risk subjects showing moderately elevated basal LDL-C level, atorvastatin 20 mg is the most cost-effective statin treatment strategy and then simvastatin 40 mg or rosuvastatin 10 mg was the second best option.

The Contribution of Abdominal Obesity and Dyslipidemia to Metabolic Syndrome in Psychiatric Patients

BACKGROUND/AIMS: Metabolic syndrome is an emerging risk factor for cardiovascular disease. This study investigated the prevalence of metabolic syndrome among psychiatric patients in order to identify the dominant factors of metabolic syndrome. METHODS: We enrolled 225 patients who had been admitted to a chronic psychiatric hospital from October 2005 to February 2006. The prevalence of metabolic syndrome was assessed based on the Adult Treatment Panel (ATP)-III with the new criterion of waist circumference in the Asia-Pacific Region. RESULTS: The study population was relatively young (41.1 +/- 8.8 years) and obese (waist in men, 91.3 +/- 9.2 cm; waist in women, 84.1 +/- 8.8 cm). Sixty percent of patients met the waist criterion of metabolic syndrome and 56% met the low high density lipoprotein (HDL) criterion. The mean serum triglycerides were high (170.0 +/- 119.7 mg/dL) and 46% of patients met the triglyceride criterion. In contrast, less than 10% of patients showed impaired fasting glucose or high blood pressure (5%, 9%, respectively). The overall prevalence of metabolic syndrome was 34.2% by applying ATP-III criteria (40% in men and 20% in women, respectively). No specific anti-psychotic drugs were related to significant increase in the incidence of metabolic syndrome. CONCLUSIONS: Abdominal obesity and dyslipidemia (low HDL and high triglycerides) were dominant contributing factors of metabolic syndrome among psychiatric patients, and the affected age groups were relatively young. These findings indicate that active and early screening, including triglycerides, HDL, and waist measurement, are absolutely essential to managing metabolic syndrome in psychiatric patients.

Control of Dyslipidemia

Lipid particles, which can be synthesized in the liver or absorbed through the terminal ileum, are indispensable for maintaining homeostasis. Inadequate life styles together with certain types of genetic background can induce and aggravate the condition of dyslipidemia. The personal status of inflammation, which is reflected by the serum C-reactive protein level, and the status of insulin resistance are considered as emerging risks for cardiovascular diseases. Therefore, together with aggressive management of correctable major risks, maintaining ideal lifestyles may be helpful to prevent the event of cardiovascular diseases. The most important goal of managing dyslipidemic conditions is to reach an ideal level of lipid profile, and aggressive drug management can be tried where indicated.

Different Gene Expression Patterns in the Lungs of Patients with Secondary Pulmonary Hypertension

BACKGROUND AND OBJECTIVES: Despite the similar degree of pressure or volume overloading, the development of secondary pulmonary hypertension (PH) shows diverse variability among individual patients. SUBJECTS AND METHODS: Using microarray technology, we compared the gene expression pattern of the lung tissues in 13 patients with secondary PH due to congenital shunt (pulmonary arterial hypertension, PAH, n=6) or valvular heart disease (pulmonary venous hypertension, PVH, n=7) with 5 normal subjects. RESULTS: As compared to the normal controls, secondary PH showed a decreased expression of genes encoding transcriptional factors (BHLHB2, EGR3, JUNB, KLF4, KLF6 and MAFF), cytoskeleton protein (VIL2 and XLKD1) and cell differentiation and viability (MCL1, SNF1LK and TNFAIP3). PVH showed an increased expression of genes encoding proliferation of pulmonary capillary endothelial cells (ESM1), cell proliferation (IGFBP2 and BMP6), collagen synthesis (COL4A2 and SERPINH1), and cytoskeleton (TMSL8) as compared with the normal controls. In patients with secondary PH, PVH showed an upregulated expression of proliferation of pulmonary capillary endothelial cells (ESM1), cell proliferation (EGR2, PLK2 and TNC) and collagen synthesis (COL4A1), and an down-regulated expression of inflammation (IL1RL1, IL7R, CCL5, CCL19, CXCR 6 and XCL1/XCL2) and immune response (IGHM and TRA@; TRAC), as compared with PAH. CONCLUSION: There were significant differences in the gene expression pattern in secondary PH patients according to the underlying mechanism. A future study is needed to determine the diagnostic and therapeutic implications of these findings.

The safety and efficacy of ezetimibe and simvastatin combination therapy in Korean patients with primary hypercholesterolemia / 대한내과학회지

BACKGROUND: The prevalence of hypercholesterolemia in Korea is growing. In spite of the wide use of HMG-CoA reductase inhibitors (statins), some patients don't reach optimal cholesterol reduction and suffer hepatotoxicity or myopathy. Combination therapy of lipid lowering agents, which inhibits hepatic synthesis of cholesterol (i.e. simvastatin) and intestinal cholesterol absorption (i.e. ezetimibe), may achieve further reduction of serum cholesterol levels and less drug side effects. This study assessed the safety and efficacy of the combination therapy with ezetimibe and simvastatin in Korean patients with primary hypercholesterolemia. METHODS: This study was a randomized, double-blind, simvastatin controlled, multi-center trial. After 4 weeks of life style modification for cholesterol reduction, patients with a baseline low-density lipoprotein cholesterol (LDL-C) 145~250 mg/dL and triglyceride (TG)

Primary Sirolimus-Eluting Stent Implantation for Patients with Acute ST-Segment Elevation Myocardial Infarction

BACKGROUND AND OBJECTIVES: Sirolimus-eluting stents (SES) have been shown to significantly inhibit neointimal hyperplasia, resulting in reduced restenosis compared with bare metal stents (BMS). However, the efficacy and safety of SES implantation for patients with acute ST-segment elevation myocardial infarction (STEMI) remain unclear. SUBJECTS AND METHODS: Primary stenting was performed using SES in 74 patients (mean age: 58.0+/-12.7 years, 59 males) and BMS in 88 patients (mean age: 59.3+/-10.7 years, 63 males) between April 2003 and July 2004. We retrospectively compared the incidence of 6-month angiographic restenosis and the major adverse cardiac events (MACE) defined as cardiac death, non-fatal myocardial infarction and target lesion revascularization (TLR), between the SES group and the BMS group. RESULTS: The SES group had smaller vessels (3.04+/-0.47 mm vs. 3.24+/-0.56 mm, respectively, p=0.02) and a longer stent length (33.7+/-14.3 mm vs. 25.0+/-9.6 mm, p=0.00). The procedural success rate (87.8% vs. 92.0%, respectively, p=0.37) and the peak creatine kinase-MB (239+/-196 ng/mL vs. 274+/-188 ng/mL, p=0.26) were similar. The 6-month angiographic restenosis rate (0.0% vs. 30.4%, respectively, p=0.00) and late loss (-0.03+/-0.55 mm vs. 1.28+/-0.58 mm, p=0.00) were significantly lower in the SES group compared with the BMS group. Stent thrombosis developed in only 1 case of the SES group (1.4% vs. 0.0%, respectively, p=0.45). At 6 months, SES implantation significantly reduced the incidence of MACE (6.9% vs. 19.5%, respectively, p=0.04), because of a reduction in the incidence of TLR (1.4% vs. 11.5%, p=0.01). Likewise, the MACE-free survival rate was significantly higher in the SES group (93.06% vs. 80.46%, respectively, p=0.03). CONCLUSION: Compared with the BMS, the SES was effective in reducing the incidence of 6-month angiographic restenosis and MACE without any increased risk of stent thrombosis in the patients with STEMI who received primary stenting.

Terminal QRS Complex Distortion on the Admission Electrocardiogram in Anterior Acute Myocardial Infarction and Association with Residual Flow and Infarct Size after Primary Angioplasty

BACKGROUND: Terminal QRS complex distortion on admission is a simple and reliable predictor of infarct size in patients with acute myocardial infarction (AMI). It is uncertain, however, whether this reflects reduced myocardial perfusion of the infarct area and a larger area of the myocardium at risk. This study was conducted to investigate whether terminal QRS distortion complex on admission is a reliable predictor of reduced residual flow and a larger area of the myocardium at risk compared to patients who are admitted without a terminal QRS distortion. METHODS: We evaluated the relationship between terminal QRS complex distortion and residual flow to the infarct zone and risk area in 46 anterior AMI patients undergoing primary angioplasty. 99mTc-sestamibi imaging was performed at baseline and 5-9 days after angioplasty. The study population was divided into those with (Group I, n=16) and without (Group II, n=30) terminal QRS complex distortion. RESULTS: Baseline characteristics were similar between the two groups. The area of the myocardium at risk was higher in Group I (59.9 +/- 15.3%) than in Group II (48.6 +/- 13.7%, p< 0.05; mean+SD) while the nadir measurement of the residual flow was lower in Group I (0.10 +/- 0.07) than in Group II (0.16 +/- 0.09, p< 0.05). Although the final infarct size was significantly higher in Group I (40.8 +/- 17.2%) than in Group II (27.1 +/- 18.1%, p< 0.05), the myocardial salvage index did not differ significantly between the two groups. CONCLUSION: Terminal QRS complex distortion seems to be associated with less residual flow to the infarct zone, a larger risk area and greater infarct size in patients with anterior AMI.

Ten centers' study on the present state of treatment for hypercholesterolemia in patients with coronary artery disease / 대한내과학회지

BACKGROUND: Previous studies showed 'treatment gap' phenomenon in the treatment of hyperlipidemia, meaning failure to adhere to the recommendation in the treatment guideline. In Korea, systematic research on this issue has never been done. This investigation was to estimate the hypercholesterolemia treatment gap in coronary artery disease (CAD) patients in tertiary care centers according to NCEP ATP-III guideline. METHODS: Ten Korean educational hospital participated in the survey, reviewing medical record of 1,048 patients. Patients were enrolled when they were documented as having coronary artery disease by coronary angiography or stress tests or medical history of myocardial infarction, percutaneous coronary intervention or bypass surgery. Thirty or more medical records per each of 3 or more cardiologists were reviewed in each hospital. Sampling was done sequentially based on outpatient or inpatient list. Pharmacological treatment for hyperlipidemia included the first and last records of prescription. Baseline and the most recent lipid profiles were collected. RESULTS: Findings from the survey was summarized as '10 to 50% rule': 10%: mean LDL-cholesterol reduction without lipid-lowering drug, 20%: LDL-cholesterol level at the treatment goal before any treatment, 30%: mean LDL-cholesterol reduction with lipid-lowering drug treatment, 40%: proportion of CAD patients without lipid-lowering drug, 50%: treatment goal achievement after treatment. CONCLUSIONS: Significant treatment gap exists in Korean cardiology practice in tertiary care centers. Systematic approach to reduce this gap is warranted.

The Effects of Coronary Artery Remodeling on the Developments of Collateral Blood Flow in Patients with Acute Myocardial Infarction Treated with Primary Angioplasty

BACKGROUND: The relation between pressure-derived fractional collateral flow (PDCF) and coronary arterial remodeling remains uncertain in acute myocardial infarction. METHODS: We evaluated the effect of arterial remodeling on the development of PDCF in 72 patients with first acute myocardial infarction (pain onset 1.0 and nonpositive remodeling as a RI 24% and insufficient collateral as PDCF index < or =24%. RESULTS: The RI was 1.04+/-0.15 in the lesions with sufficient collateral and 1.03+/-0.16 in the lesions with insufficient collateral (p=0.812). There was no significant difference in the frequency of positive remodeling between the 2 groups (55% vs. 54%, respectively, p=0.966). The PDCF index was 20+/-11% and 20+/-9% in positive and nonpositive remodeling, respectively (p=0.891). There was no significant correlation between RI and PDCF index (r=0.027, p=0.823). CONCLUSION: The pattern of coronary arterial remodeling might not influence the development of collateral blood flow in patients with acute myocardial infarction treated with primary angioplasty.

Morphometric and Serum Biochemical Analysis of Myocardial Fibrosis in Patients with Valvular Heart Disease

BACKGROUND AND OBJECTIVES: To compare the pattern of myocardial fibrosis in various valvular heart diseases (VHD), the morphometric data of the myocardial tissue and serum biochemical markers of myocardial fibrosis were analyzed in patients with aortic stenosis (AS), aortic regurgitation (AR) and mitral regurgitation (MR). SUBJECTS AND METHODS: Blood samples were obtained from 21 patients with AS, 23 with AR and 29 with MR. The serum levels of aminoterminal propeptide, of type I/III procollagen (PINP/PIIINP), and fibronectin were measured to estimate the synthesis of the extracelluar matrix. The carboxy-terminal telopeptide collagen type I (CITP), matrix metalloproteinase-1 (MMP-1, collagenase) and the tissue inhibitor, metalloproteinase-1 (TIMP-1), were also measured to estimate the collagen degradation and metabolism activities. The left ventricular mass (LVM) was calculated by echocardiography. Of the patients, myocardial tissue was obtained during surgery in 11 with AS, 8 with AR and 13 with MR;the collagen volume fraction (CVF) was calculated using picrosirius red staining. RESULTS: The LVM was significantly larger in the AS and AR groups compared to the MR group (p0.05), and the biochemical markers were no different between the AS and AR groups (p>0.05). Fibronectin was the only parameter showing a positive correlation with both the CVF (r=0.388, p=0.01) and the left ventricular mass (r=0.278, p=0.02). CONCLUSION: Different mechanisms for the matrix synthesis and degradation were present for the maintenance of myocardial fibrosis and hypertrophy according to the type of VHD, and fibronectin, a major non-collagenous extracelluar matrix, was proved to be an important factor associated with cardiac hypertrophy and myocardial fibrosis.