Rosuvastatin prevents aortic arch plaque progression and improves prognosis in ischemic stroke patients.

OBJECTIVES: Complicated aortic arch plaques (CAP) and their progression are important for recurrent ischemic stroke (IS) and its prognosis. We investigated the effects and clinical benefits of rosuvastatin therapy on this pathophysiology. The purpose of this study was to investigate whether rosuvastatin prevention of aortic arch plaque progression improved the prognosis of IS patients. METHODS: Ninety-seven consecutive acute cerebral embolism patients were retrospectively surveyed. All had transesophageal echocardiography (TEE) to assess the presence or absence of CAP, defined as aortic wall thickness ≥4 mm or plaque ulceration. Patients received conventional antithrombotic therapy as clinically indicated. All patients with CAP were recommended to receive 5 mg rosuvastatin/day, administered by their attending physicians; not all physicians followed this recommendation. Six-month follow-up TEEs were performed in patients with CAP who received rosuvastatin. Major adverse cerebrovascular events (MACEs) comprised recurrent IS and death. RESULTS: CAP was detected in 39 patients (40%), and MACEs in 15. Multivariate regression analysis showed that patients with CAP not taking rosuvastatin was an independent risk factor for MACEs (odds ratio = 18.044; 95% confidential interval = 2.089-155.846, p < 0.01). When patients were divided into three groups: those with CAP taking rosuvastatin, those with CAP not taking rosuvastatin, and those without CAP, Kaplan-Meier analysis demonstrated that patients with CAP not taking rosuvastatin had significantly more MACEs than those in the other two groups (long-rank test; χ2 = 6.553, p < 0.05). Six-month TEE follow-ups in the 26 patients with CAP taking rosuvastatin showed significant improvement in CAP diameter with improved lipid profiles; 88% (23/26 patients) showed no morphological CAP progression; 15 of these showed CAP regression. DISCUSSION: Rosuvastatin therapy prevented aortic arch plaque progression in IS patients with CAP, and may also have long-term clinical benefits.

Left atrial appendage dysfunction in acute cerebral embolism patients with sinus rhythm: correlation with pulse wave tissue Doppler imaging.

To evaluate left atrial appendage (LAA) dysfunction using left atrial pulse-wave tissue Doppler imaging (PW-TDI) in acute cerebral embolism (ACE) patients with sinus rhythm (SR), transthoracic (TTE) and transesophageal echocardiograhy (TEE) were performed in 60 consecutive patients with SR without obvious left ventricular dysfunction within 2 weeks after ACE. Two groups were identified: LAA dysfunction [LAA emptying peak flow velocity (LAA-eV) <0.55 m/s, n = 20, age 65 ± 10 years] and without LAA dysfunction (LAA-eV ≥ 0.55 m/s, n = 40, age 64 ± 10 years) on TEE. Left atrial wall motion velocity (WMV) was obtained from PW-TDI, with the sample volume placed at the left atrial anterior wall adjacent to ascending aortic inferior wall from the long axis view on TTE. WMVs showed triphasic waves: after the P wave (La') during systole (Ls'), and during early diastole. La' and Ls' were significantly lower in the group with versus without LAA dysfunction (4.9 ± 1.4 vs. 7.7 ± 1.8 cm/s, p < 0.0001; 5.3 ± 2.0 vs. 6.7 ± 1.9 cm/s, p < 0.001, respectively) and prevalence of paroxysmal atrial fibrillation, left atrial volume index, and serum levels of brain natriuretic peptide were significantly higher (60 vs. 15 %, p < 0.001; 32 ± 13 vs. 24 ± 13 ml/m(2), p < 0.05; 174 ± 279 vs. 48 ± 68 pg/ml, p < 0.01, respectively). La' was an independent predictor of LAA dysfunction (OR 0.380, 95 % CI 0.156-0.925, p < 0.05), and was significantly correlated with LAA-eV (r = 0.594, p < 0.0001) and LAA fractional area change (r = 0.682, p < 0.0001). The optimal cut-off value for LAA-eV < 0.55 m/s was 5.5 cm/s (sensitivity 83 %, specificity 88 %). La' is a useful and convenient strong predictor of LAA dysfunction in ACE patients with SR.

Rosuvastatin improves plaque morphology in cerebral embolism patients with normal low-density lipoprotein and severe aortic arch plaque.

The effect of rosuvastatin was investigated on complicated aortic arch plaque (CAP) morphology and lipid profiles in acute cerebral embolism (CE) patients with normal low-density lipoprotein-cholesterol (LDL-c) levels. Transesophageal echocardiography (TEE) studies were performed in 56 consecutive CE patients with LDL-c less than 140 mg/dL who were not taking lipid-lowering agents at baseline. CAP observed by TEE was defined as the presence of greater than 4-mm diameter, ulcerated, or mobile aortic plaque. Patients were divided into those with CAP versus without CAP (group A, n=24, age 69±8 years) and without CAP (group B, n=32, age 62±10 years). Of the 24 group A patients, 18 received 5 mg/d of rosuvastatin for 6 months and had follow-up TEE studies. In Group A, the baseline values of high-density lipoprotein-cholesterol (HDL-c) and apolipoprotein A-1 (ApoA-1) were significantly lower than in Group B (44±15 versus 55±15 mg/dL, P=.0059; 103±19 versus 137±25 mg/dL, P=.0006, respectively) and age and serum high-sensitivity C-reactive protein concentration were significantly higher (69±8 vs. 62±10 years, P=.0080; 2.34±3.05 vs. 0.67±1.00 mg/dL, P=.0054, respectively). By multivariate logistic regression analysis, ApoA-1 was shown to be an independent predictor of CAP (odds ratio=.894, 95% confidence intervals .800-.996, P=.0483). In the 18 group A patients receiving rosuvastatin for 6 months, aortic arch plaque diameter and serum LDL-c were significantly decreased (5.8±2.2 to 5.1±2.1 mm, P=.0377; 110±23 to 81±23 mg/dL, P=.0008, respectively), whereas serum HDL-c and ApoA-1 concentrations were significantly increased (42±8 to 52±9 mg/dL, P=.0002; 109±22 to 135±15 mg/dL, P=.0002, respectively). Plaques were morphologically improved in 11 patients, unchanged in 6, and worsened in 1. These data suggest that rosuvastatin improves plaque morphology concomitant with improving lipid profiles in CE patients with normal LDL-c levels.

Successful revascularization to right coronary artery by percutaneous coronary intervention after endovascular therapy for leriche syndrome.

A 69-year-old man with effort angina was admitted to our institution. Echocardiography showed poor left ventricular systolic function with akinesis of the anterior wall and severe hypokinesis of the inferior wall. We performed coronary angiography, which revealed two diseased vessels including chronic total occlusion in the left anterior descending artery and severe stenosis in the right coronary artery (RCA). In addition, aortography revealed aortoiliac occlusive disease known as Leriche syndrome. As the patient's symptom was stable, we first planned to perform endovascular therapy (EVT) for Leriche syndrome to make a route for intra-aortic balloon pumping. We prepared a bi-directional approach from bi-femoral arteries and a left brachial artery. The guidewire was passed through the occlusive area using the retrograde approach. The self-expanding stents were deployed by a kissing technique. At one week after EVT, a 6Fr sheath was inserted from the right radial artery and an intra-aortic balloon pump was successfully inserted through the right femoral artery for percutaneous coronary intervention (PCI) to the RCA. Two drug-eluting stents were successfully deployed to RCA after using an atherectomy device (rotablator). We reported the case as a successfully performed PCI to the RCA after EVT for Leriche syndrome.

Assessment of aortic arch stiffness using pulse-wave tissue Doppler imaging: a transesophageal echocardiographic comparison study of acute ischemic stroke patients and stroke-free patients.

BACKGROUND: Elevated aortic stiffness determined by transesophageal echocardiography (TEE), and presence of complicated aortic plaque provide prognostic information about cerebrovascular disease risk. Recently, pulse-wave tissue Doppler imaging (PW-TDI) has offered a new technique for assessing aortic wall stiffness. METHODS: The following aortic long-axis view TEE measurements were carried out in 103 consecutive acute ischemic stroke patients and 72 controls (stroke-free patients requiring TEE for conditions such as atrial fibrillation and valvular heart disease): (a) PW-TDI motion velocities measured as expansion peak velocity during systole (Vs) and contraction peak velocity during diastole (Vd); (b) aortic arch stiffness parameter ß (Aoß), defined as ß = ln (systolic blood pressure/diastolic blood pressure)/([Dmax - Dmin]/Dmin), where ln is the natural logarithm, Dmax is maximum aortic lumen diameter, and Dmin is minimum aortic lumen diameter. The PW-TDI of Vs and Vd was compared with conventional vessel parameters brachial-ankle pulse wave velocity (baPWV) and cardio-ankle vascular index (CAVI, calculated from blood pressure and PWV). RESULTS: Comparing acute ischemic stroke patients versus controls, Vs and Vd were significantly decreased (3.3 ± 1.6 vs. 3.9 ± 2.0 cm/sec, P < 0.05; 1.7 ± 0.6 vs. 2.1 ± 0.8 cm/sec, P < 0.01, respectively), and Aoß and aortic arch intima-media thickness (AoIMT) were significantly increased (15.3 ± 12.5 vs. 11.6 ± 6.5, P < 0.05; 3.2 ± 2.5 vs. 2.4 ± 2.1 mm, P < 0.05; respectively). Furthermore, Vs and Vd were significantly negatively correlated with age, Aoß, AoIMT, CAVI, and baPWV in all cases. CONCLUSIONS: The use of aortic arch wall PW-TDI for Vs and Vd evaluation constitutes an easily and readily assessed parameter for evaluating aortic arch stiffness.

Usefulness of albuminuria as a prognostic indicator in patients with chronic heart failure secondary to ischemic or idiopathic dilated cardiomyopathy.

Albuminuria is an established risk factor for mortality and cardiovascular events in the general population. Albuminuria might be a marker of the various pathophysiologic changes, such as diffuse vascular injury and systemic inflammation, that arise in patients with chronic heart failure (CHF). However, the relation between albuminuria and CHF has not yet been fully elucidated. Therefore, the purpose of the present study was to assess the prevalence and prognostic significance of albuminuria in patients with CHF secondary to ischemic or idiopathic dilated cardiomyopathy. Of the 712 patients with CHF, 311 had normoalbuminuria, 304 had microalbuminuria, and 97 had macroalbuminuria. The patients with albuminuria had more cardiovascular co-morbidity and worse renal function than those with normoalbuminuria. A total of 152 cardiac events occurred during the follow-up period. Kaplan-Meier analysis demonstrated that patients with albuminuria had a greater incidence of cardiac events than those without albuminuria. Furthermore, albuminuria was significantly associated with an increased risk of cardiac events, even after adjustment for other prognostic variables. In conclusion, albuminuria is a powerful and independent predictor of adverse prognosis in patients with CHF and could be useful for risk stratification of patients with CHF.

Computed tomography and scintigraphy vs. cardiac catheterization for coronary disease screening prior to noncardiac surgery.

OBJECTIVE: The goal of this study was to investigate the utility of multidetector-row computed tomography (MDCT) and adenosine triphosphate stress cardiac single photon emission computed tomography (ATP-SPECT) in evaluating coronary artery disease (CAD) in patients scheduled for non-cardiac surgery. PATIENTS AND METHODS: We routinely performed echocardiography and exercise stress electrocardiography as preoperative cardiac screening examinations for patients scheduled for non-cardiac surgery under general anesthesia. Of 848 consecutive preoperative patients (Non-invasive Group), 49 patients with abnormalities of these screening examinations had MDCT and ATP-SPECT. Of 809 consecutive preoperative patients studied at an earlier time (Invasive Group), 58 patients with abnormalities of these screening examinations had cardiac catheterization as an additional cardiac examination. RESULTS: The number of patients in the non-invasive and invasive subgroups having additional screening examinations was comparable, and there was no significant difference in perioperative cardiac events between the two subgroups. Based on results of the additional tests in the two subgroups, preoperative prophylactic invasive treatment for CAD was carried out in a small number of patients, again with no significant differences between the groups. However, total medical expenses for the additional cardiac examinations were significantly reduced in the non-invasive subgroup compared with the invasive subgroup (140,030+/-34,800 vs. 187,170+/-26,120 yen, respectively, p=0.0002). CONCLUSION: Non-invasive examination prior to noncardiac surgery using MDCT and ATP-SPECT in a subgroup of patients suspected of having CAD appears to be a useful screening procedure. Compared with invasive cardiac catheterization, CT testing has comparable diagnostic utility without an increase in perioperative cardiac events, and in addition, it has an improved cost-benefit profile.

Quadricuspid aortic valve illustrated by 64-slice multidetector computed tomography: Surgical treatment of a rare cause of severe aortic regurgitation.

The quadricuspid aortic valve (QAV) is a rare congenital malformation that usually presents with aortic regurgitation (AR). The first case was reported in 1862. Most cases were diagnosed at the time of surgery or postmortem examination. With advances in imaging techniques, more cases have been diagnosed before surgery. We describe a 59-year-old man whose QAV had not been noted until the current admission. Transthoracic echocardiography revealed dilation of the left ventricle, severe AR, and suspected QAV. The QAV was confirmed by transesophageal echocardiography and 64-slice multidetector computed tomography. This case was a QAV with three equal cusps and one smaller cusp (type B in Hurwitz and Roberts classification). Because the cardiac catheterization and aortography showed severe AR and a QAV, the patient underwent elective surgery. The surgery consisted of replacing the QAV by a mechanical prosthesis. There were no post-operative complications. The patient revealed no symptoms in the post-operative 7 months.

Transcatheter coil embolization of coronary artery fistulas.

Congenital coronary artery fistulas (CAFs), which have been known since 1865, are rare congenital cardiac abnormalities. Most of the CAFs are discovered incidentally during coronary angiography. We described our experience with successful transcatheter coil embolization of CAFs in an adult, leading to improvement of symptoms. The patient had chest pain or dyspnea on exertion. The CAFs originated from the left anterior descending coronary artery and the circumflex artery. They all drained into the pulmonary trunk. The coils were implanted through a microcatheter, which was passed through a 7F guiding catheter. The coils were used to occlude the CAFs completely. The procedures were uncomplicated. Patient's chest pain or dyspnea resolved after the procedures. Although the patient had small residual flow at the CAFs from the circumflex artery at follow-up coronary angiography, the patient was asymptomatic. Therefore, we considered the coil embolization to be successful. Transcatheter closure of CAFs with coil is a valid option, and can be regarded as an acceptable alternative to surgery nowadays.

Complete atrioventricular block due to venous stent migration from innominate vein to right ventricle: a case report.

A 78-year-old man who had been treated with maintenance hemodialysis for chronic renal failure was admitted with severe edema in left arm for 1 month. Venous angiography showed a severe stenosis in left innominate vein, then, he underwent percutaneous balloon angioplasty and venous stenting (Wall Stent RP). His arm edema soon improved after angioplasty, however, he complained of general fatigue and bradycardia 2 days after the venous angioplasty. Electrocardiogram showed complete atrioventricular block with 35 wide QRS complexes per minute. His echocardiogram showed a pipe-shaped structure with multiple slit and acoustic shadow in right ventricle. His radiographical right ventriculogram revealed the migrated venous stent from innominate vein to right ventricle. We tried to perform percutaneous transvenous stent extraction using Goose-Neck snare catheter, however, the wall stent stuck in the right external iliac vein, and contrast media leaked to the outside of the vascular wall. Therefore, we implanted this stent in the iliac vein with optimal-sized balloon inflation, and succeeded in stopping bleeding. Complete atrioventricular block was recovered to sinus rhythm with left bundle branch block just after the removal of the venous stent from right ventricle, and no cardiovascular events occurred after the treatment.

Mutagenicity of 8-nitroguanosine, a product of nitrative nucleoside modification by reactive nitrogen oxides, in mammalian cells.

8-Nitroguanosine is a nitratively modified nucleoside that is formed endogeneously under inflammatory conditions dependent on nitric oxide production, particularly associated with cancer risks. Here, we investigated the mutagenic potential of 8-nitroguanosine in mammalian cells. Treatment with 8-nitroguanosine (10-1000 microM) for 1h significantly increased (by 6-8 times) the mutation frequency of the xanthine-guanine phosphoribosyltransferase (gpt) gene in AS52 cells without cytotoxic effects. 8-Nitroguanosine treatment induced a G-to-T transversion in gpt gene at position 86. It also significantly increased levels of abasic sites in DNA. These observations suggest that formation of 8-nitroguanosine may contribute to the pathogenesis of inflammation-associated carcinogenesis.

Dynamic assessment of myocardial involvement in patients with end-stage renal disease by ultrasonic tissue characterization and serum markers of collagen metabolism.

BACKGROUND: Congestive heart failure is the most common cause of mortality in patients with end-stage renal disease (ESRD). However, noninvasive assessment for cardiac involvement in ESRD has not been established. HYPOTHESIS: Assessment of ultrasonic tissue characterization and serum markers of collagen degradation is useful for defining myocardial involvement in ESRD. METHODS: Cyclic variation of ultrasonic integrated backscatter of the ventricular septum (CV-IBS) and the serum levels of free matrix metalloproteinase-I (MMP-I) and tissue inhibitor of metalloproteinase-I (TIMP-I) were measured in 30 patients with ESRD undergoing routine hemodialysis (HD) and in 40 patients with essential hypertension (HTN). RESULTS: Compared with the group with HTN, ESRD (before HD) showed larger left ventricular (LV) mass index (217 +/- 56 vs. 146 +/- 45 g/m2, p < 0.01), worse LV diastolic function (E/A, 0.6 +/- 0.2 vs. 0.9 +/- 0.3, p < 0.05), smaller CV-IBS (9.0 +/- 1.3 vs. 12.4 +/- 0.9 dB, p < 0.01), and larger TIMP-I/MMP-I (46 +/- 10 vs. 34 +/- 10, p < 0.05), in spite of the comparable ventricular wall thickness. Thus, these indices may possibly reflect myocardial interstitial fibrosis. After HD (after the improvement of myocardial interstitial edema), a negative linear relationship between CV-IBS and TIMP-I/MMP-I was observed (r= -0.52, p < 0.05). CONCLUSIONS: Noninvasive assessment of ultrasonic tissue characterization and serum markers of collagen type I degradation may be a new diagnostic tool for defining myocardial interstitial fibrosis in patients with ESRD and LV hypertrophy.

Direct evidence that sustained dysfunction of left atrial appendage contributes to the occurrence of cardiogenic brain embolism in patients with paroxysmal atrial fibrillation.

OBJECTIVE: The goal of this study was to investigate transesophageal echocardiographic (TEE) findings after the termination of atrial fibrillation to clarify the direct evidence for occurrence of acute cardiogenic brain embolism (CBE) in patients with paroxysmal atrial fibrillation (PAF). PATIENTS AND METHODS: Among 98 consecutive patients with CBE, we investigated TEE in 16 patients with PAF (Group CBE, 72 +/- 10 years) within 7 days of the onset and 2 weeks after the first study, in comparison with 15 age-matched PAF patients without CBE (Group N). The duration from reversal to normal sinus rhythm to first TEE was 6 +/- 1 days in both groups. RESULTS: There were no significant differences in left atrial dimension and emptying flow velocity of the left atrial appendage (LAA-eV) between groups. Group CBE had significantly larger LAA area (4.3 +/- 1.3 cm2 vs. 3.1 +/- 1.0 cm2, p < 0.05), smaller LAA fractional area change (LAA-FAC) (43 +/- 25% vs. 80 +/- 22%, p < 0.001), and a higher incidence of left atrial spontaneous echo contrast (LAA-SEC) (25% vs. 7%, p < 0.05) than group N, and those abnormalities in group CBE were significantly improved at the second TEE (LAA area: to 3.2 +/- 0.9 cm2, p < 0.05; LAA-FAC: to 84 +/- 26%, p < 0.001; LAA-SEC: to 0%, p < 0.05), respectively. CONCLUSION: LAA-FAC is a more sensitive marker for LAA dysfunction than the widely used index, LAA-eV, and a sustained deterioration of LAA-FAC may be direct evidence for thrombus formation and occurrence of acute CBE in patients with PAF.

Superoxide generation mediated by 8-nitroguanosine, a highly redox-active nucleic acid derivative.

Formation of 8-nitroguanosine may be characterized as nucleic acid modification induced by nitric oxide (NO). We show here that 8-nitroguanosine is a highly redox-active nucleic acid derivative that strongly stimulated superoxide generation from various NADPH-dependent reductases, including cytochrome P450 reductase and all isoforms of NO synthase. This reaction involves these reductases in a redox cycling reaction via single-electron reduction of 8-nitroguanosine to form 8-nitroguanosine anion radical. One electron is then transferred from this radical to molecular oxygen. 8-Nitroguanosine formed in vivo may function as a potent redox cofactor that intensifies oxyradical generation by various NADPH/reductase-like enzymes and thus participates in diverse physiological and pathological events.

Molecular assembly and subcellular distribution of ATP-sensitive potassium channel proteins in rat hearts.

Cardiac ATP-sensitive K(+) (K(ATP)) channels are proposed to contribute to cardio-protection and ischemic preconditioning. Although mRNAs for all subunits of K(ATP) channels (Kir6.0 and sulfonylurea receptors SURs) were detected in hearts, subcellular localization of their proteins and the subunit combination are not well elucidated. We address these questions in rat hearts, using anti-peptide antibodies raised against each subunit. By immunoblot analysis, all of the subunits were detected in microsomal fractions including sarcolemmal membranes, while they were not detected in mitochondrial fractions at all. Immunoprecipitation and sucrose gradient sedimentation of the digitonin-solubilized microsomes indicated that Kir6.2 exclusively assembled with SUR2A. The molecular mass of the Kir6.2-SUR2A complex estimated by sucrose sedimentation was 1150 kDa, significantly larger than the calculated value for (Kir6.2)(4)-(SUR2A)(4), suggesting a potential formation of micellar complex with digitonin but no indication of hybrid channel formation under the conditions. These findings provide additional information on the structural and functional relationships of cardiac K(ATP) channel proteins involving subcellular localization and roles for cardioprotection and ischemic preconditioning.

Hemodialysis improves myocardial interstitial edema and left ventricular diastolic function in patients with end-stage renal disease: noninvasive assessment by ultrasonic tissue characterization.

Congestive heart failure is the most common cause of mortality in patients with end-stage renal disease (ESRD). Ultrasonic tissue characterization with integrated backscatter offers a promising method for the noninvasive assessment of regional myocardial contractile performance and fibrosis. The aim of this study was to investigate the effect of hemodialysis (HD) on myocardial tissue characterization and left ventricular function in ESRD patients. We examined 26 patients with ESRD undergoing routine HD (age 63 +/- 12 years, duration of HD 9.2 +/- 3.2 years) and 30 patients with essential hypertension (HT; 60 +/- 10 years). Routine echocardiographic parameters and the cyclic variation of ultrasonic integrated backscatter of the ventricular septum (CV-IBS) were measured. Left ventricular mass index was significantly larger in patients with ESRD than in those with HT (217 +/- 56 vs 146 +/- 45 g/m(2), P < 0.05). The indices for left ventricular diastolic function (E/A, the ratio of left ventricular peak early to late diastolic filling velocity; DT, the deceleration time of the early diastolic filling) and CV-IBS had deteriorated significantly in patients with ESRD before HD compared with those with HT (E/A, 0.6 +/- 0.2 vs 0.9 +/- 0.3, P < 0.05; DT, 228 +/- 23 vs 184 +/- 19 ms, P < 0.05; CV-IBS, 9.0 +/- 1.3 vs 12.4 +/- 0.9 dB, P < 0.05), possibly reflecting interstitial fibrosis. In patients with ESRD, HD reduced calculated left ventricular mass index by 19% (before HD, 217 +/- 56 vs immediately after HD, 176 +/- 45 g/m(2), P < 0.05) and CV-IBS by 19% (9.0 +/- 1.3 vs 7.3 +/- 1.1 dB, P < 0.05), that possibly reflected improvement of interstitial edema. HD also significantly improved indices for left ventricular diastolic function (E/A, 0.6 +/- 0.2 vs 0.9 +/- 0.2, P < 0.05; DT, 228 +/- 23 vs 188 +/- 21 ms, P < 0.05). HD improves myocardial interstitial edema and left ventricular diastolic function in patients with ESRD. Noninvasive assessment of ultrasonic tissue characterization is useful in defining the pathophysiological changes of ventricular myocardium in patients with ESRD.

Long-term effects of benidipine hydrochloride on severe left ventricular hypertrophy and collagen metabolism in patients with essential hypertension.

OBJECTIVES: The long-term effects of benidipine on left ventricular hypertrophy (LVH) and collagen metabolism were examined in patients with essential hypertension. METHODS: Forty patients with untreated essential hypertension were given benidipine at a dose of 6 mg a day. Routine echocardiographic parameters, serum concentrations of matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) were analyzed before and 12 months after treatment with benidipine. Patients were classified according to left ventricular mass index (LVMI) into three groups: severe LVH (LVMI > or = 159), mild LVH (159 > LVMI > or = 125) and no LVH (LVMI < 125). RESULTS: Serum levels of free TIMP-1 to MMP-1 ratio were significantly higher in patients with severe LVH than in the other two groups before treatment. There was a significant positive correlation between the free TIMP-1 to MMP-1 ratio and LVMI in all study subjects (r = 0.51, p < 0.01). Twelve months after treatment, percentage changes of the LVMI and free TIMP-1 to MMP-1 ratio were significantly larger in the patients with severe LVH (-27% and -54%) than with mild LVH (-12% and -23%) or no LVH (-4% and -11%), respectively. Changes in the systolic blood pressure but not changes in the free TIMP-1 to MMP-1 ratio correlated with changes in the LVMI in patients with mild LVH (r = 0.78, p < 0.01). Changes in the free TIMP-1 to MMP-1 ratio but not changes in the systolic blood pressure correlated with changes in the LVMI in patients with severe LVH (r = 0.69, p < 0.01). CONCLUSIONS: Long-term administration of benidipine reduced left ventricular mass and normalized systemic collagen type I degradation abnormalities in essential hypertensive patients with severe but not mild LVH.