Population pharmacokinetic investigation for optimization of amiodarone therapy in Japanese patients.

BACKGROUND: Optimal use of amiodarone (AMD) requires information regarding the drug's pharmacokinetics and the influence of various factors on the drug's disposition. This study was conducted to establish the role of patient characteristic in estimating doses of AMD using nonlinear mixed effects modeling in Japanese patients treated with oral therapy. METHODS: Serum concentrations of AMD were determined by high-performance liquid chromatography. The 151 serum trough concentrations from 23 patients receiving repetitive oral AMD were collected. Analysis of the pharmacokinetics of AMD was accomplished using a 1-compartment open pharmacokinetic model. The effect of a variety of developmental and demographic factors on AMD disposition was investigated. RESULTS: Estimates generated by nonlinear mixed effects modeling indicated that the clearance of AMD was influenced by the demographic variables: total body weight (TBW), daily dosage of AMD (DD), body mass index (BMI), gender (GEN), duration of AMD dosing (DUR), and patient clearance factor (Conc(θ); Conc = serum trough concentration of AMD). The final pharmacokinetic parameters were CL/F (L/h) = 0.072·TBW·Conc(-1.01)·1.95(DD≥200)·0.931(BMI≥25)·1.37(GEN)·DUR(-0.016), and Vd/F (L) = 78.4·TBW, where CL is total body clearance and Vd is volume of distribution. As all doses were given orally, it was impossible to assess the bioavailability (F). DD ≧200 is an indicator variable that has a value of 1 if the patient is receiving more than 200 mg daily dosage of AMD, and 0 otherwise. BMI ≧25 is an indicator variable that has a value of 1 if the BMI is 25 kg/m² and over, and 0 otherwise. GEN is an indicator variable that has a value of 1 if the patient is woman, and 0 otherwise. CONCLUSIONS: The authors developed new population pharmacokinetic parameters. Clinical application of the findings in the present study to patient care may permit selection of an appropriate initial maintenance dose, thus enabling the clinician to achieve a desired therapeutic effect.

Longitudinal analysis of blood pressure trends and prognosis in isolated systolic hypertension in elderly individuals.

BACKGROUND: With age, a larger proportion of elderly individuals have isolated systolic hypertension (ISH). However, because of a lack of longitudinal studies, much less is known about the incidence and prognosis of ISH in elderly individuals. The aims of this study were to document blood pressure (BP) trends in development of ISH in elderly individuals, and to investigate the incidence and prognosis for those with ISH. METHODS: Retrograde longitudinal analysis was conducted on 3284 subjects during 1958 to 1984. The presence of ISH in elderly individuals was defined as systolic BP of >or=160 and diastolic BP of or=60 years. Prognosis was subsequently investigated until 2002 and compared with that for age- and sex-matched non-ISH control subjects. RESULTS: Selected as ISH in elderly individuals were 185 subjects. Three subtypes were documented by BP trends: 71 subjects with "de novo" ISH, 68 with "burned out" ISH, and 46 subjects with "unclassifiable" ISH. Incidence of ISH increased with age. Mean onset age of ISH was 71.0 years. Subsequent follow-up revealed that the subjects with ISH lived long lives: 83.2% of ISH subjects and 76.2% of control subjects lived to be >80 years old. However, 58.9% of ISH subjects were found to have cardiovascular disease during the follow-up, showing a higher prevalence than among control subjects (42.2%, P = .0013). In more than 40% of subjects with ISH, cardiovascular disease occurred at >or=80 years of age. CONCLUSIONS: In this study, the incidence of ISH increased with age. Persons with ISH have good prognoses in terms of longevity, but many have late-onset cardiovascular complications, suggesting the importance of BP control even in very elderly individuals.

Fatty liver and uric acid levels predict incident coronary heart disease but not stroke among atomic bomb survivors in Nagasaki.

Relationships between fatty liver and coronary heart disease (CHD) and stroke risk remain ill defined. We investigated whether fatty liver is a predictor of CHD and stroke risk. Until December 2000 we followed 2,024 atomic bomb survivors (775 men: 62.0 +/- 9.9 years old; 1,249 women: 63.2 +/- 8.4 years old) who had basic examinations between November 1990 and October 1992 for clinical and laboratory CHD risk factors and fatty liver and who were initially free of CHD and stroke. Forty-nine cases of CHD and 84 cases of stroke were observed. At the time of the baseline examinations, significant clinical associations were found between fatty liver and obesity (p<0.001), hypertension (p<0.001), dyslipidemia (p<0.001), and glucose intolerance (p<0.001). A slight but nonsignificant association was found between fatty liver and hyperuricemia (p=0.07) as well. By using multiple Cox regression analyses, age (relative risk [RR] 1.05, 95% confidence interval [CI] 1.01-1.08), smoking (RR 2.20, 95% CI 1.02-4.74), hyperuricemia (RR 2.30, 95% CI 1.08-4.89), and fatty liver (RR 2.53, 95% CI 1.06-6.06) were shown to be significant predictors of CHD, whereas age (RR 1.08, 95% CI 1.06-1.10), smoking (RR 2.06, 95% CI 1.14-3.72), and hypertension (RR 2.14, 95% CI 1.38-3.30) predicted stroke risk. Fatty liver, which clusters clinical and laboratory CHD risk factors, is an independent predictor of CHD, but not of stroke. Fatty liver should be followed as a feature of metabolic syndrome, with the aim of preventing CHD.

Fibrotic response to angiotensin II is blunted in the kidney, but not in the heart, in insulin-sensitive long-lived transgenic dwarf rats.

Insulin resistance is a characteristic feature of cardiovascular and renal diseases, and angiotensin II (Ang II) has been suggested to induce insulin resistance. The aims of this study were to elucidate the effect of chronic Ang II infusion on vascular reactivity and organ damage in insulin-sensitive rats. We confirmed the following three points. First, there was no significant difference in pressor response to chronic Ang II infusion (600 ng/kg/min) between insulin-sensitive transgenic rats (Tg) and control rats (C). Second, there was no significant difference in cardiac hypertrophy and fibrosis by chronic Ang II infusion between the two groups. However, third, fibrotic response to chronic Ang II infusion evaluated by histopathological scoring in the kidney was significantly decreased in insulin-sensitive transgenic rats (renal fibrosis and nephropathy score: C+Ang II vs Tg+Ang II; 2.5 vs 1.3; p<0.05). Furthermore, the expression of TGF-beta, a fibrosis indicator, was also significantly suppressed in the kidneys of the transgenic rats (TGF-beta1/GAPDH ratio: C+Ang II vs Tg+Ang II; 1.15 vs 0.81; p<0.05). This result indicates that the growth hormone/insulin-like growth factor-1 axis is critically involved in the development of renal injury and fibrosis, rather than hypertension, cardiac hypertrophy, and cardiac fibrosis induced by chronic Ang II administration.

Prognostic significance of incident complete left bundle branch block observed over a 40-year period.

This case-control study was designed to assess the incidence and mortality of complete left bundle branch block (LBBB). We investigated 17,361 subjects (6,663 men and 10,698 women) who underwent biennial health examinations, including electrocardiography and cardiothoracic ratio measurements from 1958 to 2002. A total of 110 incident LBBB cases (41 men and 69 women) were observed, and their basic characteristics were compared with those of 456 age- and gender-matched controls (156 men and 300 women). Also, the possible association between LBBB and all-cause and cause-specific mortality was examined using a Cox proportional hazard model adjusted for age, gender, and underlying disease. The average age at LBBB diagnosis was 69.6 +/- 10.0 years in men and 68.3 +/- 10.9 years in women, and the incidence of LBBB increased progressively with age. Also, underlying disease, hypertension, and ischemic heart disease were significantly associated with LBBB. The cardiothoracic ratio was significantly different at the diagnosis of LBBB between those with LBBB and controls. Electrocardiographic manifestations before LBBB diagnosis included a higher rate of left ventricular hypertrophy and ST-T abnormalities in patients with LBBB. On Cox analysis, LBBB did not predict for all-cause mortality, but it did predict for mortality from congestive heart failure. In conclusion, the mean patient age at LBBB diagnosis was relatively elderly, and the LBBB incidence increased progressively with advancing age. Hypertension, ischemic heart disease, left ventricular hypertrophy, ST-T abnormalities, and an increased cardiothoracic ratio were associated with LBBB. LBBB predicted for mortality from heart failure but not for all-cause mortality, independent of age, gender, and underlying disease.

Basic characteristics of chronic hypotension cases: a longitudinal follow-up study from 1958 through 1999.

Few epidemiological studies have been conducted on the prevalence, blood pressure trends by age, and basic characteristics of chronic hypotension. Among 13,370 subjects (5,094 men and 8,276 women) examined from 1958 to 1999 in Japan, 92 were identified as chronic hypotensives (11 men and 81 women) whose systolic blood pressure (SBP, mmHg) was lower than 100 mmHg for 8 or more years. Trends of SBP and body mass index (BMI, kg/m2) were determined over a 16-year period in this group of chronic hypotensives and 276 age- and sex-matched controls (33 men and 243 women); during this 16-year period, the chronic hypotensives and controls ranged in age from 19 to 75 years. BMI, heart rate (HR, bpm), body temperature (degrees C), Hb (g/dl), and creatinine (Cre, mg/dl) were compared between the chronic hypotensives and the controls at the last examination. The chronic hypotensives had a female preponderance (0.2% in men and 1.0% in women, p=0.001), and their SBP and BMI increased little with increasing age. BMI (20.2+/-3.4), BMI-adjusted SBP (101+/-19), HR (63+/-10), body temperature (36.7+/-0.3), Hb (12.5+/-1.1), and Cre (0.81+/-0.13) were lower in the chronic hypotensives than those (22.9+/-3.4, 126+/-20, 68+/-10, 36.8+/-0.3, 12.9+/-1.1, and 0.86+/-0.12, respectively) in controls (p<0.05). The present results clearly show that chronic hypotensives have a female preponderance and low BMI, HR, body temperature, Hb, and Cre in addition to low SBP that does not increase with age.

D-dimer level influences thromboembolic events in patients with atrial fibrillation.

BACKGROUND: Elevated coagulative molecular markers could reflect the prothrombotic state in the cardiovascular system of patients with non-valvular atrial fibrillation (NVAF). A prospective, cooperative study was conducted to determine whether levels of coagulative markers alone or in combination with clinical risk factors could predict subsequent thromboembolic events in patients with NVAF. METHODS: Coagulative markers of prothrombin fragment 1+2, D-dimer, platelet factor 4, and beta-thromboglobulin were determined at the enrollment in the prospective study. RESULTS: Of 509 patients with NVAF (mean age, 66.6 +/- 10.3 years), 263 patients were treated with warfarin (mean international normalized ratio, 1.86), and 163 patients, with antiplatelet drugs. During an average follow-up period of 2.0 years, 31 thromboembolic events occurred. Event-free survival was significantly better in patients with D-dimer level < 150 ng/ml than in those with D-dimer level>or==150 ng/ml. Other coagulative markers, however, did not predict thromboembolic events. Age (>or==75 years), cardiomyopathies, and prior stroke or transient ischemic attack were independent, clinical risk factors for thromboembolism. Thromboembolic risk in patients without the clinical risk factors was quite low (0.7%/year) when D-dimer was < 150 ng/ml, but not low (3.8%/year) when D-dimer was >or==150 ng/ml. It was >5%/year in patients with the risk factors regardless of D-dimer levels. This was also true when analyses were confined to patients treated with warfarin. CONCLUSIONS: D-dimer level in combination with clinical risk factors could effectively predict subsequent thromboembolic events in patients with NVAF even when treated with warfarin.

[Plasma B-type natriuretic peptide (BNP) measuring].

Brain or B-type natriuretic peptide (BNP) is a potent natriuretic, diuretic and vasorelaxant peptide and inhibits sympathetic tone, the renin-angiotensin-aldosterone system, and synthesis of vasoconstrictive molecules. The major source of plasma BNP is the cardiac ventricles. Elevated plasma BNP concentrations correlate with increased left ventricular (LV) filling pressure. Therefore BNP is a useful biomarkers as a screening tool for LV dysfunction. It also is a strong diagnostic indicator for both systolic and diastolic LV dysfunction. Measurement of plasma BNP is proved to be not only an efficient but also a cost effective screening tool for identifying patients with acute dyspnea of unknown etiology.

Influence of advancing age on fractionated right atrial endocardial electrograms.

The influence of advancing age on atrial endocardial electrograms recorded during sinus rhythm in humans who do not have atrial fibrillation has not been assessed thus far. The prevalence of atrial arrhythmias has been reported to increase with advancing age. Right atrial endocardial catheter mapping during sinus rhythm was performed in 106 patients who had normal sinus node function and no paroxysmal atrial fibrillation to evaluate the influence of advancing age on atrial endocardial electrograms. The bipolar electrograms were recorded at 12 sites in the right atrium, and an abnormal atrial electrographic result was defined as lasting > or =100 ms and/or showing > or =8 fragmented deflections. A total of 1,272 right atrial endocardial electrograms was assessed and quantitatively measured. The mean number of abnormal atrial electrograms per patient (0.61 vs 0.14, p <0.02) and the incidence of abnormal atrial electrograms (11% vs 30%, p <0.02) were significantly greater in patients who were >60 years of age than in younger patients. The longest duration (r = 0.24, p <0.02) and the maximal number of fragmented deflections (r = 0.28, p <0.005) of atrial electrograms among the 12 right atrial sites showed a slight positive correlation with age. The process of aging modifies the electrophysiologic properties of the atrial muscle. There is a progressive increment in the extension of altered atrial muscle with advancing age in humans who do not have atrial fibrillation. Patients who are >60 years of age have significantly greater abnormalities on atrial endocardial electrograms than do younger patients.

ST-segment elevation of electrocardiogram in a patient with Shoshin beriberi.

We report a case of a 58-year-old man with Shoshin beriberi who demonstrated ST-segment elevation and myocardial damage without coronary artery stenosis. The patient subsequently recovered with thiamine treatment. We conclude that it is important to consider Shoshin beriberi as part of the differential diagnosis in patients with shock and ST-segment elevation.

Thrombosed Stanford type A dissection of the aorta in an elderly patient following a fall.

Physical or mental exertion is an important antecedent to dissection. A fall is one of the causes of hip fracture in the elderly population. We report the case of a 78-year-old woman who was diagnosed to have a thrombosed aortic dissection after a fall. We wish to emphasize with this case report that aortic dissection should be considered in the differential diagnosis of patients who complain of chest discomfort after a tumbling over.

Relationship between adrenomedullin and left-ventricular systolic function and mortality in acute myocardial infarction.

The purpose of this study was to investigate the relationship between plasma adrenomedullin concentration levels and left-ventricular systolic function in patients with acute myocardial infarction (AMI), and to assess whether these findings can be used to predict clinical outcomes, including mortality. One hundred twenty-four consecutive first AMI attack subjects were successfully reperfused with primary percutaneous coronary intervention therapy. Plasma adrenomedullin concentrations were evaluated at 24 hours from onset. Left ventriculograms of all patients taken in the acute (soon after reperfusion therapy) and subacute (21 +/-9 days after onset) phases were used to evaluate left-ventricular ejection fraction (LVEF), and the difference in LVEF (delta-LVEF) between the two stages calculated. There were significantly more patients with cardiogenic shock in the H-Adm group (above the median value of plasma adrenomedullin concentrations > or =3.5 Fmol/mL) than in the L-Adm (< 3.5 Fmol/mL) group (p<0.0001). There was significantly higher mortality in the H-Adm group (p<0.01). Multivariate analysis identified plasma adrenomedullin concentrations alone as an independent predictor of mortality (p<0.05). There were no significant differences in acute-stage LVEF between the groups. LVEF in the subacute stage was, however, significantly lower in the H-Adm group than in the L-Adm group (52 +/-12% vs 59 +/-11%, p<0.05). Also, delta-LVEF was significantly lower in the H-Adm group than in the L-Adm group (1.9 +/-9.7% vs 6.3 +/-10.3%, p<0.01). Plasma adrenomedullin concentrations in the early phase of AMI correlate closely with the severity of heart failure, and may offer important prognostic information about the risk of mortality. Our data suggest that plasma adrenomedullin concentrations may be an independent predictor of the deterioration of left-ventricular systolic function.

A histone deacetylase inhibitor enhances killing of undifferentiated thyroid carcinoma cells by p53 gene therapy.

Mutation of the p53 tumor suppressor gene is recognized to be a key event in the development of the highly aggressive behavior of undifferentiated or anaplastic thyroid carcinomas. Attempts to treat these carcinomas with p53 gene therapy have, however, been largely unsuccessful. Since epigenetic changes such as histone deacetylation are associated with loss of thyroid differentiation, we have evaluated the potential of combining p53 gene therapy with exposure to the histone deacetylase inhibitor (HDAC-1), depsipeptide. We used two carcinoma cell lines: FRO cells that express very low levels of p53 and WRO cells producing a dominant negative p53. A p53 response element luciferase assay showed that stimulation of p53 transcriptional activity by the combined treatment with the HDAC-1 and p53 was 10 to 100 times greater than with p53 alone. Western blot analysis demonstrated that the HDAC-1 increased the expression of acetylated histones, as well as of p21(cip1/waf1), but did not affect levels of total histone and endogenous p53. The combined treatment was much more effective than either treatment alone in inhibiting the growth of both cell lines, and flow cytometric analysis suggested that this was due to an increase in the sub-G1 apoptotic population. Our findings indicate that HDAC-1 enhances apoptotic killing by p53 transfer, and suggest that this combination strategy may be useful in treating undifferentiated thyroid carcinomas.

GH suppresses TGF-beta-mediated fibrosis and retains cardiac diastolic function.

The aims of this study were to elucidate the molecular mechanism by which growth hormone (GH) excess is anti-fibrotic in vitro and in vivo model. The in vivo model GH excess showed a significant increase of relative wall thickness with no concomitant disturbance of cardiac diastolic function. Western blot for extracellular matrix (ECM) structural proteins showed minimal change in the GH treatment group, compared to an Angiotensin II (Ang II) subpressor dose group. In cultured cardiac fibroblasts, we investigated the abundance of ECM proteins, phosphorylation of p38 mitogen-activated protein kinase (MAPK), and transforming growth factor-beta (TGF-beta)-specific transcriptional activity. GH down-regulated the expression of PAI-1 and fibronectin proteins activated by TGF-beta. In reporter assays, GH, but not insulin-like growth factor-1 (IGF-1), reduced TGF-beta-specific transcriptional activity. Moreover, GH markedly down-regulated TGF-beta-induced phosphorylation of p38 MAPK. These results demonstrated that a chronic excess of GH have an anti-fibrotic effect on cardiac remodeling, probably through a down-regulation of TGF-beta signaling via de-phosphorylation of p38 MAPK.

Prothrombotic activity is increased in patients with nonvalvular atrial fibrillation and risk factors for embolism.

STUDY OBJECTIVES: The aim of this study was to investigate whether risk factors for embolism would promote thrombus formation in patients with nonvalvular atrial fibrillation (NVAF). METHODS: Hemostatic markers for platelet activity (ie, platelet factor-4 and beta-thromboglobulin [TG]), thrombotic status (ie, prothombin fragments 1 and 2), and fibrinolytic status (ie, d-dimer) were determined in 246 patients with NVAF (mean age, 66.1 years) and 111 control subjects without NVAF (68.3 years). RESULTS: The beta-TG level was higher in NVAF patients than in control subjects. D-dimer levels were higher in NVAF patients having risk factors (mean [+/- SE] d-dimer level, 158.6 +/- 9.2 ng/mL) than in those without risk factors (mean d-dimer level, 92.1 +/- 6.7 ng/mL; p < 0.01) and in control subjects (mean d-dimer level: control subjects with risk factors, 79.1 +/- 10.3 ng/mL; control subjects without risk factors, 31.0 +/- 7.4 ng/mL; p < 0.01). NVAF (odds ratio [OR], 3.94; 95% confidence interval [CI], 1.87 to 8.30; p = 0.0003) and age of >/= 75 years (OR, 5.68; 95% CI, 2.87 to 11.23; p < 0.0001) emerged as predictors of elevated levels of d-dimer, and only NVAF (OR, 10.30; 95% CI, 5.67 to 18.72; p < 0.0001) emerged as a predictor of elevated levels of beta-TG. CONCLUSIONS: NVAF patients whose conditions were complicated with risk factors for embolism could be in the prothrombotic state. Advanced age is a strong predictor of the prothrombotic state in NVAF patients.

High brachial-ankle pulse wave velocity is an independent predictor of the presence of coronary artery disease in men.

Pulse wave velocity (PWV) is an index of arterial stiffness, and a simple device for measuring brachial-ankle PWV (baPWV) has recently been developed. However, the clinical application of baPWV in patients with coronary artery disease (CAD) remains to be fully evaluated. This cross-sectional study was conducted to evaluate whether a higher baPWV predicts the presence of CAD. The baPWV was measured in 123 patients (77 males, 46 females; 63.5+/-11.8 years) who were undergoing coronary angiography. CAD was defined as >50% diameter stenosis. Hemodynamic data and cardiovascular risk factors were examined according to the presence or absence of CAD. Patients with CAD were significantly older across both sexes. The presence of hypertension and chest pain, but not baPWV, was correlated with CAD in females. The baPWV, and the presence of diabetes, hyperlipidemia, and chest pain were related to the presence of CAD in males. Multivariate logistic regression analysis in male patients showed that baPWV, diabetes, hyperlipidemia, and chest pain were independent risk factors for the presence of CAD. Furthermore, high baPWV in males with or without chest pain had a positive predictive value of 81.8% and 71.7% for the presence of CAD, respectively. In conclusion, high baPWV was shown to be a good independent predictor for the presence of CAD in men.

Effects of radiation on fatty liver and metabolic coronary risk factors among atomic bomb survivors in Nagasaki.

In order to clarify the basic mechanism(s) linking radiation exposure and coronary heart disease (CHD), we here collected ultrasonographic data on fatty liver and measured levels of metabolic CHD risk factors from November 1990 through October 1992 in 1,517 Nagasaki atomic bomb survivors (575 men and 942 women). Using a cross-sectional study design, we examined the effects of radiation dose on fatty liver and CHD risk factors by means of a multiple logistic regression model. Fatty liver was related to the metabolic CHD risk factors associated with insulin resistance syndrome: obesity, hypertension, hypercholesterolemia, low high density lipoprotein (HDL)-cholesterol, hypertriglyceridemia, and abnormal glucose metabolism. Radiation dose was positively related to fatty liver, low HDL-cholesterol, and hypertriglyceridemia, whereas it had no effects on obesity, hypertension, hypercholesterolemia, or abnormal glucose metabolism. The present results suggested that radiation dose was related to 1) fatty liver, which clustered the metabolic CHD risk factors associated with insulin resistance syndrome and 2) atherogenic lipid profiles. It is suggested that these associations are involved in the basic mechanism(s) linking radiation exposure and CHD.

A serine protease inhibitor, nafamostat mesilate, suppresses aldosterone secretions in vivo.

To examine the role of serine proteases in the control of aldosterone (Ald) secretion, we studied the effects of nafamostat mesilate (Naf), a serine protease inhibitor, on in vivo Ald secretion and Ald content in the rat adrenal gland. Either Naf (2 mg/kg/h; n=10) or saline (2 ml/h; n=10) was administered intravenously for 30 min to anesthetized Wistar rats whose left adrenal vein was cannulated selectively via the inferior vena cava. Naf caused a significant decrease in Ald secretion rate compared to saline (1.99+/-0.32 vs. 3.42+/-0.56 ng/min, p <0.001), while adrenal blood flow, mean arterial pressure and plasma renin activity in the adrenal venous blood did not differ between the two groups. In a separate trial, adrenal Ald content, adrenal renin content, plasma adrenocorticotropic hormone (ACTH) and plasma potassium did not differ between rats treated with Naf (n=7) and those administered saline (n=7). These data suggested that Naf-inhibitable serine proteases may participate in the control of Ald secretion through mechanism(s) other than hemodynamic changes, adrenal renin, ACTH, and/or plasma potassium.

A rare case of aortic tube graft occlusion 35 years after coarctectomy.

A 52-year-old male with a history of repair of aortic coarctation by prosthetic tube graft replacement 35-years ago developed anterior spinal artery syndrome caused by acute functional occlusion of the aorta at the repair site where pseudoaneurysm formation was observed. The patient was rescued by an emergency axillofemoral bypass, and residual hypertension in upper limbs was improved by elective ascending aorta-descending aorta bypass grafting.

Relationship of carotid intima-media thickness, pulse wave velocity, and ankle brachial index to the severity of coronary artery atherosclerosis.

BACKGROUND: Carotid intima-media thickness (IMT), pulse wave velocity (PWV), and the ankle brachial index (ABI) are widely used noninvasive modalities for evaluating atherosclerosis. HYPOTHESIS: The aim of this study was to determine the relationship of carotid IMT, PWV, and ABI with the severity of coronary artery disease (CAD), expressed as the Gensini score, and the presence of coronary risk factors. METHODS: We examined 205 consecutive patients (mean age 65 +/- 12 years) who were clinically suspected of having CAD and were scheduled to undergo coronary angiography. Carotid intima-media thickness, brachial-ankle PWV (baPWV), and ABI were measured in all subjects before they underwent coronary angiography. RESULTS: Of the 205 patients, 124 patients were diagnosed as having CAD based on the presence of >50% stenosis in a major coronary artery; the remaining 81 patients did not have CAD. A relatively good correlation was obtained between carotid IMT and the Gensini score (R = 0.411, p < 0.0001), whereas baPWV correlated only weakly with the Gensini score (R = 0.203, p = 0.0035), and ABI did not correlate with it. A multiple regression analysis revealed that the Gensini score correlated significantly and independently with age, male gender, and carotid IMT. CONCLUSIONS: Of the three noninvasive methods, carotid IMT may be more useful for determining coronary artery atherosclerosis than baPWV or ABI.