Arteriosclerosis In Patients Research Articles

Regression of coronary sclerosis in familial hypercholesterolemia IIa by specific LDL apheresis

The long-term effect of specific LDL plasma immunabsorption on the course of coronary arteriosclerosis was tested in ten patients with familial hypercholesteremia type IIa (seven females, three males; age range 15-57 years). Available were ECG, bicycle ergometry, hemodynamic and angiographic data. These tests were repeated seriatim in the course of the LDL immunabsorption. It was found that exercise tolerance markedly increased, ischemic ST-changes became less marked and the initial hemodynamic parameters remained unchanged. The morphology of the coronary arteries was influenced lastingly: among 22 stenoses only one progressed, there was no further progression in 11 stenoses and regression in ten. When there was generalized arteriosclerosis, progression occurred in two of 79 coronary artery segments, progression was arrested in 56 and regression was noted in 21 of 79 segments. These results demonstrate that specific LDL plasma immunabsorption for the elimination of LDL cholesterol favorably influences the course of coronary arteriosclerosis in patients with familial hypercholeremia type IIa. The findings support the lipid theory of atherosclerosis and coronary arteriosclerosis, at least in this special group of patients.

Influence of Serum High-Molecular-Weight and Total Adiponectin on Arteriosclerosis in IgA Nephropathy Patients

Background/Aim: Adiponectin has attracted a great deal of attention because of its antiatherogenic properties. Previous studies have reported that high-molecular-weight (HMW) adiponectin may be the active form of this protein, but there have been no reports on the relationship between serum adiponectin and arteriosclerosis. The aim of our study was to determine whether HMW or total adiponectin levels are associated with arteriosclerosis in patients with IgA nephropathy. Methods: We enrolled 72 patients aged 34.3 ± 12.7 years, from whom interlobular arteries were obtained by renal biopsy in our hospital between 2003 and 2006 and who were confirmed to have IgA nephropathy. We assessed them in relation to age, gender, body mass index, presence of hypertension, serum total cholesterol, triglyceride, uric acid, high-sensitive C-reactive protein and HMW adiponectin and total adiponectin levels, creatinine clearance, and urinary protein excretion. The severity of arteriosclerosis was semiquantitatively evaluated and classified into the following four grades: 0 = none; 1 = mild; 2 = moderate, and 3 = severe. Results: Multiple stepwise regression analysis showed associations between arteriosclerosis grade and age [standard regression coefficient (st β) = 0.560, p < 0.001], total adiponectin (st β = –0.218, p = 0.026), triglyceride (st β = 0.222, p = 0.033), and presence of hypertension (yes = 1, no = 0; st β = 0.182, p = 0.036) in the IgA nephropathy patients as a whole and associations between arteriosclerosis grade and age (st β = 0.708, p < 0.001), HMW adiponectin (st β = –0.321, p = 0.035), and triglyceride (st β = 0.292, p = 0.038) in the male IgA nephropathy patients. Conclusions: Serum total adiponectin levels are an independent determinant of arteriosclerosis in IgA nephropathy patients. It was noteworthy that in males the serum HMW adiponectin levels correlated more strongly with arteriosclerosis grade than the total adiponectin levels did. Adiponectin may prevent renal arteriosclerosis.

Beneficial Effects of Combination Therapy with Angiotensin II Receptor Blocker and Angiotensin-Converting Enzyme Inhibitor on Vascular Endothelial Function

The combination of angiotensin I-converting enzyme inhibitors and angiotensin receptor blockers has been shown to be more effective than the individual drugs alone in the treatment of chronic kidney disease and chronic heart failure. In the present study, we evaluated the effect of treatment with the calcium channel blocker amlodipine or the angiotensin I-converting enzyme inhibitor perindopril on vascular endothelial function and arteriosclerosis in patients with essential hypertension who had already been receiving angiotensin receptor blocker monotherapy. Thirty-two patients with essential hypertension treated with angiotensin receptor blocker monotherapy were randomized to receive 5 mg of amlodipine (n=16) or 4 mg of perindopril (n=16) once daily in the morning for 24 weeks. The patients were evaluated before and after therapy to assess changes in blood pressure, flow-mediated vasodilation (a parameter of vascular endothelial function), and brachial-ankle pulse wave velocity (a parameter of arteriosclerosis). Before treatment, there were no significant differences in the above parameters between groups. After treatment, there was a similar significant decrease in blood pressure in both groups. Flow-mediated vasodilation increased significantly in the perindopril group compared with the amlodipine group; however, the decrease in brachial-ankle pulse wave velocity was not significantly different between groups. In conclusion, these results suggest that the angiotensin I-converting enzyme inhibitor perindopril is superior to the calcium channel blocker amlodipine for reducing vascular endothelial dysfunction when co-administered with angiotensin receptor blockers in patients with essential hypertension.

Invited commentary

This study [1Goland S. Trento A. Czer L.S.C. et al.Thoracic aortic arteriosclerosis in patients with degenerative aortic stenosis with and without coexisting coronary artery disease.Ann Thorac Surg. 2008; 85: 113-119Abstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar] is both timely and pertinent. Increasing numbers of elderly patients are now undergoing aortic valve surgery, many of whom have significant coronary artery disease. In this study the mean age was 75 years and 60% required both valve replacement and bypass grafting. A careful intraoperative transesophageal echocardiography study demonstrated that serious atheroma was present in nearly 2 of 3 patients with combined valve and coronary artery disease, which was much higher than that for patients with only aortic stenosis or those who were in a control cohort group. Similar findings were noted when aortic root calcification was studied.The significant finding was a stroke rate of 4.7% in the entire series; however, among 35 patients with complex arch atheroma (ie, thicker plaque with protrusion of mobile debris or ulceration, or both) the stroke rate tripled to 16%. Therefore, these findings serve as a call to action in re-evaluating our management strategy. The authors note that such strategies may include axillary cannulation, less traumatic cannula tips, balloon occlusion, soft cross clamps, circulatory arrest with aorta grafting, variations of “no touch” techniques, and recently introduced transapical valve replacement with off-pump grafting. Although these maneuvers were not used in this retrospective study, it is reasonable to assume that the stroke rate should decrease with appropriate application. This is an important article that merits careful study. Increasing numbers of elderly patients are now undergoing aortic valve surgery, and in those who required bypass grafting, severe aortic atherosclerosis is the rule not the exception. This study [1Goland S. Trento A. Czer L.S.C. et al.Thoracic aortic arteriosclerosis in patients with degenerative aortic stenosis with and without coexisting coronary artery disease.Ann Thorac Surg. 2008; 85: 113-119Abstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar] is both timely and pertinent. Increasing numbers of elderly patients are now undergoing aortic valve surgery, many of whom have significant coronary artery disease. In this study the mean age was 75 years and 60% required both valve replacement and bypass grafting. A careful intraoperative transesophageal echocardiography study demonstrated that serious atheroma was present in nearly 2 of 3 patients with combined valve and coronary artery disease, which was much higher than that for patients with only aortic stenosis or those who were in a control cohort group. Similar findings were noted when aortic root calcification was studied. The significant finding was a stroke rate of 4.7% in the entire series; however, among 35 patients with complex arch atheroma (ie, thicker plaque with protrusion of mobile debris or ulceration, or both) the stroke rate tripled to 16%. Therefore, these findings serve as a call to action in re-evaluating our management strategy. The authors note that such strategies may include axillary cannulation, less traumatic cannula tips, balloon occlusion, soft cross clamps, circulatory arrest with aorta grafting, variations of “no touch” techniques, and recently introduced transapical valve replacement with off-pump grafting. Although these maneuvers were not used in this retrospective study, it is reasonable to assume that the stroke rate should decrease with appropriate application. This is an important article that merits careful study. Increasing numbers of elderly patients are now undergoing aortic valve surgery, and in those who required bypass grafting, severe aortic atherosclerosis is the rule not the exception. Thoracic Aortic Arteriosclerosis in Patients With Degenerative Aortic Stenosis With and Without Coexisting Coronary Artery DiseaseThe Annals of Thoracic SurgeryVol. 85Issue 1PreviewThe association between the severity of arteriosclerosis in the thoracic aorta in patients with isolated aortic stenosis (AS) and with concomitant coronary artery disease (CAD) has been not evaluated. Therefore, the aim of our study was to compare the thoracic aortic atheroma extent and severity in patients with severe AS alone and with concomitant CAD by intraoperative transesophageal echocardiography. Full-Text PDF

Thoracic Aortic Arteriosclerosis in Patients With Degenerative Aortic Stenosis With and Without Coexisting Coronary Artery Disease

The association between the severity of arteriosclerosis in the thoracic aorta in patients with isolated aortic stenosis (AS) and with concomitant coronary artery disease (CAD) has been not evaluated. Therefore, the aim of our study was to compare the thoracic aortic atheroma extent and severity in patients with severe AS alone and with concomitant CAD by intraoperative transesophageal echocardiography. We retrospectively evaluated echocardiograms of 105 consecutive patients with severe degenerative AS who underwent aortic valve replacement. Sixty patients had concomitant CAD (AS/CAD) on coronary angiography and 45 had no CAD (AS alone). These patients were compared with 54 sex- and age-matched patients without AS or CAD. Aortic atheroma (localized intimal thickening of >3 mm) prevalence and morphology in three segments of aorta were assessed with echocardiography. There were 62 men, mean age 75.3 +/- 9.4 years. No difference was observed in age, sex, and risk factors for arteriosclerosis other than hypercholesterolemia among AS/CAD, AS alone, and control groups (88%, 67%, 41%, respectively; p < 0.0001). The AS/CAD group had a significantly higher rate of aortic root calcification (68%, 36%, 26%, respectively; p < 0.0001) and aortic atheroma (ascending aorta [26%, 20%, 14%, respectively; p = 0.03]; aortic arch [78%, 36%, 30%, respectively; p < 0.0001]; descending aorta [72%, 42%, 29%, respectively; p < 0.0001]) than AS alone or control subjects. Patients with AS/CAD also had more complex atheromas in the aortic arch (48%, 20%, 7%, respectively; p < 0.0001). Significant differences in extension of aortic arteriosclerosis (presence of plaques in two or three segments) were observed among the groups (70%, 31%, 18%, respectively; p < 0.0001). Patients with severe AS and coexisting CAD have more extensive arteriosclerotic changes in the thoracic aorta compared with those with AS alone and control subjects. Preoperative evaluation of the thoracic aorta and more aggressive lipid therapy should be considered in these patients.

Study of arteriosclerosis in patients with hiatal hernia and reflux esophagitis

It has been reported that the prevalence of hiatal hernia (HH) and reflux esophagitis (RE) increases with age, as does the degree of arteriosclerosis. However, it has not been investigated whether or not arteriosclerosis is correlated with the presence of HH and RE. Therefore, we prospectively investigated the degree of arteriosclerosis in patients with HH and RE compared with subjects without HH and RE. We prospectively enrolled 1683 people who visited Shimane Environment and Health Public Corporation for annual medical check-ups. All subjects were investigated by upper gastrointestinal endoscopy for the possible presence of HH and RE. Factors used for assessing cardiovascular risk were sex, age, body mass index (BMI), smoking and drinking habits, serum total cholesterol, triglyceride (TG), and high-density lipoprotein cholesterol (HDLC). Arteriosclerosis was investigated by measuring systolic blood pressure, heart-carotid pulse wave velocity (HCPWV), bilateral ankle brachial index (ABI) and heart-ankle PWV (HAPWV). The number of patients with HH and RE was 624 (37.1%) and 143 (8.5%), respectively. The HDLC level of the patients with HH was significantly lower, and the levels of BMI, TG and arteriosclerotic parameters were higher than those of the subjects without HH after adjusting for confounding factors (sex, age and smoking and drinking habits). Cardiovascular and arteriosclerosis parameters except for TG did not differ between the subjects with and without RE. Levels of arteriosclerosis parameters in patients with HH were higher than in those without HH. However, the association between arteriosclerosis and presence of RE was not clarified.

Double heterozygosity polymorphisms for platelet glycoproteins Ia/IIa and IIb/IIIa increases arterial thrombosis and arteriosclerosis in patients with the antiphospholipid syndrome or with systemic lupus erythematosus

Objective:We analysed the genetic polymorphisms in platelet glycoproteins (GP) Ib-α, Ia/IIa and IIb/IIIa and their correlation with the development of arterial thrombosis and preclinical arteriosclerosis in patients with antiphospholipid syndrome...

Pulse Wave Velocity as a Marker of Arteriosclerosis and Its Comorbidities in Chinese Patients

To obtain reliable data on the epidemiology of arteriosclerosis and the comorbidities in patients with hypertension (HP), coronary heart disease (CHD), type 2 diabetes mellitus (T2DM) and stroke, we evaluated the clinical significance of pulse wave velocity (PWV) as an indicator of arteriosclerosis and its comorbidities in Chinese patients. A total of 910 subjects, including 748 Chinese patients with one or more cardiovascular risk factors (80.2% male, mean age 73.69+/-5.03 years) and 162 healthy volunteers (78.4% male, mean age 73.60+/-5.32 years) were recruited into the study. PWV was measured in 910 subjects, and large artery arteriosclerosis was defined as PWV >or=12 m/s. Multivariable logistic regression analyses were performed to identify risk factors associated with arteriosclerosis. The prevalence of large artery arteriosclerosis in the patients overall was 67.4%, and the prevalence was higher in patients with than in those without HP (63.3% vs. 34.0%; odds ratio [OR]: 3.451), T2DM (24.8% vs. 11.1%; OR: 2.854), CHD (56.1% vs. 45.1%; OR: 1.246) and stroke (26.6% vs. 19.2%; OR: 1.236), but the OR values of CHD and stroke did not differ significantly (p>0.05). After multiple logistic regression analysis, female sex, older age, HP and T2DM were risk factors for large artery arteriosclerosis. In conclusion, PWV can be used as a routine measurement to scan arteriosclerosis in patients with HP or T2DM.

Results of Serum Lipid Concentration Measurements Associated with the Level of Arteriosclerosis in Patients with Advanced Lower Extremity Ischaemia

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Cardiovascular risk factors in patients with subclinical hypothyroidism

Overt hypothyroidism is disease associated with accelerated arteriosclerosis and coronary heart disease. Whether subclinical hypothyroidism (SH) is associated with increased cardiovascular risk is contraversial. As SH is a high prevalence thyroid dysfunction, specially in older women, it is important to evaluate cardiovascular risk factors in these patients and that was the aim of this study. We examined 30 patients with SH and 20 healthy controls. Subclinical hypothireoidism was defined as an elevated thyrotropin (TSH) (> 4.5 mU/L) and normal free thyroxine (FT4) level. In all the participants we determined body mass index (BMI), blood pressure, TSH, FT4, antibodies to thyroid peroxidase, antibodies to thyroglobulin, total cholesterol, high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol, triglicerides, total cholesterol/HDL cholesterol ratio and LDL/HDL cholesterol ratio. Mean BMI in patients with SH was significantly higher (p < 0.05), as well as diastolic blood pressure (p < 0.01) compared with the controls. Average levels of total cholesterol (5.40 +/- 0.62 vs 5.06 +/- 0.19 mmol/l, p < 0.01) and triglycerides (2.16 +/- 0.56 vs 1.89 +/- 0.24 mmol/l, p < 0.05) were also significantly higher in the group with SH. Individual analysis revealed that the percentage of patients with SH having borderline elevated total cholesterol (63.33%), hypertrigliceridemia (43.33%) and elevated total cholesterol/HDL cholesterol ratio (26.67%) were significantly higher than the percentage in the controls. No significant correlation between TSH and lipid parameters was detected. Subclinical hypothyroidism was associated with higher BMI, diastolic hypertension, higher total cholesterol and triglicerides levels and higher total cholesterol/HDL cholesterols ratio. This might increase the risk of accelerated arteriosclerosis in patients with SH.

Consequences of Iliac Arterial Atheroma on Renal Transplantation

Because recipient age has significantly increased in the last 15 years, surgeons must sometimes deal with atherosclerotic lesions of the iliac arterial system. Arterial restoration during renal transplantation should now be less frequent due to better preoperative screening and the prevention of arteriosclerosis in patients on renal transplantation waiting lists but in some patients EIA atheroma may require an additional surgical vascular procedure during renal transplantation. We describe the role of iliac artery atherosclerosis and the technical aspects of arterial restoration performed in patients who have undergone renal transplantation since 1985. In a series of 1,110 cadaveric renal transplantations performed between 1985 and 2000, 38 patients required endarterectomy during renal transplantation and 69 were considered not to require any special procedure. In the 38 patients requiring endarterectomy a total of 12 end-to-end arterial anastomoses were performed and 6 ASs (50%) were observed, while 26 side-to-end arterial anastomoses were performed with only 1 AS (4%). Patient and graft survival curves showed a significant negative correlation with the severity of atherosclerosis. Preoperative assessment of the EIA is mandatory before renal transplantation. Renal transplantation can be performed in patients with an atheromatous EIA if the artery can be clamped for endarterectomy. In our experience side-to-end anastomosis using a donor patch onto the EIA provides better results by avoiding AS after endarterectomy. However, despite vascular repair graft survival is significantly lower in patients with atheromatous lesions requiring endarterectomy.

Association of plasma homocysteine with serum interleukin-6 and C-peptide levels in patients with type 2 diabetes

Hyperhomocysteinemia is an independent risk factor for atherosclerotic disease. Because serum markers of inflammation and the metabolic syndrome are also associated with atherosclerotic disease and insulin resistance, we investigated whether plasma homocysteine (Hcy) levels were associated with serum markers of inflammation and factors of metabolic syndrome in 223 elderly patients with type 2 diabetes mellitus. The levels of plasma Hcy and serum interleukin-6 (IL-6), high-sensitivity C-reactive protein, and C-peptide were measured. The C677T mutation of methylenetetrahydrofolate reductase (MTHFR) gene was detected using the polymerase chain reaction–restriction fragment length polymorphism method. The number of abnormal metabolic factors (presence of diabetes, blood pressure ≥130/85 mm Hg, triglycerides ≥150 mg/dL, high-density lipoprotein cholesterol <35 mg/dL (men) or <39 mg/dL (women), or body mass index >25 kg/m 2) was assessed. Elevated plasma Hcy levels correlated significantly with serum IL-6 ( r = 0.25, P < .001), C-peptide ( r = 0.22, P < .01), and the number of abnormal metabolic factors ( r = 0.20, P < .01), but not with C-reactive protein. Multiple linear regression analysis revealed that log-transformed IL-6, serum C-peptide, vitamin B 12, and creatinine were significant determinants of plasma Hcy levels. The correlation between Hcy and IL-6 levels was strongest in those with TT genotype of C677T MTHFR among 3 genotypes. The association between plasma Hcy and serum IL-6 levels supports the hypothesis that the activation of innate immunity is involved in the pathogenesis of arteriosclerosis in patients with diabetes mellitus who are homozygous for the TT genotype of C677T MTHFR.

Association between pentosidine and arteriosclerosis in patients receiving hemodialysis.

It has been suggested that advanced glycation endproducts (AGEs) accumulate in arteriosclerotic lesions, playing and important role in the development and progression of arteriosclerosis. A chemical quantification method using high-performance liquid chromatography (HPLC) has been established to determine pentosidine levels in these products. Some studies reported that the abdominal aorta calcification index (ACI), obtained by computed tomography (CT), was useful for noninvasively diagnosing arteriosclerosis and determining its severity. In the present study, we measured the ACI and plasma pentosidine in patients receiving maintenance hemodialysis, and investigated the association between arteriosclerosis and pentosidine. In 73 patients receiving maintenance hemodialysis (43 men; 30 women), we determined the ACI, and investigated the association of the ACI with plasma total pentosidine, total cholesterol, triglyceride, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, serum creatinine, and parathyroid hormone (PTH), as well as the product of serum calcium and serum phosphorus, duration of dialysis, and age. The ACI did not correlate with total cholesterol, triglyceride, HDL cholesterol, LDL cholesterol, serum creatinine, PTH, or the product of serum calcium and serum phosphorus. Age, duration of dialysis, and plasma total pentosidine correlated with the ACI: (y = -33.12 + 0.913x; r = 0.407; P < 0.01), (y = 13.94 + 0.403x; r = 0.488; P < 0.01), and (y = 14.13 + 0.630x; r = 0.365; P < 0.01), respectively. It is suggested that pentosidine may be associated with arteriosclerotic development in hemodialysis patients. It has been suggested that advanced glycation endproducts (AGEs) accumulate in arteriosclerotic lesions, playing an important role in the development and progression of arteriosclerosis. A chemical quantification method using high-performance liquid chromatography (HPLC) has been established to determine pentosidine levels in these products. Some studies reported that the abdominal aorta calcification index (ACI), obtained by computed tomography (CT), was useful for noninvasively diagnosing arteriosclerosis and determining its severity. In the present study, we measured the ACI and plasma pentosidine in patients receiving maintenance hemodialysis, and investigated the association between arteriosclerosis and pentosidine.

Diagnostic value of carotid intima-media thickness and plaque score for predicting target organ damage in patients with essential hypertension.

Carotid intima-media thickness (IMT) assessed by ultrasonography is regarded as an early predictor of general arteriosclerosis in patients with essential hypertension. However, the methods of measuring IMT have not been globally standardized, and it remains unclear whether conventional measurement of IMT represents the prevalence of hypertensive target organ damage. In this study, we verified the association between several commonly used carotid ultrasonographical parameters and the severity of hypertensive target organ damage (retinal arteriosclerosis, microalbuminuria, left ventricular hypertrophy (LVH)). Carotid ultrasonography, echocardiography, urinalysis, and funduscopy were performed in 184 patients (64 +/- 12 years, 96 males and 88 females) with various stages of essential hypertension. Carotid arteriosclerosis was assessed using four methodologically different methods: conventional-IMT, maximum-IMT (Max-IMT), Mean-IMT, and Plaque Score (the sum of all plaque thicknesses). Age and all carotid ultrasonographical parameters were significantly associated with albuminuria, retinal arteriosclerosis, and left ventricular mass index. High-sensitivity CRP was significantly correlated with retinopathy and LVH. Carotid parameters in patients with histories of cardiovascular events were significantly greater in those without events. Among all carotid parameters, Max-IMT showed the highest correlation coefficient of the severity of target organ damage, and showed significant association with CRP. Stepwise regression analysis revealed that Max-IMT was the independent factor for predicting target organ damage. Max-IMT is suggested to be the most reliable and simplest parameter for predicting hypertensive target organ damage including microangiopathy in patients with essential hypertension.

Plasma fibrinogen in relation to the severity of arteriosclerosis in patients with stable angina pectoris after myocardial infarction.

Authors both of retrospective and of prospective studies have demonstrated that there is a relationship between concentration of fibrinogen in plasma and the angiographically determined severity of coronary heart disease (CHD). To determine the relevance of the plasma fibrinogen concentration for the severity of CHD, particularly in cases with additional arteriosclerotic changes in the extracranial arteries supplying the brain [cerebrovascular disease (CVD)], in the pelvic/leg arteries [peripheral occlusive arterial disease (POAD)], or in both. In a retrospective cross-sectional survey the cardiological and angiographical status of a total of 1112 male and 299 female patients with stable angina pectoris after sustained myocardial infarction and an age-matched control group of 326 male and 138 female subjects with no clinical symptoms of CHD was determined, together with measurements of plasma fibrinogen, dynamic plasma viscosity and D-dimers. More than two-thirds of the patients with arteriosclerosis had plasma fibrinogen concentrations in the uppermost tertile of the control range (men > 2.75; women > 2.83 g/l). Plasma fibrinogen concentration was correlated to the severity of CHD (for men r = 0.173, P < 0.001; for women r= 0.144, P < 0.013). Patients with generalized arteriosclerosis had higher plasma fibrinogen concentrations than did those suffering from CHD only (for men, control 2.65 +/- 0.51, CHD 3.07 +/- 0.73, CHD plus POAD 3.17 +/- 0.77 and CHD plus POAD plus CVD 3.45 +/- 0.78 g/l; for women, control 2.69 +/- 0.44, CHD 3.25 +/- 0.67, CHD plus POAD 3.19 +/- 0.77, CHD plus POAD plus CVD 3.60 +/- 0.84 g/l). Multivariate analysis showed that C-reactive protein, D-dimers and dynamic plasma viscosity accounted for 48.2% (for men) and 49.4% (for women) of the variance in plasma fibrinogen concentration. Our findings demonstrate that there is not only a correlation between plasma fibrinogen concentration and the severity of CHD, but also a correlation to the incidence of additional POAD or CVD.

Metabolism of hepatocyte growth factor in the heart in patients with coronary artery disease: implication for coronary arteriosclerosis.

HGF, one of endothelium-specific growth factors, might contribute to the repair process of vascular endothelial cell damage, suggesting that serum HGF concentration may be elevated in patients with arteriosclerosis. However, the cardiac metabolism of HGF has not been examined in patients with coronary artery disease (CAD). We examined the levels of hepatocyte growth factor (HGF) in the coronary circulation and its correlation with the severity of arteriosclerosis in patients with CAD. We measured serum HGF concentration obtained from the coronary sinus (CS) and ascending aorta (AA) in patients with atherosclerotic CAD (Group E, n = 33) or vasospastic angina (Group V, n = 26), or normal control subjects (Group N, n = 12). In Group E, the severity of coronary artery stenosis was evaluated using the Gensini's score. Serum HGF concentrations (ng ml) in the CS were 0.112 +/- 0.008 in Group E (p < 0.001 vs. Group V, p < 0.001 vs. Group N), 0.197 +/- 0.012 in Group V (p = 0.031 vs. Group N), and 0.245 +/- 0.021 in Group N. Serum HGF concentrations in the AA were 0.282 +/- 0.014 in Group E (p = 0.045 vs. Group V, p = 0.021 vs. Group N), 0.246 +/- 0.012 in Group V, and 0.237 +/- 0.009 in Group N. Serum HGF extraction in the heart (HGF in the AA-HGF in the CS) in Group E (0.170 +/- 0.018) was significantly higher compared with in Group V (0.049 +/- 0.011) or Group N (0.008 +/- 0.005). There was a significant negative correlation between the severity of coronary arteriosclerosis and serum HGF concentration in CS (r = -0.66, p < 0.001), and a significant positive correlation between the severity of coronary arteriosclerosis and HGF extraction in the heart (r = 0.75. p < 0.001). We conclude that the difference of HGF levels between CS and AA in patients with CAD are decreased, and extent of decreases in HGF levels correlates with the severity of coronary arteriosclerosis. The abnormality of HGF metabolism in the heart may contribute to the progression of coronary arteriosclerosis.

D-dimers in relation to the severity of arteriosclerosis in patients with stable angina pectoris after myocardial infarction

Plasma concentrations of D-dimers show the extent of intravascular fibrinolysis of cross-linked fibrin. Higher concentrations of D-dimers are found in the plasma of arteriosclerosis patients with increased fibrin metabolism. The present study was performed in order to investigate whether there is a relationship between the severity of arteriosclerosis and fibrinolytic activity indicated by plasma levels of D-dimer. The study populations consisted of 1112 men and 299 women with stable angina pectoris, on average 36+/-5.6 days after a myocardial infarction, as well as 326 men and 138 women with no clinical signs of cardiovascular disease. In addition to cardiological and angiological examinations, the lipid status and levels of fibrinogen, plasma viscosity, F 1+2, plasminogen, plasminogen activator inhibitor-1, D-dimer, and C-reactive protein of the participants were determined. The plasma concentration of D-dimers increases with age, both in the group with coronary artery disease and in the control group, with the female gender showing consistently higher concentrations in both groups. D-dimers correlate with other parameters of the lipid and coagulation systems, which explains 32.0% and 39.2% of the variance in D-dimer values in men and women, respectively. A significant increase in the level of D-dimers can be found in participants with generalized arteriosclerosis, with a left ventricular ejection fraction </=40% as well as those with left-ventricular aneurysm. This study indicates that there is increased fibrinolytic activity in patients with severe arteriosclerosis. This finding gives further support to the hypothesis that D-dimer concentration is dependent on the amount of fibrin associated with arteriosclerotic thrombi. However, because of the low specificity and wide overlap of D-dimer values between patients and controls, enhanced D-dimer values are of limited relevance above and beyond other lipid metabolism risk indicators for coronary artery disease or coronary artery disease and peripheral arterial occlusive disease.

Hyperhomocysteinemia is a risk factor for coronary arteriosclerosis in Japanese patients with type 2 diabetes.

An increased plasma homocysteine level is an important risk factor for vascular disease, including coronary atherosclerosis, in the general population. However, the role of hyperhomocysteinemia in the development of coronary artery disease (CAD) in patients with type 2 diabetes is unknown. Therefore, we have endeavored to determine the relationship between plasma homocysteine levels and the presence of coronary arteriosclerosis in patients with type 2 diabetes. The study group consisted of 145 Japanese patients (95 men and 50 women) who underwent routine coronary angiography to assess chest pain or suspected CAD. Plasma total homocysteine level, lipid level, and parameters of fibrinolytic activity were measured. All patients were identified as diabetic or nondiabetic by the new American Diabetes Association (ADA) criteria. The diagnoses of all patients studied were confirmed by coronary angiography. The severity of coronary artery stenosis was quantified using CAD scoring on the basis of prior reports, and subjects were graded as nonstenotic, stenotic single-vessel, stenotic two-vessel, or stenotic three-vessel based on the number of stenotic coronary arteries. Patients were classified into two groups: those with stenotic vessels and those without stenotic vessels. The plasma homocysteine level was significantly higher in patients with than in patients without stenotic vessels (13.8 +/- 3.9 vs. 11.7 +/- 3.9 mumol/l, respectively; P = 0.0009). The number of stenotic coronary arteries, which was used to grade each case as nonstenotic, stenotic single-vessel, stenotic two-vessel, or stenotic three-vessel, was related only to the total homocysteine level in the diabetic (diabetes mellitus [DM]) group, but it was associated with lipoprotein(a) in the nondiabetic (non-diabetes mellitus [non-DM]) group. Spearman's rank correlation test demonstrated that the plasma homocysteine level was strongly correlated with CAD score, both in the entire study group and in the DM group (P = 0.003 for the entire group and P = 0.011 for the DM group). Hyperhomocysteinemia, which was defined as total homocysteine level > 14.0 mumol/l, was seen in 57 (39.3%) of the patients. The CAD score was highest in diabetic patients with hyperhomocysteinemia (P < 0.05). There seems to be a clear relationship between hyperhomocysteinemia and an increased risk of coronary arteriosclerosis in Japanese patients with type 2 diabetes.

Studies on M&ouml;nckeberg's Arteriosclerosis in Patients with Diabetes Mellitus

Studies on M&ouml;nckeberg's Arteriosclerosis in Patients with Diabetes Mellitus

Stability of plasma low density lipoprotein with abnormal glycolipid composition from patients with Fabry's disease

Fabry's disease is a glycosphingolipid storage disease associated with premature generalized arteriosclerosis. Plasma low density lipoprotein (d 1.019–1.055 g/ml; LDL) was isolated from 4 healthy male volunteers (LDL-N) and from 4 patients with Fabry's disease (LDL-F), in whom plasma globotriaosylceramide (GbOse 3) levels were 2–4 times above normal. LDL-N was labeled with 131I and LDL-F with 125I by the iodine monochloride method; both were then injected together intravenously into 4 mongrel dogs. The rates at which they were metabolized were determined by measuring plasma radioiodine levels daily for 7–8 days. No significant difference (Fisher's F-test) was observed between LDL-N and LDL-F in terms of the size of the intravascular compartments (LDL-N, 86.3 ± 4.2%; LDL-F, 94.2 ± 7.7%), biological half-lives (LDL-N, 24.1 ± 4.2 h; LDL-F, 23.5 ± 3.7 h), or fractional catabolic rates (LDL-N, 0.849 ± 0.066; LDL-F, 0.796 ± 0.070). The results indicate that significant abnormalities of the neutral glycosphingolipid composition of LDL, such as occur in Fabry's disease, do not affect the metabolism of the lipoprotein apoprotein in dogs. The arteriosclerosis in patients with the disease is probably due to damage to vessel walls occurring as a result of defective GbOse 3 metabolism and accumulation of glycosphingolipid in the tissue, rather than to abnormal LDL metabolism.