Prevention of atherosclerosis progression using atorvastatin in normolipidemic coronary artery disease patients--a controlled randomized trial

BACKGROUND: Statins have been known to reduce progression of atherosclerosis when used in high dosage in patients with elevated cholesterol. A large majority of Indian patients, however, develop coronary artery disease with average or below average cholesterol level. There is insufficient data on effect of low-dose statins on progression of atherosclerosis in such patients with normal/average lipid levels. METHODS AND RESULTS: In this prospective study, 150 patients with angiographically proven coronary artery disease and baseline total cholesterol <200 mg/dl and low-density lipoprotein cholesterol <130 mg/dl were randomized to treatment with low-dose atorvastatin (10 mg) or placebo. Both groups were comparable in demographic characteristics. Progression of atherosclerosis was assessed using carotid intima media thickness as surrogate marker using standard protocol on B-mode ultrasound including common carotid artery, common carotid bifurcation and internal carotid artery measurements. Follow-up study for carotid intima media thickness was done at end of one year. A decrease in mean maximum carotid intima media thickness was recorded for all the three carotid segments individually from basal to end of one year in atorvastatin group [common carotid artery -0.008 mm (p = 0.01), common carotid bifurcation-0.022 mm (p = 0.001), internal carotid artery -0.009 mm (p = 0.01)] while the same showed an increase in placebo group [common carotid artery +0.011 mm (p = NS), common carotid bifurcation +0.013 mm (p=NS), internal carotid artery +0.007 mm (p=NS)]. The average mean carotid intima media thickness (all three segments included) decreased from 0.739 +/- 0.114 mm to 0.726 +/- 0.115 mm (difference -0.013 mm) in statin group and increased from 0.733 +/- 0.124 mm to 0.742 +/- 0.117 mm (difference + 0.009 mm) in placebo group (p < 0.001). Along side, there was a reduction in the total cholesterol from 144 +/- 26 mg/dl to 130 +/- 18 mg/dl (decreased arrow 9.7%, p = 0.05) and in low-density lipoprotein cholesterol from 86 +/- 24 mg/dl to 74 +/- 19 mg (decreased arrow 13.9%, p = 0.05) in study group and an increase in total cholesterol from 148 +/- 32 mg/dl to 154 +/- 8 mg/dl (increased arrow 4.05%, p=NS) and in low-density lipoprotein cholesterol from 84 +/- 19 mg/dl to 87 +/- 16 mg/dl (increased arrow 3.57%, p=NS) in placebo group at end of one year (p=NS). No adverse effects of statins were reported in the treatment arm. CONCLUSIONS: We conclude that low-dose statins reduce progression of atherosclerosis as observed by carotid intima media thickness in Indian patients with known coronary heart disease and normal lipid values independent of lipid lowering. The study favors use of this therapy in patients with normal/below average cholesterol levels.     

Carotid artery wall hypertrophy in children with metabolic syndrome

Preclinical vascular changes (increased stiffness and/or wall thickness) have been observed in children with known metabolic risk factors. Aim of the present study was to evaluate different carotid parameters, representative of vascular health, in children with and without metabolic syndrome (MS). We studied 38 children with MS (mean age 9.6+/-2.6 years; range 6-14 years) and 45 healthy age-matched subjects. Children who met three or more of the following criteria qualified as having the MS: fasting glucose >110 mg dl(-1), fasting triglyceride concentration >100 mg dl(-1), fasting high-density lipoprotein cholesterol concentration <50 mg dl(-1) for females or <45 mg dl(-1) for the males, waist circumference >75th percentile for age and gender and systolic or diastolic blood pressure >90th percentile for age, gender and height. Carotid B-mode ultrasound examinations were performed and intima-media thickness and diameters were measured in all subjects. Arterial geometry was further characterized by calculation of carotid cross-sectional area. Carotid intima-media thickness and lumen diameters were increased in children with MS as compared to children without MS. Moreover, carotid cross-sectional area was significantly higher in the group of children with MS 9.83+/-1.86 mm(2) [mean+/-s.d.] compared with the control group: 7.77+/-1.72 mm(2), P<0.001, even after adjustment for age, gender and height. Carotid hypertrophy is already detectable in children with MS. High-resolution B-mode ultrasound could provide a valuable tool for the cardiovascular risk stratification of children.     

Relationship of lipoprotein(a) with intimal medial thickness of the carotid artery in Type 2 diabetic patients in south India.

OBJECTIVE: The objective of this study was to investigate the association of lipoprotein(a) [Lp(a)] levels with intimal medial thickness (IMT) in Type 2 diabetic patients in south India. STUDY DESIGN: We studied 587 consecutive Type 2 diabetic patients at the M.V. Diabetes Specialities Centre, Chennai. The mean age of the study group was 55 +/- 10 years and 71.2% were males. IMT of the right common carotid artery was determined using high-resolution B mode ultrasonography. Lp(a) levels were measured using ELISA. Since the frequency distribution of Lp(a) was skewed, Lp(a) values were log transformed and the geometric mean was used for statistical analysis. The tertiles of IMT were determined to analyse the association of Lp(a) and other factors with IMT. RESULT: The mean Lp(a) level in the study patients was 18.9 +/- 3.1 mg/dl (geometric mean +/- sd) and the mean IMT of the study subjects was 0.93 +/- 0.19 mm (mean +/- sd). The prevalence of carotid atherosclerosis (defined as IMT > 1.1 mm) among subjects with elevated Lp(a) levels > 20 mg/dl was significantly higher compared with those with Lp(a) levels 相似文献   

颈动脉粥样硬化与冠状动脉粥样硬化的关系

目的　探讨颈动脉粥样硬化与冠状动脉粥样硬化的关系。方法　对 94例老年患者进行了冠状动脉造影和颈动脉超声检查。颈动脉粥样硬化斑块积分采用Sutton法。结果　单支组及多支组内膜中膜厚度、斑块积分显著高于正常组 ,多支组显著高于单支组 (P<0 .0 5 )。斑块指数与年龄、吸烟、低密度脂蛋白胆固醇与高密度脂蛋白胆固醇的比值、收缩压以及高血压病程的程度呈正相关。结论　颈动脉粥样硬化与冠状动脉粥样硬化的病变是平行的     

Carotid ultrasound for risk clarification in young to middle-aged adults undergoing elective coronary angiography

BACKGROUND: An important aspect of risk prediction is the apparent difference between calculated risk and true risk. Current risk predictor models are not sensitive enough to identify many subjects at risk for future events or to prevent overuse of expensive tests. The aim of this study was to determine the usefulness of carotid ultrasound for risk stratification in subjects undergoing elective coronary angiography. METHODS: A total of 253 individuals (men < or =55 years of age and women < or =65 years of age) who were scheduled for elective coronary angiography underwent carotid ultrasonography. Noncoronary atherosclerosis was defined based on a maximal intima-media thickness of > or =1.0 mm or the presence of focal plaque. RESULTS: Of the subjects, 236 completed all of the tests. The mean age was 51 +/- 8 years, and 58% were women and 42% men. Severe angiographic disease (> or =50%) was present in 72 subjects. Carotid atherosclerosis was present in 141 subjects. Use of the Framingham risk score classified 172 subjects as low risk. Carotid atherosclerosis was diagnosed in 57% of the low-risk group compared with 70% of the high-risk group (P = .122). Carotid atherosclerosis was associated with severe coronary angiographic disease (OR = 2.2, CI = 1.2 to 4.0). CONCLUSION: Noncoronary atherosclerosis was associated with severe coronary disease as determined by angiography. Carotid atherosclerosis had a high negative predictive value in subjects with negative stress test results or risk-stratified as low risk. Noninvasive imaging by carotid ultrasonography for noncoronary atherosclerosis may be a good adjunct to clinical risk stratification for premature coronary heart disease.     

Intimal medial thickness of the carotid artery in South Indian diabetic and non-diabetic subjects: the Chennai Urban Population Study (CUPS)

Aim/hypothesis. Increased intimal medial thickness (IMT) of the carotid arteries is considered a useful marker of atherosclerosis. The aim of this study was to compare the intimal medial thickness values in urban non-diabetic and diabetic South Indian subjects who have a high risk of coronary artery disease.¶Methods. The subjects for this study were 140 diabetic and 103 non-diabetic control subjects matched with them for age and sex selected from The Chennai Urban Population Study which is an ongoing epidemiological study. Intimal medial thickness of the right common carotid artery was determined using high resolution B mode ultrasonography.¶Results. The mean intimal medial thickness values of the diabetic subjects (0.95 ± 0.31 mm) were significantly higher than those of the non-diabetic (0.74 ± 0.14 mm) subjects (p < 0.001). Both in the normal and diabetic subjects, these values increased with age. At any given age, the diabetic subjects had higher values than the non-diabetic subjects but the difference reached statistical significance after age 50 years (p < 0.05).¶Intimal medial thickness showed a correlation with age, total cholesterol, LDL cholesterol, waist:hip ratio and systolic blood pressure in non-diabetic subjects and with age and duration of diabetes in the diabetic subjects. Multivariate linear regression analysis showed that age and diabetes were the major risk factors for intimal medial thickness.¶Conclusion/interpretation. Diabetic subjects have higher intimal medial thickness values than non-diabetic subjects. Diabetes and age are the most important risk factors associated with increased intimal medial thickness in this South Indian cohort. [Diabetologia (2000) 43: 494–499]     

Lipoprotein (a) phenotypes in south Indian patients with coronary artery disease

BACKGROUND: Plasma lipoprotein (a) levels in the Indian population are varied; this study was undertaken to determine the relationship between plasma lipoprotein (a) levels and their phenotypes in a group of south Indian patients with coronary artery disease. METHODS AND RESULTS: A total of 104 patients with angiographically proven coronary artery disease were compared with 104 age- and sex-matched controls with no risk factors such as hypertension, diabetes and smoking. Lipoprotein (a) levels were measured by an in-house ELISA method and its phenotyping was done by SDS agarose gel electrophoresis. Plasma lipoprotein (a) levels were significantly elevated in patients with coronary artery disease as compared to controls (33.4+/-26.1 mg/dl v. 21.4+/-12.8 mg/dl; p<0.01). Lipoprotein (a) phenotyping showed that low-molecular weight isoforms were found only in 19.2% of the patients with coronary artery disease and their plasma lipoprotein (a) levels were significantly elevated compared to coronary artery disease patients with higher molecular weight isoforms (50.9+/-34.2 mg/dl v. 29.24+/-20.06 mg/dl; p<0.001). CONCLUSIONS: Plasma lipoprotein (a) levels are significantly elevated in patients with coronary artery disease as compared to controls. The commoner phenotype in a South Indian population is the larger apolipoprotein (a). in which the lipoprotein (a) levels are lower. Hence the contribution of lipoprotein (a) phenotype to the lipoprotein (a) levels in our population, if any, is modest.     

Quantification of carotid atheroma, by vascular ultrasonics and spectral analysis, after myocardial infarction. Apropos of 80 cases

A prospective study of carotid artery atheroma by vascular echotomography and spectral analysis was performed in 40 patients with myocardial infarction and 40 control subjects. Carotid artery atheroma was commoner in the group of patients with myocardial infarction (72.5% +/- 6.8%), earlier (9 years), more commonly bilateral (37.5% +/- 7.6%) and more stenotic (32.5% +/- 7.4%) than in the control group (p less than 0.000a, p less than 0.0001 and p less than 0.002, respectively). The severity of carotid artery atheroma correlated with the site of coronary artery disease; the following significant relationships were found: stenosing 40% and/or bilateral carotid atherosclerosis and left anterior descending disease (p less than 0.02); carotid atherosclerosis and double or triple vessel disease (p less than 0.05). The authors conclude that detection of carotid artery atheroma after myocardial infarction is valuable for two reasons: it gives an indication as to the severity of the coronary disease; carotid endarterectomy may be considered at the same time as coronary artery bypass surgery.     

Carotid intima-media thickness in patients with isolated coronary artery ectasia

OBJECTIVE: Carotid artery intima-media thickness (IMT) is now widely used as a surrogate marker for atherosclerotic disease. Carotid IMT measured by ultrasound has been shown to be correlated with coronary artery disease as defined by angiography. However, the relation between carotid IMT and isolated coronary artery ectasia (CAE) has not been investigated. The aim of our study was to assess this relation. METHODS: Twenty-five patients with isolated CAE without stenosis and 25 control subjects with angiographically normal coronary arteries were included in this study. These were examined by B-mode ultrasound to measure the IMT at the far wall of the common carotid artery. RESULTS: Patients with isolated CAE had significantly higher carotid IMT compared to control subjects with angiographically normal coronary arteries (0.95+/-0.12 versus 0.71+/-0.10mm respectively, p<0.0001). In addition, we detected a significant positive correlation between the presence of CAE and carotid IMT (r=0.748, p<0.001). CONCLUSION: We have shown for the first time an association between increased carotid IMT and isolated CAE, suggesting that atherosclerosis may be involved in the pathogenesis of isolated CAE in the adult population.     

Carotid intima-media thickness as an independent predictor of coronary artery disease.

BACKGROUND: A noninvasive technique of measuring carotid artery intima-media thickness has recently generated considerable interest as a marker of atherosclerosis and in the prediction of clinical coronary events and coronary artery disease. The present study evaluated the association of carotid artery intima-media thickness in the prediction of coronary artery disease in a western Indian population. METHODS AND RESULTS: Carotid artery intima-media thickness was measured with a B-mode scan in an ongoing study of 266 patients, who were further subdivided into 4 subgroups: those with non-insulin dependent diabetes mellitus; hypertension; diabetes mellitus with hypertension; and those without diabetes or hypertension (labeled as controls). The maximal intima-media thickness greater than 0.8 mm at the far wall of the common carotid artery, excluding raised lesions and plaques, was selected as the highest value for comparison. The subgroups were further divided into those with and without apparent coronary artery disease. A statistically significant intima-media thickness greater than 0.8 mm was observed in 59.2% of the subjects with coronary artery disease as against 40.8% in those without the disease on univariate analysis. A higher incidence of intima-media thickness of more than 0.8 mm was observed in all subgroups with coronary artery disease as against those without the disease, which was most marked in the hypertensive group (22.2% v. 3.6%) and contributed to the increased arterial thickness in diabetics with concomitant hypertension. Multivariate regression analysis revealed carotid artery intima-media thickness to be associated with coronary artery disease with an odds ratio of 2.40. CONCLUSIONS: Carotid artery intima-media thickness is a simple, noninvasive and reproducible clinical tool to evaluate atherosclerosis and predict coronary artery disease in Indian subjects. Prospective studies in a larger number of subjects, particularly in those undergoing coronary angiography, will help in establishing the role of this technique.     

Pilot Results of the Early Detection by Ultrasound of Carotid Artery Intima-Media Thickness Evaluation (EDUCATE) study

BACKGROUND: Limitations of current models for risk stratification are known. Noninvasive imaging is being advocated as an adjunct to improve risk prediction; however, studies documenting outcomes are rare. Therefore, we aimed to evaluate the negative and positive predictive values of carotid atherosclerosis for future cardiovascular events. METHODS: The Early Detection by Ultrasound of Carotid Artery intima media Thickness Evaluation (EDUCATE) study prospectively enrolled 253 consecutive young to middle-aged adults undergoing elective coronary angiography. Bilateral carotid ultrasound and lipid profiles were performed. Carotid atherosclerosis was defined as intima media thickness >/=1.0 mm in the main body, or focal plaque within the body, bulb, or proximal branch. Future events included major (death, myocardial infarction, stroke) and minor (revascularization and new onset heart failure). RESULTS: Of the enrolled patients 236 completed all tests; mean age was 51 +/- 8 years; 58% women. Sensitivity, specificity, and negative predictive values for carotid atherosclerosis in predicting severe coronary artery disease were 72%, 49% and 79%, with an odds ratio (OR) of 2.2 (95% confidence interval [CI] 1.2-4.0). Of patients suffering major events, 90% had carotid atherosclerosis. Only 1 of 95 without carotid atherosclerosis experienced a major event. Kaplan-Meier analysis revealed differences in event-free survival in favor of subjects without carotid atherosclerosis for major (P = .051) and any event (P = .015). Cox analysis revealed a hazard ratio (HR) of 2.7 (95% CI 1.2-6.2; P = .020) for predicting future events. The relationship remained significant after adjusting for traditional risk factors (HR 2.5, 95% CI 1.1-5.9; P = .034). CONCLUSIONS: Carotid atherosclerosis is associated with severe coronary artery disease and future events. Negative carotid ultrasound is associated with excellent prognosis.     

A tertiary care hospital-based study of conventional risk factors including lipid profile in proven coronary artery disease

BACKGROUND: The prevalence and mortality rates of coronary artery disease have been known to be higher in the Indian than the Western population. Most data on lipid levels in Indians have been obtained from studies on migrant Asian Indians. There are insufficient data on lipid profile and other conventional risk factors in Indian patients living within India. METHODS AND RESULTS: The study included 2656 consecutive patients who underwent coronary angiography between March 1998 and February 2002. Of these, 2399 subjects had angiographically proven coronary artery disease (group 1) while 257 had normal coronary arteries (group 2). Lipid values were measured in the fasting state on the morning the coronary angiography was done. Patients receiving lipid-lowering agents, those having renal, hepatic or thyroid disorders, patients presenting within 8 weeks after acute myocardial infarction, and patients who were taking noncardiac drugs that affect the lipid profile were excluded from the study. Other conventional risk factors were also recorded. In subjects with coronary artery disease and normal coronary arteries, the levels of mean total cholesterol recorded were 178.5+/-42.1 mg/dl v. 154.1+/-40.2 mg/dl (p<0.001), high-density lipoprotein cholesterol 30.6+/-9 mg/dl v. 27.3+/-6.8 mg/dl (p<0.001), low-density lipoprotein cholesterol 109.8+/-35.4 mg/dl v 93.6+/-33.9 mg/dl (p<0.001), and triglyceride 190.7+/-95.4 mg/dl v. 157.6+/-73.5 mg/dl (p<0.001), respectively. In subgroup analysis by age, the younger coronary artery disease group (< or = 40 years) had significantly higher total and low-density lipoprotein cholesterol levels than the older group (> 40 years), viz. 194.6+/-51.4 mg/dl v. 176.3+/-40.2 mg/dl (p<0.001), and 118.3+/-39.6 mg/dl v. 108.7+/-36.1 mg/dl (p=0.001). Triglyceride levels were not significantly different [211.7+/-105.1 mg/dl v. 187.8+/-93.6 mg/dl (p=ns)], being equally high in both subgroups and, although high-density lipoprotein cholesterol levels were different, this difference was minimal, being equally low in both [32.7+/-9.5 mg/dl v. 30.3+/-9.0 mg/dl (p=ns)]. In the subgroup analysis of those with coronary artery disease, diabetics had significantly lower total cholesterol [174+/-41.1 mg/dl v. 180.4+/-42.4 mg/dl (p<0.001)] and low-density lipoprotein cholesterol levels [105.8+/-34 mg/dl v. 111.5+/-35.8 mg/dl (p<0.001)] than non-diabetics, whereas triglyceride and high-density lipoprotein cholesterol levels were not significantly different, triglycerides being equally high in both [186.2+/-95.5 mg/dl v. 192.5+/-95.2 mg/dl (p=ns)], and high-density lipoprotein equally low in both [30.9+/-9.3 mg/dl v. 30.5+/-9 mg/dl (p=ns)]. The commonest associated conventional risk factor in diabetics was hypertension and, in the younger age group (< or = 40 years), it was smoking and a positive family history of premature coronary artery disease. CONCLUSIONS: We conclude that in north Indians, coronary artery disease occurs at much lower levels of total cholesterol and low-density lipoprotein cholesterol than other populations, and high triglyceride and low high-density lipoprotein levels are more of a universal phenomenon in this population. Younger patients have a more atherogenic lipid profile than the older subgroup with coronary artery disease, and smoking and a family history of premature coronary artery disease are the most common associated risk factors. Total cholesterol levels seem to play a lesser role in the occurrence of coronary artery disease in diabetics, the presence of which is in itself overwhelming for the occurrence of coronary artery disease.     

Evaluation of the Association Between Coronary Calcification Detected by Electron Beam Computed Tomography and Atherosclerosis of Extracranial Carotid Arteries In Vivo

The aim of this study was to evaluate the association between carotid and coronary atherosclerosis and their diagnostic value for predicting angiographically significant coronary artery disease (CAD). We investigated 80 subjects (mean age 55 +/- 8 years) by electron beam computed tomography (EBT), the most sensitive technology for noninvasive detection of coronary calcification (a marker of coronary atherosclerosis); by carotid sonography; and by coronary angiography. Carotid ultrasound was performed with a 7.5 MHz Duplex probe, EBT was done with an EVOLUTION(R) scanner. In 47 subjects, coronary calcification as well as carotid atherosclerosis was present. Thirteen subjects showed isolated coronary calcification, 10 had isolated carotid atherosclerosis, and 10 showed neither coronary calcification nor carotid atheroscleroosis. The association between carotid atherosclerosis and CAD as well as the relationship between coronary calcification and CAD were statistically significant (p < 0.05), but the correlation between coronary calcification and CAD was higher than between carotid atherosclerosis and CAD (Pearson contingency coefficient: 0.34 vs 0.86). In subjects without carotid atherosclerosis, the mean area of coronary calcificiation was significantly (p < 0.01) lower (41 mm2) than in subjects with carotid atherosclerosis (113 mm2). For noninvasive detection of CAD, electron beam CT was superior to carotid sonography on sensitivity (95% vs 78%) and specificity (81% vs 48%). Former studies suggested that sonography of extracoronary vessels could aid in screening for CAD. In our study, the sonographic status of carotid arteries was associated with cardiovascular atherosclerosis but it did not allow us to make a judgment about the presence of CAD with sufficient reliability and it was inferior to electron beam CT as a noninvasive marker of CAD.     

Carotid intima-media thickness in pre-and postmenopausal women with suspected coronary artery disease

Carotid intima-media thickness (CIMT) is an early marker of coronary artery disease (CAD). This study aimed to evaluate CIMT value for CAD prediction in pre-and postmenopausal women referred for coronary angiography with angina-like symptoms and a positive result of the treadmill test. The study comprised 321 women referred for coronary angiography with symptoms suggesting CAD. Carotid intima-media thickness was measured in common, bifurcation, and internal carotid artery, and expressed as the mean maximum value. Coronary angiography showed coronary stenosis >/=50% in 211 (65.7%) women, including 27 with regular menses (47.3 +/- 3.4 years) and 184 postmenopausal (65.8 +/- 7.2 years). Normal coronary arteries were found in 110 women: 17 (47.3 +/- 4.9 years) with regular menses and 93 postmenopausal (64.3 +/- 6.5 years). The highest CIMT values were found in postmenopausal CAD women (1.360 +/- 0.32 mm), as compared to premenopausal with CAD (1.178 +/- 0.36 mm, P = 0.005), pre-(0.860 +/- 0.23 mm, P < 0.001) and postmenopausal (1.022 +/- 0.30 mm, P < 0.001) women without CAD. Carotid intima-media thickness (P < 0.001), hyperlipidemia (P = 0.018), and myocardial infarction (P < 0.001), but not menopause itself or the number of years since menses cessation, were found to be independent CAD predictors. By receiver operating characteristic calculation, the mean maximum CIMT cut-off values discriminating CAD were lower in premenopausal (>/=0.933 mm) than in postmenopausal women (>/=1.075 mm; P < 0.05) resulting in similar sensitivity (85.2% and 82.6%) and specificity (70.6% and 69.9%). Carotid intima-media thickness is a strong CAD predictor in both pre-and postmenopausal women, in contrast to the menopausal status.     

Relation between high-density lipoprotein cholesterol and peripheral vasomotor function

Low levels of high-density lipoprotein (HDL) cholesterol are one of the most common lipid abnormalities in patients with coronary artery disease. Endothelial dysfunction is also highly prevalent in patients with coronary artery disease. We sought to determine whether HDL cholesterol levels are correlated with endothelium-dependent vasomotion in patients being evaluated for atherosclerosis. Peripheral vascular endothelial function was assessed by high-resolution brachial artery ultrasound. Flow-mediated dilation (FMD) during reactive hyperemia was defined as the percent change in arterial diameter following 5-minute arterial occlusion. All patients underwent stress testing with nuclear single-photon emission computed tomographic imaging to determine percent left ventricular ejection fraction and define the presence or absence of coronary artery disease. One hundred fifty-one subjects (87 men, 64 women) were enrolled (average age 58 +/- 11 years). Total cholesterol, HDL cholesterol, low-density lipoprotein cholesterol, and triglyceride levels were 188 +/- 48, 47 +/- 13, 108 +/- 37 and 154 +/- 88 mg/dl, respectively. The mean FMD for the entire group was 9.9 +/- 5.2%. Subjects with an HDL cholesterol of <40 mg/dl (n = 39) had lower FMD (7.4 +/- 3.6%) compared with those with an HDL cholesterol >/=40 mg/dl (11.0 +/- 5.5%, p <0.001). There was a significant correlation between FMD and HDL cholesterol level (linear regression, p <0.001), and in multivariate analysis, HDL cholesterol was an independent predictor of FMD. Peripheral endothelial function was abnormal in subjects with low HDL cholesterol and well-preserved in those with high HDL cholesterol. These data suggest that impaired endothelial function associated with low HDL cholesterol may be an additional, previously unrecognized mechanism contributing to the increased risk of atherosclerosis in these patients.     

Plasma homocyst(e)ine levels in men with premature coronary artery disease

Plasma homocyst(e)ine (that is, the sum of free and bound homocysteine and its oxidized forms, homocystine and homocysteine-cysteine mixed disulfide) levels were determined in 170 men (mean age +/- SD 50 +/- 7 years) with premature coronary artery disease diagnosed at coronary angiography and in 255 control subjects clinically free of coronary artery disease (mean age 49 +/- 6 years). Patients with coronary artery disease had a higher homocyst(e)ine level than control subjects (13.66 +/- 6.44 versus 10.93 +/- 4.92 nmol/ml, p less than 0.001). High density lipoprotein (HDL) cholesterol levels were lower (32 +/- 10 versus 46 +/- 13 mg/dl, p less than 0.001) and triglycerides levels were higher (193 +/- 103 versus 136 +/- 106 mg/dl, p less than 0.001) in the coronary disease group. Plasma total cholesterol and low density lipoprotein (LDL) cholesterol levels were not significantly different between patients with coronary disease and control subjects. The presence of hypertension, smoking or diabetes mellitus did not significantly alter homocyst(e)ine levels in the patient or the control group. Patients who were not taking a beta-adrenergic blocking drug (n = 70) had a nonsignificantly higher homocyst(e)ine level than did patients taking this class of drugs (n = 100) (14.67 +/- 8.92 versus 12.95 +/- 3.77 nmol/ml, p = 0.087). By design, none of the control subjects were taking a beta-blocker. No significant correlations were observed between homocyst(e)ine and age, serum cholesterol, LDL cholesterol, HDL cholesterol or triglyceride levels. It is concluded that an elevated plasma homocyst(e)ine level is an independent risk factor for the development of premature coronary atherosclerosis in men.     

Lipoprotein (a) and lipid levels in young patients with myocardial infarction and their first-degree relatives.

BACKGROUND: Studies among emigrant Indians have stressed the role of a powerful genetic factor, lipoprotein (a), in the causation of premature coronary artery disease. This study was carried out to assess lipoprotein (a) and lipid levels in 50 consecutive young north Indian patients (age less than 45 years, mean age 39+/-3.7 years) with myocardial infarction, their first-degree relatives (n=125, mean age 36+/-16 years), and age- and sex-matched controls (n=50, mean age 34+/-6.9 years). METHODS AND RESULTS: Blood samples for lipid estimation were taken within 24 hours of myocardial infarction and after overnight fasting for twelve hours. Lipoprotein (a) levels were estimated by the ELISA technique using preformed antibodies while lipid levels were estimated by kits using the colorimetric method. All were male patients. The mean lipoprotein (a) level was 22.28+5.4 mg/dl in patients, 13.88+5.19 mg/dl in their first-degree relatives and 9.28+22.59 mg/dl in controls. In addition, it was significantly higher in young patients with myocardial infarction and their relatives as compared to controls (p<0.001 for patients v. controls and p<0.05 for relatives v. controls). There was no significant difference in the levels of total cholesterol and low-density lipoprotein cholesterol among the three groups. High-density lipoprotein cholesterol was significantly lower in young patients with myocardial infarction (30.16+/-9.45 mg/dl) and their first-degree relatives (33.28+/-8.45 mg/dl) as compared to controls (46.8+/-8.04 mg/dl) (p<0.001 for patients v. controls and p<0.01 for relatives v. controls). Triglyceride levels were significantly higher in patients as compared to controls (202+/-76 mg/dl v. 149 + 82.99 mg/dl, p<0.05). Smoking was more prevalent in young patients with myocardial infarction as compared to controls (44% v. 36%, p<0.05). CONCLUSIONS: Smoking, high lipoprotein (a) and triglyceride levels and low high-density lipoprotein levels may be important risk factors for coronary artery disease in the younger population; also, there is familial clustering of high lipoprotein (a) levels in first-degree relatives of young patients with myocardial infarction.     

Intracoronary ultrasound in cardiac transplant recipients. In vivo evidence of "angiographically silent" intimal thickening.

BACKGROUND. Accelerated coronary atherosclerosis is a major factor limiting allograft longevity in cardiac transplant recipients. Histopathology studies have demonstrated the insensitivity of coronary angiography for detecting early atheromatous disease in this patient population. Intracoronary ultrasound is a new imaging technique that provides characterization of vessel wall morphology. The purpose of this study was to compare in vivo intracoronary ultrasound with angiography in cardiac transplant recipients. METHODS AND RESULTS. The left anterior descending coronary artery was studied with intracoronary ultrasound in 80 cardiac transplant recipients at the time of routine screening coronary angiography 2 weeks to 13 years after transplantation. A mean and index of intimal thickening were obtained at four coronary sites. Intimal proliferation was classified as minimal, mild, moderate, or severe according to thickness and degree of vessel circumference involved. Twenty patients were studied within 1 month of transplantation and had no angiographic evidence of coronary disease. An intimal layer was visualized by ultrasound in only 13 of these 20 presumably normal hearts. The 60 patients studied 1 year or more after transplantation all had at least minimal intimal thickening. Twenty-one patients (35%) showed minimal or mild, 17 (28%) moderate, and 21 (35%) severe thickening. Forty-two of these 60 patients had angiographically normal coronary arteries, 21 (50%) of whom had either moderate or severe thickening. All 18 patients with angiographic evidence of coronary disease had moderate or severe intimal thickening, but there was no statistically significant difference in intimal thickness or index when compared with the patients with moderate or severe proliferation and normal angiograms (thickness, 0.53 +/- 0.35 mm versus 0.64 +/- 0.30 mm, p = NS; index, 0.28 +/- 0.10 versus 0.34 +/- 0.10, p = NS). CONCLUSIONS. The majority of patients 1 or more years after cardiac transplantation have ultrasound evidence of intimal thickening not apparent by angiography. Intracoronary ultrasound offers early detection and quantitation of transplant coronary disease and provides characterization of vessel wall morphology, which may prove to be a prognostic marker of disease.     

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.     

The relationship between age and carotid artery intima-media thickness, hemoglobin A1c in nondiabetic, healthy geriatric population

The aim of the study was to investigate a casual relationship between age and carotid artery intima-media thickness (IMT) and hemoglobin A1c (HbA1c) levels and to assess the effects of possible risk factors in healthy nondiabetic elderly. Seventy-two healthy, well-educated, nondiabetic, healthy elderlies (mean age: 71.5+/-5.01 years; 43 male, 29 female) were enrolled in the study. Comprehensive assessments including a battery of psychosocial and functional performance tests were performed to all subjects. All of them were also asked about health prevention topics including exercise, dietary habits, smoking, vaccination, cholesterol screening, etc. Carotid artery IMT was measured by ultrasound. Blood samples were obtained for fasting glucose, HbA1c, cholesterol, triglyceride and fibrinogen. The mean carotid artery IMT was 0.94+/-0.13 mm and the mean HbA1c level was 5.29+/-0.65 mg/dl. There was no significant correlation between age and carotid artery IMT (r(s)=0.15), HbA1c levels (r(s)=-0.08) and other possible atherosclerosis risk factors. Also there was no correlation between carotid artery IMT and HbA1c levels (r(s)=0.14). Our data indicated that the carotid artery IMT, HbA1c and age are not associated in a geriatric healthy, well-educated population. Comparative studies done on the elderly who do not benefit from preventive health care programs are needed to establish if preventive health care measures and risk factor modification are important in the elderly age group.