Risk Factor For Coronary Atherosclerosis Research Articles

A Homocysteine Metabolism–Related Dietary Pattern and the Risk of Coronary Heart Disease in Two Independent German Study Populations

A biomarker profile of high folate and vitamin B-12 and low plasma homocysteine concentrations reduces the risk of coronary heart disease (CHD) and may be linked to diet. The objectives of the present study were to identify a food pattern related to these biomarkers and to examine its association with CHD risk. Dietary patterns related to biomarker plasma concentrations were constructed from data obtained in the Coronary Risk Factors for Atherosclerosis in Women (CORA) Study (200 cases; 255 controls) using the reduced rank regression statistical method. Risks for CHD with relation to the identified pattern were estimated in the CORA study and in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam Study with 157 cases of incident myocardial infarction among 26,795 participants. In these 2 German study populations, whole-grain bread, fresh fruit, olive oil, mushrooms, cruciferous vegetables, wine, and nuts contributed the most positively and fried potatoes the most negatively to a dietary pattern that was directly associated with both plasma folate and vitamin B-12 concentrations, but inversely with plasma homocysteine. Multivariate-adjusted relative risks for CHD across increasing quintiles of the food pattern score were 1.0, 0.55, 0.52, 0.58, 0.39 (P for trend = 0.05) in the case-control sample and 1.0, 0.95, 0.75, 0.56, 0.72 (P for trend = 0.041) in the prospective study. The combination of a high intake of whole-grain bread, fresh fruit, olive oil, mushrooms, cruciferous vegetables, wine, and nuts with a low intake of fried potatoes was associated with a favorable biomarker profile of homocysteine metabolism and reduced risk of CHD.

Nutrition is a powerful independent risk factor for coronary heart disease in women—The CORA Study: a population-based case–control study

It is still common practice to rely mostly on drug treatment for preventing cardiovascular disease, although a healthy nutrition has been defined that may prevent most premature cardiovascular events. This research raises the question of the magnitude of the effect of nutrition on cardiovascular disease independent of that of clinical risk factors, which are the targets of drug therapy. The study of coronary risk factors for atherosclerosis in women compares clinical, biochemical, and lifestyle factors in 200 consecutive pre- and postmenopausal women with incident coronary heart disease (CHD) to those in 255 age-matched population-based controls. Cases reported a higher intake of energy, predominantly through animal fat and protein reflected by a higher consumption of meat and sausage, while controls ate more fruit and vegetables. Multivariate analysis adjusted for clinical risk factors depicted a high intake of meat and sausage and a low consumption of fruit and vegetables as independent risk factors with an odds ratio of 2.5 (95% confidence interval 1.1-5.7) and 0.7 (95% confidence interval 0.5-1.0) for each 100 g per day, respectively. These dietary factors were found to be significantly more pronounced in cases with any clinical risk factor identified in this population as compared to controls with the same risk factors. The CORA-study clearly indicates a major impact of dietary habits on CHD in women independent of, and additive to, that of conventional risk factors. Thus, in clinical practice, the potential of nutrition as part of a healthy lifestyle is commonly greatly underestimated in favour of drug treatment.

Lipoprotein(a) and Apolipoprotein(a) Isoforms

Elevated plasma levels of lipoprotein(a) [Lp(a)] are an independent risk factor for cardiovascular disease in whites. Blacks have 2- to 3-fold higher plasma levels of Lp(a) than whites and yet do not have a correspondingly higher rate of coronary events. It remains unclear whether elevated plasma levels of Lp(a) are an independent risk factor for coronary atherosclerosis in individuals of African descent. The relationship between plasma levels of Lp(a), apolipoprotein(a) isoform sizes, and the presence of coronary calcium was examined in 761 blacks and 527 whites (men aged >40 years, women aged >45 years) from a population-based sample. No relationship was found between plasma levels of Lp(a), apolipoprotein(a) isoform size, or a combination of these 2 variables and coronary artery calcium (CAC) in whites or blacks. No correlation was observed between plasma levels of Lp(a) and coronary calcium scores in any group, although all black men with very high plasma levels of Lp(a) (>300 micromol/L; n=7) were CAC-positive. Whites with high plasma levels of Lp(a) plus elevated plasma levels of LDL cholesterol (men) or reduced levels of HDL cholesterol (men and women) or who smoked (women) had a higher prevalence of CAC. In contrast, no joint effects between plasma levels of Lp(a) and other cardiovascular risk factors on coronary calcium were found in blacks. No consistent independent relationship between plasma levels of Lp(a) or apolipoprotein(a) isoform size and coronary calcium was found in whites or blacks.

Low plasma pyridoxal-5′phosphate and cardiovascular disease risk in women: results from the Coronary Risk Factors for Atherosclerosis in Women Study

Low plasma pyridoxal-5′phosphate and cardiovascular disease risk in women: results from the Coronary Risk Factors for Atherosclerosis in Women Study

Is Thyroid Hormone a Risk Factor of Coronary Atherosclerosis in Korean Patients?

Background and Objectives:Overt and subclinical hypothyroidism is known to be associated with developing athe- rosclerosis and adverse changes in blood lipid. There has been no data regarding the effects of a normal range of thyroid hormone on the presence of coronary atherosclerosis. Subjects and Methods:We studied 125 consecutive patients (age: 60.0±11.1 years, male: female=84: 41) who underwent diagnostic coronary angiography. The clinical diagnoses on admission were stable angina (32.0%), unstable angina (53.6%), and acute myocardial infarction (14.4%). The thyroid hormones (thyroid stimulating hormone (TSH), free thyroxine and free 3-iodothyronine), serum lipid levels, high sensitivity C-reactive protein (hsCRP) level, homocysteine and fibrinogen levels were measured. The coronary angiog- raphic results were compared with laboratory findings. Results:The angiographic diagnoses of coronary artery disea- se were no significant stenosis in 41 patients (32.8%), single vessel disease in 47 patients (37.6%) and multivessel disease in 37 patients (29.6%). The serum TSH levels showed a trend toward higher levels in the patients with multivessel disease compared to the patients with no significant stenosis (1.22±0.96 uIU/mL vs. 0.73±0.53 uIU/mL, respectively, p=0.053). According to the levels of TSH (<1.0 uIU/mL and ≥1.0 IU/mL), the incidence of multivessel disease was signi- ficantly higher in the patients with high serum TSH levels (23.1% vs. 40.0%, respectively, p=0.038). A significant correla- tion was observed between the levels of TSH and the monocyte count (r=0.251, p=0.005), hsCRP level (r=0.208, p=0.023) and homocysteine level (r=0.279, p=0.002). Conclusion:The high level of serum TSH is associated with multivessel disease, abnormal inflammatory markers and high homocysteine levels. (Korean Circulation J 2005;35:43-48)

A dietary pattern derived to explain biomarker variation is strongly associated with the risk of coronary artery disease

In previous studies, dietary patterns were derived in different populations without regard to a specific outcome. The objective was to apply a new statistical method to construct a specific dietary pattern that is strongly associated with the risk of coronary artery disease (CAD). We applied reduced rank regression to a sample of 200 cases and 255 controls from the Coronary Risk Factors for Atherosclerosis in Women (CORA) Study. The CAD-specific dietary pattern was constructed by choosing intake data for 49 food groups as predictors and 5 established biomarkers for CAD as responses. A high score for the constructed dietary pattern was characterized by high intakes of meat, margarine, poultry, and sauce and low intakes of vegetarian dishes, wine, vegetables, and whole-grain cereals. After adjustment for known CAD risk factors, the relative risks from the lowest to the highest quintiles of the pattern score were 1.0, 1.1, 3.6, 6.2, and 12.3 (95% CI: 4.9, 30.9; P for trend < 0.0001). There was an approximate 4.5-fold difference in C-reactive protein and a 2-fold difference in C-peptide between the highest and lowest score quintiles of the study population. HDL-cholesterol concentrations ranged from 70 mg/dL in the lowest quintile to 49 mg/dL in the highest quintile of dietary pattern score. The new statistical method, reduced rank regression, may be a useful tool for identifying dietary patterns that simultaneously affect the concentrations of known CAD biomarkers and the risk of developing CAD.

Peroxisome proliferator activator receptors (PPAR), insulin resistance, and cardiomyopathy: friends or foes for the diabetic patient with heart failure?

Diabetes is a risk factor for coronary atherosclerosis, myocardial infarction, and ischemic cardiomyopathy. Insulin resistance is associated with left ventricular (LV) hypertrophy and hypertensive cardiomyopathy. Even in the absence of coronary artery disease or hypertension, "diabetic cardiomyopathy" can develop because of myocardial autonomic dysfunction or impaired coronary flow reserve. The relationship between insulin resistance and cardiomyopathy is bidirectional. Systemic and myocardial glucose uptake is compromised in heart failure independent of etiology. These abnormalities are associated with cellular deficits of insulin signaling. Insulin resistance in heart failure can be detrimental, because transcriptional shifts in metabolic gene expression favor glucose over fat as a substrate for high-energy phosphate production. Although preexisting diabetes accelerates this process of "metabolic death," insulin resistance can also develop secondary to cardiomyopathy-associated overabundance of neurohormones and cytokines. Insulin resistance and fatty acid excess are potential therapeutic targets in heart failure, striving for efficient myocardial substrate utilization. Peroxisome proliferator activator receptor gamma (PPARgamma) agonists are antidiabetic agents with antilipemic and insulin-sensitizing activity. Experimental studies suggest salutary effects in limiting infarct size, attenuating myocardial reperfusion injury, inhibiting hypertrophic signaling and vascular antiinflammatory actions through cytokine inhibition. However, clinical applicability in diabetic patients experiencing heart failure has been hampered because of increased edema and even fewer reports of exacerbation associated with these compounds. Evidence to date argues for peripheral mechanisms of edema unrelated to central hemodynamics. Nevertheless, they are currently contraindicated in New York Heart Association (NYHA) III-IV patients, particularly in combination with insulin. Investigations are underway to decipher mechanisms, risks, and benefits of PPARgamma agonists, as well as the role of the structurally related PPARalpha receptor on cardiovascular metabolism and function.

Lipid profile of patients with aortic stenosis might be predictive of rate of progression

Background Aortic stenosis is one of the most commonly encountered valvular pathology requiring surgery in developed countries. There are similarities between risk factors for coronary atherosclerosis and the development of aortic stenosis. We designed a retrospective study, evaluated the lipid profile and previous echocardiographic recordings of patients with aortic stenosis, and searched the association of rate of progression and lipid profile. Methods and results The annual rates of progression in the peak and mean aortic gradients were 8.5 ± 3.2 and 6.7 ± 2.2 mm Hg/year, respectively. We classified the annual rate of progression of peak aortic gradient into 2 groups, group 1 with <10 mm Hg (“slow progressors”) and group 2 with ≥10 mm Hg annual rate of progression (“fast progressors”). The annual rate of progression in group 1 was significantly higher than that in group 2, both in peak and mean aortic gradients (12 ± 2 mm Hg and 6.4 ± 1.6 mm Hg; 9 ± 1.3 mm Hg and 5.2 ± 1.1 mmHg; P <.001 for both). There was a highly significant difference between group 1 and group 2 for total cholesterol/high-density lipoprotein (HDL) cholesterol level ratio (7.1 ± 1.4 vs 5.2 ± 1.3, P <.001). There was a significant correlation between annual rate of progression in peak gradient and total cholesterol/HDL cholesterol level ratio (r = 0.399, P = .009). Smoking ( P = .024, Beta = 0.26), presence of coronary heart disease ( P = .011, Beta = 0.31), and total cholesterol/HDL cholesterol level ratio ( P = .004, Beta = 1.98) were independently predictive of fast progression of the peak aortic gradient in the regression analysis. Conclusion In a small group of patients from Turkey with aortic stenosis, there seems to be an association between the rate of progression and total cholesterol/HDL cholesterol level ratio, with fast progression occurring in the group with higher ratios.

Coronary artery calcification and cardiovascular risk factors: impact of the analytic approach

Coronary artery calcification (CAC) may help identify novel risk factors for coronary atherosclerosis. However, analysis of CAC is challenging because of the distribution of CAC in the population. This has resulted in difficulty in interpreting and comparing results across studies. We applied several analytic approaches to CAC data in order to determine the impact of analytic methods on the association with established cardiovascular risk factors in 914 asymptomatic subjects in the Study of Inherited Risk Factors for Coronary Atherosclerosis. Multivariable analyses included: (1) linear regression of different transformations of CAC scores; (2) tobit regression of the log of (CAC+1); (3) logistic regression using CAC zero as a cut-point; and (4) ordinal logistic regression using CAC categories. Linear regression of the log CAC scores and logistic regression of CAC zero cut-point failed to detect associations with some risk factors. In contrast, linear and tobit regression of the log (CAC+1) and ordinal regression of CAC categories identified more associations and provided consistent results. Commonly applied methods of CAC analysis may fail to detect associations with cardiovascular risk factors. We present analytic approaches that are likely to provide consistent results and recommend the use of at least two distinct multivariable methods.

Sleep-Disordered Breathing: A Heart-Changing Experience?

Increasingly, sleep-disordered breathing (SDB) is recognized as an important risk factor for coronary atherosclerosis and heart disease. Several large epidemiologic studies 1 Mooe T Rabben T Wiklund U et al. Sleep-disordered breathing in women: occurrence and association with coronary artery disease. Am J Med. 1996; 101: 251-256 Abstract Full Text PDF PubMed Scopus (169) Google Scholar ,2 Shahar E Whitney CW Redline S et al. Sleep-disordered breathing and cardiovascular disease: cross-sectional results of the Sleep Heart Health Study. Am J Respir Crit Care Med. 2001; 163: 19-25 Crossref PubMed Google Scholar have demonstrated that SDB increases the risk of heart disease by approximately twofold to fourfold, independent of other risk factors. While the exact mechanisms responsible for this association are largely unknown, there is credible evidence to indicate SDB can increase systemic BP 3 Nieto FJ Young TB Lind BK et al. Association of sleep-disordered breathing, sleep apnea, and hypertension in a large community-based study. JAMA. 2000; 283: 1829-1836 Crossref PubMed Scopus (2735) Google Scholar ,4 Peppard PE Young T Palta M et al. Prospective study of the association between sleep-disordered breathing and hypertension. N Engl J Med. 2000; 342: 1378-1384 Crossref PubMed Scopus (3965) Google Scholar and sympathetic drive. 5 Phillips BG Kato M Narkiewicz K et al. Increases in leptin levels, sympathetic drive, and weight gain in obstructive sleep apnea. Am J Physiol Heart Circ Physiol. 2000; 279: H234-H237 PubMed Google Scholar It may also elevate circulating levels of fibrinogen 6 Wessendorf TE Thilmann AF Wang YM et al. Fibrinogen levels and obstructive sleep apnea in ischemic stroke. Am J Respir Crit Care Med. 2000; 162: 2039-2042 Crossref PubMed Scopus (227) Google Scholar and C-reactive protein, 7 Shamsuzzaman AS Winnicki M Lanfranchi P et al. Elevated C-reactive protein in patients with obstructive sleep apnea. Circulation. 2002; 105: 2462-2464 Crossref PubMed Scopus (803) Google Scholar triggering a cascade of events that eventually leads to thrombus formation in the coronary vasculature. Treatment of SDB, usually with continuous positive airway pressure, leads to significant improvements in these physiologic parameters. 8 Narkiewicz K Kato M Phillips BG et al. Nocturnal continuous positive airway pressure decreases daytime sympathetic traffic in obstructive sleep apnea. Circulation. 1999; 100: 2332-2335 Crossref PubMed Scopus (423) Google Scholar

Plasma concentrations of LPL and LCAT are in putative association with females and alcohol use which are independent negative risk factors for coronary atherosclerosis among Japanese

Background: Coronary heart disease (CHD) prevalence appears low among Japanese. Analysis of their negative risk factors is therefore important for public health strategy. Methods: We analyzed the impact on coronary atherosclerosis of sex, alcohol intake, plasma lipoproteins and enzymes to regulate cholesterol transport, lipoprotein lipase (LPL) and lecithin:cholesterol acyltransferase (LCAT) for the 110 patients who underwent coronary angiography, consecutively enrolled by excluding those >70 years or under hypolipidemic-drug treatment. Subgroup combinations compared were males vs. females in non-drinkers, and drinkers vs. non-drinkers in males. Results: Coronary stenosis was less in females and in drinkers, accompanied by high-density lipoprotein (HDL) in the respective comparison. LPL associated with sex (females>males) and LCAT with alcohol intake (drinkers>non-drinkers) although neither enzyme demonstrated direct correlation with coronary stenosis. LPL positively associated only with HDL in most of subgroups and LCAT correlated with low-density lipoprotein (LDL) in all subgroups but with HDL only in males. Conclusions: Among non-drinkers, females are at lower risk for coronary atherosclerosis than males mainly due to higher HDL in potential association with high LPL, and that drinkers are protected among males also by high HDL that is in apparent association with LCAT.

The Comparison of Serum Lipid Levels and Risk Factors according to the Status of Coronary Atherosclerosis in Koreans

Background and Objectives:The aims of this study were to compare the lipid distributions and risk factors in an angiographically normal coronary artery group to those of microvascular and coronary artery diseased groups of Koreans, and to find the effects of the variable risk factors on the serum lipid levels according to the coronary atherosclerosis status. Subjects and Methods:A total of 1,198 patients (563 males and 635 females), having undergone a coronary angiography (CAG) using Judkins method, were included. According to their coronary angiographic findings, they were divided into normal CAG (n=568), microvascular disease (n=230) and coronary atherosclerosis (n=400) groups. Results:The mean value of the total cholesterol in the patients with normal coronary artery was 175 mg/dl, which progressively increased to 182 mg/dl and 198 mg/dl in the patients with microvascular disease and coronary atherosclerosis, respectively. The frequencies of the risk factors for coronary atherosclerosis also progressively increased in the patients with microvascular disease and coronary atherosclerosis. The mean values of the serum total cholesterol, LDL-cholesterol and lipoprotein(a), progres-sively increased from the patients with normal angiographic findings to those with microvascular disease and coronary atherosclerosis, and the results were statistically significant. The results for the patients with microvascular disease were in between those of the patients with normal angiographic findings and those with coronary atherosclerosis. Conclusion:The correlation between coronary atherosclerosis and the serum cholesterol levels has, until now, been studied epidemiologically, and this is the first study to angiographically elucidate the positive relationship between coronary artery disease and the serum cholesterol levels. Our data showed lower ranges of lipid distributions compared to those of the ATP III guideline. (Korean Circulation J 2003;33 (6):465-474)

Increased expression of plasminogen activator inhibitor-1 by mediators of the acute phase response: a potential progenitor of vasculopathy in hypertensives.

Hypertension is an important risk factor for coronary atherosclerosis, which is accelerated by inflammation and diminished fibrinolysis. We have previously shown that levels of plasminogen activator inhibitor-1 (PAI-1), the major physiologic inhibitor of fibrinolysis, are increased with atherogenic metabolic derangement. Because the liver is one of the major sources of circulating PAI-1, we here examined the effects of two proinflammatory cytokines, interleukin (IL)-1beta, and IL-6, on PAI-1 production in a human hepatoma cell line, HepG2. IL-1beta (1 ng/ml) and IL-6 (1 ng/ml) increased the accumulation of PAI-1 in the conditioned media over 24 h (IL-1beta: 2.1 +/- 0.2 (mean +/- SD) fold over the control; IL-6:1.4 +/- 0.2 fold; Western blot, p < 0.05). The increase in PAI-1 protein accumulation correlated with the increased expression of PAI-1 mRNA (Northern blot). An HMG-CoA reductase inhibitor (mevastatin, 10 micromol/l) attenuated the PAI-1 production induced by IL-1beta and IL-6. The plasma PAI-1 activity level was higher in hypertensives than in normotensives (10.0 +/- 9.8 AU/ml vs. 6.2 +/- 4.5 AU/ml, p < 0.05). The plasma PAI-1 antigen level was also higher in hypertensives than in normotensives (30.9 +/- 22.4 ng/ml vs. 24.4 +/- 13.3 ng/ml, p < 0.05). Thus, 1) IL-1beta and IL-6 can increase PAI-1 production in hepatic cells and 2) mevastatin may exert anti-thrombotic effects by decreasing the PAI-1 protein production induced by these proinflammatory cytokines. These results provide further insights into how inflammation is involved in the atherothrombotic complications observed in hypertensives, which may be ameliorated by HMG-CoA reductase inhibitors.

Lack of association between plasma lipoprotein(a) concentrations and the presence or absence of coronary atherosclerosis

Background — Findings from previous studies relating lipoprotein(a) [Lp(a)] as an independent risk factor for coronary atherosclerosis and the presence of angiographically detectable coronary atherosclerotic lesions are not consistent.This study was performed to determine whether the plasma concentration of Lp(a) is associated with coronary atherosclerosis asessed by coronary angiography.Methods — We studied a total of 100 men and women (41 women, 59 men, age 63.7±11.0 years) who were referred for coronary angiography. Base-line data collection comprised conventional risk factors for coronary artery disease, lipids, fasting total homocysteine, and clinical characteristics.The relation between plasma Lp(a) levels and the presence or absence of coronary lesions was studied. The coronary angiograms were evaluated in a blinded manner. Any coronary stenosis was considered as coronary artery disease (CAD).Results — From the 100 patients, 40 were found to have no CAD and 60 had CAD assessed by coronary angiography. Estimates of the relative risk of coronary heart disease for the fifth quintile of plasma Lp(a) as compared with the first quintile were 0.87 (95 percent confidence interval, 0.66 to 1.34). After adjustment for age, sex, lipoproteins, and homocysteine levels, estimates of the relative risk of coronary heart disease for the fifth quintile of plasma Lp(a) as compared with the first quintile were 1.06 (95 percent confidence interval, 0.81 to 1.39).The presence of angiographic CAD was associated with patient age (p=0.048), male sex (p<0.01), high LDL-cholesterol levels (p=0.02), low HDL-cholesterol levels (p=0.02), high plasma fibrinogen levels (p<0.01) and high fasting total homocysteine levels (p=0.04).Conclusion — These results suggest that the plasma concentration of Lp(a) is not associated with the presence of coronary artery disease in patients referred for coronary angiography.

Percutaneous treatment for carotid stenosis

Stroke is the leading cause of serious long-term disability in the United States. A substantial portion of strokes are caused by atherosclerotic carotid artery disease. The conventional risk factors for coronary atherosclerosis are also responsible for carotid atherosclerosis. Carotid stenosis is encountered in medical practice in either symptomatic or asymptomatic states. In symptomatic patients, medical management with antiplatelet agents does not provide adequate protection against stroke. Carotid endarterectomy can help reduce the risk of a subsequent stroke. Asymptomatic patients with severe carotid stenosis can also benefit from surgical intervention if endarterectomy can be performed at a low operative risk. In recent years, percutaneous carotid stenting using self-expanding stents has become popular for the treatment of carotid stenosis. Although this initial experience has been reported from a high-risk patient population, the results are encouraging, with acceptable periprocedural stroke rates. Moreover, emboli protection devices, modern adjuvant pharmacotherapy, and modern self-expanding stents were not utilized in these studies. With rapidly expanding technology and advances in interventional pharmacology, improvement of clinical outcome is likely. Table 3 summarizes current recommendations for carotid stenting based on a panel of cardiologists, radiologists, and vascular surgeons. At this stage, randomized trials to compare endarterectomy with carotid stenting are underway. Cautious optimism is necessary until the optimal equipment, emboli protection devices, and adjuvant pharmacotherapies are fully investigated. Until then, carotid stenting should be restricted to high-risk candidates for carotid endarterectomy, including patients with severe cardiac comorbidities, previous neck surgeries or radiation, restenosis after endarterectomy, or other technical contraindications for surgery.

Plasma total homocysteine and cysteine levels as cardiovascular risk factors in coronary heart disease

Objectives: As an important risk factor for coronary atherosclerosis, elevated plasma total homocysteine (t-hcy) concentration has recently received greater attention than have conventional risk factors. Though less reactive than homocysteine, cysteine (cys) is the most abundant plasma thiol and may function as an extracellular regulating factor of thiol/disulfide exchange in order to maintain an adequate redox status. An increase in the total amount of this compound may be noxious depending on environmental conditions. In the present study, the aim was to investigate changes of plasma total cysteine, homocysteine and other determinants in different types of coronary heart disease. Design and methods: Plasma total homocysteine (t-hcy), cysteine (t-cys), cysteinylglycine (t-cysgly), folic acid, vitamin B 12, lipid parameters, total protein, albumin and creatinine levels were studied in plasma from 68 patients with coronary heart disease and 42 healthy controls. After reduction of disulfide bonds with tri- n-buthylphosphine, plasma total thiols were assayed using high performance liquid chromatography (HPLC) and fluorescence detection following derivatization of sulfhydryl groups with 7-fluoro-benzo-2-oxa-1,3-diazole-4-sulfonate (SBD-F). Other parameters were determined by using commercial kits. Results: Plasma t-hcy and t-cys levels were higher in patients ( P<0.0001) than in controls, but t-cysgly was unchanged. Hcy and cys levels were correlated with age in the whole study population ( r=0.49, r=0.46, P<0.01). Plasma t-hcy positively correlated with plasma t-cys ( r=0.53, P<0.01) and t-cysgly ( r=0.49, P<0.01) in patients, and with plasma t-cys ( r=0.57, P<0.01) in controls. Postmenopausal women had higher t-cys and t-hcy levels than premenopausal women among the controls ( P<0.01). Folate and vitamin B 12 levels were similar in both patients and controls. Patients with vitamin B 12 levels below normal had higher plasma t-cys and t-cysgly levels ( P<0.05). Interestingly, control subjects with lower vitamin B 12 levels had lower plasma t-hcy levels ( P<0.05). Plasma total cholesterol, HDL-cholesterol, LDL-cholesterol, total protein, albumin and creatinine levels in patients and controls were within the normal range, but only HDL-cholesterol levels in patients were lower than in controls ( P<0.0001). Triglyceride and VLDL levels of patients were also higher than those of controls ( P<0.0001). Conclusions: Higher plasma total cysteine levels are as important as higher plasma total homocysteine levels. Both parameters are intercorrelated and may act synergistically. To discern their respective roles in atherosclerotic disease, these aminothiol levels have to be considered together.

Genetic defenses against hypercholesterolemia.

An elevated plasma cholesterol level is the primary riskfactor for coronary atherosclerosis (NCEP Report Summary 2001). In humans, most circulating cholesterol istransported in low-density lipoproteins (LDL). Between60% and 70% of circulating LDL is removed from thecirculation by LDL receptor (LDLR)-mediated endocytosis in the liver (Bilheimer et al. 1984; Goldstein et al.2001). Reductions in LDLR activity result in elevationsin plasma LDL-C and deposition of cholesterol in bodytissues (Goldstein et al. 2001). The critical importance ofthe LDLR pathway in preventing the accumulation ofLDL is illustrated by the very high plasma levels of LDLand severe, premature atherosclerosis that characterizesthe two autosomal dominant forms of Mendelian hypercholesterolemia: familial hypercholesterolemia (FH) andfamilial defective apolipoprotein B-100 (FDB)...

Measurement of asialylated LDL in the blood of patients with coronary artery disease by antibody-lectin sandwich assay.

Elevated concentrations of asialylated LDL (asialo-LDL) have been reported in patients with coronary artery disease (CAD). This may stimulate lipid accumulation in arterial intima cells and promote atherosclerosis. To investigate asialo-LDL as a potential risk-factor for coronary atherogenesis, we developed an antibody-lectin sandwich assay to measure levels in serum from CAD patients and age-matched control subjects. LDL was captured with an anti-apolipoprotein (apo) B antibody and asialylated oligosaccharides measured using the biotinylated D-galactose (D-gal) binding lectin, Ricinus communis agglutinin 120 (RCA120), and a streptavidin-alkaline phosphatase conjugate. For the control and atherosclerotic subjects, median [interquartile range (IQR)] values for total concentrations of asialo-LDL were 240 mg,L (180-310 mg/L) and 220 mg/L (186-390 mg/L), respectively (P = 0.82). When expressed as a percentage of serum apo B-100, median (IQR) values were 18% (16-23%) and 19% (15-29%), respectively (P = 0.78). These results suggest asialo-LDL has little value as a risk factor for coronary atherosclerosis.

The relation between plasma cysteine, plasma homocysteine and coronary atherosclerosis

Several studies have reported that elevated plasma levels of total homocysteine (tHcy) are related to an increased risk of cardiovascular disease. Only a few studies have looked at the effect of cysteine, another amino thiol, on cardiovascular disease risk. Therefore, in the present case–control study we compared plasma total cysteine (tCys) levels and plasma tHcy levels among subjects with severe coronary atherosclerosis (cases, n=131), subjects without severe coronary atherosclerosis (coronary controls, n=88) and healthy subjects (population-based controls, n=101). Cases were defined as those having ≥90% occlusion in one and ≥40% occlusion in a second coronary artery, while coronary controls had a maximum of 50% occlusion in only one coronary artery. Both males and females, aged 26–64 years were studied. We have previously reported that plasma tHcy is an independent risk factor for coronary atherosclerosis in this study population. In the present analysis, we found that cases had statistically significant higher mean plasma tCys levels than coronary controls and population-based controls (295.8±40.2, 279.0±35.5 and 282.6±32.4 μmol/l, respectively). The odds ratio (OR) of coronary atherosclerosis for the upper tertile of tCys compared with the bottom tertile was 2.5 (95% confidence interval (CI), 1.4–4.3). However, the association between tCys and coronary atherosclerosis was confounded to a great extent by risk factors (OR, 1.0; 95% CI, 0.5–2.0). The multivariate adjusted OR of coronary atherosclerosis per 1 S.D. increase in plasma tCys was 1.0 (95% CI, 0.8–1.3). The corresponding OR per 1 S.D. increase in plasma tHcy was 1.4 (95% CI, 1.1–1.8). We conclude that plasma tCys, unlike plasma tHcy, is not an independent risk factor for atherosclerosis.

Gender- and age-dependent relationships between the E-selectin S128R polymorphism and coronary artery calcification

Development and progression of atherosclerosis involves recruitment and binding of circulating leukocytes to areas of inflammation within the vascular endothelium mediated by a diverse array of cellular adhesion molecules. A polymorphism in the endothelial-leukocyte adhesion molecule 1 (E-selectin) gene has been implicated in early-onset, angiographically defined, severe atherosclerotic disease because it profoundly affects ligand recognition and binding specificity, resulting in a significant increase in cellular adhesion. Relationships between the E-selectin S128R polymorphism and coronary artery calcification (CAC), a marker of atherosclerosis detected with noninvasive electron beam computed tomography, were examined in 294 asymptomatic women aged 40--88 years and 314 asymptomatic men aged 30--80 years from the Epidemiology of Coronary Artery Calcification Study. The E-selectin polymorphism was not associated with presence of CAC in men of any age or in women over age 50. In women 50 years of age or younger the E-selectin polymorphism was significantly associated with presence of CAC after adjustment for age, body mass index, systolic blood pressure, ratio of total cholesterol to high-density lipoprotein cholesterol, and smoking. The significant association between E-selectin and CAC in women 50 years of age or younger may suggest that the 128R allele is a risk factor for coronary atherosclerosis in younger asymptomatic women, who typically have lower levels of traditional risk factors and reduced adhesion molecule expression due to the presence of higher levels of endogenous hormones.