Hannu Jokela

Autoantibodies Against Oxidized Low Density Lipoprotein in Patients With Angiographically Verified Coronary Artery Disease

Oxidation of low density lipoproteins (LDL) obviously plays an important role in the pathogenesis of atherosclerosis. The purpose of the study was to determine whether antibodies against oxidized LDL are associated with coronary artery disease (CAD). We determined the serum levels of antibodies against copper-oxidized LDL by enzyme-linked immunosorbent assay in 58 patients with angiographically verified CAD and 34 controls without CAD. The mean antibody level, expressed in optical density units, was significantly higher in patients than in controls (0.150+/-0.088 versus 0.094+/-0.054, respectively; P=0.00089). In logistic regression analysis, high antibody level against oxidized LDL was associated significantly with CAD (P=0.0114), independent of age (P=0.00137), gender (P=0.0021), body mass index (P=0.5947), triglyceride concentration (P=0.9813), and total cholesterol-high density lipoprotein (HDL) cholesterol (P=0.0080) group. Similar analysis in nondiabetic subjects (n=79) and in men only (n=75) showed analogous results, with only minor changes in P values. The antibody level against oxidized LDL differed significantly between nonsmokers and smokers in CAD patients (P<0.00197) but not in controls (P=NS). In addition, the antibody level against oxidized LDL differed significantly between nonsmokers and smokers in subjects with low HDL cholesterol (</=0.9 mmol/L) but not in subjects with high HDL cholesterol (>0.9 mmol/L). In conclusion, elevated levels of antibodies against oxidized LDL were associated with CAD. The data suggest that oxidized LDL plays a role in the pathogenesis of atherosclerosis and suggest a protective function for HDL against LDL oxidation.

Apolipoprotein E polymorphism, serum lipids, myocardial infarction and severity of angiographically verified coronary artery disease in men and women.

In several populations, the apolipoprotein E (apo E) allele epsilon 4 is associated with high concentration of plasma total and low density lipoprotein (LDL)-cholesterol and coronary artery disease (CAD). We determined the apo E phenotypes of 309 patients with angiographically verified CAD and 38 patients without CAD by isoelectric focusing and Western blotting. In men with CAD, the plasma total and LDL-cholesterol increased according to apo E phenotype in the following order: E3/2 < E3/3 < E4/3 < E4/4 (P = 0.03 for total cholesterol, P = 0.007 for LDL-cholesterol). In women, there was a similar trend (P = 0.22 for total cholesterol, P = 0.15 for LDL-cholesterol). The relative frequency of men with three vessel CAD increased (P = 0.43) together with LDL-cholesterol levels (P = 0.05) according to apo E phenotype E3/2, E3/3, E4/3, E4/4. Total and LDL-cholesterol levels were higher in patients with three vessel CAD than in patients with less serious types of CAD (P = 0.02 for total cholesterol, P = 0.007 for LDL-cholesterol). The relative frequency of patients with myocardial infarction increased according to apo E phenotype (P = 0.51). Both in men and women, there were no differences between apo E phenotypes in age at occurrence of the first myocardial infarction. The apo E allele frequencies of patients with CAD vs. without CAD were 2.3% vs. 1.3% for epsilon 2, 79.0% vs. 76.3% for epsilon 3 and 18.7% vs. 22.4% for epsilon 4. There were no statistically significant differences in apo E allele or phenotype frequencies between patients with CAD and without CAD or between patients with CAD and the general Finnish population. Our results support previous studies in suggesting that the apo E allele epsilon 4 is a risk factor for atherosclerosis, which affects plasma total and LDL-cholesterol. In addition, our results suggest that the apo E allele determines the severity of CAD.

Women have a larger and less atherogenic low density lipoprotein particle size than men

Some epidemiological studies have shown that serum total cholesterol increases with age. especially in women. On the other hand, the risk of coronary artery disease is smaller in women than in men. Earlier studies have shown that a small dense low density lipoprotein (LDL) is more atherogenic than a large LDL. We studied LDL size and apolipoprotein E (apo E) phenotypes in premenopausal and postmenopausal women and in men at the same age. In this study 342 subjects participating in a health screening study were examined. There were four subgroups: 40-year-old men (n = 85), 40-year-old women (n = 80), 70-year old men (n = 88) and 70-year-old women (n = 89). In the present study LDL size was larger (P < 0.01) in women (26.39 +/- 0.07 nm) than in men (25.95 +/- 0.07 nm). We found that LDL size correlated highly positively (r = 0.606; P < 0.001) with serum high density lipoprotein (HDL) concentration and inversely with serum triglyceride concentration (r = -0.627; P < 0.001). Measuring serum HDL cholesterol and triglycerides in health screening studies gives information indirectly about LDL size and its atherogenicity. Apo E phenotype was not significantly associated with serum triglycerides, but was associated with LDL size, LDL cholesterol, total cholesterol and HDL cholesterol. In our sample LDL size decreased and LDL cholesterol and total cholesterol increased according to the most prevalent apo E phenotypes in the order E2/3, E3/3, E3/4 and E4/4. Subjects with phenotype apo E4/4 had the smallest LDL size (25.70 +/- 0.19 nm), the highest total cholesterol (6.53 +/- 0.35 mmol/l) and the lowest HDL cholesterol values (1.28 +/- 0.04 mmol/l). We conclude that there was a significant interaction between sex and age in serum total cholesterol which was highest in older women. However, their LDL size was larger and their LDL is less atherogenic. Apo E phenotype had a significant influence on LDL size.

A comparison of serum trypsinogen-2 and trypsin-2-α1-antitrypsin complex with lipase and amylase in the diagnosis and assessment of severity in the early phase of acute pancreatitis

OBJECTIVE:The aim of the study was to compare the recently introduced laboratory markers trypsinogen-2 and trypsin-2-α1antitrypsin complex (trypsin-2-AAT) in serum with lipase and amylase in the diagnostic and prognostic evaluation of patients with acute pancreatitis (AP).METHODS:The analytes were measured on admission in 64 consecutive patients with AP and in 30 controls with acute abdominal disease of extrapancreatic origin. Twenty-one patients had severe and 43 mild AP. As reference methods we used serum amylase and C-reactive protein.RESULTS:In subjects with AP, elevated trypsinogen-2 values (≥90 μg/L) were observed in 63 patients (98%), trypsin-2-AAT values (≥12 μg/L) in 64 patients (100%), lipase values (≥200 U/L) in 64 patients (100%), and amylase values (≥300 IU/L) in 62 patients (97%). The diagnostic accuracy of the markers was evaluated by receiver operating characteristic (ROC) analysis. On admission, trypsinogen-2, trypsin-2-AAT, lipase, and amylase differentiated patients with AP from controls with high accuracy and ROC analyses showed similar areas under the ROC curves (AUC) for trypsinogen-2 (AUC 0.960), trypsin-2-AAT (0.948), lipase (AUC 0.947), and amylase (AUC 0.930). For differentiation between severe and mild AP, trypsin-2-AAT (AUC 0.805) was slightly better than trypsinogen-2 (AUC 0.792), and they were both clearly better than lipase (AUC 0.583), C-reactive protein (AUC 0.519), or amylase (AUC 0.632) (p < 0.05).CONCLUSIONS:All the markers studied showed high accuracy for differentiating between AP and extrapancreatic diseases. However, trypsinogen-2 and trypsin-2-AAT displayed the best accuracy for predicting a severe AP already at admission, which makes these markers superior for clinical purposes.

Alcohol consumption and its relation to lipid-based cardiovascular risk factors among middle-aged women: the role of HDL3 cholesterol

Abstract To study the association of alcohol consumption and lipid-based cardiovascular risk factors among middle-age women, cross-sectional analysis among 274 middle-aged healthy women with different drinking habits and a follow-up analysis of alcoholic women during abstinence was performed. Serum total cholesterol, low and high-density lipoprotein cholesterol (LDL and HDL cholesterol), triglycerides (TG), apolipoproteins A1 (Apo A1) and B (Apo B), and HDL-cholesterol subfractions 2 (HDL 2 ) and 3 (HDL 3 ) were measured. All lipid values except LDL cholesterol positively correlated with self-reported alcohol consumption. When alcoholics were excluded the correlation was significant only for HDL cholesterol, HDL 3 , and Apo A1. The increasing trend of HDL cholesterol, HDL 3 and Apo A1 were clearly seen first in women consuming >20–40 g/day of absolute alcohol. Alcohol consumption >40 g/day increased all lipid values except LDL cholesterol. Abstinence for 2 weeks caused a significant decrease in HDL 3 cholesterol, and an increase in LDL cholesterol and Apo B. The results indicate that among middle-aged women the Apo A1 and HDL cholesterol via its HDL 3 but not HDL 2 subfraction might play a role in the beneficial coronary consequences associated with moderate alcohol consumption. However, the increasing beneficial trend first appears when daily drinking exceeds 20 g/day.

Impaired ovarian function and risk factors for atherosclerosis in premenopausal women

OBJECTIVES The aim of the study was to obtain information on the possible relationship between impaired ovarian function and risk factors for cardiovascular disease. MATERIAL AND METHODS Serum lipid levels, plasma fibrinolytic potential and histological and biochemical changes in the intima of the uterine artery were investigated in premenopausal women with irregular menstrual cycles, and the results were compared with those from regularly menstruating women. In addition, the same parameters were studied in postmenopausal women on hormone replacement therapy (HRT) and in postmenopausal women who had never used HRT. In total 64 patients undergoing hysterectomy for benign reasons were included the study. RESULTS Plasma fibrinogen concentration was significantly higher in irregularly menstruating women as compared with women with regular cycles. In women with irregular cycles thickened or sclerotic arterial intima was a significantly more common finding as compared with regularly menstruating women. A significant positive correlation was observed between plasma fibrinogen concentration and intimal esterified cholesterol content in women with thickened or sclerotic uterine artery. CONCLUSIONS These data suggest an important role for normal ovarian function in the prevention of atherosclerosis.

Combined oestrogen-progestin replacement therapy prevents atherosclerosis in postmenopausal women

The incidence of atherosclerotic plaques in the aorta and in the carotid and iliac arteries was investigated using high resolution B-mode ultrasonography in 40 postmenopausal women using sequentially combined oestradiol valerate 2 mg--levonorgestrel 0.25 mg replacement therapy. In addition, serum lipid, lipoprotein and apolipoprotein levels were measured. Similar studies were performed for 40 postmenopausal women using oestradiol valerate alone and for 40 women who had never used hormone replacement therapy (HRT). Ultrasonographically observed atherosclerotic plaques were less common (P = 0.011) in oestradiol valerate--levonorgestrel users than in women without HRT. More than three atherosclerotic plaques were observed in 62% of the women without HRT but only in 30% of the women using combined therapy (P = 0.003). The total number of plaques did not differ between the two hormone using groups. The mean serum triglyceride, total cholesterol and apolipoprotein B levels were lowest in oestradiol valerate--levonorgestrel users when compared with those of women with oestradiol valerate monotherapy and those of women without HRT. Combined oestradiol valerate--levonorgestrel replacement therapy, like oestradiol valerate monotherapy, prevents the progression of atherosclerosis in postmenopausal women. The lipid patterns were not adversely affected by the addition of the androgenic levonorgestrel.

Relationship of alcohol consumption to changes in HDL-subfractions

Abstract. Epidemiological studies have consistently shown an apparent protective effect of moderate alcohol consumption on coronary artery disease (CAD). This has been considered to be due to the rise in the high‐density cholesterol lipoprotein (HDL‐cholesterol). Since the response of the HDL‐subfractions to moderate or heavy dose of alcohol is less clear, we now compared the high‐density lipoprotein cholesterol status between groups consuming different amounts of alcohol. In this population‐based survey serum total high‐density lipoprotein cholesterol and its HDL2 and HDL3 subfractions were blindly compared between 264 consecutive middle‐aged men (37 teetotallers, 137 moderate drinkers, 90 heavy drinkers) participating in a voluntary health screening and 104 male alcoholics.

The effect of hormone replacement therapy on atherosclerotic severity in relation to ESR1 genotype in postmenopausal women

OBJECTIVE The atheroprotective action of estrogen is mediated by estrogen receptors (ESR) 1 and 2, expressed in atherosclerotic lesions. The effects of hormone replacement therapy (HRT) and ESR1 PvuII genotypes on atherosclerosis have not previously been studied prospectively in postmenopausal women. METHODS We investigated the effect of HRT on the progression of atherosclerosis in a 5-year follow-up study of 88 postmenopausal women aged 45-71 years at baseline allocated into three groups based on the use of HRT. The HRT-EVP group (n=26) used sequential estradiol valerate (EV) plus progestin (P), the HRT-EV group EV alone (n=32), and a control group (n=30) was without HRT. The atherosclerosis severity score (AS) of the abdominal aorta and carotid arteries were determined by sonography and the ESR1 PvuII genotypes (P/P, P/p and p/p) by PCR. RESULTS HRT, time and ESR1 PvuII genotype had a statistically significant or borderline significant main effect on AS during 5-year follow-up (P=0.004, P<0.001 and P=0.090, respectively), when analyzed by repeated measures analysis of variance. There was a significant genotype-by-treatment (HRT-EVP and control groups) interaction for AS (P=0.034). In response to HRT-EVP, subjects with P/P, compared with those with P/p and p/p genotypes, had a less increase in AS (1.61+/-1.14 vs. 1.71+/-1.27 vs. 2.43+/-1.27). Baseline AS as covariate in similar model does not change the significant interaction effect between HRT-EVP and control groups (P=0.036). But this effect was not found between HRT-EV and control groups. CONCLUSIONS Our results suggest that the effect of HRT-EVP in postmenopausal women on progression of AS may be determined in part by the genotype of ESR1 PvuII.

Urinary citrate excretion in patients with urolithiasis and normal subjects.

Citrate is a normal constituent of urine which combines with calcium to form a soluble salt. Urinary citrate excretion was examined in patients with urolithiasis and normal subjects by a specific enzymatic technique. There was a considerable overlap in the urinary citrate excretion between normal subjects and stone-formers, but the citrate-creatinine ratio, the citrate-calcium ratio and the citrate-magnesium-calcium ratio, which were all highly significantly lower (p less than 0.001) in stone-formers than in controls, proved most reliable in discriminating between these groups.