Effect of Continuous and Intermittent Exercises on Oxidised HDL and LDL Lipids in Runners.

We studied the effects of different types of exercises on the concentrations of oxidised HDL (oxHDLlipids) and LDL lipids (oxLDLlipids), serum lipids, antioxidant potential, paraoxonase and malondialdehyde in endurance runners by performing both a 40-min continuous run (velocity corresponding to 80% VO2max) and a 40-min intermittent run (2-min run, velocity corresponding to 100% VO2max, and 2-min rest) using a treadmill. Blood samples were taken before exercise, after 20 and 40 min of exercise, and 15 and 90 min after the end of exercise. The concentrations of oxLDLlipids remained unchanged during the running tests, but after a 90-min recovery the concentrations decreased by 4% (P<0.05) for the intermittent run and by 16% (P<0.01) for the continuous run. The acute effect of the intermittent and continuous run increased the concentrations of oxHDLlipids by 26 and 25%, respectively (P<0.001 for both). Interestingly, oxHDLlipids did not increase after the first half of the run in middle-distance runners during the intermittent run, and a similar phenomenon was seen in marathon runners during the continuous run. These results may indicate that acute physical exercise increases the transport of lipid oxidation products by HDL, although a different training history or genetic background may alter these acute responses.

Both poor cardiorespiratory and weak muscle fitness are related to a high concentration of oxidized low-density lipoprotein lipids.

Good physical fitness is associated with favorable serum lipids. Oxidized low-density lipoprotein (ox-LDL) could be even more atherogenic than serum lipids. We studied the association of ox-LDL and serum lipids with physical fitness. Healthy young (mean age 25 years) men (n=846) underwent maximal oxygen uptake (VO(2max)) and muscle fitness index (MFI) tests and completed a leisure-time physical activity (LTPA) questionnaire. Age (ANCOVA1), age+waist circumference+systolic blood pressure+fasting blood glucose+smoking (ANCOVA3) were used as covariates. The groups with the lowest VO(2max), MFI and LTPA had 23%, 16% and 8% higher concentrations of ox-LDL than the groups with the highest VO(2max) (P<0.0001), MFI (P=0.022) and LTPA (P=0.039) groups, respectively. Subjects with poor fitness (low VO(2max) or low MFI) or low LTPA had elevated levels of ox-LDL/high-density lipoprotein (HDL)-cholesterol, total cholesterol, LDL-cholesterol, triglycerides and a low level of HDL-cholesterol (ANCOVA1, in all, P<0.05). Furthermore, low VO(2max) is associated with a high level of ox-LDL/HDL-cholesterol and triglycerides, and with a low level of HDL-cholesterol (ANCOVA3, in all, P<0.05). Also, subjects with low LTPA had a high ratio of ox-LDL/HDL-cholesterol (ANCOVA1, P=0.001). In conclusion, both poor fitness (both low VO(2max) and low MFI) and low LTPA are associated with a higher concentration of ox-LDL lipids and serum lipids, which may indicate a higher risk for atherosclerosis.

Decreased training volume and increased carbohydrate intake increases oxidized LDL levels.

We studied effects of probiotics and training volume on oxidized LDL lipids (ox-LDL), serum antioxidant potential (s-TRAP) and serum antioxidants (s-α-tocopherol, s-γ-tocopherol, s-retinol, s-ß-carotene and s-ubiquinone-10) in marathon runners during 3-months training period, 6-days preparation period and marathon run. Runners (n=127) were recruited for a randomized, double-blind intervention during which they received either Lactobacillus rhamnosus GG (LGG, probiotic group) or placebo drink (placebo group) during whole study. During the preparation period, subjects decreased training and increased carbohydrate intake. Blood samples were taken at baseline, before 6-days preparation, before and immediately after the marathon. Probiotics did not have any effect on ox-LDL, s-TRAP or serum antioxidants levels during the study. Interestingly, ox-LDL increased by 28% and 33% during the preparation period and decreased by 16% and 19% during the marathon run in the placebo and probiotic groups, respectively (in all, P<0.001). No changes were seen in s-TRAP before marathon, but during run s-TRAP raised by 16% in both groups (both, P<0.001). The increase of ox-LDL level during the preparative period after several months' training suggests that aerobic training may reduce the concentration of ox-LDL and that decrease of training together with increased energy intake, mainly carbohydrate, before marathon is capable of increasing the level of ox-LDL.

Carotid artery compliance in users of plant stanol ester margarine.

OBJECTIVE: To investigate the effects of stanol ester margarine use in healthy subjects on arterial compliance, endothelial function and intima-media thickness. DESIGN: Case-control study comparing regular stanol ester margarine users to non-users. SETTING: Occupational health service clinic. SUBJECTS: We recruited 50 cases and 50 controls (mean age 51+/-8, range 26-65 years). All subjects were non-smokers and the study groups were matched for age and sex. As cases, we invited subjects who had been using regularly (daily) plant stanol ester margarine for a period of 2 years or longer. Non-invasive ultrasound was used to measure carotid artery compliance, carotid intima-media thickness and brachial artery flow-mediated endothelial dependent vasodilatation. RESULTS: The carotid artery compliance was non-significantly higher in cases compared with controls, 1.84+/-1.02 vs 1.58+/-0.76 %/10 mm Hg (P=0.13). The difference in compliance became statistically significant (P=0.04) when the unbalance between the groups in family history of coronary artery disease and years of education were taken into account. There was also a significant dose-response relationship between stanol margarine use and carotid compliance, longer use being associated with higher compliance. Serum lipoproteins, blood pressure, flow-mediated dilation and intima-media thickness values did not differ between cases and controls. CONCLUSION: These data raise the possibility that regular stanol ester margarine use may be associated with beneficial changes in arterial compliance. Intervention studies are needed to test this hypothesis and to reveal possible mechanisms.

Different hormonal response to continuous and intermittent exercise in middle-distance and marathon runners.

In order to study the effects of different athletic backgrounds on exercise-induced hormonal responses, serum testosterone, luteinizing hormone, follicle-stimulating hormone and cortisol concentrations were measured before and after intensive continuous and intermittent running in well-trained middle-distance runners (MID) and marathon runners (MAR). They performed two 40-min exercises on a treadmill: a continuous run at an intensity of 80% [tempo run (TR)] and an intermittent run (IR) at an intensity of 100% of the velocity associated with VO(2max). The testosterone response to IR and the cortisol response to TR was higher (P<0.05) in MID compared with MAR. The testosterone response to IR correlated positively with the maximal blood lactate concentration achieved after the maximal running test (r=0.46, P<0.05, n=20), while the cortisol response to TR correlated negatively with the runner's VO(2max) (r=-0.62, P<0.05, n=20). In conclusion, a continuous running exercise resulted in a lower cortisol response in runners who are adapted for longer distances, and an intermittent running exercise resulted in a higher testosterone response in runners who are adapted to middle distances.

Oxidative stress and AP-1 activity in tamoxifen-resistant breast tumors in vivo.

BACKGROUND: Most breast cancers, even those that are initially responsive to tamoxifen, ultimately become resistant. The molecular basis for this resistance, which in some patients is thought to involve stimulation of tumor growth by tamoxifen, is unclear. Tamoxifen induces cellular oxidative stress, and because changes in cell redox state can activate signaling pathways leading to the activation of activating protein-1 (AP-1), we investigated whether tamoxifen-resistant growth in vivo is associated with oxidative stress and/or activation of AP-1 in a xenograft model system where resistance is caused by tamoxifen-stimulated growth. METHODS: Control estrogen-treated, tamoxifen-sensitive, and tamoxifen-resistant MCF-7 xenograft tumors were assessed for oxidative stress by measuring levels of antioxidant enzyme (e.g., superoxide dismutase [SOD], glutathione S-transferase [GST], and hexose monophosphate shunt [HMS]) activity, glutathione, and lipid peroxidation. AP-1 protein levels, phosphorylated c-jun levels, and phosphorylated Jun NH(2)-terminal kinase (JNK) levels were examined by western blot analyses, and AP-1 DNA-binding and transcriptional activities were assessed by electrophoretic mobility shift assays and a reporter gene system. All statistical tests are two-sided. RESULTS: Compared with control estrogen-treated tumors, tamoxifen resistant tumors had statistically significantly increased SOD (more than threefold; P=.004) and GST (twofold; P=.004) activity and statistically significantly reduced glutathione levels (greater than twofold; P<.001) and HMS activity (10-fold; P<.001). Lipid peroxides were not significantly different between control and tamoxifen-resistant tumors. We observed no differences in AP-1 protein components or DNA-binding activity. However, AP-1-dependent transcription (P=.04) and phosphorylated c-Jun and JNK levels (P<.001) were statistically significantly increased in the tamoxifen-resistant tumors. CONCLUSION: Our results suggest that the conversion of breast tumors to a tamoxifen-resistant phenotype is associated with oxidative stress and the subsequent antioxidant response and with increased phosphorylated JNK and c-Jun levels and AP-1 activity, which together could contribute to tumor growth.

Long-lasting effects of tobacco smoking on pulmonary drug-metabolizing enzymes: a case-control study on lung cancer patients.

Lung tissue specimens were taken during surgery from middle-aged men with either lung cancer (LC, n = 54) or a nonneoplastic lung disease (n = 20). Aryl hydrocarbon hydroxylase (AHH), 7-ethoxycoumarin O-deethylase (ECDE), epoxide hydrolase (EH), glutathione S-transferase (GST), and UDP-glucuronosyltransferase (UDPGT) activities and glutathione and malondialdehyde contents were determined in 12,000 X g supernatant fractions from nontumorous parenchymal tissues. Interindividual differences in enzyme activities ranged from 11- to 440-fold, and glutathione content varied by 17-fold; the values showed unimodal distributions. AHH, ECDE, EH, and UDPGT activities were significantly and positively correlated to each other; a significant negative correlation was found between GST and the other enzymes. A relationship between enzyme activity and number of cigarettes smoked (pack-years) was found only for GST. Ignoring detailed smoking histories in the 6-month period preceding surgery, no difference was found in enzyme activities or glutathione content between LC and nonneoplastic lung disease patients or between smokers and nonsmokers. However, when the number of days since stopping smoking was considered, in smokers a significant increase was found for AHH, EH, and UDPGT activities and a significant decrease was found for GST activity, as compared to nonsmokers. LC patients who had smoked until the day before surgery had higher activities of AHH, ECDE, EH, and UDPGT than nonsmokers, while GST activity was reduced by one-third. The activities of these enzymes returned to the basal level found in nonsmokers within 59 (AHH), 108 (EH), 67 (UDPGT), and 40 (GST) days. LC patients who were recent smokers (within 30 days prior to surgery) had significantly induced AHH and ECDE activities when compared with smoking nonneoplastic lung disease patients. These results show that pulmonary drug metabolism can be altered by tobacco smoking and that these effects can last 40 to 108 days after cessation of smoking. These new findings should be considered in studies on the role of carcinogen-metabolizing enzymes in determining susceptibility to lung cancer.

Weight gain and inflammation regulate aromatase expression in male adipose tissue, as evidenced by reporter gene activity.

Obesity and white adipose tissue (WAT) inflammation are associated with enhanced aromatization in women, but little is known about the regulation of aromatase (CYP19A1) gene expression in male WAT. We investigated the impact of weight gain and WAT inflammation on the regulation of CYP19A1 in males, by utilizing the hARO-Luc aromatase reporter mouse model containing a >100-kb 5'-region of the human CYP19A1 gene. We show that hARO-Luc reporter activity is enhanced in WAT of mice with increased adiposity and inflammation. Dexamethasone and TNFα, as well as forskolin and phorbol 12-myristate 13-acetate, upregulate hARO-Luc activity, suggesting the involvement of promoters I.4 and I.3/II. Furthermore, we show that diet enriched with antioxidative plant polyphenols attenuates WAT inflammation and hARO-Luc activity in obese males. In conclusion, our data suggest that obesity-associated WAT inflammation leads to increased peripheral CYP19A1 expression in males, and that polyphenol-enriched diet may have the potential to attenuate excessive aromatization in WAT of obese men.

Effects of in vitro UVA irradiation and PUVA treatment on membrane fatty acids and activities of antioxidant enzymes in human keratinocytes.

Human Keratinocytes (NCTC 2544) in culture were exposed to either plain ultraviolet A (UVA) irradiation or to 8-methoxypsoralen plus UVA (PUVA) treatment. Lipid peroxidation, activities of antioxidant enzymes, and percentage amounts of 14C-arachidonic acid in various cellular lipid subclasses and in the culture medium were measured. Both UVA irradiation and PUVA treatment induced significant changes in the distribution of arachidonic acid and increased the liberation of arachidonic acid from membrane phospholipids. At 24 h after either UVA irradiation or PUVA treatment the formation of thiobarbituric acid reactive material was significantly increased, whereas the amount of conjugated dienes was unaffected. The activities of the antioxidant enzymes, catalase and superoxide dismutase, were already significantly decreased at 0.5 h after UVA irradiation or PUVA treatment. The enzyme activities were partially restored during the following 24 h incubation. From the present study, we suggest that in keratinocytes both plain UVA irradiation and PUVA treatment induce changes in the distribution of membrane fatty acids and cause an impairment in the enzymic defense system against oxidative stress.

Induction of lipid peroxidation during steroidogenesis in the rat testis.

Free radical production and lipid peroxidation are potentially important mediators in testicular physiology and toxicology. The cytochrome P450 enzymes of the steroidogenic pathway are known to produce free radicals. The present study was conducted to elucidate in vivo the gonadotropin regulation of free radical-mediated lipid peroxidation and the antioxidative defense system in the rat testis. GnRH antagonist (Org 30276; 1 mg/kg BW) and testosterone [40-mm SILASTIC brand (Dow-Corning) capsules] treatments were used to suppress serum gonadotropin levels. As expected, serum LH decreased to a very low level, whereas serum FSH decreased only slightly. Testosterone treatment for 8 days decreased the levels of the peroxide-metabolizing enzymes, catalase, glutathione peroxidase (GSH-Px), and glutathione transferase (-44%, -24%, and -31%, respectively; P < 0.01 for all). These changes predominately reflect the interstitial tissue, in which catalase and GSH-Px activities were much higher than in the seminiferous tubules. Testicular CuZn or Mn superoxide dismutase activities, which were high in the seminiferous tubules, were not affected by gonadotropin suppression. The total peroxyl radical-trapping capacity of the testis, or its components, vitamin E and ubiquinol 9, were not affected either. Lipid peroxidation was decreased after 8-day treatment, as detected by diminished formation of conjugated dienes and fluorescent chromolipids (-30% and -19%, respectively; P < 0.05 for both). Similar results of decreasing catalase and GSH-Px activities were found after gonadotropin suppression with GnRH antagonist treatment for 2 days or testosterone treatment for 5 days. Substitution with hCG, alone or in combination with recombinant human FSH, reversed the changes in enzyme activities, whereas FSH alone had no effect. After 5-day testosterone treatment, catalase messenger RNA expression was studied by Northern hybridization, and it was observed to parallel the changes in enzyme activity. The site of free radical production was studied by separating interstitial tissue and seminiferous tubules 5 h after hCG injection. GSH-Px was induced by hCG only in the interstitial tissue (+28%; P< 0.01), supporting the hypothesis of free radical production during steroidogenesis. Aminoglutethimide, an inhibitor of the P450 cholesterol side-chain cleavage enzyme, induced extensive lipid peroxidation in the testis. Presumably, aminoglutethimide leads to leakage of free radicals from the P450 enzyme when substrate oxygenation is prevented. In conclusion, the present study suggests that physiological LH action in the rat testis causes lipid peroxidation and maintains high activities of peroxide-metabolizing enzymes in the interstitial tissue.(ABSTRACT TRUNCATED AT 400 WORDS)

Baseline diene conjugation in LDL lipids: an indicator of circulating oxidized LDL.

The wide acceptance of the diene conjugation-method in monitoring low-density lipoprotein (LDL) oxidation ex vivo has led to development of an assay, which measures the amount of baseline diene conjugation (BDC) in circulating LDL, and is an indicator of oxidized LDL in vivo. The LDL-BDC assay is based on precipitation of serum LDL with buffered heparin, and spectrophotometric determination of baseline level of conjugated dienes in lipids extracted from LDL. Compared to existing methods for oxidized LDL, LDL-BDC is fast and simple to perform. Chemical studies by HPLC and NMR have verified that LDL-BDC is a specific indicator of circulating mildly oxidized LDL. Validity of the assay is further indicated by strong correlation with the titer of autoantibodies against oxidized LDL. Clinical studies have shown that LDL-BDC is closely related to coronary, carotid, and brachial atherosclerosis. Moreover, several independent studies have demonstrated surprisingly strong associations between LDL-BDC and known atherosclerosis risk factors (obesity, physical inactivity, hypertension, diabetes, and arterial functions). Indeed, these studies seem to indicate that as an indicator of the risk of atherosclerosis LDL-BDC clearly exceeds sensitivity and specificity of the common lipid markers of atherosclerosis. It is concluded that LDL-BDC is a promising candidate in search for methods for the evaluation of in vivo LDL oxidation and the risk of atherosclerosis.

Lucigenin and linoleate enhanced chemiluminescent assay for superoxide dismutase activity.

The xanthine/xanthine oxidase dependent chemiluminescence was enhanced both by lucigenin and linoleate to create a sensitive, specific, and rapid chemiluminescent method for superoxide dismutase (SOD) activity determination. A pH optimum at around 10.0 was found both for the chemiluminescence and its inhibition by SOD. At this pH, a linear inhibition response to concentrations from 0.01 to 100 ng/ml of bovine Cu,Zn SOD could be established, with a 50% inhibitory concentration of 0.75 ng/ml. As little as 0.17 fmol of Cu,Zn SOD per test can be detected. With a slightly lower sensitivity, the method is operative at pH 7.4, too. Both Cu,Zn SOD and Mn SOD can be assayed. The rationale of the assay is in combining a superoxide-producing enzymatic system with linoleate amplification to enhance the sensitivity of the chemiluminescence to inhibition by SOD activity. Applicability of the method to biological samples was tested with a standard addition experiment.

Effects of acute prolonged exercise on-serum and LDL oxidation and antioxidant defences.

We investigated the acute effects of long-distance running on oxidation of lipids and antioxidant functions in LDL and serum. Eight trained male runners who participated in a 31-km run and 22 male keep-fit runners who participated in a marathon run were enrolled into the study. Venous blood samples were taken before and immediately after the exercise. There were no changes in LDL diene conjugation (LDL-DC) or LDL antioxidant potential (LDL-TRAP) during the exercises. Serum (S-) TRAP and S-alpha-tocopherol rose during the 31-km run (by 22%, p = .0005, and by 29%, p = .011, respectively), and during the marathon (by 16%, p = .0014, and by 7%, p = .031, respectively). S-DC rose during the 31-km run (by 9%, p = .0026), but not during the marathon (p = .14). Preexercise and postexercise S-alpha-tocopherol correlated positively with pre and postexercise S-TRAP in the marathon run (r = .473, 95% CI 0.064 to 0.746, and r = .524, 95% CI 0.131 to 0.774, respectively). Thus, the paradoxical exercise-associated increase in S-TRAP is, at least in part, explained by a simultaneous rise in S-alpha-tocopherol concentration. However, acute exercise does not change LDL-DC or LDL-TRAP concentrations.

Increased serum and low-density-lipoprotein antioxidant potential after antioxidant supplementation in endurance athletes.

We studied the effect of antioxidant supplementation on acute exercise-induced lipid peroxidation and antioxidant potential measured in serum and low-density-lipoprotein (LDL) samples. Eight endurance athletes repeated a 31-km running exercise twice with an interval of 4 wk. During the 4 wk before the runs, the subjects took in a single-blind randomized order either a combination of antioxidant supplements (the antioxidant trial; 294 mg vitamin E, 1000 mg vitamin C, and 60 mg ubiquinone daily) or placebo (the placebo trial). Venous blood samples were taken before and immediately after the 31-km run in both trials. Antioxidant supplementation raised the LDL antioxidant potential (TRAP) (40% and 30%, P = 0.0031), serum TRAP (9% and 10%, P = 0.0037), and serum alpha-tocopherol concentration (by 59% and 66%, P = 0.0004) in both pre- and postexercise samples, respectively. The supplementation did not, however, affect the concentration of LDL diene conjugation (DC) or of serum DC. Physical exercise increased serum DC (by 18% and 10%, P = 0.0004) but not LDL-DC, and the quantity of the increment of serum DC was not affected by antioxidant intervention. The major cause for the increased LDL-TRAP and serum TRAP after antioxidant supplementation is apparently the elevation of the serum alpha-tocopherol concentration.

Activities of antioxidant enzymes and lipid peroxidation in endometrial cancer.

Antioxidant enzyme activities and lipid peroxidation were analysed in normal endometrium and endometrial cancer tissues from Finnish and Japanese patients. The catalase and glutathione peroxidase activities of normal endometrium were significantly lower in Finns than in Japanese. Lipid peroxidation was slightly higher in endometrial cancer as compared with normal endometrium both in the Finns and in the Japanese. When cancer tissues were compared with normal endometrium both in Finns and Japanese the activity of superoxide dismutase was significantly lower in cancer tissue than in normal endometrium. In Finns glutathione S-transferase activity was also lower in endometrial cancer tissue than in normal endometrium, and a similar tendency was also found in Japanese. This study suggests that endometrial cancer tissue is associated with an impaired enzymic antioxidant defence system.

Reduced mildly oxidized LDL in young female athletes.

We investigated the effect of physical activity and sports participation on LDL oxidation in vivo and on lipid risk factors in 183 teenage girls (9-15 years): 64 gymnasts, 61 runners, and 58 controls. Oxidized LDL was measured as baseline levels of conjugated dienes in LDL lipids (ox-LDL). The gymnasts had a 15% lower ratio of LDL conjugated dienes to LDL cholesterol (ox-LDL:LDL ratio, P = 0.0052) compared to controls, and the difference persisted when the body mass index was included as a covariate (ANCOVA, P = 0.013). Also, the gymnasts had a 12% higher ratio of HDL cholesterol to total cholesterol than the controls (ANCOVA, P = 0.046). There were no differences in the other common lipid risk factors between the groups. The ox-LDL:LDL ratio correlated negatively with HDL cholesterol (r = -0.23, P=0.0021) and with physical activity METs (multiples of resting metabolic rate) (r = -0.21, P=0.0040). Our study strengthens the evidence that the atherogenic risk is influenced favourably by physical exercise and sporting activities as early as in adolescents. This risk reduction is associated with lower mildly oxidized LDL in adolescent girls.

Constantly low HDL-cholesterol concentration relates to endothelial dysfunction and increased in vivo LDL-oxidation in healthy young men.

To test the hypothesis that low HDL-C concentration interferes with vascular endothelial function and lipoprotein oxidation, we measured endothelium-dependent flow mediated dilatation (FMD, %) of the brachial artery in young men (n=20) classified prospectively into two groups on basis of having either low or high HDL-C concentration over the past 2 years. As an estimate of in vivo low-density lipoprotein oxidation (ox-LDL), we measured LDL diene conjugation. FMD was present in the group with high HDL-C concentration, but impaired in the group with low HDL-C (5.5+/-3.2 vs 0.2+/-1.2%, P<0. 001). The group with high HDL-C level had significantly lower levels of ox-LDL compared to low HDL-C group (18.0+/-1.8 vs 22.9+/-4.4, P

Oxidized LDL and thickness of carotid intima-media are associated with coronary atherosclerosis in middle-aged men: lower levels of oxidized LDL with statin therapy.

We investigated the relation between serum lipids including oxidized LDL and the severity of coronary atherosclerosis. Serum lipids and oxidized LDL was measured in 62 men (33-66 years), who underwent diagnostic coronary angiography and sonography to measure the carotid intima-media thickness. LDL oxidation was found in chemical analyses to be due to conjugated fatty acids in cholesteryl esters and triglycerides. Regression analysis indicated that the carotid intima-media thickness and the ratio of LDL diene conjugation to LDL cholesterol (the ox-LDL:LDL ratio) were the only factors associated independently with the severity of coronary atherosclerosis. The patients with multi-vessel disease who did not use lipid lowering therapy had a 50% thicker carotid intima media (P = 0.030) and a 41% higher ox-LDL:LDL ratio (P = 0.020) than patients with normal vessels. Further, patients with multi-vessel disease on statin therapy had a 24% lower ox-LDL:LDL ratio than the subjects with multi-vessel disease who did not use lipid lowering drugs (P = 0.027), although the concentration of LDL cholesterol did not differ between the groups. This study supports the hypothesis that lipid oxidation plays a role in the development of atherosclerosis.

Reduced myocardial flow reserve relates to increased carotid intima-media thickness in healthy young men.

Increased carotid artery wall thickness and lipoprotein oxidation are key early events in atherosclerosis. To test the hypothesis that reduced myocardial flow reserve is a marker of subclinical atherosclerosis, we examined the relationships between flow reserve and carotid artery intima-media thickness (IMT) in young men free from coronary heart disease. Basal and dipyridamole stimulated coronary blood flow was measured using positron emission tomography (PET) in 55 healthy men aged 36+/-4 years. Myocardial flow reserve was calculated as the ratio of stimulated flow to basal flow. The mean carotid artery IMT was measured using high-resolution ultrasound. Oxidised LDL was measured as baseline LDL diene conjugation. Myocardial flow reserve decreased across the quartiles of increasing IMT (P=0.006), and was 5.2+/-1.9 in the lowest quartile for IMT and 3.7+/-1.2 in the highest (P=0.04, I vs. IV quartile). In univariate analysis, oxidised LDL correlated inversely with flow reserve (r=-0.35, P=0.01) and directly with IMT (r=0.51, P<0.001). The association between flow reserve and IMT remained significant (P< or =0.01) in multivariate regression model including age, blood pressure, left ventricular mass, ox-LDL, total cholesterol, HDL-cholesterol and triglycerides as covariates. These data support the concept that reduced myocardial flow reserve reflects subclinical atherosclerosis in asymptomatic subjects, and suggest that increased lipoprotein oxidation is directly related to early structural and functional atherosclerotic vascular changes.

Association of low-density lipoprotein oxidation to abnormal electrocardiographic late potentials.

In vivo oxidation of low-density lipoprotein is shown to be significantly related to another risk factor for coronary atherosclerosis, abnormal electrocardiographic late potentials, in clinically healthy pilots. Because both of these variables have been also associated with cardiac arrhythmogenic action, together they may improve the identification of patients at risk of ventricular tachyarrhythmias.