Differential diagnostics of polymyalgia rheumatica in a university hospital in Finland.

OBJECTIVES: Diagnosing polymyalgia rheumatica (PMR) can be difficult as many conditions present with similar symptoms and findings. This study aimed to analyse how often the diagnosis of PMR changes during follow-up in a university hospital setting and to determine the most common clinical conditions initially misdiagnosed as PMR. METHOD: All patients with a new primary diagnosis of PMR on at least one visit during the years 2016-2019 were identified from the hospital discharge register of Turku University Hospital, Finland. A diagnosis of PMR was confirmed if the patient met at least one of the five classification criteria, complete clinical follow-up (median 34 months) was compatible with PMR, and no other diagnosis better explained their condition. RESULTS: Of the patients initially diagnosed with PMR, 65.5% were considered to have PMR after further evaluation and clinical follow-up. The most common conditions initially diagnosed as PMR were inflammatory arthritides (34.9%), degenerative or stress-related musculoskeletal disorders (13.2%), infection (9.3%), malignancy (9.3%), giant cell vasculitis (6.2%) and other vasculitis (6.2%), and a wide range of other less common diseases. The diagnosis of PMR remained in 81.3% of patients who fulfilled the 2012 American College of Rheumatology/European League Against Rheumatism PMR classification criteria and in 45.5% of patients who did not. CONCLUSIONS: Diagnosing PMR is challenging, even in a university hospital. One-third of the initial diagnoses of PMR changed during further evaluation and follow-up. There is a substantial risk of misdiagnosis, especially in patients with atypical presentation, and the differential diagnoses of PMR must be considered carefully.

Real-world registry-based study on apremilast use in psoriasis and psoriatic arthritis in Finland.

OBJECTIVES: This study assessed the position of apremilast in the treatment pathway of psoriasis (PsO) and psoriatic arthritis (PsA) in Finnish clinical practice, compared the characteristics of apremilast and biologic therapy users, evaluated persistence with apremilast and identified factors influencing treatment discontinuation. METHOD: This retrospective study used data from Finnish national health registries. The target group was identified based on L40* diagnosis and medication records between 2015 and 2018. Treatment persistence was analysed using Kaplan-Meier curves and Cox regression. RESULTS: Of eligible patients (PsO 31 202; PsA 12 386), 1% (n = 471) used apremilast and 10% (n = 4214) biologics, apremilast users being older (mean age 55.9 vs 52.4 years, p < 0.001) with a higher Charlson comorbidity score (0.71 vs 0.54, p < 0.001). Most patients switched to apremilast from conventional synthetic therapy (PsO 75%; PsA 76%); 47% of patients remained on apremilast during the observation period (PsO 58%; PsA 42%). Most patients discontinuing apremilast switched to biologics (PsO 51%; PsA 51%). Apremilast persistence increased with age (p = 0.042) and was higher in PsO than in PsA (median 14 vs 11 months; p = 0.005). Compared to prior conventional synthetic therapy, prior biologic therapy decreased persistence (hazard ratio for discontinuation 2.15, 95% confidence interval 1.42-3.25). CONCLUSION: In Finnish clinical practice, apremilast is mainly used between conventional synthetic therapy and biologics, with at least as high treatment persistence as reported in previous studies. Apremilast users were older with higher comorbidity burden than biologics users.

The validity of rheumatoid arthritis diagnoses in Finnish biobanks.

OBJECTIVE: The aim of this study was to determine the validity of rheumatoid arthritis (RA) diagnoses in patients participating in Finnish biobanks. METHOD: We reviewed the electronic medical records of 500 Finnish biobank participants: 125 patients with at least one visit with a diagnosis of seropositive RA, 125 patients with at least one visit with a diagnosis of seronegative RA, and 250 age- and gender-matched controls. The patients were chosen from five different biobank hospitals in Finland. A rheumatologist reviewed the medical records to assess whether each patients' diagnosis was correct. The diagnosis was compared with the diagnostic codes in the Finnish Care Register for Health Care (CRHC) and special reimbursement data of the Social Insurance Institution of Finland. RESULTS: The positive predictive value (PPV) of CRHC diagnosis of RA (for seropositive and seronegative RA combined) was 0.82. For patients with a special reimbursement for anti-rheumatic medications for RA, the PPV was 0.89. The PPV was higher in patients with more than one visit. For one, two, five, and 10 visits, the PPV was 0.82, 0.85, 0.89, and 0.90, respectively, and for patients who also had the special reimbursement, the PPV was 0.89, 0.91, 0.93, and 0.94 for one, two, five, and 10 visits, respectively. In patients positive for anti-citrullinated protein antibodies, the PPV was 0.98. CONCLUSION: These results demonstrate that the validity of RA diagnoses in Finnish biobanks was good and can be further improved by including data on special reimbursement for medication, number of visits, and serological data.

The validity of systemic sclerosis diagnoses in two university hospitals in Finland.

OBJECTIVE: This study aimed to determine the validity of systemic sclerosis (SSc) diagnoses in Finnish university hospitals. METHOD: Electronic medical records for 385 patients with a registered diagnosis of SSc (ICD-10 code M34) in two Finnish university hospitals from 2008 to 2018 were reviewed to assess whether each patient's diagnosis was correct. RESULTS: The positive predictive value (PPV) of a diagnosis of SSc was 0.66 when fulfilment of the 2013 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria for SSc was required; the PPV was 0.75 if patients meeting the 2001 LeRoy and Medsger classification criteria for early SSc were also included. When a diagnosis of SSc was made in a department of rheumatology, the PPV was 0.78, and 0.90 when including patients with early SSc. For the more specific diagnosis of limited cutaneous SSc (lcSSc), the PPV was 0.80, and 0.95 when including early SSc. For an lcSSc diagnosis made in rheumatology, the PPV was 0.81, and 0.97 with early SSc included. CONCLUSION: These results demonstrate that in these two Finnish university hospitals, the diagnostic validity of a diagnosis of SSc was good if it was diagnosed in the department of rheumatology. For a more specific diagnosis of lcSSc, the most prevalent form of SSc in Finland, the validity was good even when registered in any department.

The reliability of radiation dose display of a computed tomography scanner.

BACKGROUND: Internationally, the typical allowed difference between the measured radiation dose and dose reported by a computed tomography (CT) scanner is ±20 %. The objective is to describe a method in order to analyse this difference in a CT scanner in the Emergency Department of Kanta-Häme Central Hospital, and to calculate a correction factor for more comparable radiation dose values in further studies. METHODS: Ten intra-day radiation dose measurements were performed with undisturbed setting. Measurement reports on differences between measured and displayed dose were gathered from the vendor maintenance and supervising authority over a 12-year period. Additionally, two in-house measurements were made. A total of 18 datapoints were collected, with some differences in measurement settings. Data were also analysed against imaging parameters, ambient air pressure and time to identify trends or associations in the variation of the discrepancy. RESULTS: Measured doses were generally lower than displayed doses. Differences between displayed and measured doses varied between -3.46 and -0.10 %, with a mean of -1.26 % in the intra-day measurements, and between +4.65 and -17.3 %, with a mean of -7.53 % in the long-term data. There were no trends nor connections in the variations. CONCLUSION: Since the acceptable difference between the radiation dose display and the measured dose is relevant, the average difference for every CT scanner should be determined before radiation dose studies, especially when comparing multiple scanners.

Stroke recurrence in patients with atrial fibrillation: concomitant carotid artery stenosis doubles the risk.

BACKGROUND AND PURPOSE: Atrial fibrillation (AF) and significant carotid artery stenosis (CAS) often coexist in patients with acute stroke but whether CAS affects the stroke recurrence rate in anticoagulated AF patients is largely unknown. The effect of concomitant CAS on both short- and long-term prognosis after stroke in patients with AF was evaluated. METHODS: The multicentre, retrospective FibStroke registry included AF patients with an ischaemic stroke or transient ischaemic attack (TIA) during 2003-2012. In this sub-study, 165 AF patients with ischaemic stroke or TIA with significant (>50%) CAS (CAS group) and 734 AF patients without CAS (non-CAS group) were identified. The median follow-up time after an index event was 3.5 (interquartile range 3.9) years. Long-term stroke recurrence rate, 30-day mortality, CHA2 DS2 -VASc score, other risk factors and the use and intensity of anticoagulation were assessed. RESULTS: The recurrence rate of ischaemic stroke (21.2% vs. 12.7%, P = 0.005, 8.1 vs. 3.6 events per100 follow-up years) was significantly higher in CAS patients compared to the non-CAS group despite similar anticoagulation/antithrombotic therapy. CAS patients had higher mean CHA2 DS2 -VASc scores than non-CAS patients (4.3 vs. 3.3, P < 0.001). However, in a multivariate analysis CAS was shown to be an independent risk factor for stroke recurrence (hazard ratio 2.02, 95% confidence interval 1.37-3.01, P = 0.001). The 30-day all-cause mortality was significantly higher in CAS patients (7.9% vs. 1.9%, P < 0.001) and CAS was an independent risk factor also for 30-day mortality (odds ratio 3.34, 95% confidence interval 1.51-7.38, P = 0.003). CONCLUSIONS: In patients with AF, concomitant CAS was an independent risk factor for both long-term stroke recurrence and 30-day mortality.

Prompt impact of first prospective statin mega-trials on postoperative lipid management of CABG patients: a 20-year follow-up in a single hospital.

BACKGROUND: The long-term success of coronary artery bypass grafting (CABG) depends on secondary prevention. Vast evidence provided by the results of cholesterol mega-trials over two decades has shown that effective reduction of LDL cholesterol improves the prognosis of patients with coronary heart disease. However, the implementation of these results into the clinical practice has turned out to be challenging. We analysed how the information derived from clinical statin trials and international recommendations affected the local treatment practices of dyslipidaemia of CABG patients during a 20-year time period. METHODS: The cohort includes all CABG patients (n = 953) treated in Kanta-Häme Central Hospital during the time period 1990-2009. At the postoperative visits in the cardiology outpatient clinic, each patient's statin prescription was recorded, and blood lipids were determined. RESULTS: During 1990-1994, 12.0 % of patients were on statins and during the following 5-year time periods the proportion was 57.2, 82.2 and 96.8 %, respectively. During the 20-year observation period (1990-2009), the effective statin dose increased progressively during these 5-year periods up to 36-fold, while the mean concentration of LDL cholesterol decreased from 3.7 to 2.1 mmol/l and that of apolipoprotein B from 1.3 to 0.8 g/l. In the very last year of follow-up, the mean concentrations of LDL-C and apoB were 1.83 mmol/l and 0.78 g/l, respectively. The most prominent increase in statin use and dosage took place during 1994-1996 and 2003-2005, respectively. CONCLUSIONS: Among CABG patients the lipid-lowering efficacy of statin therapy improved dramatically since 1994. This progress was accompanied by significant and favourable changes of lipid and apolipoprotein-B values. This study shows that it is possible to effectively improve lipid treatment policy once the results of relevant trials are available, and that this may happen even before international or national guidelines have been updated.

Underuse of anticoagulation in stroke patients with atrial fibrillation--the FibStroke Study.

BACKGROUND AND PURPOSE: Current guidelines recommend oral anticoagulation (OAC) for patients with atrial fibrillation (AF) and increased risk of thromboembolic events. The reasons for not using OAC in AF patients suffering stroke or transient ischaemic attack (TIA) were assessed. METHODS: This retrospective registry included 3404 patients with previously diagnosed AF who suffered a total of 2955 ischaemic strokes and 895 TIAs during 2003-2012. RESULTS: A CHA2DS2-VASc score ≥2 and a CHADS2 score ≥2 was observed in 3590 (93.2%) and in 2784 (72.3%) of the events, respectively. Of the high-risk patients (CHADS2 ≥2) only 55.1% were on OAC before the onset of stroke or TIA. The most frequently documented reasons for withholding OAC were infrequent paroxysms of AF (14%), previous bleeding episodes (13%) and the patient's decline/independent discontinuation of treatment (9%). Moreover, patients with paroxysmal AF (40% using OAC), previous bleeding (26% using OAC) and alcohol abuse (30% using OAC) were using OAC significantly less often than patients without these characteristics. A significant increase in the proportion of high-risk patients using OAC from 49% in 2003 to 65% in 2012 was seen. CONCLUSIONS: Underuse of anticoagulation is a common contributor to ischaemic strokes and TIA episodes in patients with AF. Infrequent AF episodes, previous bleeds, patient preference and alcohol abuse were the most common reasons for not using OAC.

Comparison of metabolic syndrome subjects with and without erectile dysfunction - levels of circulating oxidised LDL and arterial elasticity.

BACKGROUND: Erectile dysfunction (ED) is believed to be an early sign of systemic cardiovascular disease (CVD). Elevated levels of circulating oxidised LDL (oxLDL) and impairment of arterial elasticity have been reported to predict future cardiovascular events. We studied whether metabolic syndrome subjects with and without erectile dysfunction differ in circulating levels of oxLDL and arterial elasticity. Furthermore, we assessed whether the presence of ED acts as a clinical marker of underlying atherosclerotic process. METHODS: Seventy men with metabolic syndrome, aged 35-60 years, completed the International Index of Erectile Function questionnaire. Subject was considered to have erectile dysfunction if a sum of the questions 1-5 and 15 was ≤ 25. OxLDL was assessed by an ELISA immunoassay and arterial elasticity by a noninvasive radial artery tonometer (HDI/PulseWave™CR-2000). RESULTS: Large arterial elasticity index was significantly lower among subjects with erectile dysfunction compared with those without, 15.0 ± 3.2 ml/mmHg × 10 and 18.0 ± 3.7 ml/mmHg × 10, respectively (p = 0.001). The presence of erectile dysfunction associated with impaired large arterial elasticity, independently of traditional CVD risk factors. Reduction in arterial elasticity was also found among those with erectile dysfunction and less than 5% risk of cardiovascular death during 10 years by the SCORE. There were no significant differences in small arterial elasticity or oxLDL levels. CONCLUSION: Erectile dysfunction truly seems to be a marker of systemic vascular disease. Aggressive primary prevention should be considered for patients with metabolic syndrome and vasculogenic ED.

Ballistocardiogaphic studies with acceleration and electromechanical film sensors.

The purpose of this research is to demonstrate and compare the utilization of electromechanical film (EMFi) and two acceleration sensors, ADXL202 and MXA2500U, for ballistocardiographic (BCG) and pulse transit time (PTT) studies. We have constructed a mobile physiological measurement station including amplifiers and a data collection system to record the previously mentioned signals and an electrocardiogram signal. Various versions of the measuring systems used in BCG studies in the past are also presented and evaluated. We have showed the ability of the EMFi sensor to define the elastic properties of the cardiovascular system and to ensure the functionality of the proposed instrumentation in different physiological loading conditions, before and after exercise and sauna bath. The EMFi sensor provided a BCG signal of good quality in the study of the human heart and function of the cardiovascular system with different measurement configurations. EMFi BCG measurements provided accurate and repeatable results for the different components of the heart cycle. In multiple-channel EMFi measurements, the carotid and limb pulse signals acquired were detailed and distinctive, allowing accurate PTT measurements. Changes in blood pressure were clearly observed and easily determined with EMFi sensor strips in pulse wave velocity (PWV) measurements. In conclusion, the configuration of the constructed device provided reliable measurements of the electrocardiogram, BCG, heart sound, and carotid and ankle pulse wave signals. Attached EMFi sensor strips on the neck and limbs yield completely new applications of the EMFi sensors aside from the conventional seat and supine recordings. Higher sensitivity, ease of utilization, and minimum discomfort of the EMFi sensor compared with acceleration sensors strengthen the status of the EMFi sensor for accurate and reliable BCG and PWV measurements, providing novel evaluation of the elastic properties of the cardiovascular system.

Ballistocardiography in sitting and horizontal positions.

The purpose of this study is to examine the effect of posture in the sitting and supine positions on ballistocardiography (BCG) measurements by using EMFi (electromechanical film) sensors. The experiment, measuring the subject's electrocardiography (ECG), BCG and carotid pulse (CP) signal, was repeated in the sitting and different horizontal positions. Additionally, the duration and the amplitudes of the BCG and CP signal components were studied. Certain properties of BCG differed significantly in the sitting and horizontal positions. Amplitudes of measured signals were larger, and time intervals were greater in the sitting position compared to the supine position. Thus, posture significantly influences cardiac performance evaluated by BCG. Sitting and supine positions are clearly distinguishable in the BCG signal. This provides new methods for evaluation of the hemodynamic changes induced by the body position.

Erectile dysfunction as a risk factor for coronary heart disease: implications for prevention.

There is now mounting evidence that erectile dysfunction (ED) is an early predictor of coronary heart disease (CHD). Men presenting with ED but no other cardiovascular symptoms provide an opportunity for the treating physician to test for asymptomatic CHD and to reduce CHD risk factors.

Comparison of LDL trap assay to other tests of antioxidant capacity; effect of vitamin E and lovastatin treatment.

Oxidized low density lipoprotein (LDL) has a major impact in the development of atherosclerosis. Risk for oxidative modification of LDL is usually determined indirectly by measuring the capability of LDL to resist radical insult. We compared three different methods quantifying the antioxidative capacity of LDL ex vivo in dyslipidemic patients with coronary heart disease. Plasma samples were obtained from two double-blinded cross-over trials. The duration of all interventions (placebo, lovastatin 60 mg/day, RRR-alpha-tocopherol 300 mg/day and lovastatin + RRR-alpha-tocopherol combined) was 6 weeks. The total radical capturing capacity of LDL (TRAP) in plasma was determined using 2,2-azo-bis(2,4-dimethyl-valeronitrile) (AMVN) -induced oxidation, and measuring the extinction time of chemiluminescence. TRAP was compared to the variables characterizing formation of conjugated dienes in copper-induced oxidation. Also the initial concentrations and consumption times of reduced alpha-tocopherol (alpha-TOH) and ubiquinol in AMVN-induced oxidation were determined. Repeatability of TRAP was comparable to that of the lag time in conjugated diene formation. Coefficient of variation within TRAP assay was 4.4% and between TRAP assays 5.9%. Tocopherol supplementation produced statistically significant changes in all antioxidant variables except those related to LDL ubiquinol. TRAP increased by 57%, the lag time in conjugated diene formation by 34% and consumption time of alpha-TOH by 88%. When data of all interventions were included in the analyses, TRAP correlated with the lag time (r = 0.75, p < 10(-6)), with LDL alpha-TOH (r = 0.50, p < 0.001) and with the consumption time of alpha-TOH (r = 0.58, p < 0.0001). In the baseline data, the associations between different antioxidant variables were weaker. TRAP correlated with the lag time (r = 0.55, p < 0.001) and alpha-TOH consumption time (r = 0.48, p < 0.05), and inversely with apolipoprotein Al (r = -0.51, p < 0.05). Lag time at the baseline did not correlate with ubiquinol or tocopherol parameters, or with any plasma lipid or lipoprotein levels analyzed. Lovastatin treatment did not significantly affect the antioxidant capacity of LDL. In conclusion, TRAP reflects slightly different properties of LDL compared to the lag time. Thus, LDL TRAP assay may complement the other methods used to quantify the antioxidant capacity of LDL. However, TRAP and the lag time react similarly to vitamin E supplementation.

Effects of lovastatin therapy on susceptibility of LDL to oxidation during alpha-tocopherol supplementation.

A randomized, double-masked, crossover clinical trial was carried out to evaluate whether lovastatin therapy (60 mg daily) affects the initiation of oxidation of low density lipoprotein (LDL) in cardiac patients on alpha-tocopherol supplementation therapy (450 IU daily). Twenty-eight men with verified coronary heart disease and hypercholesterolemia received alpha-tocopherol with lovastatin or with dummy tablets in random order. The two 6-week, active-treatment periods were preceded by a washout period of at least 8 weeks. The oxidizability of LDL was determined by 2 methods ex vivo. The depletion times for LDL ubiquinol and LDL alpha-tocopherol were determined in timed samples taken during oxidation induced by 2, 2-azobis(2,4-dimethylvaleronitrile). Copper-mediated oxidation of LDL isolated by rapid density-gradient ultracentrifugation was used to measure the lag time to the propagation phase of conjugated-diene formation. alpha-Tocopherol supplementation led to a 1.9-fold concentration of reduced alpha-tocopherol in LDL (P<0.0001) and to a 2.0-fold longer depletion time (P<0.0001) of alpha-tocopherol compared with determinations after the washout period. A 43% prolongation (P<0.0001) was seen in the lag time of conjugated-diene formation. Lovastatin decreased the depletion time of reduced alpha-tocopherol in metal ion-independent oxidation by 44% and shortened the lag time of conjugated-diene formation in metal ion-dependent oxidation by 7%. In conclusion, alpha-tocopherol supplementation significantly increased the antioxidative capacity of LDL when measured ex vivo, which was partially abolished by concomitant lovastatin therapy.

Ubiquinone supplementation during lovastatin treatment: effect on LDL oxidation ex vivo.

A randomized, double-masked, placebo-controlled cross-over trial was carried out to evaluate whether ubiquinone supplementation (180 mg daily) corrects impaired defence against initiation of oxidation of low density lipoprotein (LDL) related to effective (60 mg daily) lovastatin treatment. Nineteen men with coronary heart disease and hypercholesterolemia received lovastatin with or without ubiquinone during 6-week periods after wash-out. The depletion times for LDL ubiquinol and reduced alpha-tocopherol were determined during oxidation induced by 2,2-azobis(2,4-dimethylvaleronitrile) (AMVN). Copper-mediated oxidation of LDL isolated by rapid density-gradient ultracentrifugation was used to measure the lag time to the propagation phase of conjugated diene formation. Compared to mere lovastatin therapy, ubiquinone supplementation lead to a 4.4-fold concentration of LDL ubiquinol (P < 0.0001). In spite of the 49% lengthening in depletion time (P < 0.0001) of LDL ubiquinol, the lag time in copper-mediated oxidation increased only by 5% (P = 0.02). Ubiquinone loading had no statistically significant effect on LDL alpha-tocopherol redox kinetics during high radical flux ex vivo. The faster depletion of LDL ubiquinol and shortened lag time in conjugated diene formation during high-dose lovastatin therapy may, at least partially, be restored with ubiquinone supplementation. However, the observed improvement in LDL antioxidative capacity was scarce, and the clinical relevance of ubiquinone supplementation during statin therapy remains open.

Apolipoprotein A-IFIN (Leu159-->Arg) mutation affects lecithin cholesterol acyltransferase activation and subclass distribution of HDL but not cholesterol efflux from fibroblasts.

We showed earlier that the apolipoprotein A-I Leu159-->Arg mutation (apoA-IFin) results in dominantly inherited hypoalphalipoproteinemia. In the present study we investigated the effect of the apoA-IFin mutation on lipoprotein profile, apoA-I kinetics, lecithin:cholesterol acyltransferase (LCAT) activation, and cholesterol efflux in vitro. Carriers (n = 9) of the apoA-IFin mutation exhibited several lipoprotein abnormalities. The serum HDL cholesterol level was diminished to 20% of normal, and nondenaturing gradient gel electrophoresis of HDL showed disappearance of particles at the 9.0- to 12-nm size range (HDL2-type) and the presence of small 7.8- to 8.9-nm (mostly HDL3-type) particles only. HDL3-type particles from both the mutation carriers and nonaffected family members were similarly converted to large, HDL2-type particles by phospholipid transfer protein in vitro. Studies on apoA-I kinetics in four affected subjects favored accelerated catabolism of apoA-I. Experiments with reconstituted proteoliposomes showed that the capacity of apoA-IFin protein to activate LCAT was reduced to 40% of that of the wild-type apoA-I. The impact of the apoA-IFin protein on cholesterol efflux was examined in vitro using [3H]cholesterol-loaded human fibroblasts and three different cholesterol acceptors: (1) total HDL, (2) total apoA-I combined with phospholipid, and (3) apoA-I isoform (apoA-IFin or wild-type apoA-I isoform 1) combined with phospholipid. ApoA-IFin did not impair phospholipid binding or cholesterol efflux from fibroblasts to any of the acceptors used. Only one of the nine apoA-IFin carriers appears to have evidence of clinically manifested atherosclerosis. In conclusion, although the apoA-IFin mutation does not alter the properties of apoA-I involved in promotion of cholesterol efflux, its ability to activate LCAT in vitro is defective. In vivo, apoA-IFin was found to be associated with several lipoprotein composition rearrangements and increased catabolism of apoA-I.

Enhanced oxidizability of ubiquinol and alpha-tocopherol during lovastatin treatment.

A double-blinded, placebo-controlled cross-over trial was carried out with 27 hypercholesterolemic men with coronary heart disease. During the 6-week treatment period lovastatin (60 mg/day) decreased fasting serum LDL cholesterol by 45%, LDL phosphorus by 38% and apoB by 33%. Ubiquinol content diminished by 13% as measured per LDL phosphorus. When LDL was oxidized ex vivo with AMVN both LDL ubiquinol and alpha-tocopherol were exhausted faster after lovastatin treatment compared to placebo, by 24% (P < 0.005) and 36% (P < 0.0001), respectively. Lag time in copper-induced oxidation of LDL decreased by 7% (P < 0.01). This suggests diminished antioxidant-dependent resistance of LDL to the early phase of oxidative stress.