Background-Cardiovascular disease (CVD) is overrepresented in patients with systemic lupus erythematosus (SLE). We determined the prevalence of traditional and nontraditional risk factors for CVD in SLE patients with and without CVD compared with controls. Methods and Results-Twenty-six women (aged 52Ϯ8.2 years) with SLE and a history of CVD (SLE cases) were compared with 26 age-matched women with SLE but without manifest CVD (SLE controls) and 26 age-matched population-based control women (population controls). Common carotid intima-media thickness (IMT) was measured by B-mode ultrasound as a surrogate measure of atherosclerosis. SLE cases had increased IMT compared with SLE controls (Pϭ0.03) and population controls (Pϭ0.001), whereas IMT of SLE controls did not differ from population controls. SLE cases had raised plasma concentrations of circulating oxidized LDL (OxLDL; Pϭ0.03), as measured by the monoclonal antibody EO6, and autoantibodies to epitopes of OxLDL (PϽ0.001); dyslipidemia with raised triglycerides (PϽ0.001) and lipoprotein(a) (Pϭ0.002) and decreased HDL-cholesterol concentrations (Pϭ0.03); raised ␣-1-antitrypsin (Pϭ0.002), lupus anticoagulant (Pϭ0.007), and homocysteine levels (Pϭ0.03); more frequent osteoporosis (Pϭ0.03); and a higher cumulative prednisolone dose (Pϭ0.05) compared with SLE controls. Disease duration, smoking, blood pressure, body mass index, and diabetes mellitus did not differ significantly between the groups. Conclusions-A set of distinct CVD risk factors separate SLE cases from SLE controls and population controls. If confirmed in a prospective study, they could be used to identify SLE patients at high risk for CVD in order to optimize treatment.

The effects of age and gender on heart rate variability as measured by spectral and time domain analysis of 24 h ECG recordings were evaluated in 101 healthy subjects, 49 men and 52 women (20-69 years of age). In the frequency domain, total power, very low-frequency power, low-frequency power and high-frequency power were negatively correlated to age (P < 0.001 for all variables). Total power decreased by 30% between 20-29 and 60-69 years of age. In the time domain, SDNN-index, the mean of the standard deviations of all normal R-R intervals for all 5 min segments of a 24 h ECG recording, was negatively correlated to age (P < 0.001). Total power, very low-frequency power, low-frequency power and the low-frequency/high-frequency ratio were lower in women (P < 0.05, P < 0.05, P < 0.01 and P < 0.01), although the absolute differences were much smaller than for age. There was a pronounced circadian variation; at night total power increased in all age groups (P < 0.01). The results show that age, and to a lesser degree gender, are important determinants of heart rate variability in healthy subjects. Heart rate variability is a valuable tool for risk stratification in cardiovascular disease, but the physiological effects of ageing, with diminishing heart rate variability in older age groups, must also be taken into account.

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Patients with systemic lupus erythematosus (SLE) are at high risk of cardiovascular disease (CVD). Tumour necrosis factor-alpha (TNF-alpha) has been implicated in the pathophysiological processes of both SLE and CVD. This study focuses on the role of TNF-alpha and its soluble receptors in SLE-related CVD. In summary, 26 women (52 +/- 8.2 years) with SLE and a history of CVD (SLE cases) we compared with 26 age-matched women with SLE and no clinical manifestations of CVD (SLE controls) and 26 age-matched population-based control women (population controls). Plasma concentrations of circulating TNF-alpha, TNF-alpha receptor 1 (sTNFR1) and TNF-a receptor 2 (sTNFR2) were determined by ELISA. TNF-alpha, sTNFR1 and sTNFR2 were raised in SLE cases as compared to SLE controls (P = 0.009; P = 0.001; P = 0.001, respectively), and SLE controls had higher levels than population controls (P = 0.001; P = 0.02; P = 0.001, respectively). Exclusively in the SLE case group there was a striking positive correlation between TNF-alpha and plasma triglycerides (r = 0.57, P < 0.002), VLDL triglycerides (r = 0.54, P = 0.004) and VLDL cholesterol (r = 0.58, P = 0.002). Furthermore, TNF-alpha correlated with the waist-hip ratio but not with estimated insulin resistance. TNF-alpha may thus be a major factor in SLE-related CVD acting both by contributing to hypertriglyceridaemia and by promoting atherosclerosis-related inflammation. sTNFR1 and sTNFR2 are strongly associated with CVD in SLE but their exact roles in disease development remain to be elucidated.

Background and Purpose-An increase in intima-media thickness (IMT) in the common carotid artery (CCA) is commonly used as a marker of atherosclerosis. The purpose of this study was to investigate the relationship between IMT in the CCA and atherosclerosis in the carotid bifurcation. Methods-182 consecutive patients (mean age, 67 years) referred for carotid duplex scanning were included. We measured IMT and classified plaques by means of a high-resolution ultrasound technique. Results-IMT was correlated to age, male gender, ischemic heart disease, and presence of plaques or stenoses in any of the carotid bifurcations. In men, IMT was larger on the left than on the right side. Plaques were seen in 163 carotid bifurcations, in 45 of these with Ͼ50% stenosis. On the left side but not on the right, there was a correlation between IMT in the CCA and presence of plaques or stenoses in the carotid bifurcation. Echogenic plaques were more common than echolucent, but the latter caused significantly more stenoses. No relationship was found between plaque echogenicity and IMT. Conclusions-IMT of the CCA is correlated to the degree of atherosclerosis in the carotid bifurcations in general and on the left side also to the presence of plaques or stenoses in the left carotid bifurcation. Our results support earlier observations suggesting faster development of carotid atherosclerosis on the left than on the right side. Echogenic plaques were more common and generally smaller than echolucent plaques, but there was no correlation between plaque echogenicity and IMT. (Stroke. 1998;29:1378-1382.)

Background and Purpose-We investigated whether, in a randomly selected population of 55-year-old men and women, there is a relationship between common carotid artery (CCA) diameter and intima-media (IM) thickness and conventional risk factors for cardiovascular disease such as gender, smoking, elevated blood lipids, and high blood pressure. Methods-CCA diameter and IM thickness of the distal right and left CCAs were measured by high-frequency ultrasound methods. Fifty-seven men (73% of the invited men) and 47 women (62% of the invited women) participated. Results-In the whole group the CCA diameter was correlated with gender (PϽ0.001), cholesterol (Pϭ0.007), triglycerides (PϽ0.001), apoB (PϽ0.001), apoB/A-1 (PϽ0.001), systolic blood pressure (Pϭ0.001), and glucose (Pϭ0.006). HDL was inversely correlated with mean CCA diameter (Pϭ0.003). In men the CCA diameter was correlated with a combined risk factor score (Pϭ0.005), systolic blood pressure (Pϭ0.011), platelet count (Pϭ0.033), apoB (Pϭ0.025), and occurrence of plaque (Pϭ0.003). In women the CCA diameter was correlated with a combined risk factor score (Pϭ0.010), systolic blood pressure (Pϭ0.033), body mass index (PϽ0.001), cholesterol (Pϭ0.009), triglycerides (Pϭ0.14), apoB (Pϭ0.002), and apoB/A1 (Pϭ0.003). IM thickness was correlated with systolic blood pressure (PϽ0.001). Conclusions-There are correlations between risk factors for cardiovascular disease and carotid artery diameter and IM thickness in both women and men in a population of 55-year-old subjects. The increased vessel diameter in subjects with cardiovascular risk factors may be a sign of attenuated vasoregulation, which could be an important factor during the development of atherosclerosis.

Purpose. We investigated whether, in a randomly selected population of 55-year-old men and women, there is a relationship between vascular function measured as¯ow-mediated (endothelium-dependent) and nitroglycerine-mediated (nonendotheliumdependent) dilatation of the brachial artery and conventional risk factors for cardiovascular disease such as gender, smoking, elevated blood-lipids and high blood pressure. The results are compared with those in a young healthy population of 35-year-olds. Subjects. A total of 57 men (73% of the invited males) living in the community and 47 women (62% of the invited females) participated and were compared with a previously studied 35-year-old population (52 men and 56 women). Methods. Basal brachial artery diameter was measured by high-frequency ultrasound methods. Endothelial function was measured as¯ow-mediated dilatation (FMD) in response to reactive hyperaemia. The nonendothelium-dependent vasodilatation was measured after administering sublingual nitroglycerine (NTG). Results. Flow-mediated endothelium-dependent dilatation was similar in men and women being 3.1 2.5% (mean SD) in men vs. 2.6 2.3% in women. FMD of the brachial artery was negatively correlated with vessel size in both men and women (P < 0.001). Men had larger brachial artery diameter than women (4.6 0.7 vs. 3.6 0.4 mm, P < 0.001). There was no difference in FMD or in NTG-induced dilatation in the women receiving oral oestrogen replacement therapy compared with those that did not. The women taking oral oestrogen had lower cholesterol than those not taking oral oestrogen (P 0.04). FMD was not correlated with any of the risk factors. NTG-induced vasodilatation was correlated with the body mass index (BMI) in men (P 0.01) and a combined risk factor score in women (P 0.04). There was a large increase in the number of subjects with cardiovascular risk factors in the 55-year-old men and women compared with the 35-year-olds. The distribution of risk factors was fairly equal amongst men and women. Conclusion. There are no correlations between any of the conventional cardiovascular risk factors and FMD in a population of 55-year-olds, but there is a high prevalence of risk factors in the 55-year-old age group. NTG-induced vasodilatation correlated with the BMI in men and a combined risk-factor score in women. FMD-induced vasodilatation is smaller in women at 55 years of age than at 35 years of age. FMD was similar in men at 35 and 55 years of age and in men and women at 55 years of age. The smaller FMD in women at 55 years of age, compared with at 35, could be due to postmenopausal hormonal changes.

BackgroundSystemic lupus erythematosus (SLE), is a heterogeneous disease which predominantly affects young females (90%). SLE is associated with a shorter life expectancy than in the general population. Standardized mortality ratios (SMR) of 2.4 have been reported, which is comparable to diabetes. In modern societies cardiovascular disease (CVD) is the major cause of premature mortality. Accelerated atherosclerosis is generally assumed to be the underlying cause for SLE related CVD. However, previous studies diverge regarding whether atherosclerosis is more common in SLE than in controls. With this in mind and based on own clinical experience we hypothesized that accelerated atherosclerosis is not a general feature of SLE, but prevails in SLE subgroups.Methods281 SLE patients and 281 individually age and sex matched population controls, were investigated clinically. Fasting blood samples and risk factor data were collected. All participants were subject to B-mode ultrasonography of the carotid arteries. Carotid plaque occurrence and mean intima media thickness (mIMT) were recorded. Two SLE subgroups previously described to be at high CVD risk; 1) patients with nephritis and 2) patients with anti-phospholipid antibodies (aPL), and one subgroup reported to be at comparatively lower CVD risk; patients positive for Sjögren´s syndrome antigens A/B (SSA/SSB) antibodies were analyzed separately in comparison with their respective matched controls.ResultsMedian age was 49 (IQR 36–59) years, 93% were females. Manifest CVD; ischemic heart, cerebro- and peripheral vascular disease, prevailed in patients (12% vs. 1%, p<0.0001). Overall plaque prevalence did not differ (20% vs. 16%), but patients had slightly higher mIMT than controls (0.56 vs. 0.53 mm, p<0.0033). After age adjustment plaques, but not mIMT, remained associated with previous CVD events. Therefore we focused further analyses on plaques, a more robust measure of atherosclerosis. Patients with nephritis (40%), but neither aPL (25%) nor SSA/SSB (40%) positive patients, had more plaques than their respective controls (23% vs. 11%, p = 0.008). Notably, patients with nephritis were younger than other SLE patients (45 vs.49 years, p = 0.02). To overcome the confounding effect of age we performed an age-matched nested case-control analysis, which demonstrated that patients with nephritis had twice as often plaques (23%) as both non-nephritis patients (11%, p = 0.038) and controls (12%, p = 0.035).ConclusionsIn SLE excess carotid plaques are essentially confined to the SLE subgroup with nephritis. This subgroup had plaques twice as often as age-matched non-nephritis SLE patients and population controls. Non-nephritis SLE patients, including the aPL positive subgroup, which has a high CVD risk, had similar prevalence of plaques as controls. To prevent later CVD events, this novel observation calls for risk factor screening and initiation of anti-atherosclerotic treatment selectively in SLE nephritis patients. Preferably at nephritis onset, which is often at a young age. ...