Risk factors for changes in carotid intima media thickness and plaque over 5 years in women with systemic lupus erythematosus.

OBJECTIVE: To investigate the occurrence of and risk factors for progression of carotid intima media thickness (IMT) and plaque in women with and without SLE. METHODS: A cohort of 149 women with SLE and 126 controls participated in SOLVABLE (Study of Lupus Vascular and Bone Long-term Endpoints). Demographics, cardiovascular and SLE factors, and laboratory assessments were collected at baseline. Carotid IMT and plaque were measured using B-mode ultrasound at baseline and at 5-year follow-up. Regression models were used to identify predictors of progression in carotid IMT and plaque; multivariate models were adjusted for age, hypertension and total cholesterol to high-density lipoprotein ratio. RESULTS: The mean±SD follow-up time was 5.35±0.60 years in cases and 5.62±0.66 years in controls. The mean IMT change per year was 0.008±0.015 mm in cases and 0.005±0.019 mm in controls (p=0.24). At follow-up, 31.5% of cases and 15% of controls had plaque progression, with a relative risk for plaque progression of 2.09 (95% CI 1.30 to 3.37). In SLE cases, higher fasting glucose and lower fibrinogen were associated with IMT progression after adjustment. Larger waist circumference and non-use of hydroxychloroquine were associated with plaque progression after adjustment. CONCLUSION: Potential modifiable risk factors for carotid IMT and plaque progression in women with SLE were identified, suggesting that monitoring of glucose and waist circumference and use of hydroxychloroquine may be beneficial.

Depression and Progression of Subclinical Cardiovascular Disease in Systemic Lupus Erythematosus.

OBJECTIVE: Women with systemic lupus erythematosus (SLE) have an increased incidence of premature cardiovascular disease (CVD). A relationship between depression and increased inflammation leading to CVD has been proposed. The aim of this study was to evaluate the relationship between depression and the progression of subclinical atherosclerosis in women with SLE. METHODS: In this prospective case-control study, 149 participants with SLE and 126 controls were followed over 5 years. Evaluation included laboratory studies, assessment of CVD risk factors, depression screening, ultrasound evaluations of carotid intima-media thickness (CIMT) and carotid plaque, and assessment of SLE disease activity for the SLE cases. RESULTS: The SLE group had a higher rate of depression: 29% compared with 11% in the control group (P = 0.003). When controlling for traditional CVD risk factors, the presence of baseline depression correlated with increased progression of CIMT in the SLE group, but not in the control group. The mean increase in CIMT was 0.026 mm in the SLE group without depression versus 0.064 mm in the depressed SLE group (P = 0.0096). There was no association between depression and carotid plaque in either group, with a calculated odds ratio for plaque progression in the depressed SLE group of 1.118 (95% confidence interval 0.476, 2.623) in the adjusted model. CONCLUSION: Women with SLE and concomitant depression have an increased risk of developing subclinical atherosclerosis, as measured by CIMT, but not by carotid plaque. The data suggest that depression, a potentially modifiable risk factor, may contribute to the increased risk of subclinical atherosclerosis in women with SLE.

Calcified carotid artery plaques predict cardiovascular outcomes in the elderly.

BACKGROUND: Identifying plaque composition using ultrasound may aid in stratifying patients at high risk for cardiovascular disease (CVD). Calcification is an integral part of plaque progression and may contribute to plaque vulnerability. We investigated the ability of calcified carotid plaques identified using carotid ultrasound to predict cardiovascular outcomes in older adults. METHODS: Participants included 187 hypertensive and 187 normotensive adults undergoing a duplex scan to identify the presence of calcified carotid plaques. Hypertensive participants received either blood pressure treatment or placebo, and all participants were followed for incident cardiovascular events and death for a maximum of 11 years. RESULTS: The untreated hypertensive group was significantly associated with a higher time-to-any CVD event [relative risk (RR) 2.97, 95% confidence interval (CI) 2.03-4.35, P < 0.0001] and mortality (RR 3.11, 95% CI 1.92-5.04, P < 0.0001) when compared to the normotensive group. Participants with calcified carotid plaques had higher cardiovascular event rates (RR 6.22, 95% CI 1.97-19.6, P = 0.0018) and mortality (RR 6.30, 95% CI 1.55-25.7, P = 0.010) when compared to those without plaque. After controlling for age, male sex, blood pressure status, glucose, and IMT, the presence of calcified carotid plaques remained predictive of CVD events (RR 2.35, 95% CI 1.5-3.8, P = 0.0005) and mortality (RR 2.72, 95% CI 1.4-5.2, P = 0.0021). CONCLUSION: Calcified carotid plaques may predict mortality and cardiovascular outcomes independent of traditional CVD risk factors and may serve as an additional CVD risk assessment in the elderly.

Adverse pregnancy outcomes and subsequent risk of cardiovascular disease in women with systemic lupus erythematosus.

BACKGROUND/OBJECTIVE: Patients with systemic lupus erythematosus (SLE) are at increased risk for adverse pregnancy outcomes and cardiovascular disease (CVD). The objective of this exploratory study was to investigate the association between a history of adverse pregnancy outcomes and subsequent risk of subclinical CVD assessed by imaging studies and verified clinical CVD events in 129 women with SLE. METHODS: The occurrence of adverse pregnancy outcomes, specifically pre-eclampsia, preterm birth and low birth weight was ascertained by questionnaire. Subclinical CVD was assessed by coronary artery calcium (CAC) as measured by electron beam CT and carotid plaque measured by B mode ultrasound. Clinical CVD events were verified by medical record review. Logistic regression was used to estimate the association of pregnancy complications with occurrence of subclinical CVD and clinical CVD with a priori adjustment for age, which is associated with CVD and SLE disease duration as a measure of SLE disease burden. RESULTS: Fifty-six women reported at least one pregnancy complication while 73 had none. Twenty-six women had at least one pregnancy complicated by pre-eclampsia and were more likely to have a CAC score greater than or equal to 10 (adjusted OR=3.7; 95% CI 1.2 to 11.9), but the presence of plaque was not associated with this pregnancy complication, OR=1.1, (95% CI 0.4 to 2.8). Low birth weight and preterm birth were not associated with CAC or plaque. CONCLUSIONS: Patients with SLE with a history of pre-eclampsia had a higher rate of subclinical CVD as measured by CAC score. Future studies are needed to confirm the relationship between adverse pregnancy outcomes and subsequent subclinical CVD and clinical CVD events.

Relation of carotid intima-media thickness and plaque with incident cardiovascular events in women with systemic lupus erythematosus.

Patients with systemic lupus erythematosus (SLE) are at increased risk for cardiovascular (CV) disease. The aim of this study was to investigate the association between subclinical CV disease as measured by carotid intima-media thickness (IMT) and plaque using B-mode carotid ultrasound and incident CV events in a combined cohort of female patients with SLE. This was a prospective, 2-center observational study of 392 adult women with SLE and no previous CV events with a mean 8 years of follow-up. Incident CV events confirmed by clinicians were defined as angina, myocardial infarction, percutaneous transluminal coronary angioplasty, coronary artery bypass graft, fatal cardiac arrest, transient ischemic attack, and cerebrovascular accident. Incident hard CV events excluded angina and transient ischemic attack. The mean age was 43.5 years, and most patients were Caucasian (77.3%). During follow-up, 38 patients had incident CV events, and 17 had incident hard CV events. Patients with incident hard CV events had higher mean carotid IMT (0.80 vs 0.64 mm, p <0.01) and presence of carotid plaque (76.5% vs 30.4%, p <0.01) compared with those without incident hard CV events. Baseline carotid IMT and presence of plaque were predictive of any incident hard CV event (hazard ratio 1.35, 95% confidence interval 1.12 to 1.64, and hazard ratio 4.26, 95% confidence interval 1.23 to 14.83, respectively), independent of traditional CV risk factors and medication use. In conclusion, in women with SLE without previous CV events, carotid IMT and plaque are predictive of future CV events. This suggests that carotid ultrasound may provide an additional tool for CV risk stratification in patients with SLE.

Racial differences in the association between carotid plaque and aortic and coronary artery calcification among women transitioning through menopause.

OBJECTIVE: Carotid atherosclerosis is a marker for atherosclerotic disease in other vascular beds; however, racial differences in this association have not been fully examined. The purpose of this report was to evaluate racial differences in the relationship between carotid plaque and calcification in the aorta and coronary arteries among women transitioning through menopause. METHODS: A total of 540 African American and white women with a median age of 50 years were evaluated from the Study of Women's Health Across the Nation. Carotid plaque (none vs. any) was assessed with B-mode ultrasound, and aortic calcification (AC; 0, >0-100, and >100) and coronary artery calcification (CAC; 0, >0-10, and >10) were assessed with CT. RESULTS: For the total cohort, higher prevalence of plaque was significantly associated with higher levels of AC but not CAC. The interaction of race and carotid plaque was significant in models with AC and CAC as dependent variables (P = 0.03 and 0.002, respectively). Among African Americans, there was an inverse relationship, although not significant, between carotid plaque and high AC (>100; odds ratio [OR], 0.75; 95% CI, 0.10-5.48) and between plaque and high CAC (>10; OR, 0.20; 95% CI, 0.03-1.52) in fully adjusted models. In contrast, for whites, significant positive associations existed between carotid plaque and high AC (OR, 4.12; 95% CI, 1.29-13.13) and borderline associations for high CAC (OR, 1.83; 95% CI, 0.66-5.19). CONCLUSIONS: This study demonstrates that the presence of carotid plaque seemed to be a marker for AC and potentially CAC in white women, but not African American middle-aged women, during the menopausal transition.

Progression of carotid intima-media thickness and plaque in women with systemic lupus erythematosus.

OBJECTIVE: Women with systemic lupus erythematosus (SLE) are at high risk of cardiovascular disease (CVD). The goals of this study were to determine the extent of atherosclerotic progression among women with SLE compared with a group of healthy controls and to determine whether factors attributed to SLE or its treatment were associated with atherosclerotic progression independent of traditional CVD risk factors. METHODS: A longitudinal study of women with SLE from the Pittsburgh Lupus Registry was conducted. Women 18 years of age and older (n = 217) underwent carotid ultrasound at baseline and at followup, an average of 4.19 years later. Clinical, serologic, and SLE-related factors, and disease treatment were evaluated. Outcomes were changes in carotid intima-media thickness (IMT) and plaque. Progression of CVD in a sample of women without lupus was used for comparison. RESULTS: The patients' mean +/- SD age at baseline was 45.1 +/- 10.3 years, and the mean +/- SD IMT progression rate was 0.011 +/- 0.03 mm per year. After controlling for traditional CVD risk factors, higher serum creatinine levels were associated with IMT progression (P = 0.0006). Plaque prevalence was 31% at baseline and 40% at followup; plaque progression occurred in 27% of the patients. Higher serum C3 levels and immunosuppressant use at baseline were related to plaque progression (P = 0.04 and P = 0.02, respectively) independent of traditional CVD risk factors. The plaque progression rate was higher than, and the IMT progression rate was similar to, those in the control group. CONCLUSION: SLE patients have accelerated plaque progression compared with controls. SLE-related risk factors are associated with the progression of IMT and plaque after controlling for traditional CVD risk factors. Carotid B-mode ultrasound may serve as a surrogate end point in SLE intervention trials and clinically to track SLE management.

Relationship of ankle blood pressures to cardiovascular events in older adults.

BACKGROUND AND PURPOSE: Low values of ankle-arm systolic blood pressure ratio predict mortality and cardiovascular events. High values, associated with arterial calcification, also carry risk for mortality. We focus on the extent to which low and high ankle-arm index values as well as noncompressible arteries are associated with mortality and cardiovascular events, including stroke in older adults. METHODS: We followed 2886 adults aged 70 to 79 for a mean of 6.7 years for vital status and cardiovascular events (coronary heart disease, stroke, and congestive heart failure). RESULTS: Normal ankle-arm index values of 0.91 to 1.3 were found in 80%, low values of 1.3 were obtained in 5%, and noncompressible arteries were found in 2% of the group. Increased mortality was associated with both low and high ankle-arm index values beginning at levels of <1.0 or >or=1.4. Subjects with low ankle-arm index values or noncompressible arteries had significantly higher event rates than those with normal ankle blood pressures for all end points. For coronary heart disease, hazard ratios associated with a low ankle-arm index, high ankle-arm index, and noncompressible arteries were 1.4, 1.5, and 1.7 (P<0.05 for all) after controlling for age, gender, race, prevalent cardiovascular disease, diabetes, and major cardiovascular risk factors. Noncompressible arteries carried a particularly high risk of stroke and congestive heart failure (hazard ratio=2.1 and 2.4, respectively). CONCLUSIONS: Among older adults, low and high ankle-arm index values carry elevated risk for cardiovascular events. Noncompressible leg arteries carry elevated risk for stroke and congestive heart failure specifically.

Cardiovascular risk factors associated with enlarged diameter of the abdominal aortic and iliac arteries in healthy women.

The abdominal aorta is known to be more susceptible to arterial dilation than to occlusion primarily due to the effects of vascular aging. Few studies have considered the effects of cardiovascular risk factors on arterial diameter, particularly within a population of healthy women at mid-life. This study seeks to examine associations between cardiovascular risk factors and abdominal aortic and iliac adventitial diameter. Abdominal aortic ultrasound was performed in 260 post-menopausal women aged 53.9+/-2.5 years at time of scan as a component of the Healthy Women Study. Risk factors were evaluated at premenopause and post-menopausal clinic visits closest in date to the abdominal ultrasound scan. Post-menopausal weight and change of weight from pre- to post-menopause were among the strongest correlates of larger adventitial diameter after controlling for age, systolic blood pressure, and body size using height. Other post-menopausal risk factors significantly correlated with both abdominal aortic and iliac diameter were BMI, waist circumference, HDL, and insulin (p<0.05). These data suggest that weight is a key risk factor in the promotion of vascular aging as indexed by enlarged arterial diameter. Women at mid-life should continue to be targeted for weight interventions to reduce their risk for more serious cardiovascular complications.

Weight change is associated with change in arterial stiffness among healthy young adults.

Risk factors for arterial stiffness progression have not been well characterized. We examined the relationship between arterial stiffness progression and body weight and weight gain in a group of healthy young adults. Aortic pulse-wave velocity was assessed at 2 time points approximately 2 years apart in 152 white and black adults aged 20 to 40 years, and was standardized by the time between visits to obtain annualized pulse-wave velocity changes. Blacks had 15.5 cm/s per year larger annual pulse-wave velocity increases compared with whites (P=0.02), even after multivariable adjustment for weight and blood pressure changes. Larger annual pulse-wave velocity increases were also associated with larger baseline body weight (P=0.02), waist girth (P=0.003), and body mass index (P<0.001), and greater annual weight gain (P=0.02), after adjustment for baseline pulse-wave velocity. After multivariable adjustment that included blood pressure changes, larger baseline waist girth (P=0.009), baseline body mass index (P=0.001), body mass index increase (P=0.037), and weight gain (P=0.017) remained significantly associated with larger annual pulse-wave velocity progression. Weight change showed a direct relationship with pulse-wave velocity change; mean annual pulse-wave velocity changes were -29.9 cm/s per year (regression) for those with >or=4.5 kg annual weight loss and 18.2 cm/s per year (progression) for those with >or=4.5 kg annual weight gain. These data show strong associations between weight gain and arterial stiffness progression, as well as between weight loss and arterial stiffness regression. These data greatly underscore the vascular benefit of weight loss. Successful weight loss programs in young adults, particularly blacks, are needed.

Measures of obesity are associated with vascular stiffness in young and older adults.

Obesity has reached epidemic levels and carries a risk for cardiovascular disease. Obesity's effects on the vascular systems of young adults and African Americans have not been well characterized. The aim of this study was to assess the association between measures of obesity and aortic stiffness in 186 young adults (20 to 40 years, 50% African American) and 177 older adults (41 to 70 years, 33% African American). Aortic stiffness was measured by aortic pulse-wave velocity. The median pulse-wave velocity value was 468 cm/s for young adults and 627 cm/s for older adults (P<0.001). Higher body weight, body mass index, waist and hip circumferences, and waist-hip ratio were strongly correlated with higher pulse-wave velocity, independent of age, systolic blood pressure, race, and sex overall and among both age groups (P<0.01 for all). Even among the 20- to 30-year-olds, obese individuals (body mass index>30) had a mean pulse-wave velocity value 47 cm/s higher than did nonobese individuals (P<0.001). Obesity measures were among the strongest independent predictors of pulse-wave velocity overall and for both age groups. Results were consistent by race. In conclusion, excess body weight is associated with higher aortic stiffness in whites and African Americans as young as 20 to 30 years. The strength of the association, the early age at which it appears, and the prevalence of obesity among the young warn of substantially increased cardiovascular disease incidence as this cohort ages.