Cardiovascular disease is the leading cause of death in women and the treatment of dyslipidemia is a cornerstone of secondary prevention. Pharmacologic therapy with statins can lower LDL-C by 30–50% and reduce the risk of recurrent coronary heart disease in both men and women. While significant reductions in LDL-C can be achieved with statin therapy, diet and lifestyle modification remain an essential part of the treatment regimen for cardiovascular disease. Moreover, a large proportion of the U.S. population is sedentary, overweight, and does not consume a heart-healthy diet. Non-pharmacologic treatment strategies also improve other cardiovascular risk factors and are generally easily accessible. In this review, we examine the effect of non-pharmacologic therapy on lipids as part of the secondary prevention strategy of cardiovascular disease in women.
women; dyslipidemias; cardiovascular diseases; secondary prevention; diet; lifestyle
While the Framingham Risk Score provides a reasonable estimation of risk in certain subgroups, the majority of MIs occur in individuals classified as low or moderate risk. Coronary Artery Calcium (CAC) testing provides an individualized measure of atherosclerotic burden that integrates an individual’s cumulative lifetime risk factor exposure that cannot be obtained from serum markers.
Methods and Results
We briefly summarize the existing evidence for the use of CAC scanning in primary prevention and performed a meta-analysis of the existing randomized controlled data investigating the impact of CAC screening on lifestyle modification, risk factors, and downstream testing. We identified four trials published between 2003 and 2011 with a total of 2,490 participants, >75% of whom came from the Early Identification of Subclinical Atherosclerosis by Noninvasive Imaging Research (EISNER) trial. Three of the trials reported a non-significant increase in smoking cessation in the scan versus no-scan group with a pooled mean of 1.15 (95% CI 0.77 – 1.71). A significant reduction in SBP and LDL was noted in the EISNER trial, but the pooled estimates were 0.23mmHg (95% CI −2.25 – 2.71) and 0.23mg/dL (95% CI −5.96 – 6.42), respectively. Only the EISNER trial reported medication usage according to CAC score. They found a higher CAC score associated with an increased prescription of lipid lowering medications (p=<0.001) and a CAC=0 associated with fewer prescriptions for lipid lowering medications (p=0.02).
Our meta-analysis highlights the paucity of randomized evidence linking CAC scanning to improved intermediate and hard outcomes in primary prevention. Future trials are urgently needed to determine the impact of CAC screening on lifestyle modification, risk factor modification, and downstream testing.
coronary artery disease; risk factors; primary prevention; imaging
The purpose of the study was to examine and compare the incidence and progression of coronary artery calcium (CAC) among persons with metabolic syndrome (MetS) and diabetes mellitus (DM), compared to those with neither condition.
MetS and DM are associated with subclinical atherosclerosis as evidenced by coronary artery calcium (CAC).
The Multiethnic Study of Atherosclerosis included 6,814 African-American, Asian, Caucasian, and Hispanic adults aged 45–84 free of cardiovascular disease at baseline. 5,662 subjects (51% female, mean age 61.0 ± 10.3 years) received baseline and follow-up (mean 2.4 years) cardiac CT scans. We compared the incidence of CAC in 2,927 subjects without CAC at baseline and progression of CAC in 2,735 subjects with CAC at baseline in those with MetS without DM (25.2%), DM without MetS (3.5%), or both DM and MetS (9.0%), compared to neither MetS nor DM (58%). Progression of CAC was also examined in relation to coronary heart disease events over an additional 4.9 years.
Relative to those with neither MetS nor DM, adjusted relative risks (95% confidence intervals) for incident CAC were 1.7 (1.4–2.0), 1.9 (1.4–2.4), and 1.8 (1.4–2.2) (all p<0.01) and absolute differences in mean progression (volume score) were 7.8 (4.0–11.6; p<0.01), 11.6 (2.7–20.5; p<0.05), and 22.6 (17.2–27.9; p<0.01) for those with MetS without DM, DM without MetS, and both DM and MetS, respectively. Similar findings were seen in analysis using Agatston calcium score. In addition, progression predicted CHD events in those with MetS without DM (adjusted hazard ratio 4.1, 95% CI=2.0–8.5, p<0.01) and DM (4.9 [1.3–18.4], p<0.05) among those in highest tertile of CAC increase vs. no increase).
Individuals with MetS and DM have a greater incidence and absolute progression of CAC compared to individuals without these conditions, with progression also predicting CHD events in those with MetS and DM.
atherosclerosis; diabetes; risk factors; calcification
It is unclear whether coronary artery calcium (CAC) is effective for risk stratifying patients with diabetes in whom treatment decisions are uncertain.
RESEARCH DESIGN AND METHODS
Of 44,052 asymptomatic individuals referred for CAC testing, we studied 2,384 individuals with diabetes. Subjects were followed for a mean of 5.6 ± 2.6 years for the end point of all-cause mortality.
There were 162 deaths (6.8%) in the population. CAC was a strong predictor of mortality across age-groups (age <50, 50–59, ≥60), sex, and risk factor burden (0 vs. ≥1 additional risk factor). In individuals without a clear indication for aspirin per current guidelines, CAC stratified risk, identifying patients above and below the 10% risk threshold of presumed aspirin benefit.
CAC can help risk stratify individuals with diabetes and may aid in selection of patients who may benefit from therapies such as low-dose aspirin for primary prevention.
The majority of breast cancers are diagnosed in postmenopausal women. Competing comorbidities, particularly cardiovascular disease (CVD), should be considered when individualizing adjuvant therapies for these women. We compared the 10-year predicted breast cancer recurrence risk with CVD risk among postmenopausal women with hormone receptor-positive (HR+), non-metastatic breast cancer. CVD risk factor data were prospectively collected from postmenopausal women with stage I-III, HR+ breast cancer initiating adjuvant aromatase inhibitor therapy. We compared predicted 10-year CVD risk, including the composite index heart age, computed from modified Framingham risk score, with predicted 10-year risk of breast cancer recurrence using Adjuvant! Online. We created multivariable logistic regression models to estimate the odds ratios (OR) and 95% confidence intervals (CI) for greater CVD risk than breast cancer recurrence risk. Among 415 women, mean age and heart age were 60 and 67 years, respectively. Overall, 43% of women had a predicted 10-year CVD risk equivalent to breast cancer recurrence risk and 37% had CVD risk higher than breast cancer recurrence risk. Predicted CVD risk was higher than breast cancer recurrence risk for stage I disease (OR: 6.1, 95% CI: 3.4–11.2) or heart age >65 (OR: 12.4, 95% CI: 7.0–22.6). The majority of postmenopausal women with HR+ early breast cancer had a predicted 10-year CVD risk that was equivalent to or higher than breast cancer recurrence risk. Physicians should weigh competing risks and offer early screening and cardiac prevention strategies for women at a greater risk for CVD.
Breast cancer risk; Cardiovascular disease risk; Adjuvant! Online; Modified Framingham risk score; Cancer survivorship
Despite the recognized risk of accelerated atherosclerosis in patients with rheumatoid arthritis (RA), little is known about cardiovascular risk management in contemporary cohorts of these patients. We tested the hypotheses that major modifiable cardiovascular risk factors were more frequent and rates of treatment, detection, and control were lower in patients with RA than in non-RA controls.
The prevalence of hypertension, diabetes, elevated low-density lipoprotein (LDL) cholesterol, elevated body mass index, smoking, moderate-high 10-year cardiovascular risk and the rates of underdiagnosis, therapeutic treatment, and recommended management were compared in 197 RA patients and 274 frequency-matched control subjects, and their associations with clinical characteristics were examined.
Eighty percent of RA patients and 81% of control subjects had at least 1 modifiable traditional cardiovascular risk factor. Hypertension was more prevalent in the RA group (57%) than in controls [42%, P =0.001]. There were no statistically significant differences in the frequency of diabetes, elevated body mass index, smoking, intermediate-high 10-year coronary heart disease risk, or elevated LDL in patients with RA versus controls. Rates of newly identified diabetes, hypertension, and hyperlipidemia were similar in RA patients versus controls. Rates of therapeutic interventions were low in both groups but their use was associated with well-controlled blood pressure (OR = 4.55, 95% CI: 1.70, 12.19) and lipid levels (OR = 9.90, 95% CI: 3.30, 29.67).
Hypertension is more common in RA than in controls. Other traditional cardiovascular risk factors are highly prevalent, underdiagnosed, and poorly controlled in patients with RA, as well as controls.
rheumatoid arthritis; cardiovascular risk; epidemiology
Observational studies have demonstrated a decreased incidence of cancers among users of HMG CoA reductase inhibitors (statins) and a reduced risk of recurrence among statin users diagnosed with early stage breast cancer. We initiated a prospective study to identify potential biomarkers of simvastatin chemopreventive activity that can be validated in future trials. The contralateral breast of women with a previous history of breast cancer was used as a high-risk model. Eligible women who had completed all planned treatment of a prior stage 0–III breast cancer received simvastatin 40 mg orally daily for 24–28 weeks. At baseline and end-of-study, we measured circulating concentrations of high-sensitivity C-reactive protein (hsCRP), estrogens, and fasting lipids; breast density on contralateral breast mammogram; and quality of life by Rand Short Form 36-Item health survey. Fifty women were enrolled with a median age of 53 years. Total cholesterol, LDL cholesterol, triglyceride, and hsCRP fell significantly during the study (P values < 0.001, <0.001, 0.003, and 0.05, respectively). Estrone sulfate concentrations decreased with simvastatin treatment (P = 0.01 overall), particularly among post-menopausal participants (P = 0.006). We did not observe a significant change in circulating estradiol or estrone concentrations, contralateral mammographic breast density, or reported physical functioning or pain scores. This study demonstrates the feasibility of short-term biomarker modulation studies using the contralateral breast of high-risk women. Simvastatin appears to modulate estrone sulfate concentrations and its potential chemopreventive activity in breast cancer warrants further investigation.
Simvastastin; Breast density; Chemoprevention; Breast cancer; Contralateral breast
We assessed the association between sleep apnea, snoring, incident cardiovascular (CV) events and all-cause mortality in the Multi Ethnic Study of Atherosclerosis (MESA) cohort.
Out of 5338 respondents to a sleep questionnaire administered during the second MESA exam period, 208 had physician-diagnosed sleep apnea (PDSA), 1452 were habitual snorers (HS) and 3678 were neither a habitual snorer nor had PDSA (normal participants). Cox proportional hazard analysis was used to assess the associations adjusting for age, gender, race/ethnicity, smoking, diabetes mellitus, total cholesterol, HDL, triglycerides, BMI, current alcohol use, benzodiazepine use, BP medications and statin use.
Over a 7.5 year average follow-up period, 310 adjudicated CV events including MI, stroke, angina, resuscitated cardiac arrest, stroke death and CVD death and 189 deaths occurred. Compared to HS, PDSA was associated with higher incident CV rates in both univariate and multivariable models [hazard ratio (95%); 1.89(1.22–2.93), p=0.004 and 1.91(1.20 –3.04), p=0.007 respectively]. PDSA was also associated with a higher death rates compared with HS [hazard ratio (95%); 2.13(1.25 – 3.63), p=0.006 and 2.70(1.52– 4.79), p=0.007 respectively]. Compared with normal participants, PDSA had higher incident CV event rates in both univariate and multivariable models [hazard ratio (95%); 2.23[1.39–3.60], p=0.001 and 2.16[1.30–3.58], p=0.003 respectively]. Similarly, PDSA had a higher death rate compared with normal participants in both the univariate and multivariable models [hazard ratio (95%CI); 2.44(1.36 – 4.37), p=0.003 and 2.71(1.45 – 5.08), p=0.002 respectively]. Habitual snorers had similar incident CV event rates and death rates in both univariate and multivariable models compared with normal participants.
PDSA but not habitual snoring was associated with high incident CV events and all-cause mortality in a multi-ethnic population based study of adults free of clinical CV disease at baseline.
Obstructive sleep apnea; habitual snorers; cardiovascular events; mortality; population
To explore predictors of change in measures of carotid atherosclerosis among rheumatoid arthritis (RA) patients without known cardiovascular disease (CVD) at baseline
RA patients underwent carotid ultrasonography at two timepoints, separated by an average of 3.2 ± 0.3 years. The associations of baseline and average patient characteristics with the average yearly change in mean maximal intima-medial thickness (IMT) of the common (CCA) and internal carotid arteries (ICA), and with incident or progressive plaque in the ICA/carotid bulb, were explored.
Among the 158 RA patients, maxCCA-IMT increased in 82% (median=16 μm/year; p<0.001) and maxICA-IMT increased in 70% (median=25 μm/year; p<0.001). Incident plaque was observed in 14% without baseline plaque [incidence rate=4.2/100 person-years (95% CI 1.61–6.82)]. Plaque progression was observed in 5% with baseline plaque. Among RA predictors, the adjusted average yearly change in maxCCA-IMT was significantly greater in patients with earlier RA vs. longer disease. Those prescribed TNF inhibitors at baseline had a 37% lower adjusted rate of maxCCA-IMT progression vs. non-users (14 vs. 22 μm/year; p=0.026). For maxICA-IMT, cumulative prednisone exposure was associated with progression [1.2 μm/year per gram (95% CI 0.1–2.4)] after adjustment, and was lower in patients prescribed statins concomitant with prednisone. Higher swollen joint count and higher average CRP were both associated with incident or progressive plaque, primarily in patients with elevated baseline CVD risk based on the Framingham score.
These prospective data provide evidence for inflammation as a contributor to subclinical atherosclerosis progression in RA, potentially modified favorably by TNF inhibitors and detrimentally by glucocorticoids.
Atherosclerosis; Inflammation; prediction; carotid ultrasound
While metabolic syndrome (MetS) and diabetes confer greater cardiovascular disease (CVD) risk, recent evidence suggests that individuals with these conditions have a wide range of risk. We evaluated whether screening for coronary artery calcium (CAC) and carotid intimal-medial thickness (CIMT) can improve CVD risk stratification over traditional risk factors (RFs) in people with MetS and diabetes.
RESEARCH DESIGN AND METHODS
We assessed CAC and CIMT in 6,603 people aged 45–84 years in the Multi-Ethnic Study of Atherosclerosis (MESA). Cox regression examined the association of CAC and CIMT with coronary heart disease (CHD) and CVD over 6.4 years in MetS and diabetes.
Of the subjects, 1,686 (25%) had MetS but no diabetes and 881 (13%) had diabetes. Annual CHD event rates were 1.0% among MetS and 1.5% for diabetes. Ethnicity and RF-adjusted hazard ratios for CHD for CAC 1–99 to ≥400 vs. 0 in subjects with neither MetS nor diabetes ranged from 2.6 to 9.5; in those with MetS, they ranged from 3.9 to 11.9; and in those with diabetes, they ranged from 2.9 to 6.2 (all P < 0.05 to P < 0.001). Findings were similar for CVD. CAC increased the C-statistic for events (P < 0.001) over RFs and CIMT in each group while CIMT added negligibly to prediction over RFs.
Individuals with MetS or diabetes have low risks for CHD when CAC or CIMT is not increased. Prediction of CHD and CVD events is improved by CAC more than by CIMT. Screening for CAC or CIMT can stratify risk in people with MetS and diabetes and support the latest recommendations regarding CAC screening in those with diabetes.
We hypothesized that insulin resistance, measured by the homeostatic model assessment of insulin resistance (HOMA), is independently associated with prevalent and incident extra-coronary calcification (ECC).
We studied calcium scores of the aortic valve (AVC), mitral valve (MVC), thoracic aorta (TAC) and aortic valve root (AVR) in 6,104 MESA participants not on diabetes medication who had baseline cardiac CT scans; 5,312 had follow-up scans (mean 2.4y). Relative-risk regression modeled prevalent and incident ECC adjusted for baseline demographics (model 1), and additionally for CVD risk factors (model 2).
In model 1, prevalence and incidence risk-ratios for the highest versus lowest quartile of HOMA were 20–30% higher in all ECC locations (p-value for trend ≤0.05 for all but incident-AVC). In model 2, all associations were attenuated, primarily by adjustment for metabolic syndrome components.
HOMA has a positive and graded association with ECC, but not independently of cardiovascular risk factors—particularly metabolic syndrome components.
cardiovascular calcification; insulin resistance; atherosclerosis; metabolic syndrome; computed tomography; valvular calcification; thoracic aortic calcification
The JUPITER trial demonstrated that some patients with LDL-C <130 mg/dL and hsCRP ≥2 mg/L benefit from rosuvastatin, although absolute event rates were low. We sought to determine whether coronary artery calcium (CAC) may further risk stratify a JUPITER-eligible population, and to compare hsCRP vs. CAC for risk prediction in otherwise JUPITER-eligible participants.
A total of 950 MESA participants met all JUPITER entry criteria. We compared CHD and CVD event rates and multivariable-adjusted hazard ratios after stratifying by both presence and burden of CAC (0, 1–100, >100). We also calculated 5-year number needed to treat (NNT5) by applying the benefit observed in JUPITER to the observed event rates within each CAC strata.
Median follow-up was 5.8 years. Approximately 47% of the MESA JUPITER population had CAC=0, and CHD event rates in this group were <1 per 1000 person-years. Over 2/3 of all CHD events occurred in the 25% of participants with CAC >100 (20.2 per 1000 person-years). For CHD, the predicted NNT5 for CAC 0, 1–100, and >100 was 549, 94, and 24 respectively. For CVD, the NNT5 was 124, 54, and 19. Amongst otherwise JUPITER-eligible patients, presence of CAC was associated with 4.3-fold increased CHD (95% CI 2.0 – 9.3) and 2.6-fold increased CVD (95% CI 1.5–4.5), while hsCRP was not associated with either CHD or CVD after multivariable adjustment.
Within MESA, approximately half of JUPITER-eligible participants had CAC=0 and experienced an extremely low 6-year event rate. Nearly all events occurred in patients with CAC. CAC appears to further risk stratify JUPITER-eligible patients and may be used to target a subgroup of patients expected to derive the most, and the least, absolute benefit from statin treatment. Focusing treatment on the subset of individuals with measurable atherosclerosis may represent a more appropriate allocation of resources.
hsCRP; CAC; and Clinical Events
To assess the independent and collective associations of hepatic steatosis, obesity, and the metabolic syndrome with elevated high-sensitivity CRP (hs-CRP) levels.
Methods and Results
We evaluated 2,388 individuals without clinical cardiovascular disease between December 2004 and December 2006. Hepatic steatosis was diagnosed by ultrasound, and the metabolic syndrome was defined using NHLBI criteria. The cutpoint of ≥ 3 mg/L was used to define “high” hs-CRP. Multivariate logistic regression was used to assess the independent and collective associations of hepatic steatosis, obesity, and the metabolic syndrome with high hs-CRP. Steatosis was detected in 32% of participants, 23% met criteria for metabolic syndrome, and 17% of individuals were obese. After multivariate regression, hepatic steatosis (OR 2.07; 95% CI: 1.68-2.56), obesity (OR 3.00; 95% CI: 2.39-3.80), and the metabolic syndrome (2.39; 95% CI: 1.88-3.04) were all independently associated with high hs-CRP. Combinations of these factors were associated with an additive increase in the odds of high hs-CRP, with individuals with 1, 2, and 3 factors having ORs for high hs-CRP of 1.92 (1.49-2.48), 3.38 (2.50-4.57) and 4.53 (3.23-6.35), respectively.
Hepatic steatosis, obesity, and the metabolic syndrome are independently and additively associated with increased odds of high hs-CRP levels.
Hepatic Steatosis; Obesity; Metabolic Syndrome; Inflammation; Cytokines
High-sensitivity C-reactive protein (hsCRP) levels are closely associated with abdominal obesity, metabolic syndrome, and atherosclerotic cardiovascular disease. The JUPITER trial has encouraged using hsCRP ≥2 mg/L to guide statin therapy; however the association of hsCRP to atherosclerosis, independent of obesity, remains unknown.
Methods and Results
We studied 6,760 participants from the Multi-Ethnic Study of Atherosclerosis (MESA). Participants were stratified into 4 groups: non-obese/low hsCRP, non-obese/high hsCRP, obese/low hsCRP, and obese/high hsCRP. Using multivariable logistic and robust linear regression, we described the association with subclinical atherosclerosis, using coronary artery calcium (CAC) and carotid intima-media thickness (cIMT). Mean BMI was 28.3 ± 5.5 kg/m2, and median hsCRP was 1.9 mg/L (0.84 – 4.26). High hsCRP, in the absence of obesity, was not associated with CAC and was mildly associated with cIMT. Obesity was strongly associated with CAC and cIMT independent of hsCRP. When obesity and high hsCRP were both present, there was no evidence of multiplicative interaction. Similar associations were seen among 2,083 JUPITER-eligible individuals.
High hsCRP, as defined by JUPITER, was not associated with CAC and was mildly associated with cIMT in the absence of obesity. In contrast, obesity was associated with both measures of subclinical atherosclerosis independent of hsCRP status.
obesity; hsCRP; high sensitivity C-reactive protein; subclinical atherosclerosis; coronary artery calcium; carotid intima-media thickness
Continuous variable dichotomization is a popular technique used in the estimation of the effect of risk factors on health outcomes in multivariate regression settings. Researchers follow this practice in order to simplify data analysis, which it unquestionably does. However thresholds used to dichotomize those variables are usually ad-hoc, based on expert opinions, or mean, median or quantile splits and can add bias to the effect of the risk factors on specific outcomes and underestimate such effect. In this paper, we suggest the use of a semi-parametric method and visualization for improvement of the threshold selection in variable dichotomization while accounting for mixture distributions in the outcome of interest and adjusting for covariates. For clinicians, these empirically based thresholds of risk factors, if they exist, could be informative in terms of the highest or lowest point of a risk factor beyond which no additional impact on the outcome should be expected.
Generalized additive model; Smearing estimates; Threshold detection; Recycled prediction
Even among asymptomatic people at low risk (<10%) by Framingham Risk Score (FRS), high coronary artery calcium (CAC) scores signify higher predicted risk of coronary heart disease (CHD) events. We sought to determine non-invasive factors (without radiation exposure) significantly associated with CAC in low-risk, asymptomatic persons. In a cross-sectional analysis, we studied 3046 participants from MESA at low 10-year predicted risk (FRS <10%) for CHD events. Multivariable logistic regression was used to assess the association of novel markers with presence of any CAC (CAC >0) and advanced CAC (CAC ≥ 300). CAC >0 and CAC ≥ 300 were present in 30% and 3.5% of participants, respectively. Factor VIIIc, fibrinogen and sICAM were each associated with CAC presence (P ≤ 0.02); and C-reactive protein, D-dimer and carotid intima-media thickness (CIMT) with advanced CAC (P ≤ 0.03). The base model combining traditional risk factors had excellent discrimination for advanced CAC (C-statistic, 0.808). Addition of the 2 best-fit models combining biomarkers plus/minus CIMT improved the c-statistics to 0.822 and 0.820, respectively. All 3 models calibrated well, but were similar in estimating individual risk probabilities for advanced CAC (prevalence = 9.97%, 10.63% and 10.10% in the highest quartiles of predicted probabilities versus 0.26%, 0.26% and 0.26% in the lowest quartiles, respectively). In conclusion, in low risk individuals, traditional risk factors alone predicted advanced CAC with high discrimination and calibration. Biomarker combinations +/− CIMT were also significantly associated with advanced CAC, but improvement in prediction and estimation of clinical risk were modest compared to traditional risk factors alone.
coronary calcium; biomarkers; novel markers; low-risk; risk factors
We sought to determine whether insulin resistance predicts the incidence and progression of coronary artery calcification (CAC).
RESEARCH DESIGN AND METHODS
We studied 5,464 participants not on hypoglycemic therapy from the Multi-Ethnic Study of Atherosclerosis (MESA). Each had baseline homeostasis model assessment of insulin resistance (HOMA-IR) and baseline and follow-up CAC scores. Incident CAC was defined as newly detectable CAC; progression was defined as advancing CAC volume score at follow-up.
Median HOMA-IR was 1.2 (0.8–2.0). Across all ethnicities, there was a graded increase in CAC incidence and progression with increasing HOMA-IR. When compared with those in the 1st quartile, participants in the 2nd–4th quartiles had 1.2, 1.5, and 1.8 times greater risk of developing CAC. Median annualized CAC score progression was 8, 14, and 17 higher, respectively. However, HOMA-IR was not predictive after adjustment for metabolic syndrome components.
HOMA-IR predicts CAC incidence and progression, but not independently of metabolic syndrome.
Abdominal aortic calcification (AAC) is a measure of subclinical cardiovascular disease (CVD). Data are limited regarding its relation to other measures of atherosclerosis.
Among 1,812 subjects (49% female, 21% black, 14% Chinese, and 25% Hispanic) within the population-based Multiethnic Study of Atherosclerosis, we examined the cross-sectional relation of AAC with coronary artery calcium (CAC), ankle brachial index (ABI), and carotid intimal medial thickness (CIMT), as well as multiple measures of subclinical CVD.
AAC prevalence ranged from 34% in those aged 45–54 to 94% in those aged 75–84 (p<0.0001), was highest in Caucasians (79%) and lowest in blacks (62%) (p<0.0001). CAC prevalence, mean maximum CIMT ≥ 1 mm, and ABI<0.9 was greater in those with vs. without AAC: CAC 60% vs 16%, CIMT 38% vs 7%, and ABI 5% vs 1% for women and CAC 80% vs 37%, CIMT 43% vs 16%, and ABI 4% vs 2% for men (p<0.01 for all except p<0.05 for ABI in men). The presence of multi-site atherosclerosis (≥ 3 of the above) ranged from 20% in women and 30% in men (p<0.001), was highest in Caucasians (28%) and lowest in Chinese (16%) and ranged from 5% in those aged 45–54 to 53% in those aged 75–84 (p<0.01 to p<0.001). Finally, increased AAC was associated with 2 to 3-fold relative risks for the presence of increased CIMT, low ABI, or CAC.
AAC is associated with an increased likelihood of other vascular atherosclerosis. Its additive prognostic value to these other measures is of further interest.
atherosclerosis; calcification; cardiovascular disease; epidemiology
In 2002 the United States Preventive Services Task Force and the American Heart Association recommended aspirin for the primary prevention of Coronary Heart Disease (CHD) in individuals with a Framingham risk score ≥ 6% or ≥ 10%, respectively. The regular use of aspirin (≥ 3 days per week) was examined in a cohort of 6452 White, Black, Hispanic, and Chinese individuals without cardiovascular disease in 2000-2002 and 5181 individuals from the same cohort in 2005-2007. Framingham risk scores were stratified into low (< 6%), increased (6% to 9.9%), and high risk (≥ 10%). In 2000-2002 the prevalence of aspirin use was 18% and 27% for those at increased and high risk, respectively. Whites (25%) used aspirin more than Blacks (14%), Hispanics (12%), or Chinese (14%) (P < 0.001) in the increased risk group. Corresponding prevalences for the high risk group were 38%, 25%, 17%, and 21%, respectively (P < 0.001). In 2005-2007 the prevalence of aspirin use was 31% and 44% for those at increased and high risk, respectively. Whites (41%) used aspirin more than Blacks (27%), Hispanics (24%), or Chinese (15%) in the increased risk group (P < 0.001). Corresponding prevalences for the high risk group were 53%, 43%, 38%, and 28%, respectively (P < 0.001). Racial/ethnic differences persisted after adjustment for age, gender, diabetes, income, and education. In conclusion, regular aspirin use in adults at increased and high risk for CHD remains suboptimal. Important racial/ethnic disparities exist for unclear reasons.
Framingham risk score; aspirin; coronary heart disease; race and ethnicity
Mitral annular calcification (MAC) is a fibrous, degenerative calcification of the mitral valve. The relationship between MAC and cardiovascular disease (CVD) risk factors is not well defined. Thus, we performed a cross-sectional study to determine which CVD risk factors are independently associated with MAC in the Multi-Ethnic Study of Atherosclerosis (MESA).
MESA includes 6,814 women and men ages 45–84 years old without apparent CVD in 4 ethnic groups (12% Chinese, 38% Caucasian, 22% Hispanic, and 28% African-American). MAC was defined by presence of calcium in the mitral annulus by cardiac computed tomography at enrollment. Multivariable logistic regression was used to evaluate relationships between MAC and CVD risk factors.
The overall prevalence of MAC was 9%. The prevalence of MAC was highest in Caucasians (12%), followed by Hispanics (10%), African Americans (7%) and was lowest in Chinese (5%). Characteristics associated with MAC included age (p<0.01), female gender (p<0.01), increased body mass index (BMI) (p=0.03), and former smoking status (p<0.008). The MAC group had a higher prevalence of hypertension, diabetes mellitus (DM), and family history of heart attack (all p<0.001). After adjusting for all variables, age, female gender, diabetes mellitus, and increased BMI remained strongly associated with MAC.
Age, female gender, DM, and increased BMI were significantly associated with MAC. Prevalence of MAC was strongly associated with female gender and increasing age in all ethnicities.
Mitral annular calcification; MESA; Cardiac CT; risk factors
Abdominal adiposity, especially visceral adiposity, is an emerging cardiometabolic risk factor. How abdominal fat is distributed in rheumatoid arthritis (RA) and its RA-related determinants have not been explored.
Men and women with RA were compared to non-RA controls from the Multi-Ethnic Study of Atherosclerosis. Participants underwent anthropometric measures and quantification of visceral and subcutaneous fat areas (VFA, SFA) using abdominal computed tomography.
A total of 131 RA patients were compared with 121 controls. Despite similar body mass index and waist circumference between the RA and control groups, the adjusted mean VFA was 45cm2 higher (+51%) for RA vs. control men (p=0.005) but not significantly different by RA status in women. The adjusted mean SFA was 119cm2 higher (+68%) for RA vs. control women (p<0.001) but not significantly different by RA status in men. Elevated VFA (>75th percentile) was associated with a significantly higher adjusted probability of having an elevated fasting glucose, hypertension, or the composite definition of the metabolic syndrome for the RA group compared with controls. Within the RA group, rheumatoid factor seropositivity and higher cumulative prednisone exposure were significantly associated with a higher mean adjusted VFA. Higher C-reactive protein levels and lower Sharp scores were significantly associated with both VFA and SFA.
The distribution of abdominal fat differs significantly by RA status. Higher VFA in men with RA, and the more potent association of VFA with cardiometabolic risk factors in men and women with RA, may contribute to cardiovascular risk in RA populations.
The purpose of this study was to examine the association of both a low and a high ankle-brachial index (ABI) with incident cardiovascular events in a multi-ethnic cohort.
Abnormal ankle-brachial indices (ABIs), both low and high, are associated with elevated cardiovascular disease (CVD) risk. However, it is unknown whether this association is consistent across different ethnic groups, and whether it is independent of both newer biomarkers and other measures of subclinical atherosclerotic CVD.
6647 non-Hispanic white, African-American, Hispanic, and Chinese men and women aged 45–84 years from free-living populations in six United States field centers and free of clinical CVD at baseline had extensive measures of traditional and newer biomarker risk factors, and measures of subclinical CVD, including the ABI. Incident CVD, defined as coronary disease, stroke, or other atherosclerotic CVD death, was determined over a mean follow-up of 5.3 years.
Both a low (<1.00) and a high (≥ 1.40) ABI were associated with incident CVD events. Gender- specific and ethnic-specific analyses showed consistent results. Hazard ratios were 1.77 (p<.001) for a low and 1.85 (p=.050) for a high ABI after adjustment for both traditional and newer biomarker CVD risk factors, and the ABI significantly improved risk discrimination. Further adjustment for coronary artery calcium score, common and internal carotid intimal medial thickness, and major ECG abnormalities only modestly attenuated these hazard ratios.
In this study both a low and a high ABI were associated with elevated CVD risk in persons free of known CVD, independent of standard and novel risk factors, and independent of other measures of subclinical CVD. Further research should address the cost-effectiveness of measuring the ABI in targeted population groups.
peripheral arterial disease; ankle-brachial index; cardiovascular events; risk factors; subclinical atherosclerosis
To examine the association of perceived racial/ethnic discrimination with smoking and alcohol consumption in adults participating in the Multi-Ethnic Study of Atherosclerosis.
Data on 6,680 black, Chinese, Hispanic and white adults aged 45 to 84 years of age recruited from Illinois, New York, Maryland, North Carolina, Minnesota and California during 2000 and 2002 were used for this analysis. Logistic regression was used to estimate the association of perceived racial/ethnic discrimination with smoking status and alcohol consumption for each racial/ethnic group separately.
Blacks were more likely to experience racial/ethnic discrimination (43%) than Hispanics (19%), Chinese participants (10%) or whites (4%, P<0.0001). In the fully-adjusted model, blacks reporting racial/ethnic discrimination had 34% and 51% greater odds of reporting smoking and drinking, respectively, than blacks who did not report racial/ethnic discrimination. Hispanics reporting racial/ethnic discrimination had 62% greater odds of heavy drinking. Whites reporting racial/ethnic discrimination had 88% greater odds of reporting being current smokers than whites who did not report racial/ethnic discrimination.
Our findings suggest that the experience of discrimination is associated with greater prevalence of unhealthy behaviors. Specifically, the use of smoking and alcohol may be patterned by experience of discrimination.
Racial/ethnic discrimination; discrimination; smoking; alcohol; blacks; Hispanics; Chinese; whites
A prediction model, developed in the Framingham Heart Study (FHS), has been proposed for use in estimating a given individual’s risk of hypertension. We compared this model with systolic blood pressure (SBP) alone and age-specific diastolic blood pressure (DBP) categories for the prediction of hypertension. Participants in the Multi-Ethnic Study of Atherosclerosis, without hypertension or diabetes (n=3013), were followed for the incidence of hypertension (SBP ≥ 140 mmHg and/or DBP ≥ 90 mmHg and/or the initiation of antihypertensive medication). The predicted probability of developing hypertension between four adjacent study examinations, with a median of 1.6 years between examinations, was determined. The mean (standard deviation) age of participants was 58.5 (9.7) years and 53% were women. During follow-up, 849 incident cases of hypertension occurred. The c-statistic for the FHS model was 0.788 (95% CI: 0.773, 0.804) compared with 0.768 (95% CI: 0.751, 0.785; p=0.096 compared to the FHS model) for SBP alone and 0.699 (95% CI: 0.681, 0.717; p<0.001 compared to the FHS model) for age-specific DBP categories. The relative integrated discrimination improvement index for the FHS model versus SBP alone was 10.0% (95% CI: −1.7%, 22.7%) and versus age-specific DBP categories was 146% (95% CI: 116%, 181%). Using the FHS model, there were significant differences between observed and predicted hypertension risk (Hosmer-Lemeshow goodness of fit p<0.001); re-calibrated and best-fit models produced a better model fit (p=0.064 and 0.245, respectively). In this multi-ethnic cohort of U.S. adults, the FHS model was not substantially better than SBP alone for predicting hypertension.
hypertension; epidemiology; systolic blood pressure; diastolic blood pressure; risk prediction
Individuals with exaggerated exercise blood pressure (BP) tend to develop future hypertension. It is controversial if they have higher risk of death from cardiovascular disease (CVD).
Methods and Results
6,578 asymptomatic Lipid Research Clinic Prevalence Study participants (45% women, mean age 46 years, 74% untreated baseline BP <140/90mmHg [non-hypertensive]) performing submaximal Bruce treadmill tests were followed for 20 years (385 CVD deaths occurred). Systolic and diastolic BP at rest, Bruce stage 2, and maximal BP during exercise were significantly associated with CVD death. Comparing multivariate hazard ratios (HRs) and 95% confidence intervals per 10/5mmHg BP increments, the association was strongest for rest BP (systolic 1.21 [1.14–1.27]; diastolic 1.20 [1.14–1.26]), then Bruce stage 2 BP (systolic 1.09 [1.04–1.14]; diastolic 1.09 [1.05–1.13]), then maximal exercise BP (systolic 1.06 [1.01–1.10]; diastolic 1.04 [1.01–1.08]). Overall, exercise BP was not significant after adjustment for rest BP. However, hypertension status modified the risk associated with exercise BP (p, interaction=0.03). Among non-hypertensives, whether they had normal BP (<120/80mmHg) or prehypertension, Bruce stage 2 BP >180/90 vs. ≤180/90mmHg carried increased risk independent of rest BP and risk factors (adjusted HR for systolic 1.96 [1.40–2.74], p<0.001; diastolic 1.48 [1.06–2.06], p=0.02), and added predictive value (net reclassification improvement systolic 12.0% [−0.1–24.2%], diastolic 9.9% [−0.3–20.0%]; relative integrated discrimination improvement 14.3% and 12.0%, respectively).
In asymptomatic individuals, elevated exercise BP carried higher risk of CVD death, but became non-significant after accounting for rest BP. However, Bruce stage 2 BP >180/90mmHg identified non-hypertensive individuals at higher risk of CVD death.
Exercise; blood pressure; cardiovascular disease; mortality