Primary prevention guidelines recommend calculation of lifetime cardiovascular disease (CVD) predicted risk among individuals who may not meet criteria for high short-term (10-year) ATP-III risk for coronary heart disease (CHD). Both extreme obesity and bariatric surgery are more common among women, who often have low short-term predicted CHD risk. The distribution and correlates of lifetime CVD predicted risk, however, have not yet been evaluated among bariatric surgery candidates. Using established 10-year (ATP-III) CHD and lifetime CVD risk prediction algorithms and pre-surgery risk factors, participants from the Longitudinal Assessment of Bariatric Surgery-2 study without prevalent CVD (n=2070) were stratified into 3 groups: low 10-year (<10%)/low lifetime (<39%) predicted risk, low 10-year (<10%)/high lifetime (≥39%) predicted risk, and high 10-year (≥10% predicted risk or diagnosed diabetes.) Participants were predominantly white (86%), women (80%), with a median age of 45 years and median BMI of 45.6 kg/m2. High 10-year CHD predicted risk was common (36.5%), and associated with diabetes, male sex and older age, but not with higher BMI or hs-c-reactive protein. Most (76%) participants with low 10-year predicted risk had high lifetime CVD predicted risk, which was associated with dyslipidemia and hypertension, but not with BMI, waist circumference, HDL cholesterol or hs-C-reactive protein. In conclusion, bariatric surgery candidates without diabetes or existing CVD are likely to have low short-term, but high lifetime CVD predicted risk. Current data support the need for long-term monitoring and treatment of elevated CVD risk factors among bariatric surgery patients, to maximize lifetime CVD risk reduction.
Clinical Trial Registration
Long-term Effects of Bariatric Surgery, #NCT00465829, http://www.clinicaltrials.gov/ct2/results?term=%23NCT00465829
Cardiovascular disease; extreme obesity; bariatric surgery; lipids
Levels of adiponectin are inversely associated with obesity levels. We examined the levels of adiponectin in American (n = 98) and Japanese (n = 92) men aged 40 to 49 years. Contrary to our expectations, the American men had higher evels of adiponectin than the Japanese men (13.3 ± 5.8 vs 7.3 ± 4.2 (μg/ml) despite higher levels of obesity. Smaller areas of visceral adipose tissue in American than in Japanese men may have resulted in the higher levels of adiponectin.
Ghrelin, a 28-amino-acid gastric peptide hormone, has an appetite-stimulating effect and controls the energy balance. Serum ghrelin levels inversely correlate with body mass index. Recently, several papers reported the ethnic difference in the ghrelin levels. To our knowledge, however, no studies have compared the serum ghrelin levels between Caucasian in the United States (U.S.) and the Japanese in Japan.
We conducted a cross-sectional study of 189 men 40-49 years of age (91 Caucasian in the U.S. and 98 Japanese in Japan) to examine serum ghrelin levels and metabolic and other factors.
Serum ghrelin levels correlated with waist circumferences and lipid profiles among Caucasian American and the Japanese. Serum ghrelin levels were significantly higher among Caucasian Americans than among the Japanese (904.5 (632.0, 1132.0) pg/mL, 508.0 (399.0, 1378.3) pg/mL (median and 95% confidence interval), respectively, P<0.01), although Caucasian Americans were much more obese (BMI: 26.9±3.3 kg/m2 versus 23.3±3.1kg/m2 respectively, P<0.01). The ethnic difference remained after adjusting for metabolic factors, smoking status, and other factors (P<0.01).
We have shown in our population-based study that serum ghrelin levels among men aged 40-49 are significantly higher in Caucasian Americans than in the Japanese in Japan. Reasons for the ethnic difference in the ghrelin levels are largely unknown and warrant further investigation.
gut hormones; ghrelin; ethinic difference
The use of estrogen plus progestin therapy increases both breast cancer incidence and breast tenderness. Whether breast tenderness during estrogen plus progestin therapy is associated with breast cancer risk is uncertain.
We analyzed data from the Women’s Health Initiative Estrogen plus Progestin Clinical Trial, which randomized postmenopausal women with an intact uterus to conjugated equine estrogens 0.625 mg plus medroxyprogesterone acetate 2.5 mg daily (CEE + MPA, N=8506) or placebo (N=8102). At baseline and annually, participants underwent mammography and clinical breast exam. Self-report of breast tenderness was assessed at baseline and 12 months. Invasive breast cancer incidence was confirmed by medical record review (mean 5.6 years of follow-up).
Among women without baseline breast tenderness (N=14538), significantly more women assigned to CEE + MPA than placebo experienced new-onset breast tenderness after 12 months (36.1% vs. 11.8%, P<0.001). Among women in the CEE + MPA group, breast cancer risk was significantly higher in those with new-onset breast tenderness compared to those without new-onset breast tenderness (Hazard Ratio 1.48, 95% confidence interval 1.08–2.03, P=0.02). Among women in the placebo group, breast cancer risk was not significantly associated with new-onset breast tenderness.
New-onset breast tenderness during use of CEE + MPA was associated with increased breast cancer risk. The sensitivity and specificity for the association between breast tenderness and breast cancer were similar in magnitude to those of the Gail model.
Explanations for the low prevalence of atherosclerosis in Japan versus United States are often confounded with genetic variation. To help remove such confounding, coronary artery calcification (CAC), a marker of subclinical atherosclerosis, was compared between Japanese men in Japan and Japanese men in Hawaii. Findings are based on risk factor and CAC measurements that were made from 2001 to 2005 in 311 men in Japan and 300 men in Hawaii. Men were aged 40 to 50 years and without cardiovascular disease. After age-adjustment, there was a 3-fold excess in the odds of prevalent CAC scores ≥10 in Hawaii versus Japan (relative odds [RO] = 3.2; 95% confidence interval [CI] = 2.1,4.9). While men in Hawaii had a generally poorer risk factor profile, men in Japan were 4-times more likely to smoke cigarettes (49.5 vs. 12.7%, p<0.001). In spite of marked risk factor differences between the samples, none of the risk factors provided an explanation for the low amounts of CAC in Japan. After risk factor adjustment, the RO of CAC scores ≥10 in Hawaii versus Japan was 4.0 (95% CI = 2.2,7.4). Further studies are needed to identify factors that offer protection against atherosclerosis in Japanese men in Japan.
Atherosclerosis; cohort studies; coronary disease; Japan; men; risk factors
Elevated plasma plasminogen activator inhibitor-1 (PAI-1) levels were associated with higher incidence of type II diabetes. Elucidating the determinants of PAI-1 in various ethnicities may help to understand the susceptibility to developing diabetes. The aim of our study was to compare PAI-1 levels between Americans and the Japanese in the post-war generation and to elucidate the determinants of the PAI-1 levels.
We conducted a cross-sectional study on a total of 198 men aged 40–49 in the U.S. (Body-mass index (BMI): 27.0 ± 3.3 kg/m2) and Japan (BMI: 23.3 ± 3.1 kg/m2). Examination included physique measurement (BMI and waist girth), blood analysis (lipid profiles, glucose, insulin, C-reactive protein, and PAI-1), and life-style assessment by self-administered questionnaires.
PAI-1 levels were significantly lower in American than in Japanese men, even after adjustment for age, waist girth, cigarette smoking, habitual alcohol drinking, and other factors. In the Americans, waist girth, insulin, and cigarette smoking were significantly associated with PAI-1 levels, while waist girth and triglycerides were significantly associated with PAI-1 levels in the Japanese.
PAI-1 levels were significantly lower in American than in Japanese men and the determinants of PAI-1 levels differ for American and Japanese men aged 40–49.
PAI-1; US; Japan; epidemiology; post-war generation
Coronary heart disease (CHD) incidence and mortality remain very low in Japan despite major dietary changes and increases in CHD risk factors that should have resulted in substantial increase in CHD rates (Japanese paradox). Primary genetic effects are unlikely, given the substantial increase in CHD in migrant Japanese to the U.S. For men aged 40–49, levels of total cholesterol and blood pressure have been similar in Japan and the U.S. throughout their lifetime. The authors tested the hypothesis that levels of subclinical atherosclerosis, coronary artery calcification and intima-media thickness of the carotid artery (IMT), in men aged 40–49 are similar in Japan and the U.S. The authors conducted a population-based study of 493 randomly-selected men: 250 men in Kusatsu, Shiga, Japan, and 243 white men in Allegheny County, Pennsylvania, U.S. in 2002–2005. The Japanese had a less favorable profile of many risk factors than the whites. Prevalence ratio for the presence of coronary calcium score ≥10 in the Japanese compared to the whites was 0.52 (95% CI, 0.35, 0.76). Mean (SE) IMT was significantly lower in the Japanese (0.616 (0.005) versus 0.672 (0.005) mm, p<0.01). Both associations remained significant after adjusting for risk factors. The findings warrant further investigations.
Atherosclerosis; epidemiology; men; risk factors
We have previously reported that the prevalence of coronary artery calcification (CAC) was substantially lower among Japanese than American men despite a less favorable profile of many traditional risk factors in Japanese men.
To determine whether lipoprotein-associated phospholipase A2 (Lp-PLA2) levels are related to the difference in the prevalence of CAC between the two populations.
A total of 200 men aged 40-49 were examined: 100 residents in Allegheny County, Pennsylvania, United States, and 100 residents in Kusatsu City, Shiga, Japan. Coronary calcium score (CCS) was evaluated by electron-beam tomography, Lp-PLA2 levels, nuclear magnetic resonance (NMR) lipoprotein subclasses and other factors were assessed centrally in the United States.
Lp-PLA2 levels were higher among American than Japanese men (Mean±SD 301.7±82.6 versus 275.9±104.7 ng/mL, respectively, p=0.06). Among all Japanese men and those with low density lipoprotein (LDL) cholesterol ≥130 mg/dL, there was an inverse association of the prevalence of CCS>0 with the tertile groups of Lp-PLA2 levels (p=0.08 and p=0.03, respectively). American men did not have any association between CCS>0 with the tertile groups of Lp-PLA2 (p=0.62). Although Lp-PLA2 among both populations correlated positively with LDL and total cholesterol, American and Japanese men had different correlations with NMR lipoprotein subclasses. Reported high odds ratio for CCS>0 among American compared to Japanese men was not reduced after adjusting for Lp-PLA2 levels.
Lp-PLA2 may have different mechanisms of action among American and Japanese men. Lp-PLA2 levels can not explain the observed CAC differences between the two populations.
atherosclerosis; lipoprotein-associated phospholipase A2; coronary artery disease; coronary calcification; Japanese; Caucasian
In contrast to many observational studies, women in the Women’s Health Initiative (WHI) trial randomised to oestrogen-alone had lower invasive breast cancer incidence than those assigned placebo. Influence of oestrogen use on breast cancer mortality has not been reported.
Between 1993 and 1998, the WHI enrolled 10,739 postmenopausal women from 40 US centres into a randomized, double-masked, placebo-controlled trial evaluating oral conjugated equine oestrogen (0·625 mg/d). Women aged 50–79 years with prior hysterectomy, anticipated 3-year survival, and mammography clearance were randomized by a computerized, permuted block algorithm, stratified by age group and centre, to receive oestrogen or matching placebo. The trial was terminated early, in 2004, for an adverse effect on stroke. In extended follow-up through August 2009, we assessed long-term effects of oestrogen use on invasive breast cancer incidence, tumor characteristics, and mortality. Cox regression models were used to estimate intention-to-treat hazard ratios [HRs].
After a median 11.8 (interquartile range [IQR], 9·1 to 12·9) years of follow-up, conjugated equine oestrogen-alone use for a median of 5·9 (IQR, 2·5 to 7·3) years was associated with lower invasive breast cancer incidence compared to placebo (151 vs. 199 breast cancers; annualized rates, 0·27% vs. 0·35%; HR, 0·77; 95% confidence interval [CI], 0·62 to 0·95; P=0·02) with no difference (P=0·76) between intervention-phase (HR, 0·79; 95% CI, 0·61 to 1·02) and post-intervention effects (HR, 0·75; 95% CI: 0·51 to 1·09) ). Potential effect modification by benign breast disease (P=0·01) and family history of breast cancer (P=0·02) was observed. In the oestrogen-alone group fewer women died from breast cancer (6 vs.16 deaths; annualized rates 0·009% vs. 0·024%; HR, 0·37; 95% CI, 0·13 to 0·91; P=0.03) and fewer died from all causes after a breast cancer diagnosis (30 vs. 50 deaths; annualized rates, 0·046% vs. 0·076%; HR, 0·62; 95% CI, 0·39 to 0·9;, P=0·04).
Women with hysterectomy seeking relief of climacteric symptoms may be given reassurance regarding breast cancer influence of oestrogen use consistent with durations observed in this trial. However, these findings do not support oestrogen use for breast cancer risk reduction since this benefit may not apply to populations at higher risk.
US National Heart, Lung and Blood Institute. Wyeth provided study medications.
menopausal hormone therapy; breast neoplasms; breast cancer mortality; prevention trial
Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease with increased prevalence of cardiovascular disease (CVD) and depression. Although depression may contribute to CVD risk in population-based studies, its influence on cardiovascular morbidity in SLE has not been evaluated. We evaluated the association between depression and vascular disease in SLE.
A cross-sectional study was conducted from 2002–2005 in 161 women with SLE and without CVD. The primary outcome measure was a composite vascular disease marker consisting of the presence of coronary artery calcium and/or carotid artery plaque.
In total, 101 women met criteria for vascular disease. In unadjusted analyses, several traditional cardiovascular risk factors, inflammatory markers, adiposity, SLE disease-related factors, and depression were associated with vascular disease. In the final multivariable model, the psychological variable depression was associated with nearly 4-fold higher odds for vascular disease (OR 3.85, 95% CI 1.37, 10.87) when adjusted for other risk factors of age, lower education level, hypertensive status, waist-hip ratio, and C-reactive protein.
In SLE, depression is independently associated with vascular disease, along with physical factors.
SYSTEMIC LUPUS ERYTHEMATOSUS; CARDIOVASCULAR DISEASE; DEPRESSION CALCIFICATION; CAROTID PLAQUE; PSYCHOSOCIAL FACTORS
The Women on the Move through Activity and Nutrition (WOMAN) study was designed to test whether a nonpharmacological intervention including qualitative and quantitative dietary changes to induce weight loss and increased physical activity levels would reduce blood triglyceride levels and number of low-density lipoprotein particles (LDL-P). Such decreases in lipoproteins and other risk factors could reduce or slow progression of subclinical cardiovascular disease (CVD). Study participants were randomized to either the intervention (Lifestyle Change) or assessment (Health Education) group. Most of the intervention ended at the 30-month visit. The last 48-month examination was completed in 9/2008. There was very substantial weight loss and increased exercise during the first 30 months of the trial resulting in significant decreases in CV risk factors. Most of the intervention effect was lost through 48 months. Weight loss was 3.4 kg in Lifestyle Intervention and 0.2 kg in the Health Education at 48 months (P = 0.000). There were no significant changes at 48 months in lipid levels, blood pressure (BP), glucose, insulin, or in the subclinical measures of coronary calcium, carotid intima media thickness, or plaque. There was a significant decrease in long-distance corridor walk time in the Lifestyle vs. Health Education groups. Significant lifestyle changes can be achieved that result in decreases in CV risk factors. Whether such changes reduce CV outcomes is still untested in clinical trials of weight loss or exercise. Long-term maintenance of successful lifestyle changes, weight loss and reduced risk factors is the hurdle for lifestyle interventions attempting to prevent CV and other chronic diseases.
Cerebral white matter lesions (WMLs) reflect small vessel disease, are common in elderly individuals and are associated with cognitive impairment. We sought to determine the relationships between WMLs, age, gray matter (GM) volume, and cognition in the Cardiovascular Health Study (CHS).
From the CHS we selected 740 cognitively normal controls with a 1.5 T MRI scan of the brain and a detailed diagnostic evaluation. WML severity was determined using a standardized visual rating system. GM volumes were analyzed using voxel-based morphometry implemented in the Statistical Parametric Mapping software.
WMLs were inversely correlated with GM volume, with the greatest volume loss in the frontal cortex. Age related atrophy was observed in the hippocampus and posterior cingulate cortex. Regression analyses revealed links among age, APOE*4 allele, hypertension, WMLs, GM volume, and digit symbol substitution test scores.
Both advancing age and hypertension predict higher WML load, which is itself associated with GM atrophy. Longitudinal data are needed to confirm the temporal sequence of events leading to a decline in cognitive function.
White matter lesions; age; gray matter volume; cognition
To examine the individual and combined associations of leisure-time physical activity and sleep with cardiovascular risk factors in postmenopausal women.
We analyzed cross-sectional 48-month follow-up data from 393 participants of the Woman on the Move through Activity and Nutrition (WOMAN) Study, a behavioral weight loss trial. Leisure-time physical activity data were collected with the past year Modifiable Activity Questionnaire; sleep data were collected with the Pittsburgh Sleep Quality Index. We compared physical activity and sleep categories using ANOVA, post hoc Scheffe tests, and multivariate analyses based on groups above/below median leisure-time physical activity level, above/below below sleep quality value = 5, and above/below sleep duration of 7 hrs/day.
The average sleep quality and sleep duration did not significantly differ between women with high and low physical activity levels. When comparing women with good sleep quality, higher physical activity levels were associated lower BMI (2.0 kg/m2; 0.3, 3.6), waist circumference (6.3 cm; 1.7, 10.9), and total body fat (2.1 %; 0.3, 4.0) (p<0.05). When comparing participants with poor sleep quality, highly active women had lower trunk fat, total body fat, and insulin levels than less active women (p<0.05). In multivariate analysis, physical activity was significantly associated with HDL, trunk fat, and total body fat after controlling for sleep quality, sleep duration, age, hormone therapy, smoking, and BMI.
The combined associations of leisure-time physical activity and sleep suggest that cardiovascular risk factors were more favorable in highly active women relative to less active women regardless of sleep.
Physical activity; sleep; cardiovascular risk factors; menopause
Cigarette smoking is a risk factor of coronary heart disease (CHD). Vascular calcification such as coronary artery calcium (CAC) and aortic calcium (AC) is associated with CHD. We hypothesized that cigarette smoking is associated with coronary artery and aortic calcifications in Japanese and Koreans with high smoking prevalence.
Random samples from populations of 313 Japanese and 302 Korean men aged 40 to 49 were examined for calcification of the coronary artery and aorta using electron beam computed tomography. Coronary artery calcium (CAC) and aortic calcium (AC) were quantified using the Agatston score. We examined the associations of cigarette smoking with CAC and AC after adjusting for conventional risk factors and alcohol consumption. Current and past smokers were combined and categorized into two groups using median pack-years as a cutoff point in each of Japanese and Koreans. The never smoker group was used as a reference for the multiple logistic regression analyses.
The odds ratios of CAC (score ≥10) for smokers with higher pack-years were 2.9 in Japanese (P<0.05) and 1.3 in Koreans (non-significant) compared to never smokers. The odds ratios of AC (score ≥100) for smokers with higher pack-years were 10.4 in Japanese (P<0.05) and 3.6 in Koreans (P<0.05).
Cigarette smoking with higher pack-years is significantly associated with CAC and AC in Japanese men, while cigarette smoking with higher pack-years is significantly associated with AC but not significantly with CAC in Korean men.
atherosclerosis; cigarette smoking; coronary calcium; aortic calcium; Japanese; Koreans
Recent studies have shown that individuals with 0 coronary artery calcium (CAC) scores have very low risk of coronary heart disease. In the Healthy Women Study, we evaluated development of new CAC among postmenopausal women (n=272) over a 6 year period, age 62 at the 1st and 68 at the 3rd electron beam tomography (EBT) examination. At the 1st EBT, 155 of 272 (57%) women had 0 CAC. By the 3rd, 56 (36%) of these women had developed new CAC, including 38 with >5 Agatston units. There was practically no regression from having CAC at with the 1st EBT to no CAC at the 3rd EBT. The risk of developing new CAC over 6 years among women with 0 CAC on their 1st EBT was strongly and significantly related to presence of both aortic calcium and carotid plaque at the time of 1st EBT. Baseline premenopausal risk factors, age 47, apolipoprotein B, body mass index (BMI) and triglycerides, were significant predictors of incident CAC as were the changes in BMI and low density lipoprotein cholesterol between premenopause and the 1st post exam, age 53. Risk factors measured premenopause and change in risk factors from premenopause to the 1st post exam and the extent of subclinical disease in other vascular beds are primary determinants of the risk of developing incident CAC in women over a 6 year period.
The Women On the Move through Activity and Nutrition (WOMAN) Study is the first randomized clinical trial of nonpharmacological intervention designed to modify lipoproteins, weight loss and exercise among postmenopausal women using noninvasive measures of atherosclerosis as the primary endpoint. The trial was initially designed to test whether intervention as compared to health education would be more effective in slowing progression of subclinical atherosclerosis among women on hormone therapy (HT), estrogen or estrogen+progestin. It was designed and implemented prior to the results of the Women's Health Initiative (WHI). The trial was since modified to include women who had been on HT but went off after the results of the WHI were reported. Eligible women were between the ages of 52-62, had waist circumference ≥80 cm, low density lipoprotein cholesterol between 100-160 mg% and controlled blood pressure. The intervention is low in total and saturated fat, trans fats, higher in fiber and promotes loss of 7-10% of body weight and includes at least 150 minutes of physical activity per week. The study has recruited 508 women. The primary endpoints are change in extent of carotid intima media wall thickness as measured by carotid ultrasound, pulse wave velocity as a measure of vascular stiffness and coronary artery calcium using electron beam computed tomography. Body composition is measured by dual-energy x-ray absorptiometry.
To evaluate associations between mid- and late-life obesity and risk of dementia.
Prospective cohort followed 5.4 years from 1992/4 through 1999.
Community-dwelling sample in four US sites recruited from Medicare eligibility files.
2,798 adults without dementia, mean age 74.7 years, 59.1% women, participating in the Cardiovascular Health Cognition Study completing a magnetic resonance image, measured for height and weight at baseline (late-life) and self-reporting weight at age 50 (mid-life). Body mass index (BMI) was calculated at both times.
Main Outcome Measures
Dementia, Alzheimer’s disease (AD) and vascular dementia (VaD) classified by a multidisciplinary committee using standardized criteria.
Classification resulted in 480 persons with incident dementia, 245 with AD (no VaD) and 213 with VaD (with or without AD). In evaluations of mid-life obesity, an increased risk of dementia was found for obese (BMI >30) compared to normal (BMI 20-25) persons adjusted for demographics (HR: 1.39, 95% CI: 1.03-1.87) and for caradiovascularl risk factors (HR: 1.36, 95% CI: 0.94-1.95). The risk estimates reversed in assessments of late-life BMI. Underweight persons (BMI < 20) had an increased risk of dementia (HR: 1.62, 95% CI: 1.02-2.64) while being overweight (BMI 25-30) was not associated (HR: 0.92, 95% CI: 0.72-1.18) and being obese reduced the risk of dementia (HR: 0.63, 95% CI: 0.44-0.91) compared to those with normal BMI.
These results help explain the “obesity paradox” as differences in dementia risk over time are consistent with physical changes in the trajectory toward disability.
We examined several risk factors as possible independent predictors of aortic stiffness progression among a population based sample of US men.
Methods and Results
A total of 240 men aged 40–49 from the Allegheny County site of the ERA JUMP Study, who were free of CVD at baseline were evaluated. Aortic stiffness was measured as carotid-femoral pulse wave velocity (cfPWV) at baseline and after 4.6±0.21(mean±SD) years of follow-up. Progression of cfPWV was evaluated as relative annual change in cfPWV (% change/year). Using linear regression, both baseline potential risk factors and their annual changes were evaluated as possible risk factors for cfPWV progression. Baseline age, follow-up time, race, heart rate, and medications use were forced in all models. During follow-up, relative to baseline level, cfPWV increased 0.3%±5.3% per year. In final models the independent predictors of degree of cfPWV progression were lower levels of adiponectin (β(SE): −1.8(0.8), P=0.03), higher levels of systolic blood pressure (SBP) (β(SE): 0.07(0.03), P=0.02), greater annual change in SBP (β(SE): 0.3(0.2), P=0.04), and alcohol consumption ≥ 2 times/week (β(SE): 1.6(0.7), P=0.02).
Lower levels of adiponectin, higher levels and annual changes of SBP, and alcohol consumption ≥2 times/week are associated with greater progression in aortic stiffness among relatively healthy middle-aged US men.
arteriosclerosis; hypertension; risk factors; pulse wave velocity; stiffness
Coronary artery calcification (CAC) has been associated with psychosocial factors in some but not all cross-sectional analyses. The goal of this study was to determine whether positive and negative psychosocial factors prospectively predict CAC progression in postmenopausal women.
Participants from the Healthy Women Study who also participated in the Pittsburgh Mind-Body Center protocol (n = 149) completed self-report psychosocial measures prior to two electron beam tomography scans of CAC separated by an average of 3.3 years. Results of exploratory factor analysis were used to create aggregate psychosocial indices: Psychological Risk (depressive symptoms, perceived stress, cynicism, anger-in) and Psychosocial Resources (optimism, purpose in life, mastery, self-esteem, and social support).
The Psychological Risk index predicted significantly greater CAC progression over three years (β = .16, p = .035, ΔR2 = .03) while the Psychosocial Resources index was not predictive of CAC progression (β = -.08, p = .30, ΔR2 = .01). On individual scales, higher scores on cynicism emerged as a significant predictor of CAC progression, along with a trend linking anger-in to atherosclerosis progression. A post-hoc analysis showed a significant interaction between cynicism and anger-in (β =.20, p = .01, ΔR2 = .03), such that women reporting high levels of both cynicism and anger suppression exhibited the most CAC progression.
These findings highlight psychosocial risk factors that may accelerate the progression of subclinical atherosclerosis in older women, suggest the potential importance of examining combinations of psychosocial risk factors, and represent potential targets for psychological interventions to reduce cardiovascular risk.
coronary atherosclerosis; psychosocial; atherosclerosis; women
Background and Purpose
Does progression of MRI-defined vascular disease predict subsequent vascular events in the elderly?
The Cardiovascular Health Study, a longitudinal cohort study of vascular disease in the elderly, allows the question to be answered because its participants had two MRI scans about five years apart and have been followed for about 9 years since the follow-up scan for incident vascular events.
Both MRI-defined incident infarcts and worsened white matter grade (WMG) were significantly associated with heart failure (HF), stroke and death but not transient ischemic attacks, angina, or myocardial infarction. Strongest associations occurred when both incident infarcts and worsened WMG were present: for HF, hazard ratio 1.79 (95% confidence interval 1.18–2.73); for stroke, 2.58 (1.53–4.36); for death, 1.69 (1.28–2.24); and for cardiovascular death 1.97 (1.24–3.14).
Progression of MRI-defined vascular disease identifies elderly people at increased risk of subsequent HF, stroke, and death. Whether aggressive risk factor management would reduce risk is unknown.
MRI; brain infarction; leukoaraiosis; stroke; death
The Multiple Risk Factor Intervention Trial evaluated a multifactor intervention on coronary heart disease (CHD) in 12 866 men. A priori defined endpoints (CHD death, CHD death or nonfatal myocardial infarction, cardiovascular disease [CVD] death, and all-cause death) did not differ significantly between the special intervention (SI) and usual care (UC) groups over an average follow-up period of 7 years. Event rates were lower than anticipated, reducing power. Other nonfatal CVD outcomes were prespecified but not considered in composite outcomes comparing SI with UC.
Methods and Results
Post-trial CVD mortality risks associated with nonfatal CVD events occurring during the trial were determined with Cox regression. Nonfatal outcomes associated with >2-fold risk of CVD death over the subsequent 20 years were combined with during-trial deaths to create 2 new composite outcomes. SI/UC hazard ratios and 95% confidence intervals were estimated for each composite outcome. Of 10 during-trial nonfatal events, 6 were associated (P<0.001) with >2-fold risk of CVD death. A CHD composite outcome (CHD death, myocardial infarction [clinical or serial ECG change], CHF, or coronary artery surgery) was experienced by 520 SI and 602 UC men (SI/UC hazard ratio = 0.86; 95% confidence interval, 0.76–0.97; P=0.01). A CVD composite outcome (CHD [as above], other CVD deaths, stroke, or renal impairment) was experienced by 581 SI and 652 UC men (hazard ratio = 0.89; 95% confidence interval, 0.79–0.99; P=0.04).
In post hoc analyses, composite fatal/nonfatal CHD and CVD rates over 7 years were significantly lower for SI than for UC. These findings reinforce recommendations for improved dietary/lifestyle practices, with pharmacological therapy as needed, to prevent and control major CVD risk factors.
clinical trials; primary prevention; risk factors
The SMART study was a trial of intermittent use of antiretroviral therapy (ART) (drug conservation [DC]) versus continuous use of ART (viral suppression [VS]) as a strategy to reduce toxicities, including cardiovascular disease (CVD) risk. We studied the predictive value of high sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6) and D-dimer with CVD morbidity and mortality in HIV-infected patients who were enrolled in SMART beyond other measured CVD risk factors.
A blood sample was available in 5098 participants who were enrolled in the SMART study for the measurement of IL-6, hsCRP and D-dimer. Hazard ratios (HR) with 95% CI for CVD events were estimated for each quartile (Q) for each biomarker vs the 1st quartile and for 1 SD higher levels. For both treatment groups combined, unadjusted and adjusted HRs were determined using Cox regression models.
There were 252 participants who had a CVD event over a median follow-up of 29 months. Adjusted HRs (95% CI) for CVD for Q4 vs Q1 were 4.65 (2.61, 8.29), 2.10 (1.40, 3.16), and 2.14 (1.38, 3.33) for IL-6, hsCRP and D-dimer, respectively. Associations were similar for the DC and VS treatment groups (interaction p-values were >0.30). The addition of the three biomarkers to a model that included baseline covariates significantly improved model fit (p<0.001). Area under the curve (AUC) estimates improved with inclusion of the three biomarkers in a model that included baseline covariates corresponding to other CVD risk factors and HIV factors (0.741 to 0.771; p<0.001 for difference).
In HIV-infected individuals, IL-6, hsCRP and D-dimer are associated with an increased risk of CVD independent of other CVD risk factors. Further research is needed to determine whether these biomarkers can be used to improve CVD risk prediction among HIV positive individuals.