Understanding how sex and tobacco exposure may modify lifetime risks for cancer mortality is important for effective communication of risk in targeted public health messages.
To determine lifetime risk estimates for cancer death associated with sex and smoking status in the United States.
A pooled cohort design using ten well-defined epidemiologic cohorts including middle-aged and older individuals was used to estimate the lifetime risk for cancer death at selected index ages, with death from non-cancer causes as the competing risk, by sex and smoking status.
There were a total of 11,317 cancer-related deaths. At age 45 years, the lifetime risk of cancer death for male smokers is 27.7% (95% CI 24.0% to 31.4%) compared to 15.8% (95% CI 12.7% to 18.9%) for male non-smokers. At age 45 years, the lifetime risk of cancer death for female smokers is 21.7% (95% CI 18.8% to 24.6%) compared to 13.2% (95% CI 11.0% to 15.4%) for female non-smokers. Remaining lifetime risk for cancer death declined with age, and men have a greater risk for cancer death compared to women. Adjustment for competing risk of death, particularly representing cardiovascular mortality, yielded a greater change in lifetime risk estimates for men and smokers compared to women and non-smokers.
At the population level the lifetime risk for cancer death remains significantly higher for smokers compared to non-smokers, regardless of sex. These estimates may provide clinicians with useful information for counseling individual patients and highlight the need for continued public health efforts related to smoking cessation.
Tobacco; Smoking; Cancer; Lifetime Risk; Cancer mortality; Sex
The inverse, dose-dependent association between cardiorespiratory fitness and mortality is well-established; however, the pattern of the association between low fitness and mortality across short- (0 to 10 years), intermediate- (10 to 20 years), and long-term (>20 years) follow-up has not been studied.
Methods and Results
We included 46 575 men and 16 151 women (mean age 44 years) from the Cooper Center Longitudinal Study. Participants were categorized as either “low fit” or “not low fit,” based on age- and sex- adjusted treadmill times, and were followed for mortality, determined from the National Death Index. Multivariable-adjusted Cox proportional hazards models were constructed to compare the association between fitness and traditional risk factors, with mortality outcomes across short-, intermediate-, and long-term follow-up. After a median follow-up of 16 years, there were 1295 cardiovascular disease and 2840 noncardiovascular disease deaths. Low fitness was associated with all-cause mortality across all periods in men [0 to 10 years: hazard ratios (HR), 1.99 (95% confidence interval [CI], 1.66 to 2.40); 10 to 20 years: HR, 1.61 (95% CI, 1.41 to 1.84); and >20 years: HR, 1.42 (95% CI, 1.27 to 1.60)] and in women [0 to 10 years: HR, 1.98 (95% CI, 1.27 to 3.10); 10 to 20 years: HR, 1.90 (95% CI, 1.40 to 2.56); and >20 years: HR, 1.54 (95% CI, 1.15 to 2.07)]. Similar results were seen for both cardiovascular disease and noncardiovascular disease mortality. Although these associations were also consistent across most subgroups, low fitness appeared to be most strongly associated with mortality in the short term among individuals at highest short-term risk (ie, older age, abnormal exercise test).
Similar to traditional risk factors, fitness is associated with mortality across short-, intermediate-, and long-term follow-up.
fitness; epidemiology; risk factors; survival analysis
To determine the association between fitness and lifetime risk for cardiovascular disease (CVD).
Higher levels of traditional risk factors are associated with marked differences in lifetime risks for CVD. However, data are sparse regarding the association between fitness and the lifetime risk for CVD.
We followed 11,049 men who underwent clinical examination at the Cooper Clinic in Dallas, TX before 1990 until the occurrence of CVD death, non-CVD death, or attainment of age 90 (281,469 person-years of follow-up, median follow-up 25.3 years, 1,106 CVD deaths). Fitness was measured by Balke protocol and categorized according to treadmill time into low-, intermediate-, and high- fitness with further stratification by CVD risk factor burden. Lifetime risk for CVD death determined by the National Death Index was estimated for fitness levels measured at ages 45-, 55-, and 65-years with non-CVD death as the competing event.
Differences in fitness levels (low- fitness versus high- fitness) were associated with marked differences in the lifetime risks for CVD death at each index age (age 45: 13.7% versus 3.4%; age 55: 34.2% versus 15.3%; age 65: 35.6% versus 17.1%). These associations were strongest among individuals with CVD risk factors.
A single measurement of low fitness in mid-life was associated with higher lifetime risk for CVD death, particularly among individuals with a high burden of CVD risk factors.
cardiovascular disease; epidemiology; exercise testing; lifetime risk
Prior estimates of lifetime risk (LTR) for cardiovascular disease (CVD) examined the impact of blood pressure at the index age and did not account for changes in blood pressure over time. We examined how changes in blood pressure during middle-age affect LTR for CVD, coronary heart disease (CHD) and stroke.
Methods and Results
Data from 7 diverse US cohort studies were pooled. Remaining LTR for CVD, CHD and stroke were estimated for White and Black men and women with death free of CVD as a competing event. LTR for CVD by blood pressure (BP) strata and by changes in BP over an average of 14 years were estimated. Starting at age 55, we followed 61,585 men and women for 700,000 person-years. LTR for CVD was 52.5% (95% CI 51.3–53.7) for men and 39.9% (38.7–41.0) for women. LTR for CVD was higher for Blacks and increased with increasing BP at index age. Individuals who maintained or decreased their BP to normal levels had the lowest remaining LTR for CVD, 22–41%, as compared to individuals who had or developed hypertension by the age of 55, 42–69%; suggesting a dose-response effect for the length of time at high BP levels
Individuals who experience increases or decreases in BP in middle age have associated higher and lower remaining LTR for CVD. Prevention efforts should continue to emphasize the importance of lowering BP and avoiding or delaying the incidence of hypertension in order to reduce the LTR for CVD.
cardiovascular disease; coronary heart disease; stroke; hypertension; risk factors
Clinician counseling is a catalyst for lifestyle modification in obesity. Unfortunately, clinicians do not appropriately counsel all obese patients about lifestyle modification. The extent of disparities in clinician counseling is not well understood. Obese participants (BMI ≥30 kg/m2, N = 2097) in the Dallas Heart Study (DHS), a probability-based sample of Dallas County residents ages 18–65, were surveyed regarding health-care utilization and lifestyle counseling over the year prior to DHS enrollment. Health-care utilization and counseling were compared between obese participants across three categories based on the presence of 0, 1, or 2+ of the following cardiovascular (CV) risk factors: hypertension, hypercholesterolemia, or diabetes. Logistic regression modeling was used to determine likelihood of counseling in those with 0 vs. 1+ CV risk factors, stratified by race, adjusting for age, sex, insurance status, and education. Among obese subjects who sought medical care, those with 0 CV risk factors, compared to those with 1 or 2+ CV risk factors, were less likely to report counseling about losing weight (41% vs. 67% vs. 87%, P trend <0.001), dietary changes (44% vs. 71% vs. 85%, P trend <0.001), and physical activity (46% vs. 71% vs. 86%, P trend <0.001). Blacks and Hispanics without CV risk factors had a lower odds of receiving counseling than whites without risk factors on weight loss (adjusted odds ratio (OR), 95% confidence interval (CI) for nonwhites 0.19, [0.13–0.28], whites 0.48, [0.26–0.87]); dietary changes (nonwhites 0.19, [0.13–0.27], whites 0.37, [0.21–0.64]); and physical activity (nonwhites 0.22, [0.16–0.32], whites 0.32, [0.18–0.57]). Lifestyle counseling rates by clinicians are suboptimal among obese patients without CV risk factors, especially blacks and Hispanics. Systematic education about and application of lifestyle interventions could capitalize on opportunities for primary CV risk prevention.
Myeloperoxidase (MPO) is a leukocyte-derived enzyme that appears to be directly involved in atherosclerosis development. We evaluated the association of circulating MPO with coronary and aortic atherosclerosis in a large, multiethnic population.
Methods and Results
Plasma levels of MPO were measured in 3294 subjects participating in the Dallas Heart Study, a probability-based population sample. Coronary artery calcification (CAC) was measured by EBCT, and abdominal aorta plaque prevalence (AP) and burden (APB), as well as abdominal aorta wall thickness (AWT) were determined by MRI. Associations between MPO and atherosclerosis phenotypes were assessed in multivariable analyses adjusting for traditional atherosclerosis risk factors. MPO levels in the 4th compared with 1st quartile independently associated with prevalent AP (OR 1.41, 95% CI 1.08–1.84), APB (beta coefficient 0.23, p=0.02), and AWT (beta coefficient 0.04, p=0.03), but not with prevalent CAC (OR 0.84, 95% CI 0.61–1.17). MPO remained associated with aortic atherosclerosis phenotypes but not coronary calcification after adjustment for other inflammatory biomarkers. A significant interaction was observed between race/ethnicity, MPO and AP (pinteraction=0.038), such that MPO levels in the 4th vs 1st quartile associated with prevalent AP in African Americans, (OR 1.81, 95% CI 1.23–2.65) but not in White or Hispanic participants (OR 0.99, 95% CI 0.68–1.44).
Higher levels of MPO associated with aortic but not coronary atherosclerosis, with significant associations limited to African American participants. These findings suggest that MPO might be a novel risk factor contributing to racial disparities in peripheral vascular disease.
Myeloperoxidase; atherosclerosis; peripheral vascular disease; African American
Pulmonary surfactant protein B (SP-B), an alveolar protein normally detectable at only very low concentrations in blood, circulates at higher levels among smokers and those with alveolar injury and inflammation. We hypothesized that SP-B may serve as a marker of the vascular effects of smoking, and would thus associate with subclinical measures of atherosclerosis.
Methods and Results
Plasma levels of SP-B were measured in 3,294 subjects, ages 30-65, enrolled in the Dallas Heart Study, a probability-based population sample of Dallas County adults. Coronary artery calcium (CAC) was measured by computed tomography and abdominal aortic plaque (AP) by magnetic resonance imaging. The cohort comprised 29% current and 17% former smokers. The overall prevalence of CAC was 22% and AP 39%. Median SP-B levels were 5-fold higher among current vs. never smokers (P<0.0001) and significantly correlated with estimated pack-years smoked (Spearman rho=0.35, P<0.0001). Increasing levels of SP-B also associated with other traditional cardiac risk factors and higher levels of inflammatory biomarkers. In univariable analyses, increasing SP-B quartiles associated with higher prevalence of both CAC and AP (Ptrend <0.0001 for each). In multivariable analyses adjusting for traditional cardiovascular risk factors, SP-B remained associated with AP (OR 1.87 for the 4th vs. 1st quartile, 95% CI 1.39 to 2.51; P<0.0001) but not CAC. An interaction was observed between SP-B, smoking status, and AP (Pinteraction=0.01), such that SP-B associated with AP in current smokers (adjusted OR 2.15 for the 4th vs. 1st quartile, 95% CI 1.26 to 3.67; P=0.005), but not in former or never smokers.
Circulating levels of SP-B increase with greater smoking burden and independently associate with abdominal aortic plaque among current smokers. Our findings support further investigation of the role of SP-B as a marker of the vascular effects of smoking.
We sought to establish whether cardiorespiratory fitness had important implications for long-term cardiovascular risk among individuals classified as low risk by the Framingham Risk Score (10-year coronary heart disease risk <10%). Prognostic factors of long-term cardiovascular risk are needed for low-risk subjects who make up the largest percentage of the US population.
Methods and Results
The study population was composed of men and women, 30 to 50 years of age, who had a baseline medical exam at the Cooper Clinic, Dallas, TX, between 1970 and 1983. Eligible individuals were defined as at low risk for coronary heart disease by Framingham Risk Score at the time of study entry and had no history of diabetes (n=11 190). Cardiorespiratory fitness was determined by maximum graded exercise treadmill tests. Over an average 27±2-year period, 15% of low-fit (quintile 1) compared to 6% of high-fit (quintile 5) individuals died (P<0.001). A 1–metabolic equivalent level increase in baseline fitness was associated with an 11% reduction in all-cause deaths and an 18% reduction in deaths due to cardiovascular disease (CVD) after adjustment for age, sex, body mass index, systolic blood pressure, total cholesterol, blood glucose levels, smoking, and early family history of coronary disease. There was an incremental decrease in CVD risk with increasing fitness quintile, such that the high fit had the lowest adjusted 30-year CVD mortality rate (hazard ratio 0.29, 95% CI: 0.16–0.51) compared to the low fit.
Cardiorespiratory fitness is associated with a significant reduction in long-term CVD among individuals identified as low risk by Framingham Risk Score. These data suggest that preventive lifestyle interventions geared to optimize cardiorespiratory fitness, even among a “low-risk” subset, should be considered to improve CVD-free survival. (J Am Heart Assoc. 2012;1:e001354 doi: 10.1161/JAHA.112.001354.)
cardiorespiratory fitness; risk, low; Framingham Risk Score; cardiovascular disease
The lifetime risks of cardiovascular disease have not been reported across the age spectrum in black adults and white adults.
We conducted a meta-analysis at the individual level using data from 18 cohort studies involving a total of 257,384 black men and women and white men and women whose risk factors for cardiovascular disease were measured at the ages of 45, 55, 65, and 75 years. Blood pressure, cholesterol level, smoking status, and diabetes status were used to stratify participants according to risk factors into five mutually exclusive categories. The remaining lifetime risks of cardiovascular events were estimated for participants in each category at each age, with death free of cardiovascular disease treated as a competing event.
We observed marked differences in the lifetime risks of cardiovascular disease across risk-factor strata. Among participants who were 55 years of age, those with an optimal risk-factor profile (total cholesterol level, <180 mg per deciliter [4.7 mmol per liter]; blood pressure, <120 mm Hg systolic and 80 mm Hg diastolic; nonsmoking status; and nondiabetic status) had substantially lower risks of death from cardiovascular disease through the age of 80 years than participants with two or more major risk factors (4.7% vs. 29.6% among men, 6.4% vs. 20.5% among women). Those with an optimal risk-factor profile also had lower lifetime risks of fatal coronary heart disease or nonfatal myocardial infarction (3.6% vs. 37.5% among men, <1% vs. 18.3% among women) and fatal or nonfatal stroke (2.3% vs. 8.3% among men, 5.3% vs. 10.7% among women). Similar trends within risk-factor strata were observed among blacks and whites and across diverse birth cohorts.
Differences in risk-factor burden translate into marked differences in the lifetime risk of cardiovascular disease, and these differences are consistent across race and birth cohorts. (Funded by the National Heart, Lung, and Blood Institute.)
National guidelines for primary prevention suggest consideration of lifetime risk for cardiovascular disease in addition to 10-year risk, but it is currently unknown how many U.S. adults would be identified as having low short-term but high lifetime predicted risk if stepwise stratification were employed.
Methods and Results
We included 6,329 CVD-free and nonpregnant individuals aged 20 to 79 years, representing approximately 156 million U.S. adults, from the National Health and Nutrition Examination Survey 2003–2004 and 2005–2006. We assigned 10-year and lifetime predicted risks to stratify participants into three 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. The majority of U.S. adults (56%, or 87 million individuals) are at low short-term but high lifetime predicted risk for cardiovascular disease. Twenty-six percent (41 million adults) are at low short-term and low lifetime predicted risk, and only 18% (28 million individuals) are at high short-term predicted risk. The addition of lifetime risk estimation to 10-year risk estimation identifies higher risk women and younger men in particular.
Whereas 82% of U.S. adults are at low short-term risk, two-thirds of this group, or 87 million people, are at high lifetime predicted risk for cardiovascular disease. These results provide support for use of a stepwise stratification system aimed at improving risk communication, and they provide a baseline for public health efforts aimed at increasing the proportion of Americans with low short-term and low lifetime risk for cardiovascular disease.
Experimental and clinical trial data suggest an association between fish oil intake and atrial fibrillation (AF). However, prior observational studies have reported conflicting results regarding this association. Thus, we sought to compare the association between dietary fish intake and incident AF in a large sample of older, postmenopausal women. We included 44,720 participants from the Women's Health Initiative clinical trials not enrolled in the dietary modification intervention arm and without AF at baseline. The dietary intake of non-fried fish and omega-3 fatty acid intake were estimated from a Food Frequency Questionnaire at study entry. Incident AF was determined by follow-up ECG at year 3 and year 6. Baseline characteristics and rates of incident AF were compared across quartiles (Q) of fish intake. Adjusted logistic regression models were used to evaluate the association between dietary non-fried fish intake and incident AF. There were 378 incident cases of AF in follow-up. In age-adjusted models, there was no association between dietary non-fried fish intake and incident AF [odds ratios (95% confidence intervals) 1.17 (0.88–1.57) for Q 4 vs. Q 1 of dietary fish intake). Similar findings were observed in multivariable models and in subgroup analyses. In a large cohort of healthy women, we found no evidence of an association between fish or omega-3 fatty acid intake and incident AF.
atrial fibrillation; diet; omega-3 fatty acids
Noninvasive direct vessel wall (plaque) imaging may provide a good opportunity to study unique aspects of atherosclerotic lesions in different populations. The article published by Esposito et al. provides new insights into our understanding of diabetic atherosclerotic vascular disease by using direct plaque imaging techniques. The findings from this article call for attention to more in vivo imaging to understand the nature of high-risk atherosclerosis, especially in prospective studies in diabetic patients.
See research article: http://www.biomedcentral.com/1471-2342/10/27/abstract
Endothelial cell-selective adhesion molecule (ESAM) is a junctional-type cellular adhesion molecule (CAM) that is uniquely expressed in vascular endothelium and activated platelets and mediates neutrophil and monocyte diapedesis across the endothelium. Given its role in endothelial pathobiology, we hypothesized that soluble ESAM (sESAM) would be independently associated with atherosclerosis and vascular stiffness.
Methods and Results
We measured sESAM, soluble intercellular adhesion molecule (sICAM)-1 and soluble vascular cell adhesion molecule (sVCAM)-1 in 3222 subjects participating in the Dallas Heart Study, a probability-based population sample. Coronary artery calcium (CAC) was measured by electron beam computed tomography, and abdominal aortic wall thickness (AWT), aortic plaque burden (APB), and aortic compliance (AC) by magnetic resonance imaging (MRI). Increasing levels of sESAM were associated with all major cardiovascular risk factors as well as with inflammatory markers such as monocyte chemoattractant protein-1, but only weakly correlated with sICAM-1 and sVCAM-1. In multivariate analyses, sESAM was independently associated with prevalent CAC (OR 1.2 per SD increase, 95% CI 1.1–1.3; p=0.005), AWT (p=0.035), and AC (p=0.006), but not APB (p=0.15). In contrast, no independent associations were observed between sICAM-1 or sVCAM-1 and any of the atherosclerosis phenotypes.
In this first reported clinical study of sESAM in humans, sESAM levels were independently associated with CAC, AWT, and AC, while sICAM-1 and sVCAM-1 were not. These findings support a unique role of this cellular adhesion molecule in atherosclerosis and suggest the need for further exploration of sESAM as a predictive biomarker and potential mediator of atherosclerosis.
Inflammation; Adhesion molecules; Atherosclerosis; Aortic compliance; Coronary calcium; Biomarkers
We hypothesized that individuals with low 10-year but high lifetime cardiovascular disease (CVD) risk would have a greater burden of subclinical atherosclerosis than those with low 10-year but low lifetime risk.
Methods and Results
We included 2988 individuals age ≤50 at exam year 15 from the Coronary Artery Risk Development in Young Adults (CARDIA) study and 1076 individuals age ≤50 at study entry from the Multi-Ethnic Study of Atherosclerosis (MESA). The 10-year risk and lifetime risk for CVD were estimated for each participant, permitting stratification into three groups: low 10-year (<10%)/low lifetime (<39%) risk, low 10-year (<10%)/high lifetime risk (≥39%), and high 10-year risk (≥10%) or diagnosed diabetes. Baseline levels and change in levels of subclinical atherosclerosis (coronary artery calcium [CAC] or carotid intima-media thickness [IMT]) were compared across risk strata. Among participants with low 10-year risk (91% of all participants) in CARDIA, those with a high lifetime risk compared to low lifetime risk had significantly greater common (0.83 vs 0.80 mm in men; 0.79 vs 0.75 mm in women) and internal (0.85 vs 0.80 mm; 0.80 vs 0.76 mm) carotid IMT, higher CAC prevalence (16.6 vs 9.8%; 7.1 vs 2.3%), and significantly greater incidence of CAC progression (22.3 vs 15.4%; 8.7 vs 5.3%). Similar results were observed in MESA.
Individuals with low 10-year but high lifetime risk have a greater subclinical disease burden and greater incidence of atherosclerotic progression compared to individuals with low 10-year and low lifetime risk, even at younger ages.
epidemiology; risk estimation; prevention
We sought to determine the levels of risk factors required to exceed threshold values of intermediate (≥10%) or high (>20%) predicted 10-year risk for coronary heart disease using the Adult Treatment Panel III (ATP-III) Risk Assessment Tool.
Continuous risk factor values were entered into the risk assessment tool to examine levels of predicted 10-year risk. Both individual risk factors and the joint effects of varying multiple risk factors were systematically examined.
Women only exceed 10% risk at ages ≥70 with single risk factors of HDL-cholesterol levels <30 mg/dL or systolic blood pressure >170 mm Hg. Women ≤65 only exceed 10% risk if they are smokers with low HDL-cholesterol levels. In contrast, single risk factors can cause men over 45 to exceed 10% or 20% predicted 10-year risk. Combinations of only modestly elevated risk factors cause many men to exceed 10% risk at ages ≥45, and to exceed 20% risk at ages ≥55.
Because such high risk factor levels are required for men <45 years and women <65 years to exceed ATP-III risk thresholds, additional means for risk communication may be needed for individuals with elevated risk factors in these age ranges.
risk factors; primary prevention; risk prediction; coronary heart disease
We tested the ability of the Framingham Risk Score (FRS) and the online ATP III risk estimator to estimate risk and to predict 10-year and longer term coronary heart disease (CHD) death in younger adults (age 18–39 years). Although prediction with individual risk factors has been tested in individuals less than 30 years, current multivariate risk prediction strategies have not been applied to prediction of clinical CHD in this age range.
We included 10,551 male participants of the Chicago Heart Association Detection Project in Industry (CHA) who were ages 18 to 39 years and free of baseline CHD and diabetes at enrollment in 1967–1973. CHD risk was estimated using both FRS and ATP-III online risk estimator for each individual. Men were stratified into deciles according to the magnitude of predicted risk calculated from measured baseline risk factors (CHA-predicted risk). Observed CHD mortality rates for 10-, 20-, and 30-years of follow-up were compared with estimated risks. CHD death rates were low across 30-years of follow-up.
The Framingham Risk Score remained below 10% for all deciles of CHA-predicted risk in the 18 to 29 year old cohort. Framingham-predicted risk reached 12% only in the 30 to 39 year old cohort in the highest decile of CHA-predicted risk, despite substantial risk factor burden.
Neither method classified individuals under 30 years of age as high risk despite substantial risk factor burden. Future clinical guidelines should consider alternative strategies to estimate and communicate risk in populations below age 30.
Family history of coronary heart disease (CHD) has been well studied as an independent risk factor for CHD events in the short term (<10 years). However, data are sparse on the association between family history and risk for CHD across long-term follow-up.
Methods and Results
We included 49 255 men from the Cooper Center Longitudinal Study. Premature family history of CHD was defined as the presence of angina, myocardial infarction, angioplasty, or bypass surgery in a relative <50 years of age. Cause-specific mortality was obtained from the National Death Index. The association between premature family history and cardiovascular disease (CVD) or CHD death was compared across 3 unique follow-up periods (0–10, >10–20, and >20 years). Lifetime risk was estimated by use of a modified survival analytic technique adjusted for competing risk with non-CVD death as the competing event. After 811 708 person-years of follow-up, there were 919 CHD deaths and 1456 CVD deaths. After adjustment for traditional risk factors, premature family history was associated with CHD mortality >10 to 20 years (1.59; 95% confidence interval, 1.14–2.22) and >20 years (1.43; 95% confidence interval, 1.05–1.95) with wider confidence intervals at 0 to 10 years (1.32; 95% confidence interval, 0.76–2.31). Similar findings were observed for CVD mortality. Compared with men without a family history of coronary artery disease, premature family history was associated with an ≈50% higher lifetime risk for both CHD and CVD mortality (13.7% versus 8.9% and 21% versus 14.1%, respectively).
Premature family history was associated with a persistent increase in both CHD and CVD mortality risk across long-term follow-up, resulting in significantly higher lifetime risk estimates.
cardiovascular diseases; coronary disease; heredity; risk factors