Abstract
PURPOSE
We assessed the effects of the four newly defined American Heart Association (AHA) lifestyle factors on mortality by examining the associated population attributable fractions (PAFs) of these factors.
METHODS
Slightly modified AHA cardiovascular health factors (smoking, BMI, cardiorespiratory fitness, and diet) were measured among 11,240 (24% women) participants from the Aerobics Center Longitudinal Study between 1987 and 1999. The cohort was followed to December 31, 2003 or death. PAFs were calculated as the proportionate reduction in death attributable to identified risk factors.
RESULTS
During an average 12 years of follow-up, 268 deaths occurred. Low fitness had the highest PAFs at the 5th, 10th, and 15th year of follow-up, respectively: 6.6%, 6.4%, and 5.5%. Current smokers had the second highest PAFs at the 5th, 10th, and 15th year of follow-up, respectively: 5.4%, 5.2%, and 5.0%. Additional adjusting for other confounders in the model did not change the above associations. The PAFs for overweight or obesity and unhealthy diet were not significant in the current analyses.
CONCLUSIONS
Assuming a causal relationship between smoking, low fitness and mortality, avoidance of both would have prevented 13% of the deaths in the current population. Preventive interventions to increase physical activity and stop smoking would most likely promote longevity.
INTRODUCTION
Cardiovascular disease (CVD) continues to be the leading cause of death in the United States with an average of 1 death every 39 seconds and an estimated direct and indirect cost of $286.6 billion [1]. Recently, the American Heart Association (AHA) 2020 Impact Goal defines a new construct of cardiovascular health behaviors for adults and children based on 4 lifestyle factors (smoking, body mass index (BMI), physical activity, and diet) and sets national goals for promoting cardiovascular health and reducing CVD burden [2]. Previous studies consistently show an inverse association between multiple low-risk lifestyle factors and all-cause mortality [3–7], however, widely varying definitions of the lifestyle factors are applied in these studies. To date, only two studies have used AHA cardiovascular health behavior concept to define the 4 lifestyle factors [8, 9]. Bambs and colleagues addressed the prevalence of the new AHA metrics that define cardiovascular lifestyle factors and reported 81% of all participants in the community-based Heart SCORE study presented ≤ 3 ideal lifestyle factors (nearly 60% presented zero or one ideal factor) [8]. In an ideal world with unlimited resources, targeting all the 4 modifiable factors could result in substantial improvement in overall cardiovascular health, however, with the continuing financial crisis around the globe, it may be more cost-effective to choose the one or two most important lifestyle factors for intervention.
The population attributable fraction (PAF) is an integrated measure that assesses the proportion of an outcome in a population that is attributable to exposure to 1 or more risk factors [10]. The aim of our study is to estimate the death burden that is attributable to non-ideal or poor cardiovascular lifestyle factors using a slightly modified construct defined by the AHA, and to identify one or two factors which contribute to most of the deaths while accounting for age, gender, family history and health status.
METHODS
Study Population
The Aerobics Center Longitudinal Study (ACLS) began in 1970 as an observational epidemiological study to investigate health outcomes associated with physical activity and cardiorespiratory fitness [11, 12]. Participants came to the Cooper Clinic, Dallas, Texas for a preventive medical examination and for consultation regarding their unhealthy lifestyle behaviors. They were unpaid volunteers, sent by their employers, healthcare providers, or self-referred and came from all 50 states. Participants were told the purpose of the study and provided their written informed consent to participate. The study protocol was approved annually by the Cooper Institute's institutional review board. All participants included in this study were 20 to 82 years old at entry (23.5% women), had an extensive baseline health examination, normal electrocardiograms (ECGs), a body mass index (BMI) ≥18.5 kg/m2, and complete data on the 4 lifestyle factors. Those who reported having a history of myocardial infarction, stroke, or cancer, and those who had less than one year of follow-up were excluded. Based on these inclusion and exclusion criteria, the final analysis included 11240 individuals whose baseline examination took place between 1987 and 1999. Figure 1 shows the flow diagram of the study participants.
FIGURE 1.
Participants flow diagram.
Data Collection
A medical history questionnaire at baseline provided age, sex, history of chronic diseases (myocardial infarction, stroke, cancer, hypertension, or diabetes), family history of CVD, cigarette smoking, and physical activity. Diet was assessed by a 3-day dietary record. Height and weight were measured. Blood samples were obtained after a fast of at least 12 hours and analyzed for lipids and glucose using automated bioassays in accordance with the Centers for Disease Control and Prevention Lipid Standardization Program. Diabetes was defined as glucose ≥ 7.0 mmol/L, a history of physician diagnosis, or use insulin. Hypercholesterolemia was defined as serum cholesterol ≥ 6.2 mmol/L or a history of physician diagnosis. Hypertension was defined as systolic blood pressure ≥ 140 mm Hg or diastolic blood pressure ≥ 90 mm Hg, or a history of physician diagnosis.
Modified AHA Cardiovascular Lifestyle Factors
In accordance with AHA definition of cardiovascular health [2], we classified each ideal lifestyle factors in the ACLS at baseline. Some factors from the definition of ideal cardiovascular health were slightly modified, according to the information available in the ACLS.
Smoking habits were determined from a standardized medical history questionnaire. Participants were classified as never, former, or current smokers, and ideal smoking behavior was defined as nonsmoker (never or former smoker).
Body mass index (BMI) was calculated as weight (kilograms)/the square of height (meters) which were measured using a stadiometer and balance beam scale, respectively. Ideal BMI was defined <25 kg/m2.
Physical activity and cardiorespiratory fitness
Physical activity was measured through a self-report questionnaire over the previous 3 months. We do not have uniform collection of information on activity type, frequency, duration and intensity over the entire duration of the ACLS. Therefore, for the purpose of this study, we used cardiorespiratory fitness (hereafter referred to as `fitness') as an objective marker of physical activity [13]. Fitness was assessed by a symptom-limited maximal exercise treadmill test using a modified Balke protocol [14]. Total treadmill endurance time (minutes) was used as an index of aerobic power, with time on treadmill in this protocol correlated highly (r≥0.92) with maximal oxygen uptake (VO2max) in both men [15] and women [16]. Participants were classified as `low fit' based on the lowest 20% of the age- and sex-specific distribution of treadmill exercise duration in the overall ACLS population. These cut-points are from previous reports on the relation between fitness and all-cause mortality in the ACLS [12]. Ideal fitness was defined as 80% of the age- and sex-specific distribution of treadmill duration in the overall ACLS population (moderate and high levels of fitness) and was considered as an indictor of ideal physical activity status because previous ACLS data have shown that a brisk walk of approximately 30 minutes on most days of the week was associated with moderate to high levels of fitness [17].
Diet assessment consisted of a 3-day diet record that required participants to keep detailed records of everything they ate over 2 pre-assigned weekdays and 1 weekend day. Participants were provided written instructions on how to accurately describe foods and estimate portion sizes. Participants kept an on-going, real-time written record of foods consumed during and between meals, including assessing portion sizes in common household measures. Registered dieticians at the Cooper Clinic coded and analyzed the diet records using the Cooper Clinic Nutrition and Exercise Evaluation system [18]. This provided detailed dietary information on the overall diet such as the number of foods consumed from specific food groups and the volume of micronutrients (vitamins and minerals).
The ideal cardiovascular health's definition of the dietary goals included fruits and vegetables (≥4.5 cups per day, approximated as ≥ 4.5 servings/day in the ACLS study); fish (≥ two 3.5 oz servings/week, approximated as ≥ two 3.5 oz servings/week of cooked lean meat equivalents from fish, selfish and other seafood); fiber-rich whole grains (≥ 1.1 g of fiber per 10 g of carbohydrate: three 1-oz-equivalent servings/day, approximated as ≥ 3 servings/day of whole grains); sodium (< 1500 mg per day) and sugar-sweetened beverages (≤ 450 kcal (36 oz) per week). All these dietary components were included in this study, except sugar-sweetened beverages, due to a very low number of participants with this information. Ideal diet behavior was defined as meeting at least 3 of the above 4 diet components.
Mortality Surveillance
We followed participants for mortality from the baseline examination through the date of death for decedents or December 31, 2003 for survivors using the National Death Index. We excluded participants with less than one year of follow-up to minimize potential bias due to serious underlying illness on mortality.
Statistical Analyses
The length of follow-up for each person was determined as the time from baseline to either death or censoring, whichever came first. Descriptive analyses summarized baseline characteristics of participants by survival status. The mean levels of continuous variables were compared using student t-test, while chi-square tests compared the distribution of categorical variables values. Univariate and multivariate Cox regressions were used to estimate the strength of the association (hazard ratios (HRs) and 95% confidence intervals (CIs)) between the selected potential nonmodifiable (age, gender, and family history of CVD) and modifiable lifestyle factors and all-cause mortality. With a score of 0 being allocated for each ideal lifestyle factor, non-ideal or poor lifestyle factors were coded as 1. The PAFs for smoking (current smoking), fitness (low fitness), BMI (≥ 25), and diet (meeting 0 or 1 of the 4 diet components) on all-cause mortality were calculated. The PAF for the non-ideal or poor lifestyle factor is defined as the proportionate reduction in death that would be achieved if the entire population had been unexposed to that risk factor or a combination of two lifestyle factors, compared with its current (actual) exposure pattern. Without considering confounders, the PAF can be defined by PAF(t)=1-D0 (t)/D(t), where D(t) is the probability of death during the time interval (0, t) in the overall population, and D0 (t) is the death probability in the subgroup unexposed to the studied risk factor. When considering confounders we used the definition in Chen et al., [19] which has been shown to have a causal interpretation. For the special case of a categorical confounder and a fixed time point, the adjusted PAF in Chen et al. reduces to that defined in Whittemore [20] which replaced D0 (t) in the above formula with the weighted average of confounder-stratum-specific unexposed death probability. The unadjusted/adjusted PAFs and 95% confidence intervals were estimated based on the univariate/multivariate Cox regression models and the methods developed by Chen et al.[19]. Data analyses were performed using SAS (version 9.2; SAS Institute, Cary, NC) software, C and R 2.12.2. All P values are 2-sided with an alpha level of 0.05 established for significance.
RESULTS
There were 268 deaths during 130,584 person-years of follow-up. Compared with survivors, decedents were older, had lower fitness and higher BMI, had higher prevalence of major CVD risk factors, and had lower prevalence of ideal modifiable health factors other than body weight (Table 1).
TABLE 1.
Baseline characteristics of study participants by survival status, Aerobics Center Longitudinal Study, 1987–1999.
| All | Survivor | Decedent | P-value | |
|---|---|---|---|---|
| N | 11,240 | 10,972 | 268 | |
| Age, years | 45.7 (9.7) | 45.5 (9.6) | 53.5 (11.1) | <0.0001 |
| Female, % | 23.5 | 23.7 | 14.6 | 0.0005 |
| Body mass index, kg/m2 | 25.8 (4.1) | 25.8 (4.0) | 26.4 (4.7) | 0.02 |
| Treadmill time, minutes | 18.1 (5.2) | 18.1 (5.2) | 16.5 (5.7) | <0.0001 |
| Total cholesterol, mmol/L | 5.4 (1.0) | 5.4 (1.0) | 5.6 (1.0) | 0.0003 |
| Fasting blood glucose, mmol/L | 5.5 (0.9) | 5.5 (0.9) | 5.7 (1.3) | 0.01 |
| Blood pressure, mmHg | ||||
| Systolic | 119 (14) | 119 (14) | 125 (16) | <0.0001 |
| Diastolic | 80 (10) | 80 (10) | 83 (10) | <0.0001 |
| Hypertensiona,% | 26.4 | 26.1 | 41.0 | <0.0001 |
| Diabetes mellitusb,% | 2.6 | 2.5 | 5.6 | 0.002 |
| Hypercholesterolemiac,% | 29.2 | 29.0 | 36.9 | 0.005 |
| Family history of CVD, % | 11.3 | 11.2 | 14.6 | 0.08 |
| Ideal modifiable lifestyle factors, % | ||||
| Nonsmoker | 88.6 | 88.6 | 84.7 | 0.045 |
| 18.5≤BMI <25 | 47.0 | 47.1 | 45.9 | 0.71 |
| Moderate and high fit | 91.3 | 91.4 | 86.9 | 0.01 |
| Healthy diet (3–4 components) | 37.6 | 37.5 | 43.3 | 0.05 |
Mean (Standard deviation) for continuous variables; Percentage for categorical variables. CVD=cardiovascular disease.
Hypertension is defined as systolic blood pressure ≥140 mmHg, diastolic blood pressure ≥90 mmHg, or a history of physician diagnosis.
Diabetes mellitus is defined as a fasting plasma glucose concentration ≥7.0 mmol/L, a history of physician diagnosis, or insulin use.
hypercholesterolemia is defined as total cholesterol ≥6.20 mmol/L, or a history of physician diagnosis.
We found statistically significant differences in risk of death between categories of age, gender, family history of CVD, smoking, and low fitness (Table 2). Low fitness and smoking, in addition to age, showed the strongest associations with mortality. No statistically significant interactions between the variables in the model were found, therefore, we used a model with main effects only to study their effects on the risk of death. The fully adjusted model showed similar associations between age, gender, low fitness, and smoking and death as the unadjusted model.
TABLE 2.
Estimated hazard ratios of death in categories of potential risk factors, the Aerobics Center Longitudinal Study, 1987–2003.
| No. of Deaths | Total No. of Participants | Unadjusted HR (95% CI) | Multivariate-adjusted HR (95% CI)a | |
|---|---|---|---|---|
| Nonmodifiable variables | ||||
| Age group, years | ||||
| 20–39 | 30 | 2999 | 1 | 1 |
| 40–49 | 71 | 4453 | 1.62 (1.05–2.48) | 1.58 (1.03–2.42) |
| 50–59 | 83 | 2874 | 2.91 (1.92–4.42) | 2.88 (1.88–4.41) |
| ≥ 60 | 84 | 914 | 8.48 (5.59–12.86) | 8.53 (5.55–13.13) |
| Gender | ||||
| Male | 229 | 8598 | 1 | 1 |
| Female | 39 | 2642 | 0.59 (0.42–0.82) | 0.66 (0.47–0.94) |
| Family history of CVD | ||||
| No | 229 | 9974 | 1 | 1 |
| Yes | 39 | 1266 | 1.37 (0.98–1.93) | 1.46 (1.04–2.05) |
| Non-ideal modifiable lifestyle factors | ||||
| Current smoker | 41 | 1287 | 1.50 (1.07–2.09) | 1.62 (1.16–2.28) |
| BMI ≥ 25 | 145 | 5954 | 1.81 (0.93–1.50) | 0.88 (0.68–1.14) |
| Unhealthy diet (<3 components) | 152 | 7011 | 0.87 (0.68–1.11) | 1.01 (0.79–1.29) |
| Low fitness | 35 | 981 | 1.81 (1.27–2.59) | 2.04 (1.40–2.99) |
CVD=cardiovascular disease.
Adjusted for all the variables in the table plus hypertension, diabetes, and hypercholesterolemia.
Table 3 shows the unadjusted and adjusted PAFs and their CIs for the individual modifiable lifestyle factor and 6 possible combinations of two factors in each of the 5 year follow-up intervals. Of the 4 lifestyle factors, fitness had the strongest association with risk of death, reducing it by 7% if low fit individuals had become at least moderately fit (95% CI: 2.2, 12). A reduction in smoking would have led to a 6% reduction in mortality risk. However, reduction of BMI to the ideal level had the smallest effect, the PAF being −7% (95% CI: −14–8). The unadjusted PAF estimates of fitness, smoking, and diet decreased at year 10 and year 15 comparing with the estimates at year 5, respectively. However, this pattern of associations disappeared after multivariate adjustment (Figure 2).
TABLE 3.
Unadjusted and multivariable-adjusted PAF for each 5-year time intervala using the Aerobics Center Longitudinal Study, 1987–2003.
| Unadjusted model |
||||||
|---|---|---|---|---|---|---|
| PAF5 | 95% CI | PAF10 | 95% CI | PAF15 | 95% CI | |
| Individual factor b | ||||||
| Smoking | 5% | 0.1%, 10% | 5% | 0.1%, 10% | 5% | 0.2%, 10% |
| BMI | 9% | −5%, 20% | 9% | −5%, 20% | 8% | −4%, 19% |
| Diet | −9% | −26%, 6% | −9% | −25%, 5% | −8% | −24%, 5% |
| CRF | 7% | 2%, 11% | 6% | 2%, 11% | 6% | 1%, 10% |
| Multiple factors | ||||||
| Smoking+BMI | 13% | −1%, 24% | 12% | −1%, 24% | 12% | −1%, 23% |
| Smoking+Diet | −4% | −22%, 11% | −4% | −21%, 10% | −4% | −20%, 10% |
| Smoking+CRF | 11% | 4%, 17% | 10% | 4%, 16% | 9% | 3%, 15% |
| BMI+Diet | 4% | −21%, 18% | 0.4% | −21%, 18% | 0.2% | −20%, 17% |
| BMI+CRF | 11% | −2%, 22% | 11% | −2%, 22% | 10% | −3%, 20% |
| Diet+CRF | −4% | −21%, 11% | −4% | −20%, 11% | −4% | −20%, 10% |
| Multivariate-adjusted modelc |
||||||
| PAF5 | 95% CI | PAF10 | 95% CI | PAF15 | 95% CI | |
|
| ||||||
| Individual factor b | ||||||
| Smoking | 6% | 1%, 11% | 6% | 1%, 11% | 6% | 1%%, 11% |
| BMI | −7% | −14%, 8% | −7% | −24%, 8% | −7% | −23%, 8% |
| Diet | 3% | −13%, 16% | 3% | −13%, 16% | 3% | −12%, 15% |
| CRF | 7% | 2%, 12% | 7% | 2%, 12% | 7% | 2%, 12% |
| Multiple factors | ||||||
| Smoking+BMI | −0.3% | −17%, 14% | −0.3% | −17%, 14% | −0.3% | −16%, 14% |
| Smoking+Diet | 9% | −7%, 22% | 9% | −7%, 22% | 9% | −7%, 21% |
| Smoking+CRF | 13% | 6%, 19% | 13% | 6%, 19% | 13% | 6%, 18% |
| BMI+Diet | −4% | −28%, 15% | −4% | −28%, 16% | −4% | −27%, 14% |
| BMI+CRF | 1% | −15%, 15% | 0.9% | −15%, 14% | 0.8% | −14%, 14% |
| Diet+CRF | 10% | −5%, 23% | 10% | −5%, 23% | 9% | −5%, 22% |
PAF=population attributable fraction; CI=confidence interval; BMI=body mass index; CRF=cardiorespiratory fitness; CVD=cardiovascular disease.
PAF value at 5th, 10th, and 15th year was denoted by PAF5, PAF10, and PAF15, respectively.
The definition of Smoking, BMI, Diet, CRF is the same as in Table 2.
Adjusted for age, gender, hypertension, diabetes, hypercholesterolemia, and family history of CVD.
FIGURE 2.
Estimates of the population attributable fraction (PAF) by assuming one of the four behavior factors is controlled at the ideal level. a). unadjusted model; b). multivariate-adjusted model (age, gender, hypertension, diabetes, hypercholesterolemia, and family history of CVD), the Aerobics Center Longitudinal Study, 1987–2003.
Finally, the cumulative PAF estimate obtained from the full model including any of the 2 lifestyle factors (Table 3 and Figure 3). Of the 6 combination groups, smoking plus fitness had the greatest association with PAF, reducing it by 13% if all current smokers who also had low fitness had never started smoking and also became at least moderate fit (95% CI: 6, 19). Improving diet and reducing BMI had the least effect on PAF in this population of men and women.
FIGURE 3.
Estimates of the population attributable fraction (PAF) by assuming two of the four behavior factors are controlled at the ideal level. a). unadjusted model; b). multivariate-adjusted model (age, gender, hypertension, diabetes, hypercholesterolemia, and family history of CVD), the Aerobics Center Longitudinal Study, 1987–2003.
DISCUSSION
Summary of main findings
Attributable fractions are commonly used to measure the effect of risk factors on disease outcomes in a population. In this study, we extended these static measures to functions of time because we are interested in knowing if the PAFs will change with the event time. We found that fitness and smoking were the two most important factors for reducing risk of death in our population. The fraction of deaths attributable to low fitness equal to 7% and to smoking equal to 6% after accounting other potential confounders. Considering the growing burden of CVD, this study provides some useful information for decision-makers by providing more information about identifying priority targets of modifiable health factors. Furthermore, by comparing the relative importance of these factors, we can focus policy debate concerning the opportunity of financing one intervention over another.
Comparison with other studies
Previous studies have examined the 4 individual modifiable lifestyle factor, their association with mortality, and the PAF in different populations. Smoking has long been identified as a behavior that has an inverse association with longevity. Among developed Western countries, earlier reports show that 20% of all deaths are attributed to tobacco [21] and this number has varied in recent reports due to different populations studied [22, 23]. In Asian countries there have been several reports on PAF due to smoking ranging from 25% in Japan [24] to 13% in China [25]. It is becoming more evident that physical activity and fitness have an important role on health outcomes. The Nurse's Health Study [26], a large cohort study of registered US nurses, assessed the PAFs of a wide range of risk factors, found that a total of 17% of deaths during follow-up could be attributed to lack of physical activity (<30 min of physical activity per day). Another study from the UK reported a higher PAF of 25% associated with physical inactivity among 10,059 middle-aged women under general practitioners' observation [23]. Poor diet is often commonly reported to be associated with a wide range of chronic conditions, and therefore contribute to substantial burden of disease [22]. Due to the complex nature of the diet exposure assessment, definitions of poor diet or unhealthy diet often variy significantly. The Nurse's Health Study developed a healthy eating score [26], those in the upper two fifths was defined as a low risk category. They found that a total 13% of deaths were attributed to a low diet quality. A meta-analysis of US studies shows a 17% PAF for combined poor diet and physical inactivity, but the investigators did not provide separate estimates for diet and inactivity [27]. Obesity has consistently been associated with higher risk of mortality [28]. Being overweight or obese had a higher PAF (14.2%, 95% CI = 11.6 to 16.9) in the US cohort [26], but there was no significantly higher mortality risk associated with overweight or obesity in the UK study [23].
Although there is an increasing literature on combinations of lifestyle factors with mortality [4, 23, 26, 29], few studies have estimated PAF for the individual factors [23, 26], even fewer studies have reported the PAF for a combination of factors [23], therefore, information is sparse on exactly which combination of lifestyle factors might be best to target to reduce overall disease burden. Among studies estimating PAFs, most of them failed to identify which lifestyle factor(s) is the most important one(s) to contribute to the overall mortality [4, 26, 29]. An important public health question is how to identify which lifestyle factor interventions might yield the greatest benefits in the population. The only current study that tried to answer this question is the UK study in middle-aged women [23]. Iversen and colleagues reported among the four individual lifestyle factors (smoking, physical inactivity, BMI and alcohol) smoking remains the leading cause of mortality and physical inactivity follows. When the investigators evaluated combinations of two factors, they found that smoking and physical inactivity are responsible for almost half of the deaths. They also report that a combination of three factors of smoking, physical inactivity and alcohol consumption are responsible for about 60% of the deaths. Finally, avoidance of all four unhealthy lifestyle factors would also have prevented 60% of the deaths. These analyses indicate that avoidance of all four unhealthy lifestyle risk factors would only have prevented additional 10% of the deaths when compared with the combination of smoking and inactivity. However, this study did not assess the contribution of diet on mortality.
The changes observed in “diet” and “BMI” before and after the adjustment deserve further comment. We have compared overweight/obese participants with those who had normal BMI and found that overweight/obese participants had significantly higher prevalence of hypertension, diabetes, and hypercholesterolemia, but no differences in mean age. The PAF estimate changed direction which means modifying BMI from non-ideal to ideal level did not contribute significantly to mortality after adjusting these other risk factors. We postulate this might be due to the strong effects of these negative confounders and simply improving BMI without changing other risk factors is not sufficient to change the proportion of death in the population level. On the other hand, we found ideal diet partipants were not significantly different from those with non-ideal diet regarding the above mentioned counfounders except age. Those with non-ideal diet were significantly younger than those with ideal diet. Based on Table 2, we can see that age had a significant and large effect on all-cause mortality. Therefore improving diet after adjusting other confounders especially age might influence the PAF estimate significantly.
ACLS participants were mainly white and middle to upper socioeconomic status. Although participants are similar in many respects to other US cohorts that have provided important information on disease prevention [11], the prevalences of smoking and low fitness were low (11% and 8%, respectively). However, even with such low prevalences, they were still responsible for the largest number of deaths in this population. From this point of view, our results are in fact consistent with previous cohort study and suggest that smoking cession programs and physical activity promotion have the greatest potential for reducing the total number of deaths.
Limitations
As mention previously, the ACLS population was mainly white, and of middle to upper socioeconomic status. The prevalence of the four behavior factors was lower than the US general population. Thus, these factors might have a larger population effect if they were studied in a representative sample. We used fitness instead of physical activity in the current study. Although fitness and physical activity are not interchangeable because physical activity is a behavior, whereas fitness is a functional attribute that can be influenced by other factors, physical activity is the primary determinant of fitness, and fitness is less prone to misclassification and may better reflect the adverse health consequences of a sedentary lifestyle than does self-reported physical activity exposure [13]. We were unable to evaluate the effect of changes in the factors over time on all-cause mortality because we only had baseline assessments. The PAF estimates depend on the prevalence of the studied factors and the magnitude of the association between them and the outcomes. During this long follow-up period, both the prevalence of the lifestyle factors and the observed associations between these factors and all-cause mortality are likely to change, therefore influence the PAF estimates. Future studies are needed with repeat assessment of the behaviors. In addition, the measurement of fitness and diet might not be feasible for clinical practice. Finally, the estimates presented here assume that changes in the behaviors would affect the number of deaths. Our ability to change lifestyle factors in large populations is largely untested. However, we do know that it is possible to produce lifestyle changes in clinical trials [30].
Conclusions
In conclusion, low fitness was responsible for the highest proportion of deaths in this sample of men and women, and smoking had the second highest PAF among the four cardiovascular lifestyle factors. Preventive targeted interventions to decrease the prevalence of low fitness and smoking would most likely promote reduced mortality rates. Therefore the major public health gain in the coming years will come from getting sedentary individuals to start moving as well as getting smokers to stop smoking.
ACKNOWLEDGEMENTS
This study was supported by National Institutes of Health grants AG06945, HL62508, and R21DK088195. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
The authors thank the Cooper Clinic physicians and technicians for collecting the baseline data, and staff at the Cooper Institute for data entry and data management.
Footnotes
Conflict of interest: none declared.
References
- 1.Roger VL, Go AS, Lloyd-Jones DM, Adams RJ, Berry JD, Brown TM, et al. Heart disease and stroke statistics--2011 update: a report from the American Heart Association. Circulation. 2011;123(4):e18–e209. doi: 10.1161/CIR.0b013e3182009701. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Lloyd-Jones DM, Hong Y, Labarthe D, Mozaffarian D, Appel LJ, Van HL, et al. Defining and setting national goals for cardiovascular health promotion and disease reduction: the American Heart Association's strategic Impact Goal through 2020 and beyond. Circulation. 2010;121(4):586–613. doi: 10.1161/CIRCULATIONAHA.109.192703. [DOI] [PubMed] [Google Scholar]
- 3.Khaw KT, Wareham N, Bingham S, Welch A, Luben R, Day N. Combined impact of health behaviours and mortality in men and women: the EPIC-Norfolk prospective population study. PLoS Med. 2008;5(1):e12. doi: 10.1371/journal.pmed.0050012. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Knoops KT, de Groot LC, Kromhout D, Perrin AE, Moreiras-Varela O, Menotti A, et al. Mediterranean diet, lifestyle factors, and 10-year mortality in elderly European men and women: the HALE project. JAMA. 2004;292(12):1433–1439. doi: 10.1001/jama.292.12.1433. [DOI] [PubMed] [Google Scholar]
- 5.Carlsson AC, Theobald H, Wandell PE. Health factors and longevity in men and women: a 26-year follow-up study. Eur J Epidemiol. 2010;25(8):547–551. doi: 10.1007/s10654-010-9472-2. [DOI] [PubMed] [Google Scholar]
- 6.Nothlings U, Ford ES, Kroger J, Boeing H. Lifestyle factors and mortality among adults with diabetes: findings from the European Prospective Investigation into Cancer and Nutrition-Potsdam study. J Diabetes. 2010;2(2):112–117. doi: 10.1111/j.1753-0407.2010.00069.x. [DOI] [PubMed] [Google Scholar]
- 7.Kvaavik E, Batty GD, Ursin G, Huxley R, Gale CR. Influence of individual and combined health behaviors on total and cause-specific mortality in men and women: the United Kingdom health and lifestyle survey. Arch Intern Med. 2010;170(8):711–718. doi: 10.1001/archinternmed.2010.76. [DOI] [PubMed] [Google Scholar]
- 8.Bambs C, Kip KE, Dinga A, Mulukutla SR, Aiyer AN, Reis SE. Low prevalence of “ideal cardiovascular health” in a community-based population: the heart strategies concentrating on risk evaluation (Heart SCORE) study. Circulation. 2011;123(8):850–857. doi: 10.1161/CIRCULATIONAHA.110.980151. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Folsom AR, Yatsuya H, Nettleton JA, Lutsey PL, Cushman M, Rosamond WD, et al. Community prevalence of ideal cardiovascular health, by the American Heart Association definition, and relationship with cardiovascular disease incidence. J Am Coll Cardiol. 2011;57(16):1690–1696. doi: 10.1016/j.jacc.2010.11.041. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Laaksonen MA, Knekt P, Harkanen T, Virtala E, Oja H. Estimation of the population attributable fraction for mortality in a cohort study using a piecewise constant hazards model. Am J Epidemiol. 2010;171(7):837–847. doi: 10.1093/aje/kwp457. [DOI] [PubMed] [Google Scholar]
- 11.Blair SN, Kannel WB, Kohl HW, Goodyear N, Wilson PWF. Surrogate measures of physical activity and physical fitness: Evidence for sedentary traits of resting tachycardia, obesity, and low vital capacity. Am J Epidemiol. 1989;129(6):1145–1156. doi: 10.1093/oxfordjournals.aje.a115236. [DOI] [PubMed] [Google Scholar]
- 12.Blair SN, Kampert JB, Kohl HW, III, Barlow CE, Macera CA, Paffenbarger RS, Jr., et al. Influences of cardiorespiratory fitness and other precursors on cardiovascular disease and all-cause mortality in men and women. JAMA. 1996;276(3):205–210. [PubMed] [Google Scholar]
- 13.Aadahl M, Kjaer M, Kristensen JH, Mollerup B, Jorgensen T. Self-reported physical activity compared with maximal oxygen uptake in adults. Eur J Cardiovasc Prev Rehabil. 2007;14(3):422–428. doi: 10.1097/HJR.0b013e3280128d00. [DOI] [PubMed] [Google Scholar]
- 14.Balke B, Ware RW. An experimental study of physical fitness in Air Force personnel. US Armed Forces Med J. 1959;10:675–688. [PubMed] [Google Scholar]
- 15.Pollock ML, Bohannon RL, Cooper KH, Ayres JJ, Ward A, White SR, et al. A comparative analysis of four protocols for maximal treadmill stress testing. Am Heart J. 1976;92(1):39–46. doi: 10.1016/s0002-8703(76)80401-2. [DOI] [PubMed] [Google Scholar]
- 16.Pollock ML, Foster C, Schmidt D, Hellman C, Linnerud AC, Ward A. Comparative analysis of physiologic responses to three different maximal graded exercise test protocols in healthy women. Am Heart J. 1982;103:363–373. doi: 10.1016/0002-8703(82)90275-7. [DOI] [PubMed] [Google Scholar]
- 17.Stofan JR, DiPietro L, Davis D, Kohl HW, III, Blair SN. Physical activity patterns associated with cardiorespiratory fitness and reduced mortality: The Aerobics Center Longitudinal Study. Am J Public Health. 1998;88(12):1807–1813. doi: 10.2105/ajph.88.12.1807. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18.Brodney S, McPherson RS, Carpenter RA, Welten D, Blair SN. Nutrient intake of physically fit and unfit men and women. Med Sci Sports Exerc. 2001;33(3):459–467. doi: 10.1097/00005768-200103000-00020. [DOI] [PubMed] [Google Scholar]
- 19.Chen L, Lin DY, Zeng D. Attributable fraction functions for censored time to event data. Biometrika. 2010;97:713–726. doi: 10.1093/biomet/asq023. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20.Whittemore AS. Statistical methods for estimating attributable risk from retrospective data. Stat Med. 1982;1(3):229–243. doi: 10.1002/sim.4780010305. [DOI] [PubMed] [Google Scholar]
- 21.Peto R, Lopez AD, Boreham J, Thun M, Heath C., Jr. Mortality from tobacco in developed countries: indirect estimation from national vital statistics. Lancet. 1992;339(8804):1268–1278. doi: 10.1016/0140-6736(92)91600-d. [DOI] [PubMed] [Google Scholar]
- 22.Danaei G, Ding EL, Mozaffarian D, Taylor B, Rehm J, Murray CJ, et al. The preventable causes of death in the United States: comparative risk assessment of dietary, lifestyle, and metabolic risk factors. PLoS Med. 2009;6(4):e1000058. doi: 10.1371/journal.pmed.1000058. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23.Iversen L, Hannaford PC, Lee AJ, Elliott AM, Fielding S. Impact of lifestyle in middle-aged women on mortality: evidence from the Royal College of General Practitioners' Oral Contraception Study. Br J Gen Pract. 2010;60(577):563–569. doi: 10.3399/bjgp10X515052. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24.Murakami Y, Miura K, Okamura T, Ueshima H, EPOCH-JAPAN Research Group Population attributable numbers and fractions of deaths due to smoking: a pooled analysis of 180,000 Japanese. Prev Med. 2011;52(1):60–65. doi: 10.1016/j.ypmed.2010.11.009. [DOI] [PubMed] [Google Scholar]
- 25.Jiang J, Liu B, Sitas F, Li J, Zeng X, Han W, et al. Smoking-attributable deaths and potential years of life lost from a large, representative study in China. Tob Control. 2010;19(1):7–12. doi: 10.1136/tc.2009.031245. [DOI] [PubMed] [Google Scholar]
- 26.Van Dam RM, Li T, Spiegelman D, Franco OH, Hu FB. Combined impact of lifestyle factors on mortality: prospective cohort study in US women. BMJ. 2008;337:a1440. doi: 10.1136/bmj.a1440. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 27.Mokdad AH, Marks JS, Stroup DF, Gerberding JL. Actual causes of death in the United States, 2000. JAMA. 2004;291(10):1238–1245. doi: 10.1001/jama.291.10.1238. [DOI] [PubMed] [Google Scholar]
- 28.Flegal KM, Graubard BI, Williamson DF, Gail MH. Excess deaths associated with underweight, overweight, and obesity. JAMA. 2005;293(15):1861–1867. doi: 10.1001/jama.293.15.1861. [DOI] [PubMed] [Google Scholar]
- 29.Tamakoshi A, Tamakoshi K, Lin Y, Yagyu K, Kikuchi S, JACC Study Group Healthy lifestyle and preventable death: findings from the Japan Collaborative Cohort (JACC) Study. Prev Med. 2009;48(5):486–492. doi: 10.1016/j.ypmed.2009.02.017. [DOI] [PubMed] [Google Scholar]
- 30.Unick JL, Beavers D, Jakicic JM, Kitabchi AE, Knowler WC, Wadden TA, et al. Effectiveness of lifestyle interventions for individuals with severe obesity and type 2 diabetes: results from the Look AHEAD trial. Diabetes Care. 2011;34(10):2152–2157. doi: 10.2337/dc11-0874. [DOI] [PMC free article] [PubMed] [Google Scholar]



