A favorable lifestyle lowers the risk of coronary artery disease consistently across strata of non-modifiable risk factors in a population-based cohort

The Malmö Diet and Cancer study (MDCS) is a prospective population-based cohort study that was designed to study the association between diet and other lifestyle factors on the risk of developing cancer [13]. Both male and female participants between the age of 43 and 73 years in Malmö took part in the study, with baseline examinations from March 1991 to October 1996 [14]. From the cohort of 30,446 subjects, 923 subjects with a previous CVD (coronary event or stroke) identified through local or national registers were excluded as well as 150 with history of coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI). Subjects with missing data on the main covariates (1185 with missing lifestyle score, 6 with missing age or sex and 1859 with missing educational level) were also excluded. The total study population after exclusions was 26,323.

CAD was defined as fatal or nonfatal MI, death due to ischemic heart disease, PCI, or CABG, whichever came first. Time of follow-up was counted from the date of baseline examination until first event, death, emigration or 31st December 2014. End-point adjudication was done through linkage of the personal identification number with three registers: the Swedish Hospital Discharge register, the Swedish Cause of Death Register, and the Swedish Coronary Angiography and Angioplasty Registry.

A lifestyle score was constructed using four lifestyle factors in the American Heart Association (AHA) guidelines – no current smoking, no obesity (BMI < 30 kg/m²), moderate physical activity at least once weekly, and a healthy diet. These guidelines are similar to lifestyle recommendations issued for disease prevention in Sweden. A favorable lifestyle was defined as adherence to 3 or more of the listed criteria, an intermediate lifestyle as two criteria and an unfavorable lifestyle as adherence to 1 or zero of the criteria, as previously reported [12]. Information on smoking status and physical activity was extracted from the baseline questionnaire. Non-smoking was defined as reporting never having smoked or being a former cigarette smoker. Physical activity was based on participants reporting the number of minutes per week spent on a list of 18 activities during the four seasons (adapted from the Minnesota Leisure Time Physical Activity Instrument). Physical activity at least once weekly was defined as reporting more than 1-h of activities with a proximal intensity of at least 5 METs (corresponding to moderate/vigorous intensity). The activities included digging, dancing (folkdance and ballroom), mowing the lawn (manual mower), jogging, swimming, tennis, soccer, orienteering, and climbing stairs. Absence of obesity (BMI < 30 kg/m²) was defined by calculated BMI from direct measurements of height and weight by trained nurses using standardized procedures. Dietary assessment in the MDCS was by a modified diet history method combining 1) a 7-day diet record of all prepared meals, cold beverages, and supplements, 2) a 168-item quantitative food questionnaire using pictures to assess portion sizes, and 3) a 1-h interview with a trained interviewer to check for accuracy of the diet record and food questionnaire, potential overlap, and general food habits and cooking practices [15]. Information from the diet record and food questionnaire were used to estimate g/day of different food items. The relative validity and reproducibility of the method have been published [16‐18]. A healthy diet pattern was calculated based on adherence to at least 5 of the following criteria: consumption of more fruits, nuts, vegetables, whole grains, fish, and dairy products, and less consumption of refined grains, processed meats, unprocessed red meats, and sugar-sweetened beverages. A detailed description of the included foods in the respective food groups and serving sizes used for assessing adherence is found in Additional file 1: Table S1.

Population subgroups were classified based on the following non-modifiable risk factors: age, gender, educational level, and parental history of MI. Age and sex were extracted from the subjects’ Swedish personal identification number. The participants were divided into three age groups: 43.0–54.9 years, 55.0–64.9 years, and 65.0–73.9 years with the oldest age group being defined as high-risk. Information on educational level and parental history of MI was extracted from the baseline questionnaire. Educational level was categorized in three categories: elementary, secondary, or further education/university/college degree. Elementary degree was defined as a high-risk group. Parental history of MI was determined by the participants answer on whether they have a father and/or mother with a history of myocardial infarction. For descriptive analyses of the cohort across exposure categories we further examined history of hypertension (based on blood pressure measurements above 140/90 mmHg or reported use of anti-hypertensive medication at baseline), use of lipid-lowering medication in the MDC baseline questionnaire, and history of diabetes mellitus was defined as any of the following: having a measured fasting whole blood glucose ≥6.1 mmol/l at the MDC baseline examination, or a self-reported history of physician-diagnosed diabetes, or use of diabetes medication according to the MDC baseline questionnaire, or being diagnosed and registered in any of the local or national diabetes registries. Further, in a subset of participants (n = 4995) fasting blood samples were collected at baseline as previously described [19]. For these subjects, we included analysis of baseline measurements of HbA1c (%), triglycerides (mmol/L), and high-density lipoprotein cholesterol (HDLC; mmol/L). Low-density lipoprotein cholesterol (LDLC) was estimated using Friedewald’s formula. Analyses of high-sensitivity C-reactive protein (hsCRP) was performed using the Tina-quant® CRP latex high sensitivity assay (Roche Diagnostics, Basel, Switzerland) on an ADIVA® 1650 Chemistry System (Bayer Healthcare, NY, USA).

With a mean follow-up time of 18 years (median 19.6, range 0–23.8) there was in total 469,441 person-years of observation during which 3417 incident events of CAD occurred. A favorable lifestyle was associated with a better risk profile in relation to known CAD risk factors (Table 1). Participants with a favorable lifestyle had a lower likelihood of hypertension and favorable blood-lipid levels as well as being less likely to have diabetes at baseline. Baseline characteristics across the population risk groups (age, gender, educational level, and parental history of MI) are shown in Additional file 1: Table S2-S5.

The CAD event rates over study follow-up across categories of lifestyle risk and different population risk groups are shown in Additional file 1: Fig. S1. Participants with an unfavorable lifestyle had a higher risk of CAD than those with a favorable lifestyle with a HR of 1.77 (95% CI: 1.62–1.94). Similarly, the adjusted event rate was higher among all high-risk groups compared to low-risk groups (Additional file 1: Fig. S1).

Across all strata of non-modifiable risk factors, adherence to a favorable lifestyle was associated with a lower risk of CAD (Fig. 1). Overall, a favorable lifestyle associated with a 44% lower risk of CAD (HR = 0.56, 95% CI: 0.52–0.62) compared to an unfavorable lifestyle. In the older age group (65–73 years), the participants who adhered to a favorable lifestyle had a 43% (HR = 0.57, 95% CI: 0.49–0.67) lower risk to develop CAD compared to participants at the same age with an unfavorable lifestyle. For men with a favorable lifestyle the relative risk was 40% lower (HR = 0.60, 95% CI: 0.54–0.68) compared to men with an unfavorable lifestyle. Participants with a low educational level reduced their relative risk with 45% (HR = 0.55, 95% CI: 0.49–0.63) by adhering to a favorable lifestyle. Likewise, compared to an unfavorable lifestyle subjects with a parental history of MI who adhered to a favorable lifestyle reduced their relative risk of CAD with 45% (HR = 0.55, 95% CI: 0.47–0.63) (Fig. 1 and Additional file 1: Table S6).

For participants at high age the standardized 10-year coronary event rate was 12.3% (95% CI: 10.8–13.8) among those with unfavorable lifestyle and 7.2% (95% CI: 6.4–8.0) among those with a favorable lifestyle (Fig. 2). A similar pattern was noted in the other high risk groups where a favorable lifestyle lowered the absolute risk in these groups compared to an unfavorable lifestyle. For men with an unfavorable lifestyle the 10-year coronary event rate was 10.9% (95% CI: 9.9–11.9) compared to 6.7% (95% CI: 6.1–7.3) with a favorable lifestyle. The group with elementary education and an unfavorable lifestyle had a cumulative risk of 6.9% (95% CI: 6.3–7.5) which was reduced to 3.9% (95% CI: 3.5–4.3) with a favorable lifestyle. For participants with a history of MI, an unfavorable lifestyle was associated with a 7.8% (95% CI: 7.0–8.7) absolute risk of CAD compared to a 4.4% (95% CI: 3.9–4.8) with a favorable lifestyle.