Aims Emerging evidence suggests that remnant cholesterol (RC) promotes atherosclerotic cardiovascular disease (ASCVD). We aimed to estimate RC-related risk beyond low-density lipoprotein cholesterol (LDL-C) and apolipoprotein B (apoB) in patients without known ASCVD. Methods and results We pooled data from 17 532 ASCVD-free individuals from the Atherosclerosis Risk in Communities study (n = 9748), the Multi-Ethnic Study of Atherosclerosis (n = 3049), and the Coronary Artery Risk Development in Young Adults (n = 4735). RC was calculated as non-high-density lipoprotein cholesterol (non-HDL-C) minus calculated LDL-C. Adjusted Cox models were used to estimate the risk for incident ASCVD associated with log RC levels. We also performed discordance analyses examining relative ASCVD risk in RC vs. LDL-C discordant/concordant groups using difference in percentile units (>10 units) and clinically relevant LDL-C targets. The mean age of participants was 52.3 ± 17.9 years, 56.7% were women and 34% black. There were 2143 ASCVD events over the median follow-up of 18.7 years. After multivariable adjustment including LDL-C and apoB, log RC was associated with higher ASCVD risk [hazard ratio (HR) 1.65, 95% confidence interval (CI) 1.45–1.89]. Moreover, the discordant high RC/low LDL-C group, but not the low RC/high LDL-C group, was associated with increased ASCVD risk compared to the concordant group (HR 1.21, 95% CI 1.08–1.35). Similar results were shown when examining discordance across clinical cutpoints. Conclusions In ASCVD-free individuals, elevated RC levels were associated with ASCVD independent of traditional risk factors, LDL-C, and apoB levels. The mechanisms of RC association with ASCVD, surprisingly beyond apoB, and the potential value of targeted RC-lowering in primary prevention need to be further investigated.

Taller height, family history of breast cancer, greater number of years of potential fertility and nulliparity are established non-modifiable risk factors for postmenopausal breast cancer. Greater adherence to the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) diet, physical activity and body weight recommendations has previously been shown to be associated with lower breast cancer risk. However, no prior studies have evaluated whether women with non-modifiable risk factors receive similar benefits from recommendation adherence compared to women without these risk factors. In the Iowa Women’s Health Study prospective cohort, we investigated whether associations of WCRF/AICR recommendation adherence differed by the presence/absence of non-modifiable breast cancer risk factors. Baseline (1986) questionnaire data from 36,626 postmenopausal women were used to create adherence scores for the WCRF/AICR recommendations (maximum score=8.0). Overall and single recommendation adherence in relation to breast cancer risk (n=3,189 cases) across levels of non-modifiable risk factors were evaluated using proportional hazards regression. Mean adherence score was 5.0 points (range: 0.5–8.0). Higher adherence scores (score ≥6.0 vs. ≤3.5, HR=0.76, 95% CI=0.67–0.87), and adherence to the individual recommendations for body weight and alcohol intake were associated with a lower breast cancer incidence. While not statistically significant among women with more non-modifiable risk factors (score ≥6.0 vs. ≤3.5, HR=0.76, 95% CI=0.36–1.63), hazard ratios were comparable to women with the no non-modifiable risk factors (score ≥6.0 vs. ≤3.5, HR=0.74, 95% CI=0.49–0.93) (p-interaction=0.57). WCRF/AICR recommendation adherence is associated with lower breast cancer risk, regardless of non-modifiable risk factor status.

Adherence to cancer prevention recommendations has been associated with lower incidence of breast cancer in previous studies, but evidence in African American women is limited. This project evaluated the association between adherence to the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) cancer prevention recommendations and breast cancer incidence among African American women. The Black Women’s Health Study (analytic cohort=49,103) is an ongoing prospective cohort study of African American women, ages 21–69 years at baseline (1995). Adherence scores for seven WCRF/AICR recommendations (adherent=1, partial adherence=0.5, non-adherence=0) were calculated using questionnaire data and summed for overall (Maximum=7) and diet only (Maximum=5) scores. Associations between baseline and time-varying adherence scores and breast cancer incidence (N=1,827 incident cases through 2011) were evaluated using proportional hazards regression. In this cohort, 8.5% adhered >4 recommendations. Adherence at baseline was not associated with breast cancer incidence. Higher overall time-varying adherence (per 0.5 point increase) was associated with lower breast cancer incidence (HR: 0.90, 95% CI: 0.84–0.96). Adherence to physical activity, sugar beverage, and red and processed meat recommendations were also associated with reduced risk. Adherence to the WCRF/AICR recommendations was low and may be associated with lower breast cancer incidence in African American women.

Purpose The purpose of this study was to evaluate whether adherence to the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) cancer prevention recommendations was associated with colorectal cancer incidence in the Black Women's Health Study (BWHS). Methods In this ongoing prospective cohort of African American women (analytic cohort N=49,103), 354 incident colorectal cancers were diagnosed between baseline (1995) and 2011. Adherence scores for seven WCRF/AICR recommendations (adherent=1 point, non-adherent level 1=0.5 points, non-adherent level 2=0 points) were created using questionnaire data and summed to an overall adherence score (maximum=7). Recommendation adherence and colorectal cancer incidence were evaluated using baseline and time-varying data in Cox regression models. Results At baseline, 8.5% of women adhered >4 recommendations. In time-varying analyses, the HR was 0.98 (95% CI: 0.84-1.15) per 0.5 point higher score and 0.51 (95% CI: 0.23-1.10) for adherence to >4 compared to <3 recommendations. Adherence to individual recommendations was not associated with colorectal cancer risk. Results were similar in models that considered baseline exposures only. Conclusions Adherence to cancer prevention recommendations was low and not associated with colorectal cancer risk among women in the BWHS. Research in diverse populations is essential to evaluate the validity of existing recommendations, and assess whether there are alternative recommendations that are more beneficial for cancer prevention in specific populations.