Camille Lassale

Prediction models for cardiovascular disease risk in the general population: systematic review

Objective To provide an overview of prediction models for risk of cardiovascular disease (CVD) in the general population. Design Systematic review. Data sources Medline and Embase until June 2013. Eligibility criteria for study selection Studies describing the development or external validation of a multivariable model for predicting CVD risk in the general population. Results 9965 references were screened, of which 212 articles were included in the review, describing the development of 363 prediction models and 473 external validations. Most models were developed in Europe (n=167, 46%), predicted risk of fatal or non-fatal coronary heart disease (n=118, 33%) over a 10 year period (n=209, 58%). The most common predictors were smoking (n=325, 90%) and age (n=321, 88%), and most models were sex specific (n=250, 69%). Substantial heterogeneity in predictor and outcome definitions was observed between models, and important clinical and methodological information were often missing. The prediction horizon was not specified for 49 models (13%), and for 92 (25%) crucial information was missing to enable the model to be used for individual risk prediction. Only 132 developed models (36%) were externally validated and only 70 (19%) by independent investigators. Model performance was heterogeneous and measures such as discrimination and calibration were reported for only 65% and 58% of the external validations, respectively. Conclusions There is an excess of models predicting incident CVD in the general population. The usefulness of most of the models remains unclear owing to methodological shortcomings, incomplete presentation, and lack of external validation and model impact studies. Rather than developing yet another similar CVD risk prediction model, in this era of large datasets, future research should focus on externally validating and comparing head-to-head promising CVD risk models that already exist, on tailoring or even combining these models to local settings, and investigating whether these models can be extended by addition of new predictors.

Identifying biomarkers of dietary patterns by using metabolomics

BACKGROUND Healthy dietary patterns that conform to national dietary guidelines are related to lower chronic disease incidence and longer life span. However, the precise mechanisms involved are unclear. Identifying biomarkers of dietary patterns may provide tools to validate diet quality measurement and determine underlying metabolic pathways influenced by diet quality. OBJECTIVE The objective of this study was to examine the correlation of 4 diet quality indexes [the Healthy Eating Index (HEI) 2010, the Alternate Mediterranean Diet Score (aMED), the WHO Healthy Diet Indicator (HDI), and the Baltic Sea Diet (BSD)] with serum metabolites. DESIGN We evaluated dietary patterns and metabolites in male Finnish smokers (n = 1336) from 5 nested case-control studies within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study cohort. Participants completed a validated food-frequency questionnaire and provided a fasting serum sample before study randomization (1985-1988). Metabolites were measured with the use of mass spectrometry. We analyzed cross-sectional partial correlations of 1316 metabolites with 4 diet quality indexes, adjusting for age, body mass index, smoking, energy intake, education, and physical activity. We pooled estimates across studies with the use of fixed-effects meta-analysis with Bonferroni correction for multiple comparisons, and conducted metabolic pathway analyses. RESULTS The HEI-2010, aMED, HDI, and BSD were associated with 23, 46, 23, and 33 metabolites, respectively (17, 21, 11, and 10 metabolites, respectively, were chemically identified; r-range: -0.30 to 0.20; P = 6 × 10-15 to 8 × 10-6). Food-based diet indexes (HEI-2010, aMED, and BSD) were associated with metabolites correlated with most components used to score adherence (e.g., fruit, vegetables, whole grains, fish, and unsaturated fat). HDI correlated with metabolites related to polyunsaturated fat and fiber components, but not other macro- or micronutrients (e.g., percentages of protein and cholesterol). The lysolipid and food and plant xenobiotic pathways were most strongly associated with diet quality. CONCLUSIONS Diet quality, measured by healthy diet indexes, is associated with serum metabolites, with the specific metabolite profile of each diet index related to the diet components used to score adherence. This trial was registered at clinicaltrials.gov as NCT00342992.

Diet quality scores and prediction of all-cause, cardiovascular and cancer mortality in a pan-european cohort study

Scores of overall diet quality have received increasing attention in relation to disease aetiology; however, their value in risk prediction has been little examined. The objective was to assess and compare the association and predictive performance of 10 diet quality scores on 10-year risk of all-cause, CVD and cancer mortality in 451,256 healthy participants to the European Prospective Investigation into Cancer and Nutrition, followed-up for a median of 12.8y. All dietary scores studied showed significant inverse associations with all outcomes. The range of HRs (95% CI) in the top vs. lowest quartile of dietary scores in a composite model including non-invasive factors (age, sex, smoking, body mass index, education, physical activity and study centre) was 0.75 (0.72–0.79) to 0.88 (0.84–0.92) for all-cause, 0.76 (0.69–0.83) to 0.84 (0.76–0.92) for CVD and 0.78 (0.73–0.83) to 0.91 (0.85–0.97) for cancer mortality. Models with dietary scores alone showed low discrimination, but composite models also including age, sex and other non-invasive factors showed good discrimination and calibration, which varied little between different diet scores examined. Mean C-statistic of full models was 0.73, 0.80 and 0.71 for all-cause, CVD and cancer mortality. Dietary scores have poor predictive performance for 10-year mortality risk when used in isolation but display good predictive ability in combination with other non-invasive common risk factors.

Meal patterns across ten European countries - Results from the European Prospective Investigation into Cancer and Nutrition (EPIC) calibration study

OBJECTIVE To characterize meal patterns across ten European countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) calibration study. DESIGN Cross-sectional study utilizing dietary data collected through a standardized 24 h diet recall during 1995-2000. Eleven predefined intake occasions across a 24 h period were assessed during the interview. In the present descriptive report, meal patterns were analysed in terms of daily number of intake occasions, the proportion reporting each intake occasion and the energy contributions from each intake occasion. SETTING Twenty-seven centres across ten European countries. SUBJECTS Women (64 %) and men (36 %) aged 35-74 years (n 36 020). RESULTS Pronounced differences in meal patterns emerged both across centres within the same country and across different countries, with a trend for fewer intake occasions per day in Mediterranean countries compared with central and northern Europe. Differences were also found for daily energy intake provided by lunch, with 38-43 % for women and 41-45 % for men within Mediterranean countries compared with 16-27 % for women and 20-26 % for men in central and northern European countries. Likewise, a south-north gradient was found for daily energy intake from snacks, with 13-20 % (women) and 10-17 % (men) in Mediterranean countries compared with 24-34 % (women) and 23-35 % (men) in central/northern Europe. CONCLUSIONS We found distinct differences in meal patterns with marked diversity for intake frequency and lunch and snack consumption between Mediterranean and central/northern European countries. Monitoring of meal patterns across various cultures and populations could provide critical context to the research efforts to characterize relationships between dietary intake and health.

Parity, breastfeeding and risk of coronary heart disease: A pan-European case-cohort study

Objective There is uncertainty about the direction and magnitude of the associations between parity, breastfeeding and the risk of coronary heart disease (CHD). We examined the separate and combined associations of parity and breastfeeding practices with the incidence of CHD later in life among women in a large, pan-European cohort study. Methods Data were used from European Prospective Investigation into Cancer and Nutrition (EPIC)-CVD, a case–cohort study nested within the EPIC prospective study of 520,000 participants from 10 countries. Information on reproductive history was available for 14,917 women, including 5138 incident cases of CHD. Using Prentice-weighted Cox regression separately for each country followed by a random-effects meta-analysis, we calculated hazard ratios (HRs) and 95% confidence intervals (CIs) for CHD, after adjustment for age, study centre and several socioeconomic and biological risk factors. Results Compared with nulliparous women, the adjusted HR was 1.19 (95% CI: 1.01–1.41) among parous women; HRs were higher among women with more children (e.g., adjusted HR: 1.95 (95% CI: 1.19–3.20) for women with five or more children). Compared with women who did not breastfeed, the adjusted HR was 0.71 (95% CI: 0.52–0.98) among women who breastfed. For childbearing women who never breastfed, the adjusted HR was 1.58 (95% CI: 1.09–2.30) compared with nulliparous women, whereas for childbearing women who breastfed, the adjusted HR was 1.19 (95% CI: 0.99–1.43). Conclusion Having more children was associated with a higher risk of CHD later in life, whereas breastfeeding was associated with a lower CHD risk. Women who both had children and breastfed did have a non-significantly higher risk of CHD.

Socioeconomic status, non-communicable disease risk factors, and walking speed in older adults: multi-cohort population based study

Abstract Objective To assess the association of low socioeconomic status and risk factors for non-communicable diseases (diabetes, high alcohol intake, high blood pressure, obesity, physical inactivity, smoking) with loss of physical functioning at older ages. Design Multi-cohort population based study. Setting 37 cohort studies from 24 countries in Europe, the United States, Latin America, Africa, and Asia, 1990-2017. Participants 109 107 men and women aged 45-90 years. Main outcome measure Physical functioning assessed using the walking speed test, a valid index of overall functional capacity. Years of functioning lost was computed as a metric to quantify the difference in walking speed between those exposed and unexposed to low socioeconomic status and risk factors. Results According to mixed model estimations, men aged 60 and of low socioeconomic status had the same walking speed as men aged 66.6 of high socioeconomic status (years of functioning lost 6.6 years, 95% confidence interval 5.0 to 9.4). The years of functioning lost for women were 4.6 (3.6 to 6.2). In men and women, respectively, 5.7 (4.4 to 8.1) and 5.4 (4.3 to 7.3) years of functioning were lost by age 60 due to insufficient physical activity, 5.1 (3.9 to 7.0) and 7.5 (6.1 to 9.5) due to obesity, 2.3 (1.6 to 3.4) and 3.0 (2.3 to 4.0) due to hypertension, 5.6 (4.2 to 8.0) and 6.3 (4.9 to 8.4) due to diabetes, and 3.0 (2.2 to 4.3) and 0.7 (0.1 to 1.5) due to tobacco use. In analyses restricted to high income countries, the number of years of functioning lost attributable to low socioeconomic status by age 60 was 8.0 (5.7 to 13.1) for men and 5.4 (4.0 to 8.0) for women, whereas in low and middle income countries it was 2.6 (0.2 to 6.8) for men and 2.7 (1.0 to 5.5) for women. Within high income countries, the number of years of functioning lost attributable to low socioeconomic status by age 60 was greater in the United States than in Europe. Physical functioning continued to decline as a function of unfavourable risk factors between ages 60 and 85. Years of functioning lost were greater than years of life lost due to low socioeconomic status and non-communicable disease risk factors. Conclusions The independent association between socioeconomic status and physical functioning in old age is comparable in strength and consistency with those for established non-communicable disease risk factors. The results of this study suggest that tackling all these risk factors might substantially increase life years spent in good physical functioning.

Socio-economic trajectories and cardiovascular disease mortality in older people: the English Longitudinal Study of Ageing

Abstract Background Socio-economic status from early life has been linked to cardiovascular disease risk, but the impact of life-course socio-economic trajectories, as well as the mechanisms underlying social inequalities in cardiovascular disease risk, is uncertain. Objectives We assessed the role of behavioural, psychosocial and physiological (including inflammatory) factors in the association between life-course socio-economic status and cardiovascular disease mortality in older adults. Methods Participants were 7846 individuals (44% women) from the English Longitudinal Study of Ageing, a representative study of individuals aged ≥ 50 years, established in 2002–03. Comprising four indicators of socio-economic status (father’s social class, own education, occupational position and wealth), we computed an index of socio-economic trajectory and a lifetime cumulative socio-economic score. Behavioural (smoking, physical activity, alcohol consumption, body mass index) and psychosocial (social relations, loneliness) factors, physiological (blood pressure, total cholesterol, triglycerides) and inflammatory markers (C-reactive protein, fibrinogen), measured repeatedly over time, were potential explanatory variables. Cardiovascular disease mortality was ascertained by linkage of study members to a national mortality register. Mediation was calculated using the traditional ‘change-in-estimate method’ and alternative approaches such as counterfactual mediation modelling could not be applied in this context. Results During the 8.4-year follow-up, 1301 study members died (438 from cardiovascular disease). A stable low-social-class trajectory was associated with around double the risk of cardiovascular disease mortality (hazard ratio; 95% confidence interval: 1.94, 1.37; 2.75) compared with a stable high social class across the life course. Individuals in the lowest relative to the highest life-course cumulative socio-economic status group were also more than twice as likely to die of cardiovascular disease (2.57, 1.81; 3.65). Behavioural factors and inflammatory markers contributed most to explaining this gradient, whereas the role of psychosocial and other physiological risk factors was modest. Conclusions In a population-based cohort of older individuals living in England, we provide evidence that disadvantage across the life course is linked to cardiovascular mortality. That behavioural factors and inflammatory markers partially explain this gradient may provide insights into the potential for intervention.

Alcohol intake in relation to non-fatal and fatal coronary heart disease and stroke : EPIC-CVD case-cohort study

Abstract Objective To investigate the association between alcohol consumption (at baseline and over lifetime) and non-fatal and fatal coronary heart disease (CHD) and stroke. Design Multicentre case-cohort study. Setting A study of cardiovascular disease (CVD) determinants within the European Prospective Investigation into Cancer and nutrition cohort (EPIC-CVD) from eight European countries. Participants 32 549 participants without baseline CVD, comprised of incident CVD cases and a subcohort for comparison. Main outcome measures Non-fatal and fatal CHD and stroke (including ischaemic and haemorrhagic stroke). Results There were 9307 non-fatal CHD events, 1699 fatal CHD, 5855 non-fatal stroke, and 733 fatal stroke. Baseline alcohol intake was inversely associated with non-fatal CHD, with a hazard ratio of 0.94 (95% confidence interval 0.92 to 0.96) per 12 g/day higher intake. There was a J shaped association between baseline alcohol intake and risk of fatal CHD. The hazard ratios were 0.83 (0.70 to 0.98), 0.65 (0.53 to 0.81), and 0.82 (0.65 to 1.03) for categories 5.0-14.9 g/day, 15.0-29.9 g/day, and 30.0-59.9 g/day of total alcohol intake, respectively, compared with 0.1-4.9 g/day. In contrast, hazard ratios for non-fatal and fatal stroke risk were 1.04 (1.02 to 1.07), and 1.05 (0.98 to 1.13) per 12 g/day increase in baseline alcohol intake, respectively, including broadly similar findings for ischaemic and haemorrhagic stroke. Associations with cardiovascular outcomes were broadly similar with average lifetime alcohol consumption as for baseline alcohol intake, and across the eight countries studied. There was no strong evidence for interactions of alcohol consumption with smoking status on the risk of CVD events. Conclusions Alcohol intake was inversely associated with non-fatal CHD risk but positively associated with the risk of different stroke subtypes. This highlights the opposing associations of alcohol intake with different CVD types and strengthens the evidence for policies to reduce alcohol consumption.

Elements of the complete blood count associated with cardiovascular disease incidence: Findings from the EPIC-NL cohort study.

All blood cells (white blood cells [WBC], red blood cells [RBC] and platelets) can play a role in atherosclerosis. Complete blood count (CBC) is widely available in clinical practice but utility as potential risk factors for cardiovascular disease (CVD) is uncertain. Our aim was to assess the associations of pre-diagnostic CBC with incidence of CVD in 14,362 adults free of CVD and aged 47.8 (±11.7) years at baseline, followed-up for 11.4 years (992 incident cases). Cox proportional hazards regressions were used to estimate HRs and 95%CI. Comparing the top (T3) to bottom (T1) tertile, increased total WBC, lymphocyte, monocyte and neutrophil counts were associated with higher CVD risk: 1.31 (1.10; 1.55), 1.20 (1.02; 1.41), 1.21 (1.03; 1.41) and 1.24 (1.05; 1.47), as well as mean corpuscular volume (MCV: 1.23 [1.04; 1.46]) and red cell distribution width (RDW: 1.22 [1.03; 1.44]). Platelets displayed an association for count values above the clinically normal range: 1.49 (1.00; 2.22). To conclude, total and differential WBC count, MCV, RDW and platelet count likely play a role in the aetiology of CVD but only WBC provide a modest improvement for the prediction of 10-year CVD risk over traditional CVD risk factors in a general population.

Individual and Area-Based Socioeconomic Factors Associated With Dementia Incidence in England: Evidence From a 12-Year Follow-up in the English Longitudinal Study of Ageing

Importance Lower educational attainment is associated with a higher risk of dementia. However, less clear is the extent to which other socioeconomic markers contribute to dementia risk. Objective To examine the relationship of education, wealth, and area-based deprivation with the incidence of dementia over the last decade in England and investigate differences between people born in different periods. Design, Setting, and Participants Data from the English Longitudinal Study of Ageing, a prospective cohort study that is representative of the English population, were used to investigate the associations between markers of socioeconomic status (wealth quintiles and the index of multiple deprivation) and dementia incidence. To investigate outcomes associated with age cohorts, 2 independent groups were derived using a median split (born between 1902-1925 and 1926-1943). Main Outcomes and Measures Dementia as determined by physician diagnosis and the Informant Questionnaire on Cognitive Decline in the Elderly. Results A total of 6220 individuals aged 65 years and older enrolled in the study (median [interquartile range] age at baseline, 73.2 [68.1-78.3] years; 3410 [54.8%] female). Of these, 463 individuals (7.4%) had new cases of dementia ascertained in the 12 years between 2002-2003 and 2014-2015. In the cohort born between 1926 and 1943, the hazard of developing dementia was 1.68 times higher (hazard ratio [HR] = 1.68 [95% CI, 1.05-2.86]) for those in the lowest wealth quintile compared with those in the highest quintile, independent of education, index of multiple deprivation, and health indicators. Higher hazards were also observed for those in the second-highest quintile of index of multiple deprivation (HR = 1.62 [95% CI, 1.06-2.46]) compared with those in the lowest (least deprived) quintile. Conclusions and Relevance In an English nationally representative sample, the incidence of dementia appeared to be socioeconomically patterned primarily by the level of wealth. This association was somewhat stronger for participants born in later years.