Staff Publications

Staff Publications

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    'Staff publications' is the digital repository of Wageningen University & Research

    'Staff publications' contains references to publications authored by Wageningen University staff from 1976 onward.

    Publications authored by the staff of the Research Institutes are available from 1995 onwards.

    Full text documents are added when available. The database is updated daily and currently holds about 240,000 items, of which 72,000 in open access.

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    Repositioning of the global epicentre of non-optimal cholesterol
    Taddei, Cristina ; Zhou, Bin ; Bixby, Honor ; Carrillo-Larco, Rodrigo M. ; Danaei, Goodarz ; Jackson, Rod T. ; Farzadfar, Farshad ; Sophiea, Marisa K. ; Cesare, Mariachiara Di; Iurilli, Maria Laura Caminia ; Martinez, Andrea Rodriguez ; Asghari, Golaleh ; Dhana, Klodian ; Gulayin, Pablo ; Kakarmath, Sujay ; Santero, Marilina ; Voortman, Trudy ; Riley, Leanne M. ; Cowan, Melanie J. ; Savin, Stefan ; Bennett, James E. ; Stevens, Gretchen A. ; Paciorek, Christopher J. ; Aekplakorn, Wichai ; Cifkova, Renata ; Giampaoli, Simona ; Kengne, Andre Pascal ; Khang, Young Ho ; Kuulasmaa, Kari ; Laxmaiah, Avula ; Margozzini, Paula ; Mathur, Prashant ; Nordestgaard, Børge G. ; Zhao, Dong ; Aadahl, Mette ; Abarca-Gómez, Leandra ; Rahim, Hanan Abdul ; Abu-Rmeileh, Niveen M. ; Acosta-Cazares, Benjamin ; Adams, Robert J. ; Ferrieres, Jean ; Geleijnse, Johanna M. ; He, Yuna ; Jacobs, Jeremy M. ; Kromhout, Daan ; Ma, Guansheng ; Dam, Rob M. van; Wang, Qian ; Wang, Ya Xing ; Wang, Ying Wei - \ 2020
    Nature 582 (2020)7810. - ISSN 0028-0836 - p. 73 - 77.

    High blood cholesterol is typically considered a feature of wealthy western countries1,2. However, dietary and behavioural determinants of blood cholesterol are changing rapidly throughout the world3 and countries are using lipid-lowering medications at varying rates. These changes can have distinct effects on the levels of high-density lipoprotein (HDL) cholesterol and non-HDL cholesterol, which have different effects on human health4,5. However, the trends of HDL and non-HDL cholesterol levels over time have not been previously reported in a global analysis. Here we pooled 1,127 population-based studies that measured blood lipids in 102.6 million individuals aged 18 years and older to estimate trends from 1980 to 2018 in mean total, non-HDL and HDL cholesterol levels for 200 countries. Globally, there was little change in total or non-HDL cholesterol from 1980 to 2018. This was a net effect of increases in low- and middle-income countries, especially in east and southeast Asia, and decreases in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe. As a result, countries with the highest level of non-HDL cholesterol—which is a marker of cardiovascular risk—changed from those in western Europe such as Belgium, Finland, Greenland, Iceland, Norway, Sweden, Switzerland and Malta in 1980 to those in Asia and the Pacific, such as Tokelau, Malaysia, The Philippines and Thailand. In 2017, high non-HDL cholesterol was responsible for an estimated 3.9 million (95% credible interval 3.7 million–4.2 million) worldwide deaths, half of which occurred in east, southeast and south Asia. The global repositioning of lipid-related risk, with non-optimal cholesterol shifting from a distinct feature of high-income countries in northwestern Europe, north America and Australasia to one that affects countries in east and southeast Asia and Oceania should motivate the use of population-based policies and personal interventions to improve nutrition and enhance access to treatment throughout the world.

    Dietary protein intake and kidney function decline after myocardial infarction: the Alpha Omega Cohort
    Esmeijer, Kevin ; Geleijnse, Johanna M. ; Fijter, Johan W. de; Kromhout, Daan ; Hoogeveen, Ellen K. - \ 2020
    Nephrology Dialysis Transplantation 35 (2020)1. - ISSN 0931-0509 - p. 106 - 115.
    diet - kidney function decline - myocardial infarction - protein intake

    BACKGROUND: Post-myocardial infarction (MI) patients have a doubled rate of kidney function decline compared with the general population. We investigated the extent to which high intake of total, animal and plant protein are risk factors for accelerated kidney function decline in older stable post-MI patients. METHODS: We analysed 2255 post-MI patients (aged 60-80 years, 80% men) of the Alpha Omega Cohort. Dietary data were collected with a biomarker-validated 203-item food frequency questionnaire. At baseline and 41 months, we estimated glomerular filtration rate based on the Chronic Kidney Disease Epidemiology Collaboration equations for serum cystatin C [estimated glomerular filtration rate (eGFRcysC)] alone and both creatinine and cystatin C (eGFRcr-cysC). RESULTS: Mean [standard deviation (SD)] baseline eGFRcysC and eGFRcr-cysC were 82 (20) and 79 (19) mL/min/1.73 m2. Of all patients, 16% were current smokers and 19% had diabetes. Mean (SD) total protein intake was 71 (19) g/day, of which two-thirds was animal and one-third plant protein. After multivariable adjustment, including age, sex, total energy intake, smoking, diabetes, systolic blood pressure, renin-angiotensin system blocking drugs and fat intake, each incremental total daily protein intake of 0.1 g/kg ideal body weight was associated with an additional annual eGFRcysC decline of -0.12 (95% confidence interval -0.19 to -0.04) mL/min/1.73 m2, and was similar for animal and plant protein. Patients with a daily total protein intake of ≥1.20 compared with <0.80 g/kg ideal body weight had a 2-fold faster annual eGFRcysC decline of -1.60 versus -0.84 mL/min/1.73 m2. Taking eGFRcr-cysC as outcome showed similar results. Strong linear associations were confirmed by restricted cubic spline analyses. CONCLUSION: A higher protein intake was significantly associated with a more rapid kidney function decline in post-MI patients.

    Rising rural body-mass index is the main driver of the global obesity epidemic in adults
    Bixby, Honor ; Bentham, James ; Zhou, Bin ; Cesare, Mariachiara Di; Paciorek, Christopher J. ; Bennett, James E. ; Taddei, Cristina ; Stevens, Gretchen A. ; Rodriguez-Martinez, Andrea ; Carrillo-Larco, Rodrigo M. ; Khang, Young Ho ; Sorić, Maroje ; Gregg, Edward W. ; Miranda, J.J. ; Bhutta, Zulfiqar A. ; Savin, Stefan ; Sophiea, Marisa K. ; Iurilli, Maria L.C. ; Solomon, Bethlehem D. ; Cowan, Melanie J. ; Riley, Leanne M. ; Danaei, Goodarz ; Bovet, Pascal ; Chirita-Emandi, Adela ; Hambleton, Ian R. ; Hayes, Alison J. ; Ikeda, Nayu ; Kengne, Andre P. ; Laxmaiah, Avula ; Li, Yanping ; McGarvey, Stephen T. ; Mostafa, Aya ; Neovius, Martin ; Starc, Gregor ; Zainuddin, Ahmad A. ; Abarca-Gómez, Leandra ; Abdeen, Ziad A. ; Abdrakhmanova, Shynar ; Abdul Ghaffar, Suhaila ; Abdul Hamid, Zargar ; Abubakar Garba, Jamila ; Ferrieres, Jean ; He, Yuna ; Jacobs, Jeremy M. ; Kromhout, Daan ; Ma, Guansheng ; Visser, Marjolein ; Wang, Qian ; Wang, Ya Xing ; Wang, Ying Wei - \ 2019
    Nature 569 (2019)7755. - ISSN 0028-0836 - p. 260 - 264.

    Body-mass index (BMI) has increased steadily in most countries in parallel with a rise in the proportion of the population who live in cities 1,2 . This has led to a widely reported view that urbanization is one of the most important drivers of the global rise in obesity 3–6 . Here we use 2,009 population-based studies, with measurements of height and weight in more than 112 million adults, to report national, regional and global trends in mean BMI segregated by place of residence (a rural or urban area) from 1985 to 2017. We show that, contrary to the dominant paradigm, more than 55% of the global rise in mean BMI from 1985 to 2017—and more than 80% in some low- and middle-income regions—was due to increases in BMI in rural areas. This large contribution stems from the fact that, with the exception of women in sub-Saharan Africa, BMI is increasing at the same rate or faster in rural areas than in cities in low- and middle-income regions. These trends have in turn resulted in a closing—and in some countries reversal—of the gap in BMI between urban and rural areas in low- and middle-income countries, especially for women. In high-income and industrialized countries, we noted a persistently higher rural BMI, especially for women. There is an urgent need for an integrated approach to rural nutrition that enhances financial and physical access to healthy foods, to avoid replacing the rural undernutrition disadvantage in poor countries with a more general malnutrition disadvantage that entails excessive consumption of low-quality calories.

    Dietary Approach to Stop Hypertension (DASH) diet and risk of renal function decline and all-cause mortality in renal transplant recipients
    Osté, Maryse C.J. ; Gomes-Neto, António W. ; Corpeleijn, Eva ; Gans, Rijk O.B. ; Borst, Martin H. de; Berg, Else van den; Soedamah-Muthu, Sabita S. ; Kromhout, Daan ; Navis, Gerjan J. ; Bakker, Stephan J.L. - \ 2018
    American Journal of Transplantation 18 (2018)10. - ISSN 1600-6135 - p. 2523 - 2533.
    Clinical research/practice - Graft survival - Kidney transplantation/nephrology - Nutrition - Patient survival
    Renal transplant recipients (RTR) are at risk of decline of graft function and premature mortality, with high blood pressure as an important risk factor for both. To study the association of the Dietary Approach to Stop Hypertension (DASH) diet with these adverse events, we conducted a prospective cohort study of adult RTR. Dietary data were collected using a validated 177-item food frequency questionnaire and an overall DASH-score was obtained. We included 632 stable RTR (mean ± standard deviation age 53.0 ± 12.7 years, 57% men). Mean DASH score was 23.8 ± 4.7. During median follow-up of 5.3 (interquartile range, 4.1-6.0) years, 119 (18.8%) RTR had renal function decline, defined as a combined endpoint of doubling of serum creatinine and death-censored graft failure, and 128 (20.3%) died. In Cox-regression analyses, RTR in the highest tertile of the DASH score had lower risk of both renal function decline (hazard ratio [HR] = 0.57; 95% confidence interval [CI], 0.33-0.96, P = .03) and all-cause mortality (HR = 0.52; 95%CI, 0.32-0.83, P = .006) compared to the lowest tertile, independent of potential confounders. Adherence to a DASH-style diet is associated with lower risk of both renal function decline and all-cause mortality. These results suggest that a healthful diet might benefit long-term outcome in RTR.
    Body-fat indicators and kidney function decline in older post-myocardial infarction patients : The Alpha Omega Cohort Study
    Esmeijer, Kevin ; Geleijnse, Johanna M. ; Giltay, Erik J. ; Stijnen, Theo ; Dekker, Friedo W. ; Fijter, Johan W. de; Kromhout, Daan ; Hoogeveen, Ellen K. - \ 2018
    European Journal of Preventive Cardiology 25 (2018)1. - ISSN 2047-4873 - p. 90 - 99.
    Cardiovascular disease - Kidney function - Obesity - Risk factors

    Background: Obesity increases risk of hypertension and diabetes, the leading causes of end-stage renal disease. The effect of obesity on kidney function decline in stable post-myocardial infarction patients is poorly documented. This relation was investigated in a large cohort of older post-myocardial infarction patients. Design: Data were analysed from 2410 post-myocardial infarction patients in the Alpha Omega Trial, aged 60–80 years receiving optimal pharmacotherapy treatment (79% men, 18% diabetes). Methods: Cystatin C based estimated glomerular filtration rate (eGFRcysC) was calculated at baseline and after 41 months, using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Obesity was defined as body mass index ≥ 30 kg/m2 and high waist circumference as ≥102 and ≥88 cm for men and women. The relation between body mass index, waist circumference and annual eGFRcysC decline was evaluated by linear regression. Results: At baseline, mean (standard deviation) eGFRcysC was 81.5 (19.6) ml/min/1.73 m2, 23% of all patients were obese. After multivariable adjustment, the annual mean (95% confidence interval) eGFRcysC decline in men and women was –1.45 (–1.59 to –1.31) and –0.92 (–1.20 to –0.63) ml/min/1.73 m2, respectively (p = 0.001). Obese versus non-obese patients and patients with high versus normal waist circumference experienced greater annual eGFRcysC decline. Men and women showed an additional annual eGFRcysC decline of –0.35 (–0.56 to –0.14) and –0.21 (–0.55 to 0.14) ml/min/1.73 m2 per 5 kg/m2 body mass index increment (p for interaction 0.3). Conclusions: High compared to normal body mass index or waist circumference were associated with more rapid kidney function decline in older stable post-myocardial infarction patients receiving optimal drug therapy.

    Cardiovascular Risk Factors Accelerate Kidney Function Decline in Post−Myocardial Infarction Patients : The Alpha Omega Cohort Study
    Esmeijer, Kevin ; Geleijnse, Johanna M. ; Fijter, Johan W. de; Giltay, Erik J. ; Kromhout, Daan ; Hoogeveen, Ellen K. - \ 2018
    Kidney International Reports 3 (2018)4. - ISSN 2468-0249 - p. 879 - 888.
    cardiovascular risk factors - kidney function decline - lifestyle

    Introduction: Impaired kidney function is a robust risk factor for cardiovascular mortality. Age-related annual kidney function decline of 1.0 ml/min per 1.73 m2 after age 40 years is doubled in post−myocardial infarction (MI) patients. Methods: We investigated the impact of the number of cardiovascular risk factors (including unhealthy lifestyle) on annual kidney function decline, in 2426 post-MI patients (60−80 years) of the prospective Alpha Omega Cohort study. Glomerular filtration rate was estimated by serum cystatin C (eGFRcysC) and combined creatinine−cystatin C (eGFRcr-cysC), using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations from 2012. Data were analyzed by multivariable linear and logistic regression. Results: At baseline, mean (SD) eGFRcysC and eGFRcr-cysC were 81.5 (19.6) and 78.5 (18.7) ml/min per 1.73 m2, respectively. Of all patients, 79% were men, 19% had diabetes, 56% had high blood pressure (≥140/90 mm Hg), 16% were current smokers, 56% had high serum low-density lipoprotein (LDL of ≥2.5 mmol/l), and 23% were obese (body mass index of ≥30.0 kg/m2). After multivariable adjustment, the additional annual eGFRcysC decline (95% confidence interval) was as follows: in patients with versus without diabetes, −0.90 (−1.23 to −0.57) ml/min per 1.73 m2; in patients with high versus normal blood pressure, −0.50 (−0.76 to −0.24) ml/min per 1.73 m2; in obese versus nonobese patients, −0.31 (−0.61 to 0.01) ml/min per 1.73 m2; and in current smokers versus nonsmokers, −0.19 (−0.54 to 0.16) ml/min per 1.73 m2. High LDL was not associated with accelerated eGFRcysC decline. Similar results were obtained with eGFRcr-cysC. Conclusion: In older, stable post-MI patients without cardiovascular risk factors, the annual kidney function decline was −0.90 (−1.16 to −0.65) ml/min per 1.73 m2. In contrast, in post-MI patients with ≥3 cardiovascular risk factors, the annual kidney function decline was 2.5-fold faster, at −2.37 (−2.85 to −1.89) ml/min per 1.73 m2.

    Comparative ecologic relationships of saturated fat, sucrose, food groups, and a Mediterranean food pattern score to 50-year coronary heart disease mortality rates among 16 cohorts of the Seven Countries Study
    Kromhout, Daan ; Menotti, Alessandro ; Alberti-Fidanza, Adalberta ; Puddu, Paolo Emilio ; Hollman, Peter ; Kafatos, Anthony ; Tolonen, Hanna ; Adachi, Hisashi ; Jacobs, David R. - \ 2018
    European Journal of Clinical Nutrition 72 (2018). - ISSN 0954-3007 - p. 1103 - 1110.

    Background/objectives: We studied the ecologic relationships of food groups, macronutrients, eating patterns, and an a priori food pattern score (Mediterranean Adequacy Index: MAI) with long-term CHD mortality rates in the Seven Countries Study. Subjects/methods: Sixteen cohorts (12,763 men aged 40–59 years) were enrolled in the 1960s in seven countries (US, Finland, The Netherlands, Italy, Greece, former Yugoslavia: Croatia/Serbia, Japan). Dietary surveys were carried out at baseline and only in a subsample of each cohort. The average food consumption of each cohort was chemically analyzed for individual fatty acids and carbohydrates. Results: Ecologic correlations of diet were computed across cohorts for 50-year CHD mortality rates; 97% of men had died in cohorts with 50-year follow-up. CHD death rates ranged 6.7-fold among cohorts. At baseline, hard fat was greatest in northern Europe, olive oil in Greece, meat in the US, sweet products in northern Europe and the US, and fish in Japan. The MAI was high in Mediterranean and Japanese cohorts. The 50-year CHD mortality rates of the cohorts were closely positively ecologically correlated (r = 0.68–0.92) with average consumption of hard fat, sweet products, animal foods, saturated fat, and sucrose, but not with naturally occurring sugars. Vegetable foods, starch, and the a priori pattern MAI were inversely correlated (r = −0.59 to −0.91) with CHD mortality rates. Conclusions: Long-term CHD mortality rates had statistically significant ecologic correlations with several aspects of diet consumed in the 1960s, the traditional Mediterranean and Japanese patterns being rich in vegetable foods, and low in sweet products and animal foods.

    Associations of omega-3 fatty acid supplement use with cardiovascular disease risks meta-analysis of 10 trials involving 77 917 individuals
    Aung, Theingi ; Halsey, Jim ; Kromhout, Daan ; Gerstein, Hertzel C. ; Marchioli, Roberto ; Tavazzi, Luigi ; Geleijnse, Johanna M. ; Rauch, Bernhard ; Ness, Andrew ; Galan, Pilar ; Chew, Emily Y. ; Bosch, Jackie ; Collins, Rory ; Lewington, Sarah ; Armitage, Jane ; Clarke, Robert - \ 2018
    JAMA Cardiology 3 (2018)3. - ISSN 2380-6583 - p. 225 - 234.
    IMPORTANCE Current guidelines advocate the use of marine-derived omega-3 fatty acids supplements for the prevention of coronary heart disease and major vascular events in people with prior coronary heart disease, but large trials of omega-3 fatty acids have produced conflicting results. OBJECTIVE To conduct ameta-analysis of all large trials assessing the associations of omega-3 fatty acid supplements with the risk of fatal and nonfatal coronary heart disease and major vascular events in the full study population and prespecified subgroups. DATA SOURCES AND STUDY SELECTION This meta-analysis included randomized trials that involved at least 500 participants and a treatment duration of at least 1 year and that assessed associations of omega-3 fatty acids with the risk of vascular events. DATA EXTRACTION AND SYNTHESIS Aggregated study-level datawere obtained from 10 large randomized clinical trials. Rate ratios for each trial were synthesized using observed minus expected statistics and variances. Summary rate ratios were estimated by a fixed-effects meta-analysis using 95%confidence intervals for major diseases and 99%confidence intervals for all subgroups. MAIN OUTCOMES AND MEASURES The main outcomes included fatal coronary heart disease, nonfatalmyocardial infarction, stroke, major vascular events, and all-cause mortality, as well as major vascular events in study population subgroups. RESULTS Of the 77 917 high-risk individuals participating in the 10 trials, 47 803 (61.4%) were men, and the mean age at entry was 64.0 years; the trials lasted a mean of 4.4 years. The associations of treatment with outcomes were assessed on 6273 coronary heart disease events (2695 coronary heart disease deaths and 2276 nonfatalmyocardial infarctions) and 12 001 major vascular events. Randomization to omega-3 fatty acid supplementation (eicosapentaenoic acid dose range, 226-1800mg/d) had no significant associations with coronary heart disease death (rate ratio [RR], 0.93; 99%CI, 0.83-1.03; P = .05), nonfatal myocardial infarction (RR, 0.97; 99%CI, 0.87-1.08; P = .43) or any coronary heart disease events (RR, 0.96; 95%CI, 0.90-1.01; P = .12). Neither did randomization to omega-3 fatty acid supplementation have any significant associations with major vascular events (RR, 0.97; 95% CI, 0.93-1.01; P = .10), overall or in any subgroups, including subgroups composed of persons with prior coronary heart disease, diabetes, lipid levels greater than a given cutoff level, or statin use. CONCLUSIONS AND RELEVANCE This meta-analysis demonstrated that omega-3 fatty acids had no significant association with fatal or nonfatal coronary heart disease or any major vascular events. It provides no support for current recommendations for the use of such supplements in people with a history of coronary heart disease.
    Pure epicatechin and inflammatory gene expression profiles in circulating immune cells in (pre) hypertensive adults; a randomized double-blind, placebo-controlled, crossover trial
    Esser, D. ; Dower, J.I. ; Matualatupauw, J.C. ; Geleijnse, J.M. ; Kromhout, D. ; Hollman, P.C.H. ; Afman, L.A. - \ 2018
    Wageningen University
    Homo sapiens - GSE84453 - PRJNA329219
    Introduction: There is increasing evidence that consumption of cocoa products have a beneficial effect on cardio-metabolic health, but the underlying mechanisms remain unclear. Cocoa contains a complex mixture of flavan-3-ols. Epicatechin, a major monomeric flavan-3-ol, is considered to contribute to the cardio-protective effects of cocoa. We investigated effects of pure epicatechin supplementation on whole genome gene expression profiles of circulating immune cells. Methods: In a randomized, double blind, placebo-controlled cross-over trial, 37 (pre)hypertensive (40-80y) subjects received two 4-week interventions; epicatechin (100mg/day) or placebo with a wash-out period of 4-week between both interventions. Whole genome gene expression profiles of peripheral blood mononuclear cells were determined before and after both interventions. Results: After epicatechin supplementation 1180 genes were significantly regulated, of which 234 were also significantly regulated compared to placebo. Epicatechin supplementation up-regulated gene sets involved in transcription/translation and tubulin folding and down-regulated gene sets involved in inflammation. Only a few genes within these regulated gene sets were actually significantly changed upon epicatechin supplementation. Upstream regulators that were shown to be inhibited were classified as cytokine or inflammatory type molecules. Conclusion: Pure epicatechin supplementation modestly reduced gene expression related to inflammation signalling routes in circulating immune cells. These routes are known to play a role in cardiovascular health.
    Pure flavonoid epicatechin and whole genome gene expression profiles in circulating immune cells in adults with elevated blood pressure: A randomised double-blind, placebo-controlled, crossover trial
    Esser, Diederik ; Geleijnse, Johanna M. ; Matualatupauw, Juri C. ; Dower, James I. ; Kromhout, Daan ; Hollman, Peter C.H. ; Afman, Lydia A. - \ 2018
    PLoS ONE 13 (2018)4. - ISSN 1932-6203 - 15 p.
    Cocoa consumption has beneficial cardiometabolic effects, but underlying mechanisms remain unclear. Epicatechin, the cocoa major monomeric flavan-3-ol, is considered to contribute to these cardio-protective effects. We investigated effects of pure epicatechin supplementation on gene expression profiles of immune cells in humans. In a double blind, placebo-controlled cross-over trial, 32 (pre)hypertensive subjects aged 30 to 80, received two 4-week interventions, i.e. epicatechin (100mg/day) or placebo with a 4-week wash-out between interventions. Gene expression profiles of peripheral blood mononuclear cells were determined before and after both interventions. Epicatechin regulated 1180 genes, of which 234 differed from placebo. Epicatechin upregulated gene sets involved in transcription and tubulin folding and downregulated gene sets involved in inflammation, PPAR signalling and adipogenesis. Several negatively enriched genes within these gene sets were involved in insulin signalling. Most inhibited upstream regulators within the epicatechin intervention were cytokines or involved in inflammation. No upstream regulators were identified compared to placebo. Epicatechin, a cocoa flavan-3-ol, reduces gene expression involved in inflammation, PPAR-signalling and adipogenesis in immune cells. Effects were mild but our findings increase our understanding and provide new leads on how epicatechin rich products like cocoa may affect immune cells and exert cardiometabolic protective effects.
    Risk thresholds for alcohol consumption: combined analysis of individual-participant data for 599 912 current drinkers in 83 prospective studies
    Wood, Angela M. ; Kaptoge, Stephen ; Schoufour, Josje ; Kromhout, D. ; Voortman, Trudy ; Sweeting, Michael ; Verschuren, W.M.M. ; Salomaa, Veikko ; Danesh, John - \ 2018
    The Lancet 391 (2018)10129. - ISSN 0140-6736 - p. 1513 - 1523.
    Background Low-risk limits recommended for alcohol consumption vary substantially across different national guidelines. To define thresholds associated with lowest risk for all-cause mortality and cardiovascular disease, we studied individual-participant data from 599 912 current drinkers without previous cardiovascular disease. Methods We did a combined analysis of individual-participant data from three large-scale data sources in 19 high-income countries (the Emerging Risk Factors Collaboration, EPIC-CVD, and the UK Biobank). We characterised dose–response associations and calculated hazard ratios (HRs) per 100 g per week of alcohol (12·5 units per week) across 83 prospective studies, adjusting at least for study or centre, age, sex, smoking, and diabetes. To be eligible for the analysis, participants had to have information recorded about their alcohol consumption amount and status (ie, non-drinker vs current drinker), plus age, sex, history of diabetes and smoking status, at least 1 year of follow-up after baseline, and no baseline history of cardiovascular disease. The main analyses focused on current drinkers, whose baseline alcohol consumption was categorised into eight predefined groups according to the amount in grams consumed per week. We assessed alcohol consumption in relation to all-cause mortality, total cardiovascular disease, and several cardiovascular disease subtypes. We corrected HRs for estimated long-term variability in alcohol consumption using 152 640 serial alcohol assessments obtained some years apart (median interval 5·6 years [5th–95th percentile 1·04–13·5]) from 71 011 participants from 37 studies. Findings In the 599 912 current drinkers included in the analysis, we recorded 40 310 deaths and 39 018 incident cardiovascular disease events during 5·4 million person-years of follow-up. For all-cause mortality, we recorded a positive and curvilinear association with the level of alcohol consumption, with the minimum mortality risk around or below 100 g per week. Alcohol consumption was roughly linearly associated with a higher risk of stroke (HR per 100 g per week higher consumption 1·14, 95% CI, 1·10–1·17), coronary disease excluding myocardial infarction (1·06, 1·00–1·11), heart failure (1·09, 1·03–1·15), fatal hypertensive disease (1·24, 1·15–1·33); and fatal aortic aneurysm (1·15, 1·03–1·28). By contrast, increased alcohol consumption was log-linearly associated with a lower risk of myocardial infarction (HR 0·94, 0·91–0·97). In comparison to those who reported drinking >0–≤100 g per week, those who reported drinking >100–≤200 g per week, >200–≤350 g per week, or >350 g per week had lower life expectancy at age 40 years of approximately 6 months, 1–2 years, or 4–5 years, respectively. Interpretation In current drinkers of alcohol in high-income countries, the threshold for lowest risk of all-cause mortality was about 100 g/week. For cardiovascular disease subtypes other than myocardial infarction, there were no clear risk thresholds below which lower alcohol consumption stopped being associated with lower disease risk. These data support limits for alcohol consumption that are lower than those recommended in most current guidelines.
    Assessment of residential environmental exposure to pesticides from agricultural fields in the Netherlands
    Brouwer, Maartje ; Kromhout, Hans ; Vermeulen, Roel ; Duyzer, Jan ; Kramer, Henk ; Hazeu, Gerard ; Snoo, Geert De; Huss, Anke - \ 2018
    Journal of Exposure Science and Environmental Epidemiology 28 (2018)2. - ISSN 1559-0631 - p. 173 - 181.
    environmental monitoring - exposure modeling - pesticides
    We developed a spatio-temporal model for the Netherlands to estimate environmental exposure to individual agricultural pesticides at the residential address for application in a national case-control study on Parkinson's disease (PD). Data on agricultural land use and pesticide use were combined to estimate environmental exposure to pesticides for the period 1961 onwards. Distance categories of 0-50 m, >50-100 m, >100-500 m and >500-1000 m around residences were considered. For illustration purposes, exposure was estimated for the control population (n=607) in the PD case-control study. In a small validation effort, model estimates were compared with pesticide measurements in air and precipitation collected at 17 stations in 2000-2001. Estimated exposure prevalence was higher for pesticides used on commonly cultivated (rotating) crops than for pesticides used on fruit and bulbs only. Prevalence increased with increasing distance considered. Moderate-to-high correlations were observed between model estimates (>100-500 m and >500-1000 m) and environmental pesticide concentrations measured in 2000-2001. Environmental exposure to individual pesticides can be estimated using relevant spatial and temporal data sets on agricultural land use and pesticide use. Our approach seems to result in accurate estimates of average environmental exposure, although it remains to be investigated to what extent this reflect personal exposure to agricultural pesticides.
    Dietary patterns and physical activity in the metabolically (un)healthy obese: the Dutch Lifelines cohort study
    Slagter, Sandra N. ; Corpeleijn, Eva ; Klauw, Melanie M. Van Der; Sijtsma, Anna ; Swart-Busscher, Linda G. ; Perenboom, Corine W.M. ; Vries, Jeanne H.M. De; Feskens, Edith J.M. ; Wolffenbuttel, Bruce H.R. ; Kromhout, Daan ; Vliet-Ostaptchouk, Jana V. Van - \ 2018
    Nutrition Journal 17 (2018)1. - ISSN 1475-2891
    Background
    Diversity in the reported prevalence of metabolically healthy obesity (MHO), suggests that modifiable factors may be at play. We evaluated differences in dietary patterns and physical activity between MHO and metabolically unhealthy obesity (MUO).
    Methods
    Cross-sectional data of 9270 obese individuals (30–69 years) of the Lifelines Cohort Study was used. MHO was defined as obesity and no metabolic syndrome risk factors and no cardiovascular disease history. MUO was defined as obesity and ≥2 metabolic syndrome risk factors. Sex-specific associations of dietary patterns (identified by principal component analysis) and physical activity with MHO were assessed by multivariable logistic regression (reference group: MUO). Analyses were adjusted for multiple covariates.
    Results
    Among 3442 men and 5828 women, 10.2% and 24.4% had MHO and 56.9% and 35.3% MUO, respectively. We generated four obesity-specific dietary patterns. Two were related to MHO, and in women only. In the highest quartile (Q) of ‘bread, potatoes and sweet snacks’ pattern, odds ratio (OR) (95% CI) for MHO was 0.52 (0.39–0.70). For the healthier pattern ‘fruit, vegetables and fish’, an OR of 1.36 (1.09–1.71) in Q3 and 1.55 (1.21–1.97) in Q4 was found for MHO. For physical activity, there was a positive association between moderate physical activity and vigorous physical activity in the highest tertile and MHO in women and men, respectively (OR 1.19 (1.01–1.41) and OR 2.02 (1.50–2.71)).
    Conclusion
    The healthier diet -characterized by ‘fruit, vegetables and fish’- and moderate physical activity in women, and vigorous physical activity in men may be related to MHO. The (refined) carbohydrate-rich ‘bread, potatoes and sweet snacks’ dietary pattern was found to counteract MHO in women.
    The strength of the multivariable associations of major risk factors predicting coronary heart disease mortality is homogeneous across different areas of the Seven Countries Study during 50-year follow-up
    Menotti, Alessandro ; Puddu, Paolo Emilio ; Adachi, Hisashi ; Kafatos, Anthony ; Tolonen, Hanna ; Kromhout, Daan - \ 2018
    Acta Cardiologica 73 (2018)2. - ISSN 0001-5385 - p. 148 - 154.
    coefficients - Coronary heart disease - hazard ratios - homogeneity - mortality - prediction - risk factors

    Objectives: To compare the magnitude of multivariable coefficients and hazard ratios of four cardiovascular risk factors across five worldwide regions of the Seven Countries Study in predicting 50-year coronary deaths. Material and methods: A total of 13 cohorts of middle-aged men at entry (40–59 years old) were enrolled in the mid-1900s from five relatively homogeneous groups of cohorts (areas): USA, Finland and Zutphen – the Netherlands, Italy and Greece, Serbia, Japan for a total of 10,368 middle-aged men. The major risk factors measured at baseline were age, number of cigarettes smoked, systolic blood pressure and serum cholesterol. Cox proportional hazards models were solved for 50-year (45 years for Serbia) deaths from coronary heart disease (CHD), and the multivariable coefficients were compared for heterogeneity. Results: The highest levels of risk factors and CHD death rates were found in Finland and Zutphen – the Netherlands and the lowest in Japan. All four risk factors were predictive for long-term CHD mortality in all regions, except serum cholesterol in Japan where the mean levels and CHD events were lowest. Tests of heterogeneity of coefficients for single risk factors in predicting CHD mortality were non-significant across the five areas. The same analyses for the first 25 years of follow-up produced similar findings. Conclusions: The strength of the multivariable associations of four major traditional CHD risk factors with long-term CHD mortality appears to be relatively homogeneous across areas, pending needed further evidence.

    Worldwide trends in body-mass index, underweight, overweight, and obesity from 1975 to 2016: a pooled analysis of 2416 population-based measurement studies in 128·9 million children, adolescents, and adults
    Bentham, James ; Cesare, Mariachiara Di; Bilano, Ver ; Bixby, Honor ; Zhou, Bin ; Stevens, Gretchen A. ; Riley, Leanne M. ; Taddei, Cristina ; Hajifathalian, Kaveh ; Lu, Yuan ; Savin, Stefan ; Cowan, Melanie J. ; Paciorek, Christopher J. ; Chirita-Emandi, Adela ; Hayes, Alison J. ; Katz, Joanne ; Kelishadi, Roya ; Kengne, Andre Pascal ; Khang, Young Ho ; Laxmaiah, Avula ; Li, Yanping ; Ma, Jun ; Miranda, J.J. ; Mostafa, Aya ; Neovius, Martin ; Padez, Cristina ; Rampal, Lekhraj ; Zhu, Aubrianna ; Bennett, James E. ; Danaei, Goodarz ; Bhutta, Zulfiqar A. ; Ezzati, Majid ; Abarca-Gómez, Leandra ; Abdeen, Ziad A. ; Hamid, Zargar Abdul ; Abu-Rmeileh, Niveen M. ; Acosta-Cazares, Benjamin ; Acuin, Cecilia ; Adams, Robert J. ; Aekplakorn, Wichai ; Afsana, Kaosar ; Aguilar-Salinas, Carlos A. ; Ferrieres, Jean ; Jacobs, Jeremy M. ; Kromhout, Daan ; Ma, Guansheng ; Peeters, Petra H. ; Wang, Qian ; Wang, Ya Xing ; Wang, Ying Wei ; Geleijnse, J.M. - \ 2017
    The Lancet 390 (2017)10113. - ISSN 0140-6736 - p. 2627 - 2642.

    Background Underweight, overweight, and obesity in childhood and adolescence are associated with adverse health consequences throughout the life-course. Our aim was to estimate worldwide trends in mean body-mass index (BMI) and a comprehensive set of BMI categories that cover underweight to obesity in children and adolescents, and to compare trends with those of adults. Methods We pooled 2416 population-based studies with measurements of height and weight on 128·9 million participants aged 5 years and older, including 31·5 million aged 5–19 years. We used a Bayesian hierarchical model to estimate trends from 1975 to 2016 in 200 countries for mean BMI and for prevalence of BMI in the following categories for children and adolescents aged 5–19 years: more than 2 SD below the median of the WHO growth reference for children and adolescents (referred to as moderate and severe underweight hereafter), 2 SD to more than 1 SD below the median (mild underweight), 1 SD below the median to 1 SD above the median (healthy weight), more than 1 SD to 2 SD above the median (overweight but not obese), and more than 2 SD above the median (obesity). Findings Regional change in age-standardised mean BMI in girls from 1975 to 2016 ranged from virtually no change (−0·01 kg/m2 per decade; 95% credible interval −0·42 to 0·39, posterior probability [PP] of the observed decrease being a true decrease=0·5098) in eastern Europe to an increase of 1·00 kg/m2 per decade (0·69–1·35, PP>0·9999) in central Latin America and an increase of 0·95 kg/m2 per decade (0·64–1·25, PP>0·9999) in Polynesia and Micronesia. The range for boys was from a non-significant increase of 0·09 kg/m2 per decade (−0·33 to 0·49, PP=0·6926) in eastern Europe to an increase of 0·77 kg/m2 per decade (0·50–1·06, PP>0·9999) in Polynesia and Micronesia. Trends in mean BMI have recently flattened in northwestern Europe and the high-income English-speaking and Asia-Pacific regions for both sexes, southwestern Europe for boys, and central and Andean Latin America for girls. By contrast, the rise in BMI has accelerated in east and south Asia for both sexes, and southeast Asia for boys. Global age-standardised prevalence of obesity increased from 0·7% (0·4–1·2) in 1975 to 5·6% (4·8–6·5) in 2016 in girls, and from 0·9% (0·5–1·3) in 1975 to 7·8% (6·7–9·1) in 2016 in boys; the prevalence of moderate and severe underweight decreased from 9·2% (6·0–12·9) in 1975 to 8·4% (6·8–10·1) in 2016 in girls and from 14·8% (10·4–19·5) in 1975 to 12·4% (10·3–14·5) in 2016 in boys. Prevalence of moderate and severe underweight was highest in India, at 22·7% (16·7–29·6) among girls and 30·7% (23·5–38·0) among boys. Prevalence of obesity was more than 30% in girls in Nauru, the Cook Islands, and Palau; and boys in the Cook Islands, Nauru, Palau, Niue, and American Samoa in 2016. Prevalence of obesity was about 20% or more in several countries in Polynesia and Micronesia, the Middle East and north Africa, the Caribbean, and the USA. In 2016, 75 (44–117) million girls and 117 (70–178) million boys worldwide were moderately or severely underweight. In the same year, 50 (24–89) million girls and 74 (39–125) million boys worldwide were obese. Interpretation The rising trends in children's and adolescents' BMI have plateaued in many high-income countries, albeit at high levels, but have accelerated in parts of Asia, with trends no longer correlated with those of adults. Funding Wellcome Trust, AstraZeneca Young Health Programme.

    Kidney function and specific mortality in 60-80 years old post-myocardial infarction patients : A 10-year follow-up study
    Hoogeveen, Ellen K. ; Geleijnse, Johanna M. ; Giltay, Erik J. ; Soedamah-Muthu, Sabita S. ; Goede, Janette de; Oude Griep, Linda M. ; Stijnen, Theo ; Kromhout, Daan - \ 2017
    PLoS ONE 12 (2017)2. - ISSN 1932-6203 - 17 p.

    Chronic kidney disease (CKD) is highly prevalent among older post-myocardial infarction (MI) patients. It is not known whether CKD is an independent risk factor for mortality in older post-MI patients with optimal cardiovascular drug-treatment. Therefore, we studied the relation between kidney function and all-cause and specific mortality among older post-MI patients, without severe heart failure, who are treated with state-of-the-art pharmacotherapy. From 2002-2006, 4,561 Dutch post-MI patients were enrolled and followed until death or January 2012. We estimated Glomerular Filtration Rate (EGFR) with cystatin C (cysC) and creatinine (cr) using the CKD-EPI equations and analyzed the relation with any and major causes of death using Cox models and restricted cubic splines. Mean (SD) for age was 69 years (5.6), 79% were men, 17% smoked, 21% had diabetes, 90% used antihypertensive drugs, 98% used antithrombotic drugs and 85% used statins. Patients were divided into four categories of baseline EGFRcysC: ≥90 (33%; reference), 60-89 (47%), 30-59 (18%), and <30 (2%) ml/min/1.73m2. Median follow-up was 6.4 years. During follow-up, 873 (19%) patients died: 370 (42%) from cardiovascular causes, 309 (35%) from cancer, and 194 (22%) from other causes. After adjustment for age, sex and classic cardiovascular risk factor, hazard ratios (95%-confidence intervals) for any death according to the four EGFRcysC categories were: 1 (reference), 1.4 (1.1-1.7), 2.9 (2.3-3.6) and 4.4 (3.0-6.4). The hazard ratios of all-cause and cause-specific mortality increased linearly below kidney functions of 80 ml/min/1.73 m2. Weaker results were obtained for EGFRcr. To conclude, we found in optimal cardiovascular drug-treated post-MI patients an inverse graded relation between kidney function and mortality for both cardiovascular as well as non-cardiovascular causes. Risk of mortality increased linearly below kidney function of about 80 ml/min/1.73 m2.

    Re-calibration of coronary risk prediction : An example of the Seven Countries Study
    Puddu, Paolo Emilio ; Piras, Paolo ; Kromhout, Daan ; Tolonen, Hanna ; Kafatos, Anthony ; Menotti, Alessandro - \ 2017
    Scientific Reports 7 (2017)1. - ISSN 2045-2322
    We aimed at performing a calibration and re-calibration process using six standard risk factors from Northern (NE, N = 2360) or Southern European (SE, N = 2789) middle-aged men of the Seven Countries Study, whose parameters and data were fully known, to establish whether re-calibration gave the right answer. Greenwood-Nam-D'Agostino technique as modified by Demler (GNDD) in 2015 produced chi-squared statistics using 10 deciles of observed/expected CHD mortality risk, corresponding to Hosmer-Lemeshaw chi-squared employed for multiple logistic equations whereby binary data are used. Instead of the number of events, the GNDD test uses survival probabilities of observed and predicted events. The exercise applied, in five different ways, the parameters of the NE-predictive model to SE (and vice-versa) and compared the outcome of the simulated re-calibration with the real data. Good re-calibration could be obtained only when risk factor coefficients were substituted, being similar in magnitude and not significantly different between NE-SE. In all other ways, a good re-calibration could not be obtained. This is enough to praise for an overall need of re-evaluation of most investigations that, without GNDD or another proper technique for statistically assessing the potential differences, concluded that re-calibration is a fair method and might therefore be used, with no specific caution.
    Mediterranean style diet is associated with low risk of new-onset diabetes after renal transplantation
    Osté, Maryse C.J. ; Corpeleijn, Eva ; Navis, Gerjan J. ; Keyzer, Charlotte A. ; Soedamah-Muthu, Sabita S. ; Berg, Else Van Den; Postmus, Douwe ; Borst, Martin H. De; Kromhout, Daan ; Bakker, Stephan J.L. - \ 2017
    BMJ Open Diabetes Research and Care 5 (2017)1. - ISSN 2052-4897
    Objective: The incidence of new-onset diabetes after transplantation (NODAT) and premature mortality is high in renal transplant recipients (RTR). We hypothesized that a Mediterranean Style diet protects against NODAT and premature mortality in RTR. Research design and methods: A prospective cohort study of adult RTR with a functioning graft for >1 year. Dietary intake was assessed with a 177- item validated food frequency questionnaire. Patients were divided based on a 9-point Mediterranean Style Diet Score (MDS): low MDS (0-4 points) versus high MDS (5-9 points). A total of 468 RTR were eligible for analyses. Logistic multivariable regression analyses were used to study the association of MDS with NODAT and Cox multivariable regression models for the association with all-cause mortality. Results: Mean±SD age was 51.3±13.2 years and 56.6% were men. About 50% of the patients had a high MDS. During median follow-up of 4.0 (IQR, 0.4-5.4) years, 22 (5%) RTR developed NODAT and 50 (11%) died. High MDS was significantly associated with both a lower risk of NODAT (HR=0.23; 95% CI 0.09 to 0.64; p=0.004) and allcause mortality (HR=0.51; 95% CI 0.29 to 0.89, p=0.02) compared to low MDS, independent of age and sex. Adjustment for other potential confounders, including total energy intake, physical activity and smoking status, did not materially change the results of the analyses. Conclusions: Dietary habits leading to high MDS were associated with lower risk of NODAT. These results suggest that healthy dietary habits are of paramount importance for RTR.
    Effect of omega-3 fatty acid supplementation on plasma fibroblast growth factor 23 levels in post-myocardial infarction patients with chronic kidney disease : The alpha omega trial
    Borst, Martin H. de; Baia, Leandro C. ; Hoogeveen, Ellen K. ; Giltay, Erik J. ; Navis, Gerjan ; Bakker, Stephan J.L. ; Geleijnse, Johanna M. ; Kromhout, Daan ; Soedamah-Muthu, Sabita S. - \ 2017
    Nutrients 9 (2017)11. - ISSN 2072-6643
    Cardiovascular - Chronic kidney disease - Fibroblast growth factor 23 - Myocardial infarction - N-3 polyunsaturated fatty acids
    Fibroblast growth factor 23 (FGF23) is an independent risk factor for cardiovascular mortality in chronic kidney disease. Omega-3 (n-3) fatty acid consumption has been inversely associated with FGF23 levels and with cardiovascular risk. We examined the effect of marine n-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and plant-derived alpha-linolenic acid (ALA) on plasma FGF23 levels in post-myocardial infarction patients with chronic kidney disease. In the randomized double-blind Alpha Omega Trial, 4837 patients with a history of myocardial infarction aged 60–80 years (81% men) were randomized to one of four trial margarines supplemented with a targeted additional intake of 400 mg/day EPA and DHA, 2 g/day ALA, EPA-DHA plus ALA, or placebo for 41 months. In a subcohort of 336 patients with an eGFR < 60 mL/min/1.73 m2 (creatinine-cystatin C-based CKD-EPI formula), plasma C-terminal FGF23 was measured by ELISA at baseline and end of follow-up. We used analysis of covariance to examine treatment effects on FGF23 levels adjusted for baseline FGF23. Patients consumed 19.8 g margarine/day on average, providing an additional amount of 236 mg/day EPA with 158 mg/day DHA, 1.99 g/day ALA or both, in the active intervention groups. Over 79% of patients were treated with antihypertensive and antithrombotic medication and statins. At baseline, plasma FGF23 was 150 (128 to 172) RU/mL (mean (95% CI)). After 41 months, overall FGF23 levels had increased significantly (p < 0.0001) to 212 (183 to 241) RU/mL. Relative to the placebo, the treatment effect of EPA-DHA was indifferent, with a mean change in FGF23 (95% CI) of −17 (−97, 62) RU/mL (p = 0.7). Results were similar for ALA (36 (−42, 115) RU/mL) and combined EPA-DHA and ALA (34 (−44, 113) RU/mL). Multivariable adjustment, pooled analyses, and subgroup analyses yielded similar non-significant results. Long-term supplementation with modest quantities of EPA-DHA or ALA does not reduce plasma FGF23 levels when added to cardiovascular medication in post-myocardial patients with chronic kidney disease.
    Use of Repeated Blood Pressure and Cholesterol Measurements to Improve Cardiovascular Disease Risk Prediction : An Individual-Participant-Data Meta-Analysis
    Paige, Ellie ; Barrett, Jessica ; Pennells, Lisa ; Sweeting, Michael ; Willeit, Peter ; Angelantonio, Emanuele Di; Gudnason, Vilmundur ; Nordestgaard, Børge G. ; Psaty, Bruce M. ; Goldbourt, Uri ; Best, Lyle G. ; Assmann, Gerd ; Salonen, Jukka T. ; Nietert, Paul J. ; Verschuren, W.M.M. ; Brunner, Eric J. ; Kronmal, Richard A. ; Salomaa, Veikko ; Bakker, Stephan L.J. ; Dagenais, Gilles R. ; Sato, Shinichi ; Jansson, Jan Håkan ; Willeit, Johann ; Onat, Altan ; La Cámara, Agustin Gómez De; Roussel, Ronan ; Völzke, Henry ; Dankner, Rachel ; Tipping, Robert W. ; Meade, Tom W. ; Donfrancesco, Chiara ; Kuller, Lewis H. ; Peters, Annette ; Gallacher, John ; Kromhout, Daan ; Iso, Hiroyasu ; Knuiman, Matthew W. ; Casiglia, Edoardo ; Kavousi, Maryam ; Palmieri, Luigi ; Sundström, Johan ; Davis, Barry R. ; Njølstad, Inger ; Couper, David ; Danesh, John ; Thompson, Simon G. ; Wood, Angela M. - \ 2017
    American Journal of Epidemiology 186 (2017)8. - ISSN 0002-9262 - p. 899 - 907.
    Cardiovascular disease - Longitudinal measurements - Repeated measurements - Risk factors - Risk prediction
    The added value of incorporating information from repeated blood pressure and cholesterol measurements to predict cardiovascular disease (CVD) risk has not been rigorously assessed. We used data on 191,445 adults from the Emerging Risk Factors Collaboration (38 cohorts from 17 countries with data encompassing 1962-2014) with more than 1 million measurements of systolic blood pressure, total cholesterol, and high-density lipoprotein cholesterol. Over a median 12 years of follow-up, 21,170 CVD events occurred. Risk prediction models using cumulative mean values of repeated measurements and summary measures from longitudinal modeling of the repeated measurements were compared with models using measurements from a single time point. Risk discrimination (Cindex) and net reclassification were calculated, and changes in C-indices were meta-analyzed across studies. Compared with the single-time-point model, the cumulative means and longitudinal models increased the C-index by 0.0040 (95% confidence interval (CI): 0.0023, 0.0057) and 0.0023 (95% CI: 0.0005, 0.0042), respectively. Reclassification was also improved in both models; compared with the single-time-point model, overall net reclassification improvements were 0.0369 (95% CI: 0.0303, 0.0436) for the cumulative-means model and 0.0177 (95% CI: 0.0110, 0.0243) for the longitudinal model. In conclusion, incorporating repeated measurements of blood pressure and cholesterol into CVD risk prediction models slightly improves risk prediction.
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