Associations of Dietary Cholesterol and Egg Consumption with Incident Cardiovascular Disease and Total Mortality

Associations of Dietary Cholesterol and Egg Consumption with Incident Cardiovascular Disease and Total Mortality

Associations of Dietary Cholesterol and Egg Consumption with Incident Cardiovascular Disease and Total Mortality

 

By Kevin C. Maki, PhD and Heather Nelson Cortes, PhD

 

Despite decades of research, the association between dietary cholesterol consumption, cardiovascular disease (CVD) and mortality remains controversial.  Adding to this controversy are the confusing recommendations in the 2015-2020 Dietary Guidelines for Americans.1,2  The Guidelines state that cholesterol is not a nutrient of concern for overconsumption, but also recommend that individuals should consume as little dietary cholesterol as possible while following a healthy eating pattern.  A meta-analysis of prospective cohort studies published in 2015 did not show statistically significant associations between dietary cholesterol consumption and incident CVD, coronary artery disease or stroke, although higher dietary cholesterol intake was associated with an increased level of low-density-lipoprotein cholesterol (LDL-C).3  Because a large chicken egg (~50 g) contains roughly 186 mg of cholesterol,4 limiting egg consumption has been recommended as a way to decrease dietary cholesterol and to possibly reduce the risk of CVD.

 

Zhong et al. recently published an analysis of the associations between intakes of dietary cholesterol and eggs with incident CVD and total mortality from the Lifetime Risk Pooling Project.5  The Lifetime Risk Pooling Project contains data from 6 cohorts in which usual dietary intake, fatal and nonfatal coronary heart disease, stroke, heart failure and CVD from other causes were assessed. The 6 cohorts were the Atherosclerosis Risk in Communities (ARIC) Study,6 Coronary Artery Risk Development in Young Adults (CARDIA) Study,7 Framingham Heart Study (FHS),8  Framingham Offspring Study (FOS),9 Jackson Heart Study (JHS)10 and the Multi-Ethnic Study of Atherosclerosis (MESA).11  The analysis included 29,615 participants (mean [standard deviation] age at baseline, 51.6 [13.5] years).5  There were 13,299 (44.9%) men and 9,204 (31.1%) subjects were black.  The median follow-up was 17.5 years (interquartile limits, 13.0-21.7; maximum, 31.3) during which there were 5,400 incident CVD events and 6,132 all-cause deaths. 

 

Dietary cholesterol and egg consumption showed linear associations with incident CVD and all-cause mortality (all P values for nonlinear terms, 0.19-0.83).  The addition of each 300 mg of dietary cholesterol per day was associated with higher risk of incident CVD (adjusted hazard ratio [HR] 1.17, 95% confidence interval [CI], 1.09-1.26 and adjusted absolute risk difference [ARD] 3.24%, 95% CI 1.39%-5.08%).  The same increment of dietary cholesterol per day was also associated with higher risk of all-cause mortality (adjusted HR 1.18, 95% CI 1.10-1.26 and adjusted ARD 4.43%, 95% CI 2.51%-6.36%). Consumption of each additional half egg per day was associated with higher risk of incident CVD:  adjusted HR 1.06, 95% CI 1.03-1.10; adjusted ARD 1.11%, 95% CI 0.32%-1.89% and all-cause mortality:  adjusted HR 1.08, 95% CI 1.04-1.11; adjusted ARD 1.93%, 95% CI 1.10%-2.76%.

 

The associations between egg consumption and incident CVD (adjusted HR 0.99, 95% CI 0.93-1.05) and all-cause mortality (adjusted HR 1.03, 95% CI 0.97-1.09) were no longer significant after adjusting for dietary cholesterol consumption.  The associations between dietary cholesterol intake and incident CVD, as well as mortality, remained statistically significant after adjusting for traditional CVD risk factors (including non-high-density lipoprotein cholesterol [non-HDL-C] concentration), various nutrient intakes and measures of diet quality.

 

Comment.  This new analysis by Zhong et al. has several strengths, including a long follow-up period and the availability and analysis of a great deal of dietary information, such as indices of diet quality, including the Alternative Healthy Eating Index, a Dietary Approaches to Stop Hypertension score and a Mediterranean Diet index.  The supplemental material for the paper includes extensive information from sensitivity analyses.

 

Despite these strengths, the results are difficult to interpret, in our view, for several reasons.  First, adjustment for non-HDL-C level did not materially alter the association between dietary cholesterol intake and incident CVD.  This is curious because the presumed mechanistic link between dietary cholesterol intake and incident CVD is through the effect of dietary cholesterol to raise the circulating concentrations of LDL-C and non-HDL-C, which are well-established major CVD risk factors that are believed to be causally related to CVD incidence.  In a communication with the authors, we were told that adjustment for non-HDL-C and HDL-C levels had virtually no impact on the point estimates for CVD risk.  Data were missing for LDL-C for 900 subjects, so this was not assessed separately.  Given the lack of effect of adjustment for lipid levels, if the association between dietary cholesterol intake and CVD risk is causal, one must hypothesize mechanisms other than the effect of dietary cholesterol to raise atherogenic cholesterol (LDL-C and non-HDL-C) levels.

 

A second issue is that within the range of typical cholesterol intakes in the United States (<300 mg/d), no significant increases in risk for incident CVD or all-cause mortality were observed.  For example, for intakes of 200 to <300 mg/d compared to <100 mg/d, the HR for CVD in model 3 (adjusted for CVD risk factors and medication use) was 0.99, 95% CI 0.87-1.12 and for mortality was 0.95, 95% CI 0.84-1.06.  Therefore, the traditional recommendation to limit dietary cholesterol intake to <300 mg/d is supported by these analyses.

 

Finally, the relationship between cholesterol intake and non-CVD mortality is similar to that for all-cause mortality, with model 3 HR for all-cause mortality of 1.15 (95% CI 1.07-1.23) compared with 1.13 (95% CI 1.04-1.22) for non-CVD mortality (eFigure 5 in the supplemental material).  We are not aware of biologically plausible mechanisms that would explain an increase in non-CVD mortality as a consequence of higher dietary cholesterol intake.  Therefore, the possibility of residual confounding must be considered.

 

It is also notable that two other recent publications have reported on the association between egg consumption and incident CVD.  In the EPIC-Norfolk cohort,12 the top quintile of egg consumption (median 40 g/d) was associated with a non-significantly lower adjusted incidence of ischemic heart disease compared with the lowest quintile (HR 0.93, 95% CI 0.86-1.01), with a p-value for trend across quintiles of 0.37.  Also, in a large study in China with nearly 500,000 participants,13 those who consumed eggs daily had lower risks for incident CVD (HR 0.89, 95% CI 0.87-0.92) and ischemic heart disease (HR 0.88, 95% CI 0.84-0.93) than those who rarely or never consumed eggs, with significant inverse trends (p < 0.001) over the range of egg intake categories.  So, within the space of one year we have seen publications from observational studies reporting associations ranging from a significant inverse association, to no significant relationship, to a significant positive association of egg intake with incident CVD and/or ischemic heart disease.

 

Our view is that the available data show convincingly that higher dietary cholesterol intake modestly raises the level of LDL-C, a major CVD risk factor, with linear models indicating a rise of ~2 mg/dL of LDL-C for each increment of 100 mg/d of dietary cholesterol.3,14,15  The results from the Zhong et al. study do not suggest elevations in CVD incidence or mortality risk for intakes of dietary cholesterol below the traditional recommendation of <300 mg/d (i.e., for intake of 200-299 mg/d compared with <100 mg/d).5  Their results also showed that the relationship between egg consumption and CVD and mortality risk could be accounted for by the cholesterol content of eggs.  Therefore, we believe it is reasonable to suggest that whole eggs can be a part of a healthy dietary pattern, provided that total dietary cholesterol intake is not excessive, with the traditional recommendation being not to exceed 300 mg/d.  For those with hypercholesterolemia, it may be reasonable to further restrict dietary cholesterol intake.  The National Lipid Association recommendations for management of dyslipidemia suggest that dietary cholesterol be limited to <200 mg/d for those with hypercholesterolemia, and further restriction may be prudent for those who are known to be hyperresponders, i.e., those who have a larger than average increase in LDL-C in response to an increase in dietary cholesterol.16  Additional research will be needed to determine whether a dietary cholesterol intake >300 mg/d is causally related to adverse health outcomes, and, if so, what mechanisms account for these relationships.

 

References

  1. US Department of Health and Human Services and US Department of Agriculture. 2015-2020 Dietary Guidelines for Americans. 8th Edition. December 2015. https://health.gov/dietary guidelines/2015/guidelines/.
  2. Dietary Guidelines Advisory Committee. Scientific Report of the 2015 Dietary Guidelines Advisory Committee: Advisory Report to the Secretary of Health and Human Services and the Secretary of Agriculture. Washington, DC: US Dept of Agriculture, Agricultural Research Service; 2015.
  3. Berger S, Raman G, Vishwanathan R, et al. Dietary cholesterol and cardiovascular disease. Am J Clin Nutr. 2015;102:276-294.
  4. US Department of Agriculture. Agricultural Research Service, Nutrient Data Laboratory. USDA National Nutrient Database for Standard Reference, Release 28. Version Current: September 2015. https://ndb.nal.usda.gov/ndb/.
  5. Zhong VW, Van Horn L, Cornelis MC, et al. Associations of dietary cholesterol or egg consumption with incident cardiovascular disease and mortality. JAMA. 2019;321:1081-1095.
  6. The ARIC Investigators. The Atherosclerosis Risk in Communities (ARIC) study: design and objectives. Am J Epidemiol. 1989;129:687-702.
  7. Friedman GD, Cutter GR, Donahue RP, et al. CARDIA: study design, recruitment, and some characteristics of the examined subjects. J Clin Epidemiol. 1988;41:1105-1116.
  8. Wong ND, Levy D. Legacy of the Framingham Heart Study: rationale, design, initial findings, and implications. Glob Heart. 2013;8:3-9.
  9. Feinleib M, Kannel WB, Garrison RJ, et al. The Framingham Offspring Study: design and preliminary data. Prev Med. 1975;4:518-525.
  10. Taylor HA Jr, Wilson JG, Jones DW, et al. Toward resolution of cardiovascular health disparities in African Americans. Ethn Dis. 2005;15(suppl 6):4-17.
  11. Bild DE, Bluemke DA, Burke GL, et al. Multi-Ethnic Study of Atherosclerosis: objectives and design. Am J Epidemiol. 2002;156:871-881.
  12. Key TJ, Appleby PN, Bradbury KE, et al. Consumption of meat, fish, dairy products, eggs and risk of ischemic heart disease: a prospective study of 7198 incident cases among 409,885 participants in the Pan-European EPIC cohort. Circulation. 2019; Epub ahead of print.
  13. Qin C, Lv J, Bian Z, et al. Associations of egg consumption with cardiovascular disease in a cohort study of 0.5 million Chinese adults. Heart. 2018;104:1756-1763.
  14. Vincent MJ, Allen B, Palacios OM, Haber LT, Maki KC. Meta-regression analysis of the effects of dietary cholesterol intake on LDL and HDL cholesterol. Am J Clin Nutr. 2019;109:7-
  15. Clarke R, Frost C, Collins R, Appleby P, Peto R. Dietary lipids and blood cholesterol: quantitative meta-analysis of metabolic ward studies. BMJ. 1997;314:112-117.
  16. Jacobson TA, Ito MK, Maki KC, et al. National Lipid Association recommendations for patient-centered management of dyslipidemia: part 2. J Clin Lipidol. 2015;9(6 Suppl):S1-S122.e1.

 

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Association of Long-term Consumption of Sugar-Sweetened and Artificially Sweetened Beverages with Total and Cause-specific Mortality

Association of Long-term Consumption of Sugar-Sweetened and Artificially Sweetened Beverages with Total and Cause-specific Mortality

By Heather Nelson Cortes, PhD and Kevin C Maki, PhD

In the United States, sugar sweetened beverages (SSBs) account for the largest source of added sugar in the diet 1,2.  These types of drinks (e.g., carbonated, noncarbonated, fruit, sports) have added caloric sweeteners like high fructose corn syrup, sucrose, or fruit juice concentrates.  Currently it is recommended that adults consume no more than 10% of their total energy intake from added sugar 3.

While consumption rates of SSBs had been declining in the US over the past 10 years, recent research has suggested a reversal in that trend, with increased consumption among adults of all ages averaging around 145 kcal/day (6% of energy)4.  In younger adults, SSBs are responsible for 9.3% of daily calories in men and 8.2% of daily calories in women 5-7.

Studies have shown a positive association between intake of SSBs and weight gain, as well as higher risks of type 2 diabetes, coronary heart disease and stroke 8-11.  Artificially sweetened beverages (ASBs) are used as alternatives to the calorically heavy SSBs, yet there has been little research on the long-term health effects of ASBs or on the relationship between SSB consumption and total mortality.

In an analysis of two ongoing prospective cohort studies, Malik et al. examined the association between intakes of SSBs and ASBs with total and cause-specific mortality 12.  The analysis included data from the Nurses’ Health Study (NHS) and the Health Professionals Follow-up Study (HPFS).  The NHS study has been collecting data since 1976 and includes 121,700 female nurses, age 30-55 years at study entry.  The HPFS began in 1986 and includes 51,529 male health professionals, age 40-75 years at entry. 

Mean consumption of SSBs decreased in both cohorts over the follow-up periods, which were 34 years in the NHS and 28 years in the HPFS.  Intakes of SSBs and ASBs were inversely correlated in both the NHS (r = −0.06, P < 0.001) and the HPFS (r = −0.16, P < 0.001).  Overall, there were 36,436 deaths, including 7,896 from cardiovascular disease (CVD) and 12,380 from cancer during a total of 3,415,564 person-years of follow-up.

After adjusting for major diet and lifestyle factors, consumption of SSBs was associated with a higher risk of total mortality (Table).  SSBs were also associated with increased CVD mortality (hazard ratio comparing extreme categories of 1.31 [95% confidence interval, 1.15-1.50], P trend < 0.0001) and cancer mortality (1.16 [1.04-1.29], P trend = 0.0004).  ASB intake was associated with increased risk for total and CVD mortality only in the highest intake group (Table).  Interestingly, intake of ASBs was associated with total mortality in the NHS, but not the HPFS (P interaction = 0.01).  ASBs were not associated with cancer mortality in either cohort.

 

 

Table:  SSB and ASB Consumption and Mortality Risk (Total, CVD, Cancer)

Pooled Hazard Ratios (95% confidence intervals) from NHS and HPFS

 

<1/month

1-4/month

2-6/week

1-<2/d

>2/d

P trend

Total Mortality

SSB

1.0

 

1.01

(0.98, 1.04)

1.06

(1.03, 1.09)

1.14

(1.09, 1.19)

1.21

(1.13, 1.28)

<0.0001

ASB

1.0

 

0.96

(0.93, 0.99)

0.97

(0.95, 1.00)

0.98

(0.94, 1.03)

1.04

(1.02, 1.12)

0.01

CVD Mortality

SSB

1.0

1.06

(1.00, 1.12)

1.10

(1.04, 1.17)

1.19

(1.08, 1.31)

1.31

(1.15, 1.50)

<0.0001

ASB

1.0

0.93

(0.87, 1.00)

0.95

(0.89, 1.00)

1.02

(0.94, 1.12)

1.13

(1.02, 1.25)

0.02

Cancer Mortality

SSB

1.0

1.03 

(0.98, 1.08)

1.06

(1.01, 1.11)

1.12

(1.03, 1.21)

1.16

(1.04, 1.29)

0.0004

ASB

1.0

1.01

(0.96, 1.07)

0.99

(0.94, 1.04)

1.00

(0.93, 1.07)

1.04

(0.96, 1.12)

0.58

 

Comment.  Results from this study highlight the importance of minimizing SSB intake because consumption of SSBs has been consistently associated with adverse health outcomes and a less favorable cardiometabolic risk factor profile.8-11  Substituting ASBs for SSBs will help decrease added sugar intake, but it is important to note that the possible health impacts of long-term consumption have not been well documented.  It is uncertain whether the modest increases in total (4%) and CVD (13%) mortality associated with consuming ≥2 ASBs per day represent causal relationships.  Nevertheless, it is reasonable to recommend moderation in the consumption of these products.

 

References

  1. Hu FB, Malik VS. Sugar-sweetened beverages and risk of obesity and type 2 diabetes: epidemiologic evidence. Physiol Behav. 2010;100:47–54.
  2. National Cancer Institute: Division of Cancer Control & Population Sciences. Epidemiology and Genomics Research Program. Sources of Calories from Added Sugars among the US population, 2005–2006. Updated April 20, 2018. http://riskfactor.cancer.gov/diet/foodsources/added_sugars/.
  3. S. Department of Health and Human Services and U.S. Department of 
Agriculture. 2015–2020 Dietary Guidelines for Americans. 8th Edition. December 2015. http://health.gov/dietaryguidelines/2015/guidelines/.
  4. Welsh JA, Sharma AJ, Grellinger L, Vos MB. Consumption of added sugars is decreasing in the United States. Am J Clin Nutr. 2011;94:726–734.
  5. Ogden CL, Kit BK, Carroll MD, Park S. Consumption of sugar drinks in the United States, 2005–2008. NCHS Data Brief. 2011:1–8. 

  6. Rosinger A, Herrick K, Gahche J, Park S. Sugar-sweetened beverage consumption among U.S. adults, 2011–2014. NCHS Data Brief. 2017:1–8. 

  7. Malik VS, Pan A, Willett WC, Hu FB. Sugar-sweetened beverages and weight gain in children and adults: a systematic review and meta-analysis. Am J Clin Nutr. 2013;98:1084–1102.
  8. Malik VS, Popkin BM, Bray GA, Després JP, Willett WC, Hu FB. Sugar- sweetened beverages and risk of metabolic syndrome and type 2 diabetes: a meta-analysis. Diabetes Care. 2010;33:2477–2483.
  9. Fung TT, Malik V, Rexrode KM, Manson JE, Willett WC, Hu FB. Sweetened beverage consumption and risk of coronary heart disease in women. Am J Clin Nutr. 2009;89:1037–1042.
  10. de Koning L, Malik VS, Kellogg MD, Rimm EB, Willett WC, Hu FB. Sweetened beverage consumption, incident coronary heart disease, and biomarkers of risk in men. Circulation. 2012;125:1735–41, S1.
  11. Bernstein AM, de Koning L, Flint AJ, Rexrode KM, Willett WC. Soda consumption and the risk of stroke in men and women. Am J Clin Nutr. 2012;95:1190–1199.
  12. Malik VS, Li Y, Pan A, De Koning L, Schernhammer E, Willett WC, Hu FB. Long-term consumption of sugar-sweetened and artificially sweetened beverages and risk of mortality in US adults.  2019;139: doi: 10.1161/circulationaha.118.037401.

 

 

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Meta-regression Characterizes the Relationships Between Changes in Dietary Cholesterol Intake and Plasma Low-density and High-density Lipoprotein Cholesterol Changes

Meta-regression Characterizes the Relationships Between Changes in Dietary Cholesterol Intake and Plasma Low-density and High-density Lipoprotein Cholesterol Changes

By Kevin C Maki, PhD and Orsolya M Palacios, PhD

 

Our group recently collaborated with scientists from the University of Cincinnati to conduct meta-regression analyses that investigated the dose-response relationships between changes in dietary cholesterol intake and changes in lipoprotein-cholesterol levels.  The results from these analyses were presented in June at the American Society for Nutrition’s annual Nutrition 2018 meetings,1,2 and have also recently been accepted for publication in the American Journal of Clinical Nutrition.This summary is also available in the Fall 2018 Newsletter of MB Clinical Research.

 

Elevated low-density lipoprotein cholesterol (LDL-C) is a major cardiovascular risk factor, and there is a strong inverse association between high-density lipoprotein cholesterol (HDL-C) concentration and cardiovascular risk.4  Dietary guidance generally recommends reducing intakes of saturated fatty acids (SFA) and trans fatty acids (TFA) to reduce LDL-C levels, but in recent years there has been a step back from making specific quantitative recommendations with regard to limiting dietary cholesterol intake.5,6  A key recommendation from the 2010 Dietary Guidelines was to limit consumption of dietary cholesterol to <300 mg/day, but this was not included in the 2015-2020 Dietary Guidelines, although they did explain that “this change does not suggest that dietary cholesterol is no longer important to consider when building healthy eating patterns.”6  The 2015 guidelines stated “Strong evidence from mostly prospective cohort studies but also randomized controlled trials has shown that eating patterns that include lower intake of dietary cholesterol are associated with reduced risk of CVD…”.6  However, the committee concluded that “More research is needed regarding the dose-response relationship between dietary cholesterol and blood cholesterol levels.  Adequate evidence is not available for a quantitative limit for dietary cholesterol specific to the Dietary Guidelines.” 6  The 2013 American Heart Association/American College of Cardiology Lifestyle Management Guideline also concluded “There is insufficient evidence to determine whether lowering dietary cholesterol reduces LDL-C.”5  One problem with the available evidence is that there are limited data examining how much of an impact on lipoprotein lipid levels is attributable to dietary cholesterol after controlling for intakes of dietary fatty acids (i.e., SFA, TFA, polyunsaturated fatty acids [PUFA] and monounsaturated fatty acids [MUFA]).

 

Therefore, the goal of these meta-regression analyses was to examine the impacts of changes in dietary cholesterol on lipoprotein cholesterol levels, after accounting for dietary fatty acids.1,2  This meta-regression examined results from 55 randomized controlled dietary intervention trials (n = 2652 subjects) using a Bayesian approach (with Markov chain Monte Carlo techniques) and adjustment for dietary fatty acids to determine the best fitting mathematical models to the data.7  No significant associations were observed between change in dietary cholesterol intake and change in triglyceride or very low density lipoprotein cholesterol level.

 

For LDL-C, the meta-regression results indicated a positive correlation using a linear model and two non-linear models (Michaelis-Menten and Hill models), even after accounting for intakes of SFA, PUFA, MUFA and, where possible, TFA.  The relationship was best characterized by the non-linear models across the full range of cholesterol changes (0-1500 mg/day).  A 100 mg/day dietary cholesterol change was predicted to be associated with an increase in LDL-C of ~ 4.5 mg/dL in LDL-C.  Baseline cholesterol intake was not a significant predictor of the LDL-C response to a change in dietary cholesterol.  The relationship between baseline LDL-C and LDL-C response was unclear, and needs further exploration.  For HDL-C, the meta-regression analyses did not indicate a clear relationship between the change in dietary cholesterol intake and the change in HDL-C levels when both men and women were included.  However, when analyzed according to sex, the linear model and the Michaelis-Menten non-linear model demonstrated an inverse relationship in men, and a positive relationship in women.  This suggests a possible interaction between sex and HDL-C response to dietary cholesterol.

 

Using the Mensink et al. equation, which is designed to calculate the effects of changes in carbohydrate and fatty acid intakes on serum lipid and lipoprotein levels, each 1% increase in SFA in exchange for carbohydrate is predicted to increase LDL-C by 1.23 mg/dL.8  These findings suggest that increasing dietary cholesterol by 100 mg/day or 200 mg/day would have effects comparable to increasing dietary SFA by 3.7% and 5.5%, respectively.

 

These results suggest that there is a clinically meaningful effect of dietary cholesterol on LDL-C concentration.  This finding from a pooled analysis of results from 55 studies aligns with those from the best-controlled individual studies, such as two published by Ginsberg et al.9,10  This dose-response analysis provides reference for clinicians and nutrition scientists on how changes in dietary cholesterol intake may impact plasma cholesterol levels, although considerable interindividual variability should be expected.9-11  The clinical implications of changes in HDL-C associated with increased dietary cholesterol intake remain uncertain.

 

References:

  1. Vincent MJ, Allen B, Maki KC, Palacios OM, Haber LT. Non-linear models best characterize the relationship between dietary cholesterol intake and circulating low-density lipoprotein cholesterol levels. Presented at American Society of Nutrition’s Nutrition 2018 meetings, June 9-12, 2018, Boston MA.
  2. Palacios OM, Vincent MJ, Allen B, Haber LT, Maki KC. The effect of dietary cholesterol on high-density lipoprotein cholesterol levels in men and women: a meta-analysis of randomized controlled trials. Presented at American Society of Nutrition’s Nutrition 2018 meetings, June 9-12, 2018, Boston MA.
  3. Vincent MJ, Allen B, Palacios OM, Haber LT, Maki KC. Meta-regression analysis of the effects of dietary cholesterol intake on low- and high-density lipoprotein cholesterol. Am J Clin Nutr. 2018; In Press.
  4. Jacobson TA, Ito MK, Maki KC, Orringer CE, Bays HE, Jones PH, McKenney JM, Grundy SM, Gill EA, Wild RA, Wilson DP, Brown WV. National Lipid Association recommendations for patient-centered management of dyslipidemia: part 1 – executive summary. J Clin Lipidol. 2014;8:473-488.
  5. Eckel RH, Jakicic JM, Ard JD, de Jesus JM, Houston Miller N, Hubbard VS, Lee IM, Lichtenstein AH, Loria CM, Millen BE, Nonas CA, Sacks FM, Smith SC Jr., Svetkey LP, Wadden TA, Yanovski SZ; American College of Cardiology/American Heart Association Task Force on Practice Guidelines. 2013 AHA/ACC guideline on lifestyle managemnet to reduce cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2014;63(25 Pt B):2960-2984.
  6. U.S. Department of Health and Human Services and U.S Department of Agriculture. 2015-2020 Dietary Guidelines for Americans. 8th edition. December 2015. Available at https://health.gov/dietaryguidelines/2015/resources/2015-2020_Dietary_Guidelines.pdf.
  7. The Stan Development Team. RStan: the R interface to Stan. R package version 2.16.2. 2017. Available at http://mc-stan.org.
  8. Mensink RP, Zock PL, Kester AD, Katan MB. Effects of dietary fatty acids and carbohydrates on the ratio of serum total to HDL cholesterol and on serum lipids and apolipoproteins: a meta-analysis of 60 controlled trials. Am J Clin Nutr. 2003;77:1146-1155.
  9. Ginsberg HN, Karmally W, Siddiqui M, Holleran S, Tall AR, Rumsey SC, Deckelbaum RJ, Blaner WS, Ramakrishnan R. A dose-response study of the effects of dietary cholesterol on fasting and postprandial lipid and lipoprotein metabolism in healthy young men. Arterioscler Thromb. 1994;14:576-586.
  10. Ginsberg HN, Karmally W, Siddiqui M, Holleran S, Tall AR, Blaner WS, Ramakrishnan R. Increases in dietary cholesterol are associated with modest increases in both LDL and HDL cholesterol in healthy young women. Arterioscler Thromb Vasc Biol. 1995;15:169- 178.
  11. Jacobson TA, Maki KC, Orringer CE, Jones PH, Kris-Etherton P, Sikand G, La Forge R, Daniels SR, Wilson DP, Morris PB, Wild RA, Grundy SM, Daviglus M, Ferdinand KC, Vijayaraghavan K, Deedwania PC, Aberg JA, Liao KP, McKenney JM, Ross JL, Braun LT, Ito MK, Bays HE, Brown WV, Underberg JA, NLA Expert Panel. National Lipid Association recommendations for patient-centered management of dyslipidemia: Part 2. J Clin Lipidol. 2015;9(6 Suppl):S1-S122.
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Changes in Diet Quality and Mortality

Changes in Diet Quality and Mortality

Changes in Diet Quality and Mortality

By Kevin C Maki, PhD

Background
Sotos-Prieto and colleagues from the Departments of Nutrition and Epidemiology at Harvard University published an analysis of the relationships between changes in diet quality scores and mortality [all-cause, cardiovascular (CV), and cancer] in a recent issue of the New England Journal of Medicine.1  These relationships were examined in two large cohorts of health professionals, the US Nurses’ Health Study (women) and the US Health Professionals Follow-up Study (men).

Previous studies have shown that higher diet quality scores are associated with lower mortality.  Of course, the potential problem with observational evidence is that it is difficult to know whether it is higher diet quality per se that is responsible for the relationship to lower mortality, or other differences between those with lower and higher diet quality scores.  People who consume diets that conform to recommendations from health authorities often have other characteristics that might contribute to better outcomes.  They tend to be more health conscious, have higher educational attainment, exercise more regularly, have lower body mass index, and be less likely to smoke, use illicit substances and consume alcohol to excess, just to name a few of the differences.

Epidemiologists attempt to adjust for these differences using statistical techniques to reduce the potential for bias and confounding by differences other than the exposure of interest; in this case diet quality score.  It is often impossible to identify and adjust for all of the variables that may be relevant.  The ultimate goal is to identify exposures that are causally related to disease status and modifiable, which can serve as the basis for public health actions, including recommendations for the characteristics of a healthy diet.

While far from perfect, it is useful to investigate the relationships between changes in exposure variables over time and disease risk.  For example, it bolstered the case for a causal relationship between cigarette smoking and risks for lung cancer and heart disease when it was shown that risks declined over time in those who quit smoking, but did not in those who continued to smoke.  Similarly, the Harvard group sought to assess whether changes in diet quality scores over time predicted risks for all-cause and cause-specific mortality.

Methods
In order to address this question, the researchers calculated changes over time in three scores:  the Alternative Healthy Eating Index (aHEI), the Alternative Mediterranean Diet (aMED) score, and the Dietary Approaches to Stop Hypertension (DASH) score.  Scores were calculated based on responses to the Willett Food Frequency Questionnaire that was administered every 4 years over long periods in both cohorts.  For the main analysis, changes in diet quality were calculated from 1986 to 1998 and follow-up was through 2010 (12 years).  The analysis included data from 73,739 participants (65% women).

The aHEI used scores from 0-10 for 11 food components selected on the basis of their relationships with chronic diseases.  Thus, the score could be from 0 to 110.  The aMED score included 9 components and were scored as 0 or 1 according to whether intake was above or below the cohort-specific median, allowing a score from 0 to 9.  The DASH score included 8 components, each scored 1-5, thus producing scores ranging from 8 to 40.  For all, a higher score indicated higher diet quality.

Results
Participants who increased their diet quality scores reported increased intakes of whole grains, vegetables and omega-3 fatty acids, as well as reduced intakes of sodium.  Compared to participants with relatively stable scores (middle quintile for change), those in the top 20% for increases (roughly 15-16 points for aHEI, 2-3 points for aMED, and 5-6 points for DASH), had 9-14% lower mortality risk, all p < 0.05 for the fifth vs. the third quintile in multivariable-adjusted models.  Similar results were obtained when a 20-percentile increase in score was modeled (8-17% lower risk for mortality).

Results were somewhat less consistent for deaths from CV causes and cancer.  A 20-percentile increase in aHEI was associated with 15% lower CV mortality (p < 0.05), while the same increase in aMED was associated with a 7% lower CV mortality (p < 0.05), and a 20-percentile increase in DASH score was associated with a non-significant 4% reduction in mortality.  For cancer mortality, a 20-percentile increase was associated with 6-9% lower mortality, which was only statistically significant (p < 0.05) for the DASH score (9%).

Having constant high diet quality score was associated with reductions of 9-14% in all-cause mortality over 12 years compared to those with constant low scores.  The investigators also looked at 8-year and 16-year changes.  In general, the effect became more pronounced with longer periods.  This was particularly evident for the aHEI, although that may be due to the greater range of values possible, which increases the variation in the populations studied.

Comment
This study adds support for the healthy eating patterns recommended in the Dietary Guidelines for Americans (2015-2020).2  Although confounding by unmeasured, or crudely measured, factors cannot be ruled out, the available data are consistent with a causal association between a healthy diet pattern and reduced risks for all-cause and CV mortality.  The evidence for a reduction in cancer mortality with a healthy dietary pattern is less convincing.  These results particularly support the recommendations for increased consumption of whole grains, fruits, vegetables, and fish/omega-3 fatty acids, compared with the average American diet, since these were the foods that were primarily responsible for changes in diet quality scores over time.

As I have stated repeatedly, public policy recommendations regarding diet often have to be based on evidence from observational studies assessing disease risk and intervention studies of biomarkers for disease risk, because few randomized, controlled dietary intervention studies have been completed to assess effects on disease incidence.  The strongest recommendations should be reserved for those areas where we have alignment between results from all three types of studies.

The results from the Prevención con Dieta Mediterránea (PREDIMED) study support health benefits, including reduced incidence of CV events (particularly stroke) and diabetes associated with advice to consume a Mediterranean diet pattern supplemented with nuts or olive oil, compared to low-fat diet advice.3 PREDIMED was not a perfect trial.  More randomized, controlled dietary intervention trials with outcomes of disease incidence are badly needed to answer questions about risks and benefits of various types of dietary advice.  PREDIMED demonstrates the feasibility of completing such studies.

For now, despite a number of caveats and uncertainties, the best available evidence suggests that the dietary patterns recommended in the Dietary Guidelines for Americans (healthy US diet, Mediterranean diet, DASH diet) are associated with a variety of favorable outcomes, including reduced total and CV mortality.

References:

  1. Sotos-Prieto M, Bhupathiraju SN, Mattei J, et al. Association of changes in diet quality with total and cause-specific mortality. N Engl J Med. 2017;377:143-153.
  2. US Department of Health and Human Services and US Department of Agriculture. Dietary Guidelines for Americans 2015-2020. 8th December 2016. Available at https://health.gov/dietaryguidelines/2015/resources/2015-2020_Dietary_Guidelines.pdf.
  3. Estruch R, Martínez-González MA, Corella D, et al.; PREDIMED Study Investigators. Effects of a Mediterranean-style diet on cardiovascular risk factors: a randomized trial. Ann Intern Med. 2006;145:1-11.

 

 

Changes in Diet Quality and Mortality