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Ruddy meat intake and risk of coronary heart disease among Us men: prospective cohort study

BMJ 2020; 371 doi: https://doi.org/x.1136/bmj.m4141 (Published 02 December 2020) Cite this as: BMJ 2020;371:m4141

Laila Al-Shaar , postdoctoral research fellow1,
Ambika Satija , postdoctoral research fellow1,
Dong D Wang , member of the faculty of medicine12,
Eric B Rimm , professor of epidemiology and nutrition123,
Stephanie A Smith-Warner , senior lecturer13,
Meir J Stampfer , professor of epidemiology and nutrition123,
Frank B Hu , professor of epidemiology and nutrition123,
Walter C Willett , professor of epidemiology and nutrition123

^oneDepartment of Nutrition, Harvard Th Chan School of Public Health, 655 Huntington Artery, Boston, MA 02115, USA
²Channing Division of Network Medicine, Department of Medicine, Brigham and Women'southward Infirmary, Harvard Medical School, Boston, MA, USA
³Department of Epidemiology, Harvard Thursday Chan Schoolhouse of Public Health, Boston, MA, United states

Correspondence to: Westward C Willett wwillett{at}hsph.harvard.edu

Accepted 14 October 2020

Abstruse

Objectives To study full, processed, and unprocessed red meat in relation to take a chance of coronary heart disease (CHD) and to estimate the effects of substituting other poly peptide sources for red meat with CHD take chances.

Design Prospective cohort study with repeated measures of diet and lifestyle factors.

Setting Health Professionals Follow-Up Study cohort, United states of america, 1986-2016.

Participants 43 272 men without cardiovascular illness or cancer at baseline.

Primary issue measures The master upshot was total CHD, comprised of astute non-fatal myocardial infarction or fatal CHD. Cox models were used to estimate hazard ratios and 95% conviction intervals beyond categories of red meat consumption. Exchange analyses were conducted by comparison coefficients for red meat and the culling food in models, including carmine meat and alternative foods every bit continuous variables.

Results During 1 023 872 person years of follow-up, 4456 incident CHD events were documented of which 1860 were fatal. After multivariate adjustment for dietary and not-dietary take chances factors, total, unprocessed, and processed red meat intake were each associated with a modestly higher chance of CHD (adventure ratio for i serving per day increment: i.12 (95% conviction interval 1.06 to i.18) for full red meat, 1.eleven (i.02 to 1.21) for unprocessed reddish meat, and one.fifteen (ane.06 to 1.25) for candy ruby-red meat). Compared with cerise meat, the intake of ane serving per mean solar day of combined plant poly peptide sources (nuts, legumes, and soy) was associated with a lower risk of CHD (0.86 (0.eighty to 0.93) compared with total crimson meat, 0.87 (0.79 to 0.95) compared with unprocessed red meat, and 0.83 (0.76 to 0.91) compared with processed ruby-red meat). Substitutions of whole grains and dairy products for total red meat and eggs for processed ruby-red meat were likewise associated with lower CHD chance.

Conclusions Substituting high quality establish foods such as legumes, basics, or soy for cherry meat might reduce the take chances of CHD. Substituting whole grains and dairy products for total red meat, and eggs for processed red meat, might likewise reduce this chance.

Introduction

Substantial evidence from randomized trials and observational studies suggests that high consumption of ruby-red meat, especially candy red meat, is associated with an increased risk of mortality123 and major chronic diseases,456789 including coronary heart disease (CHD).101112 Consequently, the 2015-20 US Dietary Guidelines for Americans13 encourage dietary patterns that are low in cherry and candy meat intake. Increases in run a risk were non, all the same, seen in Asian populations with low consumption of red meat, or in populations in which consumption of red meat has recently increased.141516 These inconsistencies could be due to the variable amounts and duration of crimson meat consumed in unlike populations,1516 inadequate differentiation betwixt processed and unprocessed red meat,15171819 differences in the levels of controlling for confounding,1518 and, importantly, differences in the comparison sources of energy.15202122 In detail, in most populations, most energy intake come from refined starches, sugar, potatoes, and fats that are highly saturated or partially hydrogenated. Thus, analyses that neglect to specify comparing foods are past default mainly comparing cherry-red meat with these suboptimal sources of energy intake. Therefore, lack of an association of red meat with disease outcomes simply implies that red meat is as unhealthy as these alternative foods.

To accost these problems in study design and analysis, we examined the relation between total, processed, and unprocessed reddish meat and take a chance of CHD in the large prospective Health Professionals Follow-upwardly Study accomplice with repeated measures of nutrition during thirty years of follow-up. We estimated the effects of substituting other protein sources for ruby-red meat with CHD hazard and evaluated the temporal relation of cerise meat consumption to risk of developing CHD.

Methods

Report population

The Health Professionals Follow-upwards Study started in 1986 when 51 529 US male wellness professionals (29 683 dentists, 10 098 veterinary surgeons, 4185 pharmacists, 3745 optometrists, 2218 osteopathic physicians, and 1600 podiatrists) aged 40 to 75 years provided detailed information on their medical history, lifestyle, and typical diet. Questionnaires have been completed biennially to update information on potential risk factors and occurrence of new diseases. A detailed description of the cohort has been published elsewhere.23

Dietary data were not included if participants left more than 70 items blank in the nutrient frequency questionnaire or had implausible full energy intake (<800 kcal/day (1 kcal=4.eighteen kJ=0.00418 MJ) or >4200 kcal/solar day)24 in whatever of the food frequency questionnaires. Participants were excluded if at baseline they had a history of cancer (n=1645), myocardial infarction, angina, or coronary artery bypass graft (CABG, n=3696), or stroke (n=221). A total of 43 272 participants were included and subsequently followed upward.

Dietary assessment

Participants completed a semiquantitative nutrient frequency questionnaire in 1986 and every iv years thereafter. Participants were asked how oft, on average, they had consumed a standard portion of food in the past year. Nine responses were possible and ranged from "never" to "more half-dozen times per twenty-four hour period." The items on candy cerise meat included beef or pork hotdogs, salary, salami, bologna, or other processed meat sandwiches, in addition to other processed meats such equally sausages and kielbasa. Items on unprocessed red meat included hamburger (lean or extra lean), regular hamburgers, beef, pork, or lamb as a main or mixed dish or sandwich. Total red meat included processed and unprocessed red meat. Other protein sources, apart from reddish meat, included poultry, fish, eggs, high fat dairy products, low fatty dairy products, nuts, legumes, soy, and whole grains (supplemental table 1). Found based protein foods included basics, legumes, and soy foods.

The reproducibility and validity of the food frequency questionnaire in measuring food intake have been described in detail previously.25 The correlation coefficients between the questionnaire and multiple dietary records were 0.59 for unprocessed red meat; 0.52 for processed red meat; 0.48 for poultry; 0.74 for fish; 0.56 for eggs; 0.62 for each of high fat and low fatty dairy products; 0.46 for legumes, including soybeans and tofu; 0.45 for basics; and 0.27 for whole grains.24 In this report, nosotros as well calculated a modified diet score of the Alternative Healthy Eating Index to assess overall diet quality after removing the cherry meat components.26

Observation of effect

The principal result for this study was total CHD, comprised of acute non-fatal myocardial infarction or fatal CHD, occurring later the return of the 1986 food frequency questionnaire but before 31 Jan 2016. Myocardial infarction was initially self-reported and confirmed by medical records documenting symptoms and either diagnostic electrocardiographic changes or raised levels of cardiac specific enzymes. Physicians blinded to the participants' exposure status reviewed the medical records. For those with unavailable medical records, the diagnosis was considered probable (10.3% of total participants) if supported by telephone interview or other supplemental information. Deaths were identified from searches of vital records, the National Death Index, and reports past the participant'due south next of kin or the postal organisation.1227 Using these methods, at least 98% of deaths were ascertained.27 Fatal CHD included fatal myocardial infarction, or if CHD was listed as cause of decease on the death document and at that place was testify of previous coronary illness. Sudden death within ane hr of the onset of symptoms in men with no other plausible cause of expiry (other than coronary disease) was considered as fatal CHD.

Cess of covariates

In the biennial follow-up questionnaires, we inquired about and updated information on known or potential take a chance factors for CHD, including body mass index (BMI; <21, 21-22.9, 23-24.nine, 25-26.ix, 27-29.9, 30-32.9, 33-34.ix, 35-39.ix, ≥xl), cigarette smoking (never smoker, former smoker, current 1-14 cigarettes/day, electric current 15-24 cigarettes/solar day, current ≥25 cigarettes/twenty-four hour period), alcohol consumption (0, 0.1-iv.9, v.0-9.9, 10-14.ix, or ≥fifteen.0 g/solar day), total energy intake (in fifths), family history of myocardial infarction or stroke (divers every bit event before age 65 years for a participant's female parent or before age 55 years for a participant'south father), multivitamin employ (yes, no), aspirin use (yeah, no), race or ethnicity (white, black, Asian, other), work status (full time, function time, retired), profession (dentist, chemist, optometrist, podiatrist, veterinary surgeon), living arrangement (lives with family, lives lonely, other), and marital status (married, divorced, widowed, never married). Data on physical action (<3, 3-8.9, 9-17.9, eighteen-26.nine, and ≥27 in metabolic equivalents of task per week) were also collected using the validated physical action questionnaire.28 In example of missing data, the terminal value was carried forwards for i two year wheel. If the final value was missing, then a missing indicator was created.

Statistical analysis

Age adjusted and multivariate adjusted Cox proportional hazard models were used to estimate hazard ratios and 95% conviction intervals beyond the fifths of total, processed, and unprocessed reddish meat consumption in relation to CHD chance. Person years of follow-up were calculated from the return of the 1986 nutrient frequency questionnaire to the engagement of the first CHD event, death, or end of follow-up, whichever came start. The main models were adapted for age (in months), calendar fourth dimension (two year follow-upwards periods), and energy intake, in addition to BMI, physical activity, smoking status, alcohol intake, family history of myocardial infarction or stroke, multivitamin use, aspirin use, race or ethnicity, work condition, profession, living arrangement, and marital status. We further adjusted for other dietary variables, including poultry (unprocessed), fish, egg, high fat dairy, depression fat dairy, nuts, legumes, soy, whole grains, fruit, vegetables, coffee, and glycemic index (all in fifths).

To better represent long term diet and minimize inside person variation, we calculated the cumulative boilerplate of nutrient intake from baseline up to the beginning of each 2 year follow-upwardly interval. We then investigated the cumulative boilerplate intake in relation to risk of CHD from the showtime of each follow-upward interval until the side by side follow-upwards interval. To minimize the possibility of opposite causation bias, we stopped updating diet after the participant's diagnosis of cancer or stroke, or after reporting diabetes, angina, or CABG.

We investigated the associations of substituting a unmarried serving of alternative foods for red meat (total, processed, or unprocessed) with CHD risk by including the culling foods as continuous variables in the same multivariable model and bookkeeping for other dietary and not-dietary variables equally well as total energy intake. The deviation in the β coefficients of the 2 foods existence compared, and their variances and covariances, were used to estimate the risk ratio and 95% conviction interval for the substitution.12

Stratified analysis by historic period (<65, ≥65 years), BMI (<25, ≥25), agenda time (<2000, 2000 or afterwards), and total fiber intake (<28, ≥28 yard/mean solar day) were also performed. Effect modification was tested subsequently including the multiplicative interaction term between the continuous dietary variables included in the exchange model and each of age, BMI, calendar time, and total fiber intake.

Time lagged assay with varying not-overlapping lag time periods (0-4 years, 4-8 years, 8-12 years, 12-xvi years, 16-twenty years, or 20-24 years) was conducted to predict the risk of CHD. For example, for latency of 4-8 years, nosotros used dietary intake of 1986 to predict CHD risk during 1990 to 1994, the dietary intake of 1994 for CHD events occurring from 1998 to 2002, dietary intake in 1998 for CHD events occurring from 2002 to 2006, and then forth. The lagged analyses allow an evaluation of the latency between consumption of a dietary factor and occurrence of the effect just do not account for correlation of intakes over time.

We besides conducted several sensitivity analyses to test the robustness of our results. To cheque for possible confounding by other aspects of diet, we performed a sensitivity analysis adjusting for a modified diet score of the Culling Healthy Eating Index that excluded the red meat components. In another sensitivity analysis, we included as covariates baseline history of diabetes, hypertension, and hypercholesterolemia, which might human activity as intermediates on the pathway linking red meat consumption and take a chance of CHD. Sensitivity analyses after excluding probable events were similar, so but total numbers of acute myocardial infarction events were presented. In addition to using the cumulative boilerplate intake updated until the development of major diseases (ie, incidence of cancer, stroke, diabetes, or angina, or CABG), we used baseline diet; most contempo nutrition; cumulative average, which was continually updated fifty-fifty after the diagnosis of a major disease; and cumulative updated average adjusted for the incidence of major diseases (cancer, stroke, diabetes, angina, or CABG) in the multivariate model.

The proportional hazards supposition was tested past including an interaction term between red meat intake and months to events. To test for linear trend, the median intakes for each fifth were modeled as a single continuous variable. Information were analyzed in SAS software (version 9.4, SAS Establish) at a 2 tailed α level of 0.05.

Patient and public involvement

No participants were involved in setting the research question or the outcome measures, nor were they involved in the design and implementation of the study. Results from the Health Professionals Follow-Upward Study cohort are routinely disseminated to study participants through the study website and social media outlets. Nosotros plan to disseminate these findings to participants in our annual newsletter and to the general public in a press release.

Results

During 1 023 872 person years of follow-up of 43 272 participants, 4456 incident CHD events were documented of which 1860 were fatal. At baseline, participants were on average aged 53 (SD 9.5) years and had a mean BMI of 25.5 (SD three.iii). Around 54% were never smokers, 20% had a history of hypertension, two% had diabetes, and 10% had high cholesterol levels. Those with college total red meat consumption were more probable to smoke, consume alcohol, have diabetes, and utilize aspirin. They had higher intakes of full energy and trans fatty acids but were less physically agile and less likely to have hypercholesterolemia or a family history of cardiovascular diseases. They had lower intakes of multivitamins, fruit, vegetables, and cereal fiber compared with those in the lower fifths of total red meat intake. Similar distributions were observed with processed and unprocessed red meat consumption (table 1).

Table 1

Age standardized baseline characteristics of participants (north=43 272) by fifths of full, unprocessed, and candy red meat intake. Values are numbers (percentages) unless stated otherwise

In age adjusted analyses, college intakes of full blood-red meat, unprocessed red meat, and candy red meat were each positively associated with higher risk of CHD (table 2). Later on further adjustment for not-dietary cardiovascular illness risk factors and free energy intake, the associations of total, processed, and unprocessed blood-red meat consumption with CHD chance each remained statistically meaning merely attenuated. Adjusting for other major dietary variables such as poultry, fish, egg, high fat dairy products, low fat dairy products, nuts, legumes, soy, and whole grains in addition to fruit, vegetables, coffee, and glycemic index further attenuated the associations, but total, unprocessed, and candy red meat remained significantly associated with take a chance of CHD (comparing the fifth fifth (high intake) with the beginning fifth, hazard ratio 1.28 (95% conviction interval one.fourteen to 1.45, P<0.001 for trend) for full red meat, 1.18 (1.05 to i.32, P=0.01 for tendency) for unprocessed red meat, and i.nineteen (ane.07 to i.33, P=0.001 for trend) for processed red meat consumption, see table 2). For an increment of one serving per solar day, total carmine meat was associated with a 12% (95% confidence interval 6% to 18%) higher risk of CHD. Similar associations were observed for unprocessed and processed crimson meat (table 2).

Table 2

Hazard ratios (95% confidence intervals) for full coronary eye affliction associated with fifths of total, unprocessed, and processed cerise meat intake (n=43 272)

Associations of each of full, unprocessed, and processed ruby meat with fatal CHD were slightly stronger (1.38 (1.fifteen to ane.66) for total red meat, 1.29 (ane.08 to ane.53) for unprocessed red meat, and 1.21 (1.02 to ane.43) for candy red meat) (see supplemental table two).

In sensitivity analyses, the associations between red meat intake and CHD take chances became slightly weaker after including baseline history of diabetes, hypertension, and hypercholesterolemia in the model, or after adjusting for the modified AHEI score (see supplemental tabular array 3).

Compared with intakes of total, unprocessed, or candy red meat, intakes of basics, legumes, soy, and combined plant poly peptide sources (nuts, legumes, and soy) were each associated with a significantly lower risk of CHD (fig 1, supplemental table 4). Specifically, the hazard ratios for total, unprocessed, and processed red meat intake were 0.86 (0.80 to 0.93), 0.87 (0.79 to 0.95), and 0.83 (0.76 to 0.91) when compared with one serving per 24-hour interval of combined plant protein sources (fig 1). Intake of high fatty dairy products, low fat dairy products, and whole grains were also associated with a lower CHD risk compared with intake of full, unprocessed, and processed red meat (fig one, supplemental table 4). Egg intake was additionally associated with a lower CHD risk compared with intake of processed reddish meat (0.87 (0.76 to 0.99), fig 1).

Fig 1

Hazard ratios (95% confidence intervals) for total coronary heart affliction associated with replacement of one serving per day of full, unprocessed, and processed red meat with i serving per day of other protein sources. *Replacing ≥2 servings/week of red meat with ≥2 servings/calendar week of soy

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Milk (both skimmed and whole), yogurt, and cheese were each associated with a 10% to 22% lower gamble of CHD compared with red meat (table 3). These associations were more pronounced when one serving of processed scarlet meat was replaced with i serving of each of these dairy products (tabular array 3).

Tabular array 3

Hazard ratios (95% conviction intervals) for total coronary heart disease associated with replacement of 1 serving per 24-hour interval of total, unprocessed, and processed ruby-red meat with one serving per 24-hour interval of each type of dairy production

Replacement of red meat with total fish was not associated with CHD risk. In a more detailed analysis according to types of fish (night meat fish, canned tuna, and other fish), on stratifying by calendar year of follow-up (<2000, ≥2000), intake of nighttime meat fish was observed to exist associated with a lower CHD risk compared with intake of total ruddy meat (0.56 (0.33 to 0.95), unprocessed scarlet meat (0.54 (0.31 to 0.92), and processed red meat (0.52 (0.30 to 0.90; table 4), in 2000 or later but not earlier. Other fish intake was, however, associated with college CHD adventure compared with intake of total, unprocessed, and processed ruddy meat.

Table 4

Run a risk ratios (95% confidence intervals) for total coronary heart disease associated with replacement of one serving per day of full, unprocessed, and processed cerise meat with i serving per twenty-four hour period of each type of fish, stratified by follow-up period (<2000, ≥2000)

The associations comparison specific protein sources in relation to hazard of CHD did not differ past BMI (<25, ≥25) or flow (<2000, ≥2000), (P>0.05 for interaction). However, stronger associations were observed in the comparisons of nuts and establish based proteins with red meat among older men (0.84 (0.76 to 0.92) for nuts and 0.82 (0.75 to 0.90) for constitute based proteins) and was attenuated only remained significant among those with low cobweb intake (0.93 (0.85 to one.00) for basics and 0.92 (0.85 to 1.00) for plant based proteins) (supplemental figures 1 and two). The associations between cherry-red meat and egg intake were stronger among younger men in whom the replacement of red meat with egg was associated with a 20% (95% confidence interval ii% to 35%) lower take chances of CHD.

Results were comparable with the primary assay (in which the updating of diet was stopped later the incidence of intermediate outcomes), when cumulatively updated boilerplate diet continued to be used throughout follow-upwards, with and without adjusting for the incidence of major diseases (supplemental figure iii). Weaker associations were observed when the most recent diet solitary (except for poultry) was compared with cumulative updated diet (supplemental figure iii). Total red meat consumption was on average 0.99 (SD 0.73) servings/day at baseline, 0.87 (0.72) servings/twenty-four hours using the well-nigh recent diet, and 0.91 (0.64) servings/day using the cumulative average.

Latency analyses were also performed to further evaluate the temporal relation between cess of diet and diagnosis of CHD. Overall, the associations observed in the substitution analyses did not seem to diminish with upwards to 20 years of latency; with greater than 20 years, the associations tended to exist weaker, merely the number of events was relatively small (supplemental figure 4).

Discussion

In this prospective cohort written report of men with at least 30 years of follow-upwards, greater intakes of total, unprocessed, and processed reddish meat were associated with a college risk of CHD, independent of other dietary and non-dietary cardiovascular disease risk factors. Compared with intake of total, unprocessed, or processed red meat, intake of high quality plant based protein foods such as nuts, legumes, and soy in addition to whole grains and dairy products were each associated with a lower risk of CHD. Substituting nuts and plant based proteins for full red meat was each associated with a lower CHD run a risk among those older but non younger than 65 years and remained statistically meaning but attenuated among those with low cobweb intake. The latency analyses suggested that the inverse associations of substituting red meat with major protein sources did non diminish with lags upward to 20 years before the diagnosis of CHD. Also, associations were stronger using cumulative boilerplate intakes than with unmarried dietary assessments, likely reflecting the less precise measurement of long term diet when using a single questionnaire compared with using the cumulative average of repeated assessments. This was consistent with the larger standard departure of total carmine meat intake observed when single measurements were used (baseline and near recent diet) compared with using the cumulative average of multiple measurements.

The weaker associations observed when using the most contempo dietary data might also be influenced by reverse causation bias, every bit participants could accept changed their nutrition afterward developing symptoms or a cardiovascular affliction related diagnosis.

Comparison with other studies

Our finding of red meat consumption beingness associated with an increased run a risk of CHD is in line with several previous studies. In our study, nosotros additionally included substitution analysis that explicitly compared crimson meat with specific sources of proteins while accounting for total energy intake. Analyses that do non specify a comparison would exist implicitly comparing the food under study with a mixture of all other energy contributing foods in the diet, thus making conclusions and dietary recommendations more difficult. In 25 153 California 7th Day Adventists, daily meat consumption was associated with a 70% (among men) and 37% (among women) higher risk of fatal ischemic heart disease.17 In that study, all the same, the type of meat was not specified, and the simultaneous aligning for dietary factors was limited to eggs, cheese, milk, and coffee intake. In a contempo assay of individual level data of six prospective U.s.a. accomplice studies, an additional ii servings per week of unprocessed red meat was associated with a 3% greater risk of cardiovascular diseases. Participants who consumed two servings per week of processed meat were also at a 7% higher take chances of CVD compared with not-consumers.21 Similar to other studies, substitution assay was non performed and only baseline data were analyzed. In a meta-analysis study of 17 prospective cohorts, one serving per day of total red meat was associated with a 19% higher take chances of cardiovascular affliction mortality, and this risk was mostly associated with processed carmine meat. Unprocessed red meat was associated with higher cardiovascular affliction bloodshed among the The states populations only,sixteen thus highlighting the importance of considering the consumption levels of the populations under report. In an older meta-analysis of observational studies, processed meat intake was associated with an increased chance of CHD,11 and no statistically significant association was observed with unprocessed red meat. All the same, the included studies were limited past either a small number of events (769 events beyond all studies), brusque follow-upwards, no adjustment for total free energy intake, not specifying the comparison nutrient, or not using prospectively collected data. In a recent meta-assay of prospective cohorts, even so, a reduction of 3 servings per week of unprocessed and processed red meat was each associated with a lower risk of all cause and cardiovascular illness mortality and a lower take a chance of myocardial infarction.twenty In this meta-analysis, the comparing nutrient was not specified, and the results could take been underestimated.

Nonetheless, we previously found that higher intake of total red meat was statistically significantly associated with an increased risk of CHD amid 84 136 women of the Nurses' Health Study cohort, especially when compared with alternative poly peptide sources.12 A prospective study of 409 885 men and women in nine European countries showed that the risk of ischemic centre disease was 19% greater for every 100 g/day increase in the intake of total and candy red meat.29 Substituting 100 kcal/d of fat fish, yogurt, cheese, or eggs for 100 kcal/d of red and processed meat was associated with a 15-24% lower hazard of ischemic centre disease.29 Although the authors did non examine plant sources of proteins, their overall conclusion was consistent with the findings of our study showing that red and candy meat were associated with a higher risk of ischemic center disease. In some other prospective The states accomplice study, the dietary intake of processed and unprocessed red meat was each associated with higher risk of mortality from eye disease.30 All the same, both prospective cohorts used ane dietary measurement at baseline.2930

Possible explanations and implications

Several mechanisms might contribute to an adverse effect of red meat intake on take a chance of CHD. A meta-analysis of randomized clinical trials showed that consumption of red meat was associated with increased blood levels of low density lipoprotein cholesterol compared with consumption of plant based protein sources, consistent with the high saturated fatty and cholesterol content of cherry meat.31 In a network meta-analysis of randomized trials, nuts, legumes, and whole grains were each shown to be more effective in reducing low density lipoprotein cholesterol compared with carmine meat.32 In addition, red meat is depression in polyunsaturated fat, and reduction of risk of CHD past replacement of saturated fat with polyunsaturated fat has been supported past both observational cohort studies and randomized trials.33 Dietary heme fe found in scarlet meat has been associated with myocardial infarction and fatal CHD in many epidemiologic studies.343536 Excessive fe intake might catalyze several cellular reactions involved in the production of reactive oxygen species, thus increasing the levels of oxidative stress.37 L-carnitine, which is relatively high in red meat, might be metabolized by intestinal microbiota into proatherogenic compounds, trimethylamine-North-oxide, promoting atherosclerosis.38 Likewise, the sialic acid N-glycolylneuraminic acid in red meat has been hypothesized to generate a proinflammatory, atherogenic state in humans.39 The high sodium content of processed meats is likely to increase the run a risk of CHD past increasing blood pressure4041 and vascular resistance. Preservatives in candy red meat, such equally nitrates and nitrate byproducts, have been associated with endothelial dysfunction, atherosclerosis, and insulin resistance in some animal models.4243

In our analysis, intake of loftier quality plant based protein foods such as basics, legumes, and soy was associated with a lower take a chance of CHD compared with intake of red meat. Such replacement would not only decrease the amounts of saturated fats, cholesterol, and heme iron, but likewise increase the intake of unsaturated fat, fiber, antioxidants, polyphenols, and many constituents that could reduce the take chances of CHD. A reduction in CHD risk with such commutation therefore could be related to multiple changes in intakes of nutrients and phytochemicals. Since hypercholesterolemia, oxidative stress, and endothelial dysfunction increment with age, people older than 65 years might be at a higher risk of developing cardiovascular morbidities. Substitution of constitute based proteins for red meat could peradventure improve the cardiometabolic profile of this loftier gamble group and consequently lower the run a risk of CHD, thus explaining the more favorable exchange effect of plant based proteins seen among older men.

In this written report, the replacement of scarlet meat with total fish was not associated with CHD hazard. However, when unlike types of fish were analyzed, intake of night meat fish was inversely associated with CHD risk compared with intake of red meat in 2000 and afterwards. This could be due to the variation in the method of food preparation over time, as fish were mostly consumed after beingness deep fried in the earlier years. Other fish intake was positively associated with CHD risk, mayhap considering this food group as well included processed breaded fish, fish cakes, fish pieces, and fish sticks.

Strengths and limitations of this report

Our study has multiple strengths and limitations. The 30 years of follow-up, the large number of CHD events, and the availability of updated dietary data and other risk factors, provided an opportunity to evaluate candy and unprocessed reddish meat and potential replacements with alternative foods in relation to CHD. The cumulative averages of repeated assessments of intake were used to minimize random measurement error resulting from within person variation and to business relationship for existent changes in nutrition over fourth dimension. The use of isocaloric models enabled us to interpret food substitution analyses by specification of the comparison foods. Although nosotros are non able to assume causality of the observed relations considering of the observational nature of the study, the consistency with findings of randomized studies documenting the benefits on blood lipids when red meat is replaced past plant protein sources supports causality. Inevitable measurement fault in dietary assessment leading to inaccurate cess or misclassification bias, even though reduced by using the average of repeated assessments, would have tended to underestimate the true associations with scarlet meat. Because our study blueprint was prospective, any measurement error would likely be independent of the outcome and therefore would attenuate the observed associations toward the goose egg. Residual and unmeasured misreckoning cannot be excluded despite the aligning for important personal and lifestyle factors. Finally, our patients were mostly non-Hispanic white men, fatigued from a cohort of wellness professionals of higher socioeconomic status than the overall population, thus affecting the generalizability of the results to other populations. This homogeneity tin, all the same, assistance reduce unmeasured confounding related to socioeconomic status.3 Our group has published similar associations with CHD amongst women of the Nurses' Health Report accomplice,12 and the associations of carmine meat consumption with all cause, cardiovascular disease, and cancer mortality were likewise similar among participants of the Nurses' Health Report and Wellness Professionals Follow-Up Study.3

Conclusion

We found that greater intakes of full, unprocessed, and processed red meat were each associated with a higher adventure of CHD. Compared with total, unprocessed, or processed crimson meat, other dietary components such every bit soy, nuts, and legumes were associated with a lower hazard of CHD. These associations were stronger amidst older men. These findings are consistent with the effects of these foods on low density lipoprotein cholesterol levels and support a health do good of limiting blood-red meat consumption and replacement with institute protein sources; this would likewise take important ecology benefits.44 We also found that substituting whole grains or dairy products for full ruby-red meat and substituting eggs for processed red meat were also associated with a lower CHD risk. Further enquiry on the exchange of dairy products and egg intake for red meat are needed in other cohorts to ostend the generalizability of these findings.

What is already known on this topic

The relation between cherry-red meat intake and gamble of coronary center disease (CHD) has long been debated
Discrepant results could exist partly due to not-specific characterization of the alternatives to meat sources of protein and energy

What this study adds

Compared with intake of total, unprocessed, or processed red meat, intake of other dietary components such as soy, nuts, and legumes was associated with a lower chance of CHD
Substitutions of whole grains and dairy products for total red meat, and eggs for processed red meat, were as well associated with a lower gamble of CHD

Acknowledgments

Nosotros thank the participants and staff of the Wellness Professionals Study for their invaluable contributions.

Footnotes

Contributors: LA, AS, DW, and WCW conceived the report. LA and AS analyzed the information. LA, Equally, DW, and WCW provided statistical expertise. LA wrote the kickoff draft of the paper. WCW, EBR, and MJS obtained funding. All authors contributed to the interpretation of the results and disquisitional revision of the manuscript for important intellectual content and approved the final version of the manuscript. The results of the study are presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation. The authors assume full responsibility for analyses and interpretation of these information. LA is the guarantor. The respective author attests that all listed authors run into authorship criteria and that no others meeting the criteria have been omitted.
Funding: The cohort was supported by the National Institutes of Wellness (grants U01 CA167552 and R01 HL35464). LA received research support from the National Institutes of Health (training grant T32 HL 098048). The funders had no office in considering the written report blueprint or in the collection, analysis, estimation of data, writing of the report, or decision to submit the commodity for publication.
Competing interests: All authors accept completed the ICMJE uniform disclosure form at world wide web.icmje.org/coi_disclosure.pdf and declare: support from the National Institutes of Health for the submitted piece of work. no financial relationships with any organizations that might accept an interest in the submitted work in the previous 3 years; no other relationships or activities that could appear to have influenced the submitted work.
Ethical approving: The study protocol was approved by the institutional review board of the Harvard Thursday Chan School of Public Health. The return of the completed self-administered questionnaire was considered to imply informed consent.
Data sharing: No additional information available.
The atomic number 82 author (LA) affirms that the manuscript is an honest, authentic, and transparent account of the study being reported; that no of import aspects of the study have been omitted; and that any discrepancies from the written report as planned (and, if relevant, registered) have been explained.
Dissemination to participants and related patient and public communities: Findings will be disseminated through the media departments of the authors' institute. Results from the Health Professionals Follow-Up Study cohort are routinely disseminated to study participants through the study website, Twitter feed, and annual newsletter.
Provenance and peer review: Non deputed; externally peer reviewed.

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Source: https://www.bmj.com/content/371/bmj.m4141