Myocardial Infarction and the Role of Nutrition in Primary Prevention: A Narrative Review.

 1. Introduction

According to the most recent statistics published by the American Heart Association (AHA), Cardiovascular Disease (CVD) remains the leading cause of death globally (Tsao et al., 2023). Nearly half of the global population is affected by some form of CVD, including ischemic heart disease (IHD), the key precursor to myocardial infarction (MI). In US alone, every 40 seconds somebody is having a heart attack. Out of every five of them, four are completely new and one is “silent”, meaning without relevant symptomatology prior to the incidence (Tsao et al., 2023).

 

Despite the high prevalence and insidious nature of MI, a significant portion can be prevented through lifestyle modifications (Lichtestain et al., 2021). Hypertension, diabetes, sedentary life and smoking are just some of them (Thygesen et al., 2012). Besides these modifiable risk factors, a potentially contributing role for dietary factors has been proposed. In particular, it has been demonstrated that adherence to healthier dietary patterns and lifestyle choices may contribute to lower the risk of CVDs and MI in particular (Lichtestain et al., 2021).

 

In spite of this acknowledgement, there is a notable scarcity of comprehensive reviews that encompass the entire spectrum of nutritional influences on MI risk. Most existing studies tend to focus narrowly on specific nutritional elements, leaving a significant gap in the literature. This shortfall is particularly critical as it overlooks the nuanced and specific relationship between dietary patterns and the direct risk of MI, a more focused area compared to the broader scope of CVD risk. Therefore, there is a need for a compendious review that not only collates the most robust and emerging research but also clarifies the most debated and controversial aspects of nutrition in the primary prevention of MI. Such a synthesis would offer the medical community and public health practitioners an updated, all-encompassing guide, crucial for developing strategies to combat this leading cause of mortality.

 

This narrative literature review aims to explore and synthesize the current literature on the relationship between various nutrients and their impact on the primary prevention of MI. It will begin by providing a brief background on MI, including its presentation, diagnosis, pathophysiology and prevention. The review seeks to offer an up-to-date (February 2024) analysis of how mainstream dietary and nutritional components contribute to the development and prevention of MI. Through this examination, the review intends to enhance the understanding of the nutritional implications in the primary prevention of MI, thereby contributing to the field of cardiovascular health (CVH) and disease prevention.

 

2. Methods

 

2.1 Literature Search Strategy

 

The literature search, conducted from October 2023 to February 2024, was based on the framework indicated by Green et al. (2006) and Ferrari et al. (2015). MEDLINE (PubMed) was utilized for its comprehensive coverage, essential for capturing the entire spectrum of emerging research on MI and nutrition; while EMBASE (Elsevier Science-Direct) was used to incorporate more robust, peer-reviewed articles, thereby streamlining the critical appraisal process. The search strategy incorporated a combination of keywords and Medical Subject Headings (MeSH) terms, including "Myocardial Infarction," "Primary Prevention," "Nutrition," and "Dietary Supplements,". Boolean operators were strategically used to refine the search. The search was limited to articles published in English, accessible in full-text format and involving human subjects only.

 

2.2 Inclusion and Exclusion Criteria

 

Randomized Controlled Trials (RCTs) published between January 2019 and January 2024, along with Systematic Reviews/ Meta-analyses dating back to January 2014, were almost exclusively included. Studies were excluded based on them (1) not being directly relevant to the nutrition-MI link, (2) focusing on secondary or tertiary MI prevention and (3) examining dietary patterns rather than individualized nutrients. Non-peer-reviewed articles, anecdotal evidence, case reports, and studies lower in the evidence hierarchy were generally excluded, except for those providing significant insights into the specific relationship between MI and nutrition (Burns, Rohrich & Chung, 2011).

 

2.3. Study Limitations

 

As indicated in the introduction, the review's narrow focus on the specific relationship between nutrition and MI may limit its comprehensiveness, as it excludes broader cardiovascular studies and focuses solely on specific foods or isolated nutrients rather than dietary patterns, potentially not accounting for holistic eating behaviors. Challenges in analyzing the vast and complex data for each nutrient, alongside inadequate presence of RCTs could affect the interpretation and reliability of the findings. Furthermore, inadequate evaluation of data heterogeneity, p-value significance, fatal and non-fatal MI outcomes may compromise the applicability of the results, necessitating further research to understand the nutritional impact on disease prevention.

2.4 Selection Process

 

The selection process for this narrative review is detailed on Table 1.

 

3. Myocardial Infarction

 

As defined by the lastest publications from the American Health Organization (AHA) (Thygesen et al., 2018) and the International Classification of Diseases - 11th Revision (ICD-11), the term myocardial infarction, should be exclusively used when there is evidence of myocardial injury or necrosis in a clinical setting consistent with acute myocardial ischemia.

 

MI typically presents as a medical emergency with the sudden onset of chest pain, often radiating to the left arm or jaw, potentially accompanied by shortness of breath, nausea, and sweating. The pain may be described as a heavy, squeezing sensation, and in some cases, particularly in women, the elderly, or people with diabetes, it may be less pronounced or even absent. Quick identification and treatment are critical for survival and better outcomes (Thygesen et al., 2012)

 

3.1. Diagnosis

 

For that reason, the same leading authorities (AHA & ICD-11) have established a framework for the definitive diagnosis of MI which comprises of evidence from both myocardial injury and myocardial ischemia, each verified through distinct sets of clinical indicators:

 

Myocardial Injury is definitively confirmed only via the detection of elevated cardiac troponins (negative predictive value of 99.4%, for serum troponin of <5 ng/L; Thygesen et al., 2012).

 

Myocardial Ischemia requires at least one of the following:

Clinical Symptoms that may include but are not limited to: chest discomfort, painupper extremities, jaw, or epigastric area during exertion or rest, dyspnea, or fatigue.

ECG abnormalities which can include either the development of ST-segment/ T wave alterations, or of a left bundle branch block (LBBB), or of pathological Q waves.
Imaging evidence demonstrating either loss of viable myocardium, or some type of regional wall motion abnormality consistent with ischemia, or the discovery of a coronary thrombus via angiography or autopsy (Thygesen et al., 2018).

 

3.2. Pathophysiology

 

MI, although considered an acute condition, most commonly arises from a chronic inflammatory response to endothelial dysfunction, known as atherosclerosis. The first step in this process, endothelial dysfunction (Figure 1), begins with gradual injury to the intimal endothelium of the epicardial coronary arteries. This injury, caused by various modifiable factors such as nutrition, leads to disturbances in permeability and results in ineffective vascular homeostasis. Ineffective homeostasis allows the entry and accumulation of oxidized low-density lipoprotein (LDL) and other cholesterol crystals. This accumulation triggers an inflammatory process, leading to monocyte differentiation into macrophages that engulf oxidized LDL, forming foam cells. These cells characterize the first macroscopic feature of atherosclerosis; fatty streaks. These streaks progressively evolve into complex atherosclerotic plaques as smooth muscle cells migrate and synthesize collagen, developing an outer fibrous cap that stabilizes the plaque. Due to chronic mechanical stress and persistent inflammation, this cap can become unstable and suddenly rupture, exposing thrombogenic materials of the plaque to blood. This exposure prompts acute platelet aggregation and thrombus formation, which can occlude the coronary artery, disrupting myocardial perfusion and oxygenation. Without reperfusion, this process can lead to myocardial injury and necrosis, manifesting as MI. (Bentzon et al., 2014; Vinay Kumar, Abul K. Abbas, Jon C. Aster, 2017; Thygesen et al., 2012).

3.3 Prevention

 

Understanding the pathophysiology of MI underscores the importance of effective prevention strategies: Primary Prevention involves strategies to prevent MI from occurring in the first place; including healthy diet and nutrition, regular exercising, tobacco cessation, limiting alcohol consumption, stress management, and maintaining a healthy weight. Secondary Prevention focuses on individuals with existing CVD or at high risk for it, involving regular monitoring and control of blood pressure, cholesterol, and diabetes, adherence to medications like statins or aspirin, and aforementioned lifestyle changes. Tertiary Prevention aims to reduce the chances of recurrence and enhance the patient’s life quality post-MI, through cardiac rehabilitation, psychological support, education, and monitoring for heart failure or other complications (Arnett et al., 2019).

 

For a detailed overview of the risk factors contributing to myocardial infarction, refer to Table 2.

 

4. Nutrition

 

4.1. Macronutrients

 

4.1.1. Fatty Acids Overview

 

Fats or fatty acids, categorized into saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs), and polyunsaturated fatty acids (PUFAs), play arguably the most significant role in modulating atherosclerotic progress.

 

Beginning with a study that, despite its age, remains highly influential; the Minnesota Coronary Experiment (1968-73). Originally conducted by Frantz Jr. et al. (1989), focused on whether a serum cholesterol-lowering diet would reduce atherosclerosis, autopsy-confirmed myocardial infarcts, and strokes. Their analysis, along with a more recent re-evaluation (Ramsden et al., 2016), found that replacing SFAs with vegetable oils rich in linoleic acid (omega-6, PUFA) did not show a benefit in reducing the risk of MI (RR: 1.08). While the treatment diet lowered serum cholesterol by 14,5%, it did not support the hypothesis that this reduction would translate to a lower risk of death from IHD or other causes.

 

Similarly, de Suza et al.’s meta-analysis (2015) along with Wang et al. (2016) cohort study, concluded that SFAs intake was not significantly associated with increased risk of CVD (RR: 1.06, 95% CI & HR: 1.05, 95% CI, respectively). However, the cohort study along with another meta-analysis (Hamley et al., 2017) found that substitution with PUFAs or MUFAs was inversely associated with CVD mortality (HR: 0.73) and total IHD events (RR: 0.80, CI:95%), respectively.

 

The Prospective Urban Rural Epidemiology (PURE) study (Dehghan et al., 2017), identified subtle differences among these fatty acids in relation to overall mortality (HR for SFAs=0.86, PUFAs=0.80, MUFAs=0.81, all 95% CI); though no significant association were observed between these fats and the risk for MI or CVD mortality.

 

Amidst this uncertainty, a faint trend can be observed, suggesting a potential for negative association between SFAs intake and the risk of MI along with a positive one, between PUFAs and MUFAs with MI risk.

The 2011 review by Hooper et al. reported that a reduction in dietary SFAs was linked to a 14% decrease in cardiovascular events. However, it did not provide conclusive evidence for specific outcomes like MI. A decade later, Hooper et al. (2020) managed to confirm this exact association (RR: 0.90, 95% CI); along with a 27% decrease in cardiovascular events when SFAs were substituted with PUFAs. On that note, Li et al.’s (2015) cohort study found that replacing just 5% of energy intake from SFAs with PUFAs or MUFAs led to lower IHD risk (PUFAs HR: 0.75, 95% CI; MUFAs HR: 0.85, 95% CI) and even more striking was the findings of Ismail et al., (2018); that high total SFAs intake, particularly from palm oil, was associated with an astonishing three-fold increase in the risk of MI.

 

Li et al.'s (2022) meta-analysis, encompassing nearly 50 prospective studies, effectively resolves remaining debates by demonstrating a clear link between higher total circulating levels of SFAs and an elevated risk for CVD (RR: 1.50, 95%CI) and IHD (RR: 1.63, 95%CI). For every 50% increase in total SFAs, there was a considerable trend towards higher CVD risk (RR: 1.15, 95% CI).

 

4.1.2. Protein Sources

 

4.1.2.1 Meat

 

The 2014 meta-analysis by Abete et al. found that there was no significant association between processed meat consumption (RR: 1.52; 95% CI, I2=81.7), red meat consumption (RR: 1.02; 95% CI), total meat consumption (RR: 1.52; 95% CI, I²=70.3%) and white meat consumption (RR: 1.00; 95% CI) and IHD-specific mortality. On the contrary, Bethchold et al. (2017) found that individuals consuming the highest levels of red and processed meat showed 14,5% combined elevated risk of IHD compared to those consuming the. Additionally, for every additional 100g of red meat or 50g of processed meat, an increased risk of IHD was observed (RR: 1.15; 95% CI & RR: 1.27; 95% CI, respectively). Zeraatkar et al. (2019) found an actual association between MI, claiming that reducing red meat intake by three servings per week is associated with a small reduction in MI risk (RR: 0.94, 95% CI).

 

4.1.2.2. Fish

 

Jayedi et al. (2019) and Zhang et al. (2020), found that the highest compared to the lowest category of fish intake was associated with a 27% lower risk of MI (I2 = 72%), with an additional 4% reduction per serving per week; and a 9% IHD risk reduction, along with a 15% reduction in IHD-specific mortality, respectively. The 2020 umbrella review by Jayedi & Shab-Bidar, concluded that each 100-gram per day increment in fish consumption, was strongly associated with lower risks of IHD (RR: 0.88; 95% CI) and MI (RR: 0.75; 95% CI). In the systematic review by Krittanawong et al. (2021), most of the cohort studies did not show a significant association.

 

4.1.2.3. Eggs

 

Alexander et al. (2016) and Bechthold et al. (2017) both reported no significant link between egg intake and IHD risk (RR: 0.97, 95% CI & RR: 0.99; 95% CI, respectively), with Bechthold et al. also finding no association with increased egg consumption in a dose-response analysis (RR: 1.00; 95% CI). Furthermore, Krittanawong et al. (2020) and Drouin-Chartier et al. (2020) complemented these findings, showing no substantial risk increase for CVD with higher egg consumption (HR: 0.99, 95% CI & HR: 0.98, 95% CI, respectively); with Drouin-Chartier et al. findings being consistent even among participants who consumed at at least two eggs per day, compared with those who consumed less than one (HR: 0.91 ,95% CI).

 

4.1.2.4. Nuts

 

The 2023 review by Glenn et al. highlighted that in studies assessing IHD incidence, high nut consumption correlated with an 18% lower risk, while for IHD mortality, the reduction was 24%. Different types of nuts were linked to a 15–23% lower risk of IHD incidence, but no significant effect was observed for peanut butter consumption. For IHD mortality, peanut consumption showed an inverse relationship with risk.

 

The PREDIMED (Prevención con Dieta Mediterránea) trial (Estruch et al., 2018), randomized participants to a Mediterranean diet supplemented with either extra-virgin olive oil (EVOO) and nuts and demonstrated 31% (HR: 0.69, 95% CI) and 28% (HR: 0.72, 95% CI) reductions, respectively, in the combined endpoint, but the improved outcome was driven largely by the reduction in stroke, with no significant improvement over the control diet for MI.

4.1.3. Plant-based Foods

Bechthold et al. (2017) found that higher vegetable and fruit consumption is inversely associated with IHD risk (RR: 0.92; 95% CI & RR: 0.89; 95% CI, respectively), with each additional daily 100g of associated with a reduced risk (RR: 0.97, 95% CI & RR: 0.94; 95% CI, respectively). Satija et al. (2017) reported that higher adherence to a plant-based diet is independently associated with a reduced risk of IHD (HR: 0.92; 95% CI).

Viguiliuk et al. (2019) found that high consumption of dietary pulses, such as legumes, is linked to reduced CVD and IHD incidence (RR: 0.91, 95% CI), but not associated with MI incidence. Bechthold et al. (2017), compared the highest to the lowest categories of legume intake, and reported a reduced risk of IHD (RR: 0.91, 95% CI) and a small inverse association with each additional daily intake of 50g of legumes (RR: 0.96, 95% CI).

4.2. Micronutrients

 

4.2.1. Vitamins

Vitamin A, a fat-soluble micronutrient, along with its precursor, β-carotene have been extensively studied in relation to CVH. An et al. (2022) reported that β-carotene supplementation could increase the risks CVD mortality, whereas Yang et al. (2022) found no significant link between β-carotene supplementation and MI incidence (RR: 0.99, 95% CI). Ingles et al. (2020) presented a more nuanced perspective, noting that while some reviews did not establish an association between CVD and supplementation, others suggested that higher β-carotene intake was correlated with a notably lower risk of all-cause mortality (RR = 0.83, 95% CI). However, they also cautioned that high-doses might have a counterproductive effect in all-cause mortality.

Vitamin B complex is present in foods like whole grains, meats, dairy, and leafy greens. An et al. (2022) highlightd the cardiovascular benefits of folic acid (B9) supplementation, even in MI risk reduction, especially where fortification of foods is not practiced. Ingles et al. (2020) noted that vitamins B6, B9 and B12, are instrumental in lowering homocysteine levels. Meanwhile, Christen et al. (2018) observed that while these vitamins do reduce homocysteine, they do not significantly affect biomarkers of vascular inflammation or confer a clear cardiovascular benefit.

Vitamin C, also known as ascorbic acid, is thought to offer cardiovascular protection through its antioxidant effects and support of endothelial cells. Ingles et al. (2020) noted that while high-dose vitamin C supplementation is associated with improvements in endothelial function and reduced blood pressure, these benefits do not extend to a reduction of cardiovascular events or all-cause mortality.

Vitamin D, known for its role in bone health, has been rigorously investigated for its potential effects on CVH. Ford et al. (2014) reported that vitamin D supplementation in the RECORD trial indicated a significant reduction in cardiac failure events, although it had no substantial impact on MI (RR: 0.97 95% CI). Manson et al. (2024), Barbarawi et al. (2019), Pei et al. (2022), Ruiz-Garcia (2023), and Mattumpuram et al. (2024) all reported non-significant associations, indicating no substantial effect of vitamin D on MI prevention.

Vitamin E a potent antioxidant with anti-inflammatory properties, is involved in mechanisms like lipid peroxidation, key in atherosclerosis. Ingles et al. (2020) indicated that despite potential cardiovascular benefits, meta-analyses don't strongly support its cardioprotective efficacy. Contrarily, Loffredo et al.'s 2015 meta-analysis showed that vitamin E supplementation could actually reduced MI incidence (RR: 0.84; 95% CI).

Recent studies consistently show that multivitamins (MVM) do not significantly impact CVD. O'Connor et al. (2022) and Kim et al. (2018) both concluded that multivitamin and mineral  supplements offer no substantial protective effect against CVD, IHD or all-cause mortality in healthy adults (RR: 0.95-1.02, 95% CI). Additionally, Jenkins et al. (2018) found that antioxidant mixtures had no beneficial effect on CVD outcomes and even increased all-cause mortality when selenium studies were excluded (RR 1.06, 95% CI).

4.2.2 Dietary Supplements

 

4.2.2.1. Omega 3

 

In 2019, both Manson et al.’s RCT, and Hu et al.’s meta-analysis; a reduction in total CVD (HR: 0.92, 95% CI & RR: 0.97, 95% CI, respectively) and in MI (HR: 0.72, 95% CI & RR: 0.92, 95% CI, respectively) was demonstrated. Hu et al. also associated the supplementation with reduced IHD-specific mortality (RR: 0.92, 95% CI) and total IHD events (RR: 0.95, 95% CI).

 

The ongoing VITamin D and OmegA-3 TriaL (VITAL) study, analyzed by Ogata et al. (2023), showed a benefit of omega-3 supplementation for primary CVD outcome (HR: 0.92, 95% CI) and a significant reduction in MI risk (RR: 0.71, 95% CI). Notably, participants with lower baseline fish consumption experienced greater benefits for the primary CVD outcome (RR: 0.79, 95% CI) compared to those with higher fish intake (RR: 1.05, 95% CI).

 

4.2.2.2. Omega 6

 

The 2014 study by Farvid et al., revealed that higher dietary linoleic acid (LA, omega 6, PUFA) intake was associated with reduced IHD risk. Specifically, the highest LA intake compared to the lowest was linked to a 15% lower risk of IHD events and a 21% lower risk of IHD death. Additionally, replacing 5% of energy from saturated fats with LA resulted in a 9% reduction in IHD events and a 13% reduction in IHD deaths. Hooper et al. (2018) explored the impact of increasing omega-6 fats on the risk of MI and found a 12% risk reduction when intake was increased.

4.2.2.3. Calcium

The 2022 study by Yuan et al. utilized Mendelian randomization to investigate the health effects of high serum calcium levels. The study found that the odds of experiencing an MI increased by 18% for each one standard deviation increase in genetically predicted serum calcium levels (OR: 1.18, 95% CI). The 2019 meta-analysis by Yang et al. indicated that dietary calcium intake did not significantly affect the risk of CVD (RR: 0.96, 95% CI) or IHD (0.98, 95% CI). Calcium supplements were associated with a 14% increased risk of MI, and this risk increased to 21% when taking them alone. Dietery calcium intake was associated with a 16% lower risk of CVD when the duration was not more than 10 years.

4.2.2.4. Coenzyme Q10 (CoQ10)

Coenzyme Q10 (CoQ10) is an emerging antioxidant with a great potential for cardiovascular benefits. Al Saadi et al. (2021) found low-quality evidence with inconclusive results for the risk of MI (RR 1.62, 95% CI) in the CoQ10 group compared to the control group. Ingles et al. (2020) found to be associated with anti-inflammatory and lipid-reducing effects. However, due to variations in intervention periods and doses, formal recommendations are limited.

4.3. Miscellaneous

 

4.3.1 Fiber

 

The 2016 systematic review by Hajishafiee et al. and the 2024 review by Ramezani et al. collectively highlight the importance of dietary fiber in reducing CVD mortality. Hccajishafiee et al. found a 18% lower risk of CVD mortality with cereal fiber consumption (RR: 0.82; 95% CI), while Ramezani et al. reported a 26% reduction in CVD-related mortality from higher dietary fiber intake, emphasizing the superior impact of insoluble fiber and particularly fiber from nuts and seeds, which decreased CVD-related death risk by 43% (HR: 0.57; 95% CI).

 

4.3.2. Avocado

 

Analyzing data from two large cohorts over 30 years, Pacheco et al. (2022) found that individuals with higher avocado intake (≥2 servings/week) had a significantly lower risk of CVD (HR: 0.84, 95% CI) and IHD (HR: 0.79, 95% CI), compared to non-consumers. Additionally, each half serving of avocado intake per day, was associated with a 20% reduction in CVD risk. Noteworthy are the results of a meta-analysis (Lee Bravatti et al., 2018), which indicated that virtually all types of cholesteroles were significantly reduced in groups consuming almonds compared to those without almonds or with almond substitutes (summary net change: −5.83 mg/dL, 95% CI).

4.3.3. Sugar Sweetened Beverages (SSBs)

 

Bechthold et al. (2017) and Yang et al. (2022), both identified a positive correlation between SSB intake and the risk of IHD (RR: 1.10, 95% CI, & HR: 1.20, 95% CI, respectively). Yang et al. also reported that consuming more than one serving of SSB per day was linked to a higher risk of IHD (HR = 1.35, 95% CI) and Narain et al. highlighted that for each extra serving, the risk of MI was linearly raised (RR: 1.22, 95% CI).

4.3.4. Chocolate

Chocolate is one of the most important dietary sources of flavonoids, polyphenolic compounds that may have cardioprotective effects due to hypothetical endothelial and platelet function and important antioxidant action (Gianfredi et al., 2018). Gianfredi et al. (2018) found that chocolate consumption was associated with a 29% reduced risk of IHD. Specifically, it was associated with a 22% reduced risk of MI and a 47% reduced risk IHD. However, Sesso et al. (2022) conducted the COcoa Supplement and Multivitamin Outcomes Study (COSMOS) and found that while there was a significant reduction in CVD death (HR: 0.73, 95& CI), no significant reductions were observed for MI and stroke.

5. Conclusion

In summing up this extensive exploration, it becomes evident that our dietary choices are not just a matter of personal preference, but powerful determinants of our CVH. The evidence strongly supports the detrimental impact of SFAs on MI and CVD risk. Conversely, PUFAs, MUFAs, plant-based foods, and the use of omega-3 and omega-6 supplements demonstrate robust negative associations with MI and CVD risks. We also observe moderate positive links with SSBs and a moderate negative relationship with the consumption of fish, nuts, and avocados. Meat shows limited positive associations with MI risk, while fiber and eggs exhibit limited negative associations. Emerging evidence suggests the potential benefits of CoQ10, while chocolate and vitamins exhibit variable effects.

Based on these findings, it is imperative that future dietary guidelines prioritize the replacement of SFAs with PUFAs and MUFAs, an increase in the consumption of plant-based foods, and a reduction in the intake of processed meats and SSBs. These measures are crucial for effective primary prevention of MI and CVD. Further research is needed to clarify the roles of specific vitamins and minerals, ensuring that future recommendations are based on robust and up-to-date scientific evidence.

6. References

·  Abete, I., Romaguera, D., Vieira, A.R., Lopez de Munain, A. & Norat, T. (2014). Association between total, processed, red and white meat consumption and all-cause, CVD and IHD mortality: a meta-analysis of cohort studies. The British journal of nutrition, 112(5), pp.762–75. https://doi.org/10.1017/S000711451400124X

·  Alexander, D.D., Miller, P.E., Vargas, A.J., Weed, D.L. & Cohen, S.S. (2016). Meta-analysis of Egg Consumption and Risk of Coronary Heart Disease and Stroke. Journal of the American College of Nutrition, 35(8), pp.704–716. https://doi.org/10.1080/07315724.2016.1152928

·  An, P., Wan, S., Luo, Y., Luo, J., Zhang, X., Zhou, S., Xu, T., He, J., Mechanick, J.I., Wu, W.-C., Ren, F. & Liu, S. (2022). Micronutrient Supplementation to Reduce Cardiovascular Risk. Journal of the American College of Cardiology, 80(24), pp.2269–2285. https://doi.org/10.1016/j.jacc.2022.09.048

·  Arnett, D.K., Blumenthal, R.S., Albert, M.A., Buroker, A.B., Goldberger, Z.D., Hahn, E.J., Himmelfarb, C.D., Khera, A., Lloyd-Jones, D., McEvoy, J.W., Michos, E.D., Miedema, M.D., Muñoz, D., Smith, S.C., Virani, S.S., Williams, K.A., Yeboah, J. and Ziaeian, B. (2019). 2019 ACC/AHA guideline on the primary prevention of cardiovascular disease. Circulation, 140(11), pp.e596–e646. https://doi.org/10.1161/cir.0000000000000678

·  Barbarawi, M., Kheiri, B., Zayed, Y., Barbarawi, O., Dhillon, H., Swaid, B., Yelangi, A., Sundus, S., Bachuwa, G., Alkotob, M.L. & Manson, J.E. (2019). Vitamin D Supplementation and Cardiovascular Disease Risks in More Than 83 000 Individuals in 21 Randomized Clinical Trials. JAMA Cardiology, 4(8). https://doi.org/10.1001/jamacardio.2019.1870

·  Bechthold, A., Boeing, H., Schwedhelm, C., Hoffmann, G., Knüppel, S., Iqbal, K., De Henauw, S., Michels, N., Devleesschauwer, B., Schlesinger, S. & Schwingshackl, L. (2017). Food groups and risk of coronary heart disease, stroke and heart failure: A systematic review and dose-response meta-analysis of prospective studies. Critical Reviews in Food Science and Nutrition, 59(7), pp.1071–1090. https://doi.org/10.1080/10408398.2017.1392288

·  Bentzon, J.F., Otsuka, F., Virmani, R. & Falk, E. (2014). Mechanisms of Plaque Formation and Rupture. Circulation Research, 114(12), pp.1852–1866. https://www.ahajournals.org/doi/full/10.1161/CIRCRESAHA.114.302721

·  Burns, P.B., Chung, K.C. & Rohrich, R.J. (2012). The Levels of Evidence and Their Role in evidence-based Medicine. Plastic and Reconstructive Surgery, 128(1), pp.305–310. https://doi.org/10.1097/PRS.0b013e318219c171

·  Christen, W.G., Cook, N.R., Van Denburgh, M., Zaharris, E., Albert, C.M. & Manson, J.E. (2018). Effect of Combined Treatment With Folic Acid, Vitamin B 6, and Vitamin B 12 on Plasma Biomarkers of Inflammation and Endothelial Dysfunction in Women. Journal of the American Heart Association, 7(11). https://doi.org/10.1161/jaha.117.008517

·  Drouin-Chartier, J.-P., Chen, S., Li, Y., Schwab, A.L., Stampfer, M.J., Sacks, F.M., Rosner, B., Willett, W.C., Hu, F.B. & Bhupathiraju, S.N. (2020). Egg consumption and risk of cardiovascular disease: three large prospective US cohort studies, systematic review, and updated meta-analysis. BMJ, [online] 368(513), p.m513. https://doi.org/10.1136/bmj.m513

·  Estruch, R., Ros, E., Salas-Salvadó, J., Covas, M.-I., Corella, D., Arós, F., Gómez-Gracia, E., Ruiz-Gutiérrez, V., Fiol, M., Lapetra, J., Lamuela-Raventos, R.M., Serra-Majem, L., Pintó, X., Basora, J., Muñoz, M.A., Sorlí, J.V., Martínez, J.A., Fitó, M., Gea, A. & Hernán, M.A. (2018). Primary Prevention of Cardiovascular Disease with a Mediterranean Diet Supplemented with Extra-Virgin Olive Oil or Nuts. New England Journal of Medicine, 378(25), p.e34. https://doi.org/10.1056/nejmoa1800389

·  Farvid, M.S., Ding, M., Pan, A., Sun, Q., Chiuve, S.E., Steffen, L.M., Willett, W.C. & Hu, F.B. (2014). Dietary Linoleic Acid and Risk of Coronary Heart Disease: A Systematic Review and Meta-Analysis of Prospective Cohort Studies. Circulation, 130(18), pp.1568–1578. doi:https://doi.org/10.1161/circulationaha.114.010236.

·  Ferrari, R. (2015). Writing narrative style literature reviews. Medical Writing, 24(4), pp.230–235. Available at: https://www.tandfonline.com/doi/abs/10.1179/2047480615Z.000000000329

·  Ford, J.A., MacLennan, G.S., Avenell, A., Bolland, M., Grey, A. & Witham, M. (2014). Cardiovascular disease and vitamin D supplementation: trial analysis, systematic review, and meta-analysis. The American Journal of Clinical Nutrition, 100(3), pp.746–755. https://doi.org/10.3945/ajcn.113.082602

·  Frantz, I.D., Dawson, E.A., Ashman, P.L., Gatewood, L.C., Bartsch, G.E., Kuba, K. & Brewer, E.R. (1989). Test of effect of lipid lowering by diet on cardiovascular risk. The Minnesota Coronary Survey. Arteriosclerosis: An Official Journal of the American Heart Association, Inc., 9(1), pp.129–135. https://doi.org/10.1161/01.atv.9.1.129

·  Gianfredi, V., Salvatori, T., Nucci, D., Villarini, M. & Moretti, M. (2018). Can chocolate consumption reduce cardio-cerebrovascular risk? A systematic review and meta-analysis. Nutrition, 46, pp.103–114. https://doi.org/10.1016/j.nut.2017.09.006

·  Glenn, A.J., Aune, D., Freisling, H., Mohammadifard, N., Kendall, C.W.C., Salas-Salvadó, J., Jenkins, D.J.A., Hu, F.B. & Sievenpiper, J.L. (2023). Nuts and Cardiovascular Disease Outcomes: A Review of the Evidence and Future Directions. Nutrients, 15(4), p.911. https://doi.org/10.3390/nu15040911

·  Green, B.N., Johnson, C.D. & Adams, A. (2006). Writing narrative literature reviews for peer-reviewed journals: Secrets of the trade. Journal of Chiropractic Medicine, 5(3), pp.101–117. https://doi.org/10.1016/s0899-3467(07)60142-6

·  Hamley, S. (2017). The effect of replacing saturated fat with mostly n-6 polyunsaturated fat on coronary heart disease: a meta-analysis of randomised controlled trials. Nutrition Journal, 16(1). https://doi.org/10.1186/s12937-017-0254-5

·  Hajishafiee, M., Saneei, P., Benisi-Kohansal, S. & Esmaillzadeh, A. (2016). Cereal fibre intake and risk of mortality from all causes, CVD, cancer and inflammatory diseases: a systematic review and meta-analysis of prospective cohort studies. British Journal of Nutrition, 116(2), pp.343–352. https://doi.org/10.1017/s0007114516001938

·  Hooper, L., Al-Khudairy, L., Abdelhamid, A.S., Rees, K., Brainard, J.S., Brown, T.J., Ajabnoor, S.M., O’Brien, A.T., Winstanley, L.E., Donaldson, D.H., Song, F. & Deane, K.H. (2018). Omega-6 fats for the primary and secondary prevention of cardiovascular disease. Cochrane Database of Systematic Reviews. https://doi.org/10.1002/14651858.cd011094.pub3

·  Hooper, L., Martin, N., Jimoh, O.F., Kirk, C., Foster, E. & Abdelhamid, A.S. (2020). Reduction in saturated fat intake for cardiovascular disease. Cochrane Database of Systematic Reviews, 5(5). https://doi.org/10.1002/14651858.cd011737.pub2

·  Hooper, L., Summerbell, C.D., Thompson, R., Sills, D., Roberts, F.G., Moore, H. & Davey Smith, G. (2011). Reduced or modified dietary fat for preventing cardiovascular disease. Cochrane Database of Systematic Reviews. https://doi.org/10.1002/14651858.cd002137.pub2

·  Hu, Y., Hu, F.B. & Manson, J.E. (2019). Marine Omega‐3 Supplementation and Cardiovascular Disease: An Updated Meta‐Analysis of 13 Randomized Controlled Trials Involving 127 477 Participants. Journal of the American Heart Association, 8(19). https://doi.org/10.1161/jaha.119.013543

·  Ingles, D.P., Cruz Rodriguez, J.B. & Garcia, H. (2020). Supplemental Vitamins and Minerals for Cardiovascular Disease Prevention and Treatment. Current Cardiology Reports, 22(4). https://doi.org/10.1007/s11886-020-1270-1

·  Ismail, S.R., Maarof, S.K., Siedar Ali, S. & Ali, A. (2018). Systematic review of palm oil consumption and the risk of cardiovascular disease. PLOS ONE, 13(2), p.e0193533. https://doi.org/10.1371/journal.pone.0193533

·  Jayedi, A. & Shab-Bidar, S. (2020). Fish Consumption and the Risk of Chronic Disease: An Umbrella Review of Meta-Analyses of Prospective Cohort Studies. Advances in Nutrition. https://doi.org/10.1093/advances/nmaa029

·  Jayedi, A., Zargar, M.S. & Shab-Bidar, S. (2019). Fish consumption and risk of myocardial infarction: a systematic review and dose-response meta-analysis suggests a regional difference. Nutrition Research, 62, pp.1–12. doi:https://doi.org/10.1016/j.nutres.2018.10.009.

·  Jenkins, D.J.A., Spence, J.D., Giovannucci, E.L., Kim, Y.-I., Josse, R.G., Vieth, R., Sahye-Pudaruth, S., Paquette, M., Patel, D., Blanco Mejia, S., Viguiliouk, E., Nishi, S.K., Kavanagh, M., Tsirakis, T., Kendall, C.W.C., Pichika, S.C. & Sievenpiper, J.L. (2021). Supplemental Vitamins and Minerals for Cardiovascular Disease Prevention and Treatment: JACC Focus Seminar. Journal of the American College of Cardiology, 77(4), pp.423–436. https://doi.org/10.1016/j.jacc.2020.09.619

·  Kim, J., Choi, J., Kwon, S.Y., McEvoy, J.W., Blaha, M.J., Blumenthal, R.S., Guallar, E., Zhao, D. & Michos, E.D. (2018). Association of Multivitamin and Mineral Supplementation and Risk of Cardiovascular Disease. Circulation: Cardiovascular Quality and Outcomes, 11(7). https://doi.org/10.1161/circoutcomes.117.004224

·  Krittanawong, C., Isath, A., Hahn, J., Wang, Z., Narasimhan, B., Kaplin, S.L., Jneid, H., Virani, S.S. & Tang, W.H.W. (2021). Fish Consumption and Cardiovascular Health: A Systematic Review. The American Journal of Medicine, 134(6), pp.713–720. https://doi.org/10.1016/j.amjmed.2020.12.017

·  Krittanawong, C., Narasimhan, B., Wang, Z., Virk, H.U.H., Farrell, A.M., Zhang, H. & Tang, W.H.W. (2021). Association Between Egg Consumption and Risk of Cardiovascular Outcomes: A Systematic Review and Meta-Analysis. The American Journal of Medicine, 134(1), pp.76-83.e2. https://doi.org/10.1016/j.amjmed.2020.05.046

·  Lee-Bravatti, M.A., Wang, J., Avendano, E.E., King, L., Johnson, E.J. & Raman, G. (2019). Almond Consumption and Risk Factors for Cardiovascular Disease: A Systematic Review and Meta-analysis of Randomized Controlled Trials. Advances in Nutrition, 10(6), pp.1076–1088. https://doi.org/10.1093/advances/nmz043

·  Lichtenstein, A. H., Appel, L. J., Vadiveloo, M., Hu, F. B., Kris-Etherton, P. M. et al. (2021). 2021 Dietary Guidance to Improve Cardiovascular Health: A Scientific Statement From the American Heart Association. Circulation, 144(23), e472–e487. https://doi.org/10.1161/CIR.0000000000001031

·  Li, Y., Hruby, A., Bernstein, A.M., Ley, S.H., Wang, D.D., Chiuve, S.E., Sampson, L., Rexrode, K.M., Rimm, E.B., Willett, W.C. & Hu, F.B. (2015). Saturated Fats Compared With Unsaturated Fats and Sources of Carbohydrates in Relation to Risk of Coronary Heart Disease. Journal of the American College of Cardiology, 66(14), pp.1538–1548. https://doi.org/10.1016/j.jacc.2015.07.055

·  Li, Z., Lei, H., Jiang, H., Fan, Y., Shi, J., Li, C., Chen, F., Mi, B., Ma, M., Lin, J. & Ma, L. (2022). Saturated fatty acid biomarkers and risk of cardiometabolic diseases: A meta-analysis of prospective studies. Frontiers in Nutrition, 9, p.963471. https://doi.org/10.3389/fnut.2022.963471

·  Loffredo, L., Perri, L., Di Castelnuovo, A., Iacoviello, L., De Gaetano, G. & Violi, F. (2015). Supplementation with vitamin E alone is associated with reduced myocardial infarction: A meta-analysis. Nutrition, Metabolism and Cardiovascular Diseases, 25(4), pp.354–363. https://doi.org/10.1016/j.numecd.2015.01.008

·  Manson, J.E., Cook, N.R., Lee, I-Min., Christen, W., Bassuk, S.S., Mora, S., Gibson, H., Gordon, D., Copeland, T., D’Agostino, D., Friedenberg, G., Ridge, C., Bubes, V., Giovannucci, E.L., Willett, W.C. & Buring, J.E. (2019). Marine n−3 Fatty Acids and Prevention of Cardiovascular Disease and Cancer. New England Journal of Medicine, 380(1), pp.23–32. https://doi.org/10.1056/nejmoa1811403

·  Manson, J.E., Cook, N.R., Lee, I-Min., Christen, W., Bassuk, S.S., Mora, S., Gibson, H., Albert, C.M., Gordon, D., Copeland, T., D’Agostino, D., Friedenberg, G., Ridge, C., Bubes, V., Giovannucci, E.L., Willett, W.C. & Buring, J.E. (2019). Vitamin D Supplements and Prevention of Cancer and Cardiovascular Disease. New England Journal of Medicine, 380(1), pp.33–44. https://doi.org/10.1056/nejmoa1809944

·  Mattumpuram, J., Maniya, M.T., Faruqui, S.K., Ahmed, A., Jaiswal, V. & Harshakumar, S.P. (2024). Cardiovascular and Cerebrovascular Outcomes With Vitamin D Supplementation: A Systematic Review and Meta-Analysis. Current Problems in Cardiology, 49(1 Pt C), p.102119. https://doi.org/10.1016/j.cpcardiol.2023.102119

·  Narain, A., Kwok, C.S. & Mamas, M.A. (2016). Soft drinks and sweetened beverages and the risk of cardiovascular disease and mortality: a systematic review and meta-analysis. International Journal of Clinical Practice, 70(10), pp.791–805. https://doi.org/10.1111/ijcp.12841

·  Ogata, S., Manson, J.E., Kang, J.H., Buring, J.E., Lee, I.-M., Nishimura, K., Sakata, Y., Danik, J.S., D’Agostino, D., Mora, S., Albert, C.M. & Cook, N.R. (2023). Marine n-3 Fatty Acids and Prevention of Cardiovascular Disease: A Novel Analysis of the VITAL Trial Using Win Ratio and Hierarchical Composite Outcomes. Nutrients, 15(19), p.4235. https://doi.org/10.3390/nu15194235

·  O’Connor, E.A., Evans, C.V., Ivlev, I., Rushkin, M.C., Thomas, R.G., Martin, A. & Lin, J.S. (2022). Vitamin and Mineral Supplements for the Primary Prevention of Cardiovascular Disease and Cancer. JAMA, 327(23), p.2334. https://doi.org/10.1001/jama.2021.15650

·  Pacheco, L.S., Li, Y., Rimm, E.B., Manson, J.E., Sun, Q., Rexrode, K., Hu, F.B. & Guasch‐Ferré, M. (2022). Avocado Consumption and Risk of Cardiovascular Disease in US Adults. Journal of the American Heart Association, 11(7). https://doi.org/10.1161/jaha.121.024014

·  Pei, Y.-Y., Zhang, Y., Peng, X.-C., Liu, Z.-R., Xu, P. & Fang, F. (2022). Association of Vitamin D Supplementation with Cardiovascular Events: A Systematic Review and Meta-Analysis. Nutrients, 14(15), p.3158. https://doi.org/10.3390/nu14153158

·  Ramezani, F., Pourghazi, F., Eslami, M., Gholami, M., Mohammadian Khonsari, N., Ejtahed, H.-S., Larijani, B. & Qorbani, M. (2023). Dietary fiber intake and all-cause and cause-specific mortality: An updated systematic review and meta-analysis of prospective cohort studies. Clinical Nutrition (Edinburgh, Scotland), 43(1), pp.65–83. https://doi.org/10.1016/j.clnu.2023.11.005

·  Ramsden, C.E., Zamora, D., Majchrzak-Hong, S., Faurot, K.R., Broste, S.K., Frantz, R.P., Davis, J.M., Ringel, A., Suchindran, C.M. & Hibbeln, J.R. (2016). Re-evaluation of the traditional diet-heart hypothesis: analysis of recovered data from Minnesota Coronary Experiment (1968-73). BMJ, p.i1246. https://doi.org/10.1136/bmj.i1246

·  Ruiz-García, A., Pallarés-Carratalá, V., Turégano-Yedro, M., Torres, F., Sapena, V., Martin-Gorgojo, A. & Martin-Moreno, J.M. (2023). Vitamin D Supplementation and Its Impact on Mortality and Cardiovascular Outcomes: Systematic Review and Meta-Analysis of 80 Randomized Clinical Trials. Nutrients, 15(8), p.1810. https://doi.org/10.3390/nu15081810

·  Satija, A., Bhupathiraju, S.N., Spiegelman, D., Chiuve, S.E., Manson, J.E., Willett, W., Rexrode, K.M., Rimm, E.B. & Hu, F.B. (2017). Healthful and Unhealthful Plant-Based Diets and the Risk of Coronary Heart Disease in U.S. Adults. Journal of the American College of Cardiology, 70(4), pp.411–422. https://doi.org/10.1016/j.jacc.2017.05.047

·  Sesso, H. D., Manson, J. E., Aragaki, A. K., Rist, P. M., Johnson, L. G., Friedenberg, G., Copeland, T., Clar, A., Mora, S., Moorthy, M. V., Sarkissian, A., Carrick, W. R., Anderson, G. L. (2022). Effect of cocoa flavanol supplementation for the prevention of cardiovascular disease events: the COcoa Supplement and Multivitamin Outcomes Study (COSMOS) randomized clinical trial. The American journal of clinical nutrition, 115(6), 1490–1500. https://doi.org/10.1093/ajcn/nqac055

·  Thygesen, K., Alpert, J.S., Jaffe, A.S., Chaitman, B.R., Bax, J.J., Morrow, D.A. & White, H.D. (2018). Fourth Universal Definition of Myocardial Infarction (2018). Journal of the American College of Cardiology, 72(18), pp.2231–2264. https://doi.org/10.1016/j.jacc.2018.08.1038

·  Thygesen, K., Alpert, J.S., Jaffe, A.S., Simoons, M.L., Chaitman, B.R., White, H.D. et al. (2012). Third universal definition of myocardial infarction. European Heart Journal, 33(20), pp.2551-2567. https://doi.org/10.1093/eurheartj/ehs184

·  Tsao, C.W., Aday, A.W., Almarzooq, Z.I., Anderson, C.A.M., Arora A.M. et al. (2023). Heart Disease and Stroke Statistics-2023 Update: A Report From the American Heart Association. Circulation, 147(8), pp.e93-e621. https://doi.org/10.1161/CIR.0000000000001123

·  Viguiliouk, E., Glenn, A.J., Nishi, S.K., Chiavaroli, L., Seider, M., Khan, T., Bonaccio, M., Iacoviello, L., Mejia, S.B., Jenkins, D.J.A., Kendall, C.W.C., Kahleová, H., Rahelić, D., Salas-Salvadó, J. & Sievenpiper, J.L. (2019). Associations between Dietary Pulses Alone or with Other Legumes and Cardiometabolic Disease Outcomes: An Umbrella Review and Updated Systematic Review and Meta-analysis of Prospective Cohort Studies. Advances in Nutrition, 10(Supplement_4), pp.S308–S319. https://doi.org/10.1093/advances/nmz113

·  Vinay Kumar, Abbas, A.K., Aster, J.C., Wojciech Biernat, Włodzimierz Olszewski, Perkins, J.A., Stanley Leonard Robbins, Chang, A.C., Burstein, H.J. & Urban, E. (2019). Robbins Basic Pathology (Robbins Pathology). 10th ed. Wrocław: Edra Urban & Partner, © Copyright.

·  Wang, D.D., Li, Y., Chiuve, S.E., Stampfer, M.J., Manson, J.E., Rimm, E.B., Willett, W.C. & Hu, F.B. (2016). Association of Specific Dietary Fats With Total and Cause-Specific Mortality. JAMA internal medicine, [online] 176(8), pp.1134–45. https://doi.org/10.1001/jamainternmed.2016.2417

·  Yang, B., Glenn, A.J., Liu, Q., Madsen, T., Allison, M.A., Shikany, J.M., Manson, J.E., Chan, K.H.K., Wu, W.-C., Li, J., Liu, S. & Lo, K. (2022). Added Sugar, Sugar-Sweetened Beverages, and Artificially Sweetened Beverages and Risk of Cardiovascular Disease: Findings from the Women’s Health Initiative and a Network Meta-Analysis of Prospective Studies. Nutrients, 14(20), p.4226. https://doi.org/10.3390/nu14204226

·  Yang, C., Shi, X., Xia, H., Yang, X., Liu, H., Pan, D. & Sun, G. (2019). The Evidence and Controversy Between Dietary Calcium Intake and Calcium Supplementation and the Risk of Cardiovascular Disease: A Systematic Review and Meta-Analysis of Cohort Studies and Randomized Controlled Trials. Journal of the American College of Nutrition, 39(4), pp.352–370. https://doi.org/10.1080/07315724.2019.1649219

·  Yuan, S., Yu, L., Gou, W., Wang, L., Sun, J., Li, D., Lu, Y., Cai, X., Yu, H., Yuan, C., Zheng, J., Larsson, S.C., Theodoratou, E. & Li, X. (2022). Health effects of high serum calcium levels: Updated phenome-wide Mendelian randomisation investigation and review of Mendelian randomisation studies. eBioMedicine, 76, p.103865. https://doi.org/10.1016/j.ebiom.2022.103865

·  Zhang, B., Xiong, K., Cai, J. & Ma, A. (2020). Fish Consumption and Coronary Heart Disease: A Meta-Analysis. Nutrients, 12(8), p.2278. https://doi.org/10.3390/nu12082278

·  Zeraatkar, D., Han, M.A., Guyatt, G.H., Vernooij, R.W.M., El Dib, R., Cheung, K., Milio, K., Zworth, M., Bartoszko, J.J., Valli, C., Rabassa, M., Lee, Y., Zajac, J., Prokop-Dorner, A., Lo, C., Bala, M.M., Alonso-Coello, P., Hanna, S.E. & Johnston, B.C. (2019). Red and Processed Meat Consumption and Risk for All-Cause Mortality and Cardiometabolic Outcomes. Annals of Internal Medicine, 171(10), p.703. https://doi.org/10.7326/m19-0655

7. Figures and Tables