MINISTRY OF HEALTHCARE OF THE RUSSIAN FEDERATION FEDERAL STATE

BUDGETARY EDUCATIONAL INSTITUTION OF HIGHER EDUCATION ‘’KÍROV

STATE
MEDICAL UNIVERSITY’’ OF THE MINISTRY OF HEALTHCARE OF THE RUSSIAN
FEDERATION

Department of polyclinic therapy

Head of the department

Lecturer

NUTRITIONOLOGY IN CARDIOLOGY

STUDENT NAME .

KHAN MASOOD ALAM 501

Kirov 2024
Abstract
Cardiovascular disease (CVD) remains the preeminent cause of mortality in Western
societies, accounting for nearly 30% of global fatalities. Robust evidence underscores
the pivotal role of adopting salubrious dietary paradigms and lifestyles in mitigating the
burden of CVD. The escalating incidence of CVD over the past quarter-century has
emerged as a paramount public health concern, accentuating the imperative of
lifestyle interventions in its prevention. Current scientific inquiry underscores that
juxtaposed against conventional Western dietary norms, the embrace of healthier
regimens such as the Mediterranean diet (MeDiet) precipitates a diminution in the
overproduction of proinflammatory cytokines while fostering the synthesis of anti-
inflammatory counterparts. Notably, dietary interventions afford a synergistic interplay
of multifarious foods and nutrients, underscoring the nuanced and comprehensive
benefits of holistic dietary patterns over singular nutrient supplementation. This review
seeks to delineate potential targets—ranging from overarching dietary patterns to
individual foods and specific nutrients—for the prevention of CVD, elucidating the
magnitude of observed beneficial effects. Additionally, the review endeavors to
elucidate the mechanistic underpinnings of this cardioprotective phenomenon,
encompassing inflammation modulation, nutrient bioavailability, and allied factors.
Advanced Introduction
As of 2013, cardiovascular disease (CVD) had cemented its status as the leading
cause of mortality in Western nations, exacting a toll of 17.3 million lives annually
worldwide, representing 31.5% of global deaths, albeit displaying a modest downtrend
over the preceding decade[1,2]. CVD casts a long shadow over mortality rates,
accounting for one in three fatalities in the United States and one in four in Europe[3].
Projections indicate that by 2035, an excess of 130 million adults in the US alone will
grapple with clinically evident CVD[1,4]. The CVD umbrella encompasses a spectrum
of maladies afflicting the cardiovascular system, spanning from hypertension and
stroke to atherosclerosis, peripheral artery disease, and venous disorders[4]. The
genesis of CVD intertwines with deleterious dietary practices marked by the
overconsumption of sodium-laden processed foods, added sugars, unhealthy fats,
and the insufficient intake of fruits, vegetables, whole grains, fiber, legumes, fish, and
nuts[5,6,7]. Lifestyle factors such as sedentarism, obesity, stress, alcohol use, and
smoking further compound the risk landscape. Additionally, CVD frequently coexists
with comorbid conditions including obesity, diabetes, hypertension, and dyslipidemia,
collectively constituting top-tier risk factors for global all-cause mortality[8]. The
burgeoning incidence of CVD over the past quarter-century has underscored the
imperative of prioritizing lifestyle interventions for primary prevention[9]. Nutrition
emerges as a linchpin in the preventive armamentarium against CVD mortality and
offers promise in the potential regression of heart disease[10]. Furthermore, dietary
interventions hold sway in the management of ancillary risk factors such as obesity,
hypertension, diabetes, and dyslipidemia[8]. Hence, the delineation and stratification
of nutrients, food items, or dietary regimens that furnish enhanced protection against
CVD represent a pressing exigencyUnhealthy dietary habits, compounded by
sedentary lifestyles, obesity, advancing age, gender
disparities, genetic predisposition, and smoking, among other variables, are implicated
in the pathogenesis of cardiovascular disease (CVD)[8]. Atherosclerosis,
characterized by chronic inflammation, stands as a key driver of CVD morbidity and
mortality. Nutrition emerges as a modifiable determinant capable of mitigating
oxidative stress and systemic inflammation[8]. Excessive caloric intake and physical
inactivity serve as precipitating factors for the secretion of pro-inflammatory cytokines,
further exacerbating the inflammatory milieu associated with CVD.
Atherosclerosis, in its early stages, entails the internalization of lipids, predominantly
low-density lipoproteins (LDL), within the intima, precipitating endothelial
dysfunction[10,11,12,13]. This disruption fosters an inflammatory cascade, thrombus
formation, and a spectrum of pathological sequelae, including calcifications, stenosis,
rupture, or hemorrhage[14]. The inflammatory milieu is augmented by the infiltration
of LDL particles into the extracellular matrix (ECM), while circulating monocytes
adhere to the endothelium, differentiating into macrophages and infiltrating the sub-
endothelial space. LDL retention within the ECM is mediated by proteoglycans,
facilitating its entrapment in the intima[15]. Subsequently, LDL particles within the
intima undergo oxidative modifications by reactive oxygen species (ROS) and
enzymatic processes released by inflammatory cells, transforming macrophages into
foam cells upon absorption of oxidized LDL (oxLDL) particles. Concurrently,
endothelial dysfunction exacerbates platelet adhesion, prompting the secretion of
chemotactic substances and growth factors that drive plaque progression[17,18,19].
Vascular smooth muscle cells (VSMCs) also contribute to plaque evolution, with foam
cell-derived growth factors and cytokines stimulating VSMC migration to the intima,
where they participate in fibrous cap formation[20,21,22,23]. Persistent lipid
accumulation fosters foam cell and macrophage apoptosis, concomitant with the
secretion of pro-thrombotic molecules. Atherosclerotic plaque advancement and
disruption, catalyzed by pro-thrombotic agents, instigate platelet activation and
aggregation, triggering the coagulation cascade and subsequent thrombus
formation[24,25,26,27]. The clinical ramifications of advanced atherosclerosis
encompass coronary heart disease, ischemic stroke, peripheral artery disease, heart
failure, or sudden death[28,29,30].
2. Dietary Patterns
Numerous studies have established a correlation between healthy dietary patterns and
reduced levels of pro-inflammatory markers in plasma, while a Western-style diet
(characterized by a high consumption of meat) is linked to elevated levels of low-grade
inflammation[58]. Consequently, guidelines for cardiovascular disease (CVD)
management advocate for adopting a healthy diet[31]. Dietary interventions afford a
synergistic blend of various foods and nutrients, thereby conferring a more robust
array of beneficial effects compared to singular nutrient supplementation[59]. Healthy
dietary patterns typically entail a high intake of fiber, antioxidants, vitamins, minerals,
polyphenols, monounsaturated fatty acids (MUFA), and polyunsaturated fatty acids
(PUFA), coupled with low consumption of salt, refined sugar, saturated and trans fats,
and carbohydrates with a low glycemic load[59]. This translates to an emphasis on
fruits, vegetables, legumes, fish, seafood, nuts, seeds, whole grains, vegetable oils
(particularly extra virgin olive oil), and dairy products, with limited intake of pastries,
soft drinks, and red and processed meats[60].
Mediterranean and Dietary Approaches to Stop Hypertension (DASH) dietary
interventions have garnered substantial attention for their cardiovascular benefits.
Both dietary patterns exhibit potential in reducing CVD incidence by mitigating low-
grade inflammation, improving weight management, and ameliorating other risk
factors, thereby correlating with a diminished occurrence of clinical events[59,60].
Hence, this study will focus on exploring the cardiovascular outcomes associated with
these dietary interventions[60].
2.1. Mediterranean Diet
The Mediterranean diet (MeDiet) has long been heralded for its cardiovascular
benefits, primarily attributed to its efficacy in controlling various risk factors such as
blood pressure, lipid profile, glucose metabolism, arrhythmic risk, and modulation of
the gut microbiome[59, figure 2]. Some evidence suggests that the MeDiet exerts an
anti-inflammatory effect within the vascular wall, potentially elucidating its association
with lower CVD prevalence. Intriguingly, the MeDiet appears to modulate the
expression of pro-atherogenic genes such as cyclooxygenase-2 (COX-2), monocyte
chemoattractant protein-1 (MCP-1), and low-density lipoprotein receptor-related
protein (LRP1), while also reducing plasma levels of molecules associated with plaque
stability and rupture, including matrix metalloproteinase-9 (MMP-9), interleukin-10 (IL-
10), interleukin-13 (IL-13), and interleukin-18 (IL-18)[61,62,63].

2.2. DASH Diet

A wealth of evidence substantiates the association between adherence to the Dietary
Approaches to Stop Hypertension (DASH) dietary regimen and favorable outcomes
across various health parameters[85]. Adherence to the DASH diet has been linked to
improvements in blood pressure regulation, body weight management, glucose-insulin
homeostasis, lipid profile, inflammation status, endothelial function, modulation of the
gut microbiome, cardiovascular disease (CVD) risk reduction, and overall mortality
rates[86,87].
The DASH diet is characterized by a dietary pattern rich in fruits, vegetables, legumes,
low-fat dairy products, whole grain products, nuts, fish, and poultry. It entails a reduced
intake of saturated fats, red meat, processed meats, and sugary beverages, as well
as limited consumption of sodium and refined grains 5. Foods[88,89,90]
3.1. Fruits and Vegetables
The European Society of Cardiology (ESC) and the American Heart Association
Nutrition Committee advocate for the daily consumption of multiple servings of fruits
and vegetables to mitigate cardiovascular disease (CVD) risk[106,107]. These
recommendations draw from extensive epidemiological studies and meta-
analyses[106,107,108,109,110,112,113]. A recent meta-analysis encompassing 83
studies, comprising 71 clinical trials and 12 observational studies, demonstrated a
significant inverse association between higher fruit or vegetable intake and levels of
C-reactive protein (CRP) and tumor necrosis factor-alpha (TNF-α), alongside a direct
correlation with increased proliferation of γδ-T cell populations.Furthermore, specific
investigations have elucidated the relationship between biomarkers of systemic
inflammation and individual fruit intake. For instance, Corley et al[108]. examined 792
participants from the Lothian Birth Cohort
1936 and found that higher fresh fruit intake was associated with lower CRP levels.
Similarly, in a cross-sectional study involving 285 healthy adolescents, serum CRP
levels were inversely associated with fruit intake[111]. The HELENA Cross-Sectional
Study, conducted among 464 adolescents, demonstrated negative associations
between fruits and nuts with interleukin-4 (IL-4) and TNF-α, whereas vegetables
exhibited significant inverse correlations with soluble E-selectin.[112]
Moreover, a cross-sectional analysis among 1005 Chinese women revealed that
higher cruciferous vegetable intake was linked to reduced concentrations of TNF-α,
interleukin-1β (IL-1β), and interleukin-6 (IL-6)[113]. However, no significant association
was observed between cruciferous vegetable consumption and oxidative stress
markers. These findings underscore the anti-inflammatory properties and potential
cardiovascular benefits conferred by regular consumption of fruits and vegetables,
particularly highlighting the role of specific varieties such as cruciferous vegetables in
modulating inflammatory markers[114].
4. Nutrients
Emphasizing the potential benefits of specific nutrient intake is crucial to mitigate the
risk of deficiencies that can predispose individuals to atherosclerotic disease. While
our focus is primarily on fiber, certain vitamins, and minerals, it's important to note that
other nutrients such as carbohydrates, fats, and proteins also play a role in
atherosclerosis development, although they are not extensively covered in this
discussion[132].
4.1. Fiber
A plethora of studies and scientific literature underscores the health advantages of
dietary fiber intake in reducing cholesterol levels and blood pressure, while deficiency
in fiber intake is associated with heightened risk of cardiovascular disease (CVD)[155].
Numerous meta-analyses have demonstrated that higher dietary fiber consumption is
correlated with a lower relative risk of total all-cause mortality, ranging from 16% to
23%. Mechanistically, dietary fiber is purported to diminish glucose absorption and
down-regulate the expression of oxidative stress-related cytokines, thereby mitigating
inflammation mediated by gut microbiota exposure to fiber[156,157,158].
Observational investigations have further elucidated the association between dietary
fiber intake and inflammatory markers[159]. For instance, in a study of
postmenopausal women, higher dietary fiber consumption was linked to elevated
levels of inflammatory markers such as C-reactive protein (CRP) and interleukin-6 (IL-
6). Similarly, in the Women’s Health Initiative Observational Study, increased fiber
intake was associated with lower plasma concentrations of IL-6 and TNFR2 compared
to lower fiber intake groups. Comparable findings were reported by other studies,
highlighting the inverse relationship between dietary fiber intake and concentrations of
inflammatory markers like CRP and TNFR2[159].
Moreover, cross-sectional data from the Insulin Resistance Atherosclerosis Study
revealed an inverse correlation between intake of whole grain products and plasma
concentrations of plasminogen activator inhibitor-1 (PAI-1) and CRP, further
underscoring the anti-inflammatory properties of dietary fiber and whole grains.
Despite ongoing research efforts, the precise mechanisms underlying the beneficial
effects of dietary fiber on inflammation remain to be fully elucidated.
4.2. Micronutrients
Contemporary evidence from experimental, epidemiological, and clinical studies
underscores the protective role of micronutrient intake against cardiovascular disease
(CVD)[168,169,170]. Micronutrients exert their cardioprotective effects through
several mechanisms, including the reduction of endothelial cell damage, enhancement
of nitric oxide (NO) production, and inhibition of low-density lipoprotein cholesterol
(LDL-c) oxidation[169,169,170].
Both in adolescence and adulthood, dietary antioxidants such as zinc (Zn), selenium
(Se), and vitamins C and E have been associated with lower levels of pro-inflammatory
biomarkers. Deficiency in these micronutrients is linked to an increased risk of CVD.
Meta-analyses have further reinforced the potential of micronutrient supplementation
in reducing inflammation markers. For instance, magnesium (Mg) supplementation
has been shown to significantly decrease serum C-reactive protein (CRP) levels,
particularly in individuals with baseline CRP values exceeding 3
mg/L[171,172,173,174].
Similarly, vitamin D supplementation has been associated with lower levels of tumor
necrosis factor-alpha (TNF-α), suggesting its anti-inflammatory properties. However,
findings regarding other inflammatory markers such as CRP, interleukin-10 (IL-10),
and interleukin-6 (IL-6) have been inconclusive[175].
In contrast, supplementation with vitamin E has shown promise in reducing serum
CRP levels, highlighting its potential as an anti-inflammatory agent. These findings
collectively underscore the importance of adequate micronutrient intake in mitigating
inflammation and reducing the risk of cardiovascular disease.[180]
5. Bioactive Compounds
Various bioactive compounds found in the diet, such as omega-3 fatty acids, lycopene,
and polyphenols, have been associated with beneficial effects on the development of
atherosclerosis. These compounds function by reducing levels of low-density
lipoprotein cholesterol (LDL-c) and improving inflammatory and oxidative stress
biomarkers. Let's delve into the analysis of omega-3 fatty acids[189].
5.1. Omega-3 Fatty Acids
Polyunsaturated fatty acids (PUFAs), including omega-3 fatty acids such as α-linolenic
acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), have
emerged as potential anti-atherogenic agents in the atherosclerotic process. Their
mechanisms of action in reducing cardiovascular (CV) risk are multifaceted and
encompass improvements in lipid and lipoprotein profiles, reduction of oxidation and
thrombosis, enhancement of endothelial function, modulation of blood pressure,
promotion of plaque stability, mitigation of CV mortality, inhibition of platelet
aggregation, and modulation of pro-inflammatory markers and immune
cells[190,191,192].Meta-analyses have provided compelling evidence supporting the
cardiovascular benefits of omega-3 PUFA intake. For instance, a meta-analysis of
randomized placebo-controlled trials revealed that omega-3 PUFA supplementation
led to a significant increase in flow-mediated dilation (FMD), a marker of endothelial
function. Additionally, another meta-analysis demonstrated substantial reductions in
serum triglyceride levels among healthy individuals following daily consumption of EPA
and DHA, particularly at doses exceeding 4 grams per day[197].
Observational studies have further underscored the importance of omega-3 fatty acids
in cardiovascular health. For example, low serum concentrations of DHA have been
linked to increased cardiovascular risk, with DHA serving as a predictive marker for
endothelial dysfunction. These findings highlight the potential of omega-3 fatty acids,
particularly EPA and DHA, in mitigating cardiovascular risk and improving vascular
health.[197]
5.2. Lycopene
Lycopene, a lipophilic and unsaturated carotenoid, is abundantly found in red-colored
fruits and vegetables such as tomatoes, papaya, and watermelons[200,201].
Epidemiological observational and interventional studies suggest that lycopene may
play a role in reducing atherosclerotic risk, particularly in the early stages of
atherosclerosis, by preserving endothelial function, enhancing nitric oxide (NO)
bioavailability, and mitigating low-density lipoprotein (LDL) oxidation[202].
Lycopene exerts its effects through various mechanisms, including improvement of the
metabolic profile by inhibiting cholesterol synthesis and lowering blood pressure
through reductions in arterial stiffness. Moreover, lycopene has been shown to
modulate the expression of pro-inflammatory markers and inhibit platelet
aggregation[202].
Dietary intake of lycopene has been associated with cardiovascular benefits, including
a significant reduction in cardiovascular mortality and major cardiovascular events,
particularly in postmenopausal women free of cardiovascular disease or cancer.
Several studies have highlighted lycopene's antioxidant properties as a potential
mechanism underlying its health benefits and its ability to mitigate the risk of
developing atherosclerosis[203].
Overall, lycopene appears to confer cardiovascular protection by preserving
endothelial function, reducing oxidative stress, and modulating inflammatory
responses, thereby potentially reducing the risk of atherosclerosis and its associated
cardiovascular complications[202].
6. Polyphenols
Polyphenols, the most abundant dietary antioxidants found in plant-based foods and
beverages, offer a broad spectrum of health effects in cardiovascular disease (CVD)
prevention[209,210]. These compounds are prevalent in fruits and vegetables, red
wine, black and green tea, coffee, extra virgin olive oil (EVOO), chocolate, as well as
nuts, seeds, herbs, and spices.
A plethora of scientific evidence accumulated in recent years suggests that
polyphenols may delay the progression of atherosclerosis through various
mechanisms. These mechanisms include the regulation of signaling and transcription
pathways such as NF-κβ, enhancement of antioxidant systems, inhibition of leukocyte
migration and infiltration into plaques, reduction of adhesion molecule levels,
suppression of pro-inflammatory cytokine production, augmentation of nitric oxide
(NO) production leading to blood pressure reduction, and improvement of lipid
metabolism,coagulationactivity,andendothelial function.[211,212,213].Epidemiological
studies have consistently reported a negative association between polyphenol
consumption or intake of polyphenol-rich foods and CVD[209]. For instance, a meta-
analysis encompassing 14 prospective cohort studies revealed that moderate coffee
consumption (three to five cups per day) was associated with a lower risk of CVD
compared to non-consumers[209]. Similar findings were observed in another meta-
analysis assessing the relationship between tea consumption and stroke risk, where
daily intake of three or more cups of tea was linked to a reduced risk of stroke,
particularly ischemic stroke[210].These findings underscore the potential
cardiovascular benefits of polyphenols and polyphenol-rich foods, suggesting their
role in mitigating the risk of CVD and its associated complications.[210]
9. Conclusions
The intricate interplay between nutrition and cardiovascular disease (CVD)
underscores the imperative of promoting healthy dietary habits and active lifestyles,
particularly from early childhood through young adulthood. Evidence overwhelmingly
supports the consumption of healthy dietary patterns, exemplified by the
Mediterranean diet or DASH diet, over less favorable dietary patterns typified by high
levels of salt, added sugars, saturated fats, and trans-fats commonly found in Western
diets.While numerous studies have highlighted the potential health benefits of various
foods, nutrients, bioactive compounds, and dietary antioxidants such as polyphenols
in mitigating cardiovascular risk factors and directly impacting CVD development, the
need for further interventional research with larger sample sizes and longer follow-up
periods is evident. Despite a wealth of data, many studies have yielded inconclusive
results or even contradictory findings, underscoring the complexity of the relationship
between diet and cardiovascular health.A critical gap in our understanding lies in
elucidating the underlying mechanisms implicated in the cardioprotective effects of
dietary interventions, specific foods, nutrients, or bioactive compounds. Therefore,
future research endeavors should prioritize investigating these mechanisms to
advance our comprehension of the intricate interactions between diet and
cardiovascular health and inform evidence-based strategies for CVD prevention and
management.[MY OWN]

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