Volume 5, No. 7 July, 2024
p ISSN 2723-6927-e ISSN 2723-4339
Surrogate
Biomarker to Identify Obesity and Predict Cardiovascular Disease Risk: A
Systematic Review
Farchan Azzumar1,
Helda2, Qonita Nur Salamah3,
Rahma Dewi Handari4, Ramadhani5, Reihana
Ramadlani Ibna6, Yanti Herawati7
University of Indonesia, Depok, Indonesia
Email: azzumar.farchan@gmail.com
This study investigates the relationship between
obesity and cardiovascular disease (CVD) risk by comparing the use of body mass
index (BMI) versus other biomarkers in predicting CVD risk among obese
individuals. It conducts a systematic literature review following the PRISMA
guidelines, searching databases for relevant articles published from 2017-2022.
The review analyzes 12 eligible articles and finds that factors beyond just
BMI, such as genetics, physical activity, metabolic disorders, previous heart
disease history, nutrition, fat distribution, and changes in BMI, can
significantly impact the prognosis of heart disease in obese individuals.
Importantly, the study shows that measures of fat distribution like
waist-to-height ratio, waist circumference, log-transformed body shape index
(LBSIZ), and the ratio of visceral adipose tissue (VAT) to subcutaneous adipose
tissue (SAT) are superior to BMI in predicting CVD risk among those with
obesity. The key takeaway is that while obesity is strongly linked to CVD risk,
BMI alone often fails to predict that risk accurately. Fat distribution measures
may be a more effective tool for identifying obesity status and predicting
associated CVD risk compared to relying solely on BMI. The findings imply that
future research should further explore these alternative biomarkers, and
clinical practice may benefit from incorporating them into risk assessment
protocols. Explicitly stating the significance or impact of these findings
strengthens the abstract and highlights the potential implications for future
research and clinical practice.
Keywords: Body Mass Indeks, Biomarkers, Cohort, Cardiovascular Disease, Obesity, Fat Distribution, Risk Assessment.
INTRODUCTION
Cardiovascular disease (CVD) poses a significant
global public health challenge and stands as the leading cause of death
worldwide. Over the last decade, CVD-related deaths have risen notably,
escalating from 12.1 million to 18.6 million. In Indonesia, CVD represents a
critical area of focus for the Ministry of Health as part of efforts to reform
the healthcare system, particularly in enhancing referral services. The
prevalence of CVD among Indonesians continues to increase, resulting in
heightened levels of illness, disability, and socioeconomic burdens affecting
individuals, families, communities, and the nation at large. According to
Indonesia's Sample Registration System (SRS), cardiovascular disease (CVD)
ranks as the second most common cause of death in the country following stroke,
comprising 12.9% of all leading causes of mortality. This underscores the
escalating public health challenge posed by CVD, both on a global scale and
within Indonesia. It emphasizes CVD's significance as a focal point for
healthcare system improvements and acknowledges its substantial impact on
mortality rates and socioeconomic burdens in the country
Obesity
is strongly associated with diabetes, hypertension, and other metabolic
disorders, all of which contribute to an increased risk of cardiovascular
disease (CVD). This has led to a widespread global health crisis, with obesity
rates experiencing significant growth over the past 35 years. Current estimates
indicate that approximately 39% to 49% of the worldwide population, equivalent
to 2.8-3.5 billion people, are affected by obesity. In Indonesia, the
prevalence of central obesity has notably increased from 18.8% in 2007 to 31%
in 2018, highlighting a concerning upward trend. These trends underscore the
critical role of obesity in escalating CVD risk on a global scale
Cardiovascular
disease (CVD) comprises various disorders that impact the heart, blood vessels,
or both. This category includes conditions like coronary heart disease (CHD),
cerebrovascular disease, rheumatic heart disease, congenital heart disease,
deep vein thrombosis, and pulmonary embolism. CVD generally arises from a
combination of multiple risk factors rather than a singular cause. Effective
management and prevention of these risk factors can play a crucial role in
controlling and preventing cardiovascular diseases
Obesity or
overweight refers to a condition where an individual's weight significantly
exceeds the normal range, stemming from an imbalance between energy intake and
expenditure. According to the World Health Organization (WHO), being overweight
is characterized by a body mass index (BMI) of 25 to 30 kg/m², while obesity is
defined by a BMI exceeding 30 kg/m². However, abdominal obesity can manifest
independently of overall obesity as defined by BMI. This condition, termed
"normal weight obesity," can lead to the misclassification and
underdiagnosis of cardiovascular and cardiometabolic diseases. It primarily
affects individuals with excess abdominal fat who do not meet the standard BMI
criteria for obesity
Despite numerous studies confirming a link between
obesity and cardiovascular disease (CVD), ongoing discussions persist regarding
the underlying mechanisms driving this association. Intriguingly, some research
has identified a paradoxical phenomenon wherein specific subgroups exhibit
lower mortality rates among individuals who are overweight or obese. This
suggests that the relationship between obesity and mortality from CVD may not
be straightforward and could be influenced by factors such as age, ethnicity,
or concurrent health conditions. Further research is essential to
comprehensively grasp these intricate dynamics and their implications for
public health strategies aimed at preventing cardiovascular diseases
Due
to the ongoing debate, it is crucial to conduct a systematic review of the
literature to thoroughly investigate the relationship between obesity and
cardiovascular disease (CVD). Presently, there seems to be a shortage of
studies or literature reviews, especially in Indonesia, that specifically
examine this connection. Therefore, we conducted a systematic literature review
to identify, evaluate, and analyze existing research to ascertain the presence
and extent of the association between obesity and CVD. This review seeks to
offer a comprehensive understanding of the current state of research in this
area, highlighting any discrepancies or knowledge gaps in the findings.
RESEARCH METHODS
This systematic literature review adheres to the
PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses)
methodology, which encompasses four main stages: identification, screening,
eligibility, and inclusion of pertinent studies. A comprehensive search was
conducted using electronic databases like PubMed, ScienceDirect, and Sage
Journals to retrieve relevant journal articles. The review encompasses various
study types, with a particular focus on cohort studies aimed at exploring the
correlation between obesity and cardiovascular disease. This approach is
designed to systematically collect, assess, and synthesize available evidence
from the literature, ensuring a rigorous evaluation of the relationship between
obesity and CVD
The inclusion criteria at the beginning of the search in the database were
English-language journals, articles with full-text open access, publication
time with the range of 2017 2022, respondents of all ages and genders in the
field of public health and cardiology, and journals that discuss risk factors
for obesity with cardiovascular disease. Meanwhile, the exclusion criteria
include literature in the form of non-journals, systematic reviews, and
duplicate titles that will be issued in this study, journals or articles that
discuss cardiovascular risk factors other than obesity
RESULTS AND DISCUSSION
Following the initial literature search using keywords such as
obesity, cohort, and cardiovascular disease, a meticulous screening process was
conducted based on pre-defined inclusion criteria and the publication timeframe
from 2017 to 2022. This screening yielded a total of 12 suitable pieces of
literature that met the criteria for further detailed review and analysis.
These selected studies will now undergo a thorough evaluation to assess the
relationship between obesity and cardiovascular disease, as reported in the
literature during the specified period.
Table 1. Results of Literature Study
|
No. |
Writer |
Research Results |
|
1. |
Honda et al, |
Over
the course of the 5-year study, the 2,140 participants showed an average
weight loss of 1.6%. Among them, 496 individuals (23.2%) maintained their
obesity status, while 103 participants (4.8%) shifted from being obese to
non-obese. Furthermore, the majority, 1,462 participants (68.3%), remained
non-obese throughout the study period, while 78 participants (3.6%)
transitioned from non-obese to obese. Both
groups that experienced changes in obesity statustransitioning from obese to
non-obese and from non-obese to obeseshowed elevated risks of cardiovascular
disease (CVD). The group that shifted from obese to non-obese exhibited the
smallest increase in CVD risk, with predictions rising from 5.9% to 6.9% in
2007, a statistically significant finding (P < 0.01). Conversely, the
non-obese-to-obese group showed the largest increase in CVD risk prediction,
increasing from 5.7% to 8.2% in 2007, which was also statistically
significant (P < 0.08). These findings underscore the impact of changes in
obesity status on cardiovascular health outcomes. Additional
investigation uncovered a relationship between changes in body weight
percentage and shifts in cardiovascular disease (CVD) risk indicators.
Notably, weight gain was significantly associated with rises in waist
circumference, blood pressure levels, fasting blood sugar levels, hemoglobin
concentrations, and cholesterol levels, while also correlating with a decline
in serum HDL cholesterol levels over the course of the research period. These
results underscore the influence of body weight fluctuations on multiple
factors that contribute to increased risk of cardiovascular disease. |
|
2. |
Lee et al, |
Over a decade-long study involving 1,015
participants, averaging 56.4 years in age and predominantly male, 37.5%
developed Coronary Artery Calcification (CAC). Key contributors to CAC
included a body mass index (BMI) of ≥25 kg/m², increased waist
circumference, and a high ratio of visceral adipose tissue to subcutaneous
tissue. Notably, individuals with a visceral adipose tissue dominance of
≥30% exhibited a significantly heightened risk of CAC development,
indicated by a hazard ratio of 2.20 and a statistically significant P-value
of less than 0.001. This highlights the independent predictive capability of
visceral fat levels in assessing the risk of CAC, regardless of changes in
BMI and waist circumference.. |
|
3. |
Oh et al, |
Participants in the study were categorized
according to their body shape using the z-score of the log-transformed body
shape index (LBSIZ) into four distinct groups. These groups included
metabolically healthy non-obese (MHNO), which acted as the reference
category, as well as metabolically healthy obese (MHO), metabolically
unhealthy non-obese (MUNO), and metabolically unhealthy obese (MUO). This
classification enabled a thorough examination of how different body shapes
and metabolic statuses correlate with health outcomes among the study
participants. During the 12-year study period from 2001 to
2012, the incidence rate of cardiovascular disease (CVD) was 8.53 cases per
1,000 person-years. Analysis of the data revealed varying hazard ratios (HR)
for CVD events among different groups: the metabolically unhealthy obese
(MUO) group exhibited the highest HR of 1.82 (95% CI 1.45-2.27), followed by
the metabolically unhealthy non-obese (MUNO) group with an HR of 1.46 (95% CI
1.15-1.85), and the metabolically healthy obese (MHO) group with an HR of
1.29 (95% CI 0.96-1.73). These HRs were compared to the reference group of
metabolically healthy non-obese (MHNO) individuals. Furthermore, individuals categorized in the
metabolically healthy obese (MHO) group showed an increased risk of
cardiovascular disease (CVD) events, particularly those in the third
trimester with a hazard ratio (HR) of 2.40 (95% CI 1.28-4.51). This risk
escalated further in the fourth trimester, where the HR elevated to 3.67 (95%
CI 1.99-6.74), compared to participants classified in the metabolically
healthy non-obese (MHNO) group. These findings highlight the diverse risks
associated with both metabolic health and obesity status in relation to
cardiovascular outcomes observed over the course of the study. |
|
4. |
Polemiti et al, |
In this study,
macrovascular events were defined as occurrences of myocardial infarction and
stroke, whereas microvascular events encompassed kidney disease, retinopathy,
and neuropathy. Body mass index (BMI) classifications were categorized
according to World Health Organization (WHO) guidelines: normal (18.524.9
kg/m²), overweight (25.029.9 kg/m²), obese I (30.034.9 kg/m²), and obese II
(≥35.0 kg/m²). Changes in BMI were classified as increased BMI (>1%
gain), stable BMI (≤1% gain/loss), and decreased BMI (>1% loss).
These criteria were employed to investigate the relationship between BMI
fluctuations and the incidence of both macrovascular and microvascular events
within the study population. Over an
average follow-up period of 10.8 years, the study recorded 85 macrovascular
events, such as myocardial infarction and stroke, and 347 microvascular
events, including kidney disease, neuropathy, and retinopathy. The analysis
did not find any clear link between BMI measured prior to the diagnosis of
diabetes mellitus (DM) and changes in BMI concerning the occurrence of
macrovascular events. Higher body
mass index (BMI) before diabetes diagnosis was found to be significantly
associated with an increased risk of microvascular complications.
Specifically, for every 5 kg/m² increase in BMI, the hazard ratio for
microvascular complications was 1.21 (95% CI: 1.07-1.36). This association
was particularly strong for kidney disease, with a hazard ratio of 1.39 (95%
CI: 1.21-1.60), and less pronounced for neuropathy, with a hazard ratio of
1.12 (95% CI: 0.96-1.31). These findings highlight the impact of higher BMI
levels before diabetes onset on the risk of developing microvascular
complications among study participants. The analysis of BMI changes revealed that a
reduction in BMI greater than 1% was associated with a decreased risk of
microvascular complications. Specifically, this reduction in BMI was linked
to a lower risk of kidney disease (HR 0.57; 95% CI: 0.40-0.81) and showed a
trend towards reduced risk of neuropathy (HR 0.73; 95% CI: 0.52-1.03),
compared to individuals whose BMI remained stable. In contrast, there was no
clear association found between BMI changes and macrovascular complications,
with an HR of 1.04 (95% CI: 0.62-1.74). These findings highlight the
potential benefit of BMI reduction in mitigating the risk of microvascular
complications among individuals studied, underscoring the importance of
weight management in diabetes care. |
|
5 |
Chien et al, |
The ASIAN-HF study, which involved 5,964
participants with a mean age of 60.8 years and a diagnosis of heart failure,
examined the relationship between body mass index (BMI) and waist-to-height
ratio (WHtR) with heart failure outcomes. The study found that a high WHtR
was associated with a significant increase in body fat percentage (0.38%) and
increased the risk of heart failure events, regardless of whether the
ejection fraction was reduced (HFrEF) or preserved (HFpEF). Notably, individuals with a high WHtR and lower
BMI (< 24.5 kg/m²) had a higher hazard ratio (HR) of 1.93 (95% CI
1.17-3.18; P-value 0.010) for these events compared to those with obesity.
This suggests that WHtR is a more significant predictor of adverse outcomes
in heart failure, regardless of BMI status. These findings highlight the
importance of considering WHtR in addition to BMI when assessing heart
failure risk and managing patients with heart failure The study found that individuals classified as
underweight, particularly those with a high Waist-to-Height Ratio (WHtR), had
a significantly higher risk of death during hospitalization for heart
failure. The Hazard Ratio (HR) for this group was 2.01 (95% CI 1.113.65, p =
0.022). Additionally, the study observed a notable increase in cardiovascular
disease (CVD) mortality among underweight individuals compared to those who
were obese, with a statistically significant p-value of 0.026. These findings
emphasize the heightened risks associated with being underweight in the
context of heart failure and cardiovascular outcomes. The study found that individuals with a lower
BMI (< 24.5 kg/m²) and higher Waist-to-Height Ratio (WHtR) (≥ 0.55)
had a significantly increased risk of developing composite heart failure.
This association was consistent across different types of heart failure,
including Heart Failure with Preserved Ejection Fraction (HFpEF) and Heart
Failure with Reduced Ejection Fraction (HFrEF). Specifically, the Hazard
Ratio (HR) for this group was 1.93 (95% CI 1.17 to 3.18, p = 0.01). This
highlights the importance of considering both BMI and WHtR in assessing heart
failure risk and managing patients with heart failure. |
|
6 |
Kaltoft et al, |
A comprehensive study spanning 8.7 years and
involving 108,304 participants found a significant correlation between
genetically elevated body mass index (BMI) and increased risks associated
with aortic valve stenosis and the need for valve replacement surgery.
Specifically, each 1 kg/m² increase in BMI was linked to a 52% higher
relative risk (RR) of developing aortic valve stenosis (95% CI: 1.23 - 1.87)
and a 49% higher RR of requiring aortic valve replacement surgery (95% CI:
1.07 - 2.05). Additionally, hazard ratios (HR) indicated a 6% increased risk
(HR 1.06, 95% CI: 1.05 - 1.08) for both aortic valve stenosis and the need
for valve replacement surgery (HR 1.06, 95% CI: 1.03 - 1.08). These findings
highlight the significant and independent association between higher BMI
influenced by genetic factors and heightened risks of aortic valve conditions
necessitating medical intervention. |
|
7 |
Tan et al, |
The Cardiac Ageing Study, conducted from 2014
to 2017, involved 970 participants with an average age of 73 years. The study
found that 124 individuals (12.8%) met the criteria for obesity based on BMI
measurements, while 347 participants (35.7%) were classified as obese
according to waist circumference measurements. Notably, the assessment based
on waist circumference revealed a higher prevalence of obesity among women,
particularly in the elderly age group. The study found that obesity, as determined by
both BMI and waist circumference measurements, is significantly associated
with myocardial relaxation disorders (E/A ratio) and cardiac fitness (Vo2
Max). Specifically, individuals classified as obese based on BMI criteria
tend to have a notably lower E/A ratio compared to non-obese individuals
(1.13 ± 0.46 vs 0.98 ± 0.35; p < 0.001). Additionally, individuals with a
healthy BMI but elevated waist circumference exhibit greater left atrial
volume (Left Aatrium) with a statistical significance of p = 0.003. These
findings highlight the distinct impacts of BMI and waist circumference on
cardiovascular parameters, underscoring their relevance in assessing cardiac
health. Waist circumference is also a significant
predictor of myocardial relaxation disorders, with a beta coefficient of
-0.114 (standard error 0.024, p < 0.001). This underscores the substantial
association between abdominal obesity and cardiovascular parameters,
indicating that waist circumference is essential for assessing cardiac health
beyond BMI alone. |
|
8 |
Chien et al, |
Obesity and malnutrition, characterized by high
body mass index (BMI) and low skeletal muscle area (SA), are linked to more
significant left ventricular remodeling and poorer diastolic function. This
is reflected in higher left ventricular mass index (44.2 ± 1.52 vs 33.8 ±
8.28 gm/m²), lower tissue Doppler imaging early diastolic velocity (TDI-e0:
7.97 ± 2.16 vs 9.87 ± 2.47 cm/s), higher E/e' ratio (9.19 ± 3.01 vs 7.36 ±
2.31), and increased left atrial volume index (19.5 ± 7.66 vs 14.9 ± 5.49
mL/m²) compared to individuals with low BMI and high SA, as well as other subgroups
(p < 0.001 for all comparisons). Moreover, they exhibited the highest
risk, with a Hazard Ratio (HR) of 2.49 (95% CI 1.43 to 4.34, p = 0.001).
These findings emphasize that both obesity and malnutrition, characterized by
high BMI and low skeletal muscle area (SA), play significant roles in adverse
cardiac remodeling and impaired diastolic function. They indicate a
heightened cardiovascular risk associated with these body composition
profiles compared to other studied groups. |
|
9 |
Pandey et al, |
The study analyzed the relationship between
leisure-time physical activity (LTPA) and Body Mass Index (BMI) in 51,451
participants. Over the study period, there were 3,180 incidents of heart
failure, categorized into HFpEF (1,252 cases), HFrEF (914 cases), and
unclassified cases (1,014). The adjusted analysis showed a gradual
association between BMI levels and the overall risk of heart failure, with
higher BMI levels correlating with an elevated risk. Notably, the link
between BMI and HFpEF risk was more pronounced and consistent compared to
HFrEF risk. This suggests that BMI may have a more significant impact on
predisposing individuals to HFpEF relative to HFrEF, indicating distinct
effects of BMI on different types of heart failure The relationship between body mass index (BMI)
and the risk of heart failure (HF) is complex and nuanced. Studies have shown
that higher BMI levels are associated with a graded increase in the overall
risk of HF. Overweight individuals exhibit a modest elevation in risk, with an
adjusted hazard ratio (HR) of 1.18 (95% CI 1.081.30), while class I obesity
shows a higher risk with an adjusted HR of 1.38 (95% CI 1.241.54). The
greatest risk is observed among participants classified as obesity class
II-III, with an adjusted HR of 2.19 (95% CI 1.942.48), compared to those
with a normal BMI.However, when focusing on heart failure with reduced
ejection fraction (HFrEF), the study reveals that only participants
classified in obesity class II-III exhibit a significantly increased risk (adjusted
HR 1.49, 95% CI 1.181.89). In contrast, overweight individuals and those in
class I obesity do not show a significant difference in HFrEF risk compared
to the normal-weight group. These findings underscore a nuanced association
between BMI categories and heart failure risk, emphasizing that higher BMI
categories are more predictive of overall heart failure risk rather than
specifically HFrEF There exists a clear and graded relationship
between BMI and the risk of heart failure with preserved ejection fraction
(HFpEF), as observed across various BMI categories compared to individuals of
normal weight. Adjusted hazard ratios (HR) demonstrated a 38% increased risk
of HFpEF among those classified as overweight (BMI 25 to <30 kg/m²), with
an HR of 1.38 (95% CI 1.181.61). Class 1 obesity (BMI 30 to <35 kg/m²)
showed a 56% higher risk, with an HR of 1.56 (95% CI 1.301.87). The risk
escalated significantly in obesity class II-III (BMI ≥35 kg/m²), where
the HR was markedly elevated at 2.72 (95% CI 2.243.32). Participants
categorized as extremely obese (BMI ≥35 kg/m²) demonstrated the highest
risk not only for HFpEF but also for heart failure with reduced ejection
fraction (HFrEF). These findings emphasize a distinct association between
higher BMI categories and increased risk of HFpEF, with obesity class II-III
identified as the highest-risk group across both HFpEF and HFrEF. |
|
10 |
Caleyachetty et al, |
Data extracted from The Health Improvement
Network (THIN) database, spanning from 1995 to 2015, encompassed 3.5 million
adults aged 18 years and above without prior cardiovascular disease history.
The study categorized participants into BMI groups: underweight, normal
weight, overweight, and obese categories. Its objective was to assess the
relationship between BMI and the risk of three metabolic disorders: diabetes,
hypertension, and hyperlipidemia. During a median follow-up period of 5.4 years,
individuals classified as obese but without any of the studied metabolic
disorders showed notably higher risks compared to normal-weight individuals
who did have these disorders. Specifically, in comparison to normal-weight
individuals with metabolic disorders, obese individuals without these
conditions had a 49% increased risk of coronary heart disease (HR: 1.49, 95%
CI: 1.451.54), a 7% higher risk of cerebrovascular disease (HR: 1.07, 95%
CI: 1.041.11), and nearly double the risk of heart failure (HR: 1.96, 95% CI:
1.862.06). Furthermore, the likelihood of developing
coronary heart disease, cerebrovascular disease, and heart failure
progressively rose across normal-weight, overweight, and obese categories as
the number of metabolic disorders increased. These findings underscore the
significant impact of both BMI and metabolic health on cardiovascular risks,
highlighting the intricate interplay between body size phenotypes and
metabolic disorders in determining outcomes related to cardiovascular
disease. |
|
11 |
Mongraw-Chaffin et al, |
A study involving 6,809 participants indicated
that early-stage metabolically healthy obesity (MHO) did not show a
significant association with increased cardiovascular disease (CVD) incidence
compared to metabolically healthy individuals of normal weight. However,
nearly half of the participants developed metabolic syndrome (MetS) during
the follow-up period, suggesting that MHO often transitions over time.
Individuals with unstable MHO had a 60% higher likelihood of developing CVD
(odds ratio [OR]: 1.60; 95% confidence interval [CI]: 1.14 to 2.25) compared
to those with stable MHO or consistently healthy normal weight. The study found a clear and increasing
relationship between the duration of metabolic syndrome (MetS) and the risk
of cardiovascular disease (CVD), demonstrating a significant linear trend.
Participants diagnosed with MetS once had an odds ratio (OR) of 1.62 (95% CI:
1.27 to 2.07), those diagnosed twice had an OR of 1.92 (95% CI: 1.48 to
2.49), and those diagnosed three or more times had the highest OR of 2.33
(95% CI: 1.89 to 2.87). These associations were highly statistically
significant, with p-values for trends all below 0.001. Furthermore, the study highlighted that
metabolic syndrome (MetS) accounted for approximately 62% (ranging from 44%
to 100%) of the association between obesity at any point during the follow-up
period and the development of cardiovascular disease (CVD). This underscores
the critical role of metabolic health, particularly the stability of MetS
over time, in influencing cardiovascular risk among individuals classified as
metabolically healthy obese (MHO). |
|
12 |
Pfaller et al, |
In a study involving 790 pregnancies, the distribution of body mass
index (BMI) among women was as follows: 19% were classified as obese (BMI
≥ 30 kg/m²), 25% were overweight (BMI 25 to 29.9 kg/m²), 53% were
normal-weight (BMI 18.5-24.9 kg/m²), and 3% were classified as thin (BMI <
18.5 kg/m²). Obese women experienced significantly higher rates of pregnancy
complications, specifically cesarean delivery (CE), compared to normal-weight
women (23% vs. 14%; p = 0.006). In the multivariate analysis, both obesity (odds ratio: 1.7; 95%
confidence interval: 1.0 to 2.7) and elevated CARPREG II scores (Canadian
Cardiac Disease in Pregnancy Study II) (odds ratio: 1.7; 95% confidence
interval: 1.5 to 1.9) independently correlated with increased odds of
cesarean delivery. Furthermore, obese women exhibited a higher incidence of
pre-eclampsia compared to those with normal weight (8% vs. 2%; p = 0.001).
These findings underscore the significant risks associated with obesity
during pregnancy, including elevated rates of cesarean delivery and a greater
prevalence of pre-eclampsia. This highlights the importance of addressing weight
management and health conditions both before and during pregnancy to optimize
maternal and fetal health outcomes. |
Discussion
Factors Influencing the Prognosis of
Heart Disease in Obesity
The Framingham Study has established obesity as a significant risk
factor for heart disease through extensive epidemiological research. However,
conflicting findings exist in various studies regarding whether obesity
directly causes heart disease independently. This systematic review
consolidates multiple scientific articles that investigate obesity and its
interactions with other factors influencing heart disease risk. The review
identifies several critical elements that impact the relationship between
obesity and heart disease, such as genetic predispositions, levels of physical
activity, presence of metabolic disorders like diabetes, history of prior heart
disease, nutritional status, distribution of body fat, and fluctuations in body
mass index. Together, these factors collectively contribute to determining the
overall risk of developing heart disease.
The systematic review highlights the
multifaceted impact of obesity on cardiovascular health, encompassing various
heart-related issues and clinical outcomes. The comprehensive analysis
synthesizes evidence from diverse studies to illustrate the intricate interplay
of factors contributing to the development and progression of heart disease.
Key aspects covered include:
- Cardiac Remodeling: Obesity leads to
structural and functional changes in the heart, including left ventricular
hypertrophy (LVH) and dilation, which can result in diastolic and systolic
dysfunction.
- Aortic Stenosis (AS): Obesity is
associated with an increased risk of aortic stenosis, which can further
exacerbate cardiovascular complications.
- Coronary Artery
Calcification (CAC): Excessive adipose tissue accumulation
is linked to increased coronary artery calcification, a significant risk
factor for coronary heart disease.
- Heart Function: Obesity affects
cardiac function by altering blood volume, plasma volume, and cardiac
output, leading to increased wall tension and potentially systolic
dysfunction.
- Clinical Events: Obesity is a major
risk factor for various cardiovascular events, including heart failure
(HF), coronary heart disease, cerebrovascular disease, hospitalization,
and mortality.
- Mortality: Obesity is
associated with increased morbidity and mortality rates, with a
significant impact on overall survival.
The review underscores the complex
interplay of factors that contribute to the development and progression of
heart disease in obese individuals, emphasizing the need for comprehensive
understanding and effective interventions to mitigate these risks.
Body Mass Index (BMI) as a Biomarker of Obesity
to Predict CVD
The
World Health Organization (WHO) defines obesity based on body mass index (BMI),
classifying individuals with a BMI above 30 kg/m² as obese. A comprehensive
study involving approximately 3.5 million participants in the UK categorized
them by BMI (underweight, normal-weight, overweight, and obesity) and metabolic
health status (presence of diabetes, hypertension, and hyperlipidemia). Over a
study period of 5.4 years, the research assessed the risk of cardiovascular
diseases (CVD), including coronary artery disease (CAD), cerebrovascular disease,
heart failure (HF), and peripheral vascular disease (PVD) among all
participants. The study found that individuals with obesity were at a higher
risk of developing these cardiovascular diseases compared to those with normal
weight or overweight. This underscores the importance of maintaining a healthy
BMI and metabolic health to reduce the risk of cardiovascular complications.
The study results
indicated that obese individuals without metabolic disorders faced
significantly higher risks compared to non-obese individuals without these
health issues. Specifically, they had a 49% increased risk of coronary artery
disease (CAD) (adjusted hazard ratio [aHR]: 1.49; 95% confidence interval [CI]:
1.45 1.54), a 7% higher risk of cerebrovascular disease (aHR: 1.07; 95% CI:
1.04 1.11), and nearly double the risk of heart failure (HF) (aHR: 1.96; 95%
CI: 1.86 2.06). These findings underscore the independent impact of obesity,
defined by BMI, on the incidence of major cardiovascular diseases, even in the absence
of metabolic health issues. They emphasize the critical need to address obesity
as a significant public health concern to mitigate the burden of cardiovascular
disease (CVD)
Two meta-analyses
involving large participant cohorts, totaling 250,016 and 414,587 individuals,
respectively, suggested an 'obesity paradox' in people with type 2 diabetes
mellitus (T2DM), where being overweight or obese seemed to offer protection
against cardiovascular disease (CVD). This paradox could be attributed to
limitations in these studies' ability to track different patterns of obesity
progression over time accurately. Polemiti et al.
These results imply
that although the obesity paradox might be observed in specific scenarios like
cardiovascular disease risk in type 2 diabetes, actively managing weight and
achieving BMI reductions could lower the risk of microvascular complications
associated with diabetes.
Other Obesity Biomarkers to Predict CVD
Obesity
poses a substantial risk for cardiometabolic diseases such as type 2 diabetes
mellitus (T2DM), cardiovascular disease (CVD), and various cancers, which are
increasingly recognized as significant global health challenges. While body
mass index (BMI) is commonly used to classify obesity, its effectiveness in
predicting cardiovascular disease risk has been questioned. BMI lacks
consideration for fat distribution and cannot differentiate between weight
gained from fat versus muscle mass. Consequently, researchers are currently
engaged in epidemiological investigations aimed at identifying obesity
biomarkers that offer more precise predictions of clinical outcomes across a
spectrum of cardiovascular diseases compared to BMI assessments.
Coronary artery disease (CAD) ranks among the primary causes of sudden
death worldwide, and the assessment of coronary artery calcification scores
(CACS) through CT scans is widely recognized for its reliability in detecting
CAD
Additionally, Tan et
al. (2022) conducted a prospective cohort study involving 970 participants with an average age of 73 ± 4 years, which revealed
a link between obesity and alterations in cardiovascular structure and
function. The research found that increased waist circumference (WC) independently
correlated with diminished cardiac function, as measured by VO2 max, and
impaired heart muscle relaxation, assessed using echocardiography to determine
the E/A ratio for diastolic left ventricular function. In contrast, body mass
index (BMI) did not demonstrate any association with compromised heart function
or structural cardiac changes.
Oh et al.
The findings indicated
that participants classified in the MUO group demonstrated the highest
likelihood of developing cardiovascular disease (CVD). Notably, individuals in
the MHO and MHNO groups showed comparable risks for CVD (HR: 1.29; 95% CI:
0.961.73). Importantly, using LBSIZ as a measure of body shape effectively
differentiated the risk of CVD, providing additional insights beyond
traditional BMI classifications and metabolic health status.
The Asian Sudden Cardiac Death in Heart Failure
(ASIAN-HF) registry encompassed 5,964 patients across 11 Asian countries,
including Taiwan, Hong Kong, China, India, Malaysia, Thailand, Singapore,
Indonesia, Philippines, Japan, and South Korea. This registry was conducted at
46 research centers and enrolled patients between October 1, 2016, and October
6, 2016. The registry aimed to investigate heart failure categorized into three
types based on systolic function: HFrEF (HF with reduced ejection fraction,
< 40%), HFmrEF (HF with mid-range ejection fraction, 40-49%), and HFpEF (HF
with preserved ejection fraction, ≥ 50%).
The ASIAN-HF study categorized patients into four groups based on
their body mass index (BMI) and waist-to-height ratio (WHtR): Obese-Thin (BMI
≥ 24.5 kg/m² and WHtR < 0.55), Overall Obese (BMI ≥ 24.5 kg/m²
and WHtR ≥ 0.55), Overall Lean (BMI < 24.5 kg/m² and WHtR < 0.55),
and Lean-Fat (BMI < 24.5 kg/m² and WHtR ≥ 0.55). Patients in the
Lean-Fat group were predominantly female (35.4%) and more likely to reside in
low-income countries (47.7%). They also exhibited a higher prevalence of
diabetes (46%) and reported a lower mean quality of life score (63.3 ± 24.2).
Furthermore, they experienced elevated rates of mortality and hospitalization
due to heart failure (22%).
Multivariate regression analysis revealed that individuals in the
Lean-Fat group faced the highest risk compared to the other categories
(adjusted hazard ratio [aHR] 1.93, 95% CI 1.173.18, p = 0.01). This heightened
risk was consistent across both HF with reduced ejection fraction (HFrEF) and HF
with preserved ejection fraction (HFpEF), indicating that the Lean-Fat
phenotype significantly influences heart failure outcomes. The findings suggest
that the Lean-Fat group, characterized by low BMI and high WHtR, is associated
with the worst outcomes in patients with heart failure, underscoring the
importance of considering both BMI and WHtR in assessing cardiovascular risk.
Other Factors that Can Predict CVD in Obesity
Conditions
Genetic
factors play a crucial role in determining susceptibility to obesity,
influenced by specific single nucleotide polymorphisms (SNPs) that impact
weight gain. Identified SNPs include FTO (rs9939609), MC4R (rs17782313), TMEM18
(rs6548238), BDNF (rs10767664), and GNPDA2 (rs10938397). These SNPs
collectively contribute to an unweighted allele score that categorizes
individuals based on the number of risk alleles they carry: 03 alleles (9% of
the population), four alleles (19%), 56 alleles (52%), and 710 alleles (20%).
Research
has shown that individuals with a higher genetic predisposition to obesity, as
measured by the number of alleles, tend to have a significantly higher body
mass index (BMI). Specifically, those in the 710 alleles group have a BMI that
is 0.87 kg/m² higher compared to those in the 03 alleles group. Furthermore,
each 1 kg/m² increase in BMI is associated with a higher risk of aortic valve
stenosis and replacement. The relative risks (RR) for these conditions are 1.52
(95% CI: 1.231.87) and 1.49 (95% CI: 1.072.08), respectively. Additionally,
each 1 kg/m² rise in BMI is correlated with a higher hazard ratio (HR) for
these conditions, with values of 1.06 (95% CI: 1.051.08) and 1.06 (95% CI:
1.031.08). These findings underscore the substantial influence of genetic
predisposition on health outcomes related to obesity, such as cardiovascular
disease.
Besides
genetic factors, several variables influence the risk of cardiovascular disease
(CVD) and related heart disorders, including malnutrition, physical activity
levels, and metabolic diseases. Obese individuals with malnutrition (defined as
BMI ≥ 25 kg/m² and serum albumin [SA] < 45 g/L) tend to show more
severe cardiac remodeling. This is indicated by a higher left ventricular mass
index (44.2 ± 1.52 vs. 33.8 ± 8.28 gm/m²) and relative wall thickness (0.39 ±
0.05 vs. 0.38 ± 0.06). They also typically exhibit poorer diastolic function,
characterized by lower tissue Doppler imaging velocity (TDI-e0: 7.97 ± 2.16 vs.
9.87 ± 2.47 cm/s), a higher E/e0 ratio (9.19 ± 3.01 vs. 7.36 ± 2.31), and
increased left atrial volume index (19.5 ± 7.66 vs. 14.9 ± 5.49 mL/m²),
compared to individuals with a normal BMI and higher SA levels. These findings
underscore the intricate interplay between obesity, nutritional status, and
cardiovascular health, underscoring the detrimental impact of malnutrition in
obese populations on both heart structure and function.
In a study by Pandey
et al.
In a study conducted
by Mongraw-Chaffin et al.
Individuals
classified as metabolically healthy obese (MHO) did not exhibit a statistically
significant association with cardiovascular disease (CVD) incidence compared to
metabolically healthy normal-weight individuals (MHN). However, nearly half of
those initially categorized as MHO experienced transitions to metabolic
syndrome (MetS) during the follow-up period, indicating an unstable MHO status.
Those with unstable MHO status showed a significantly increased risk of
developing CVD (odds ratio [OR]: 1.60, 95% CI 1.142.25) compared to
individuals who maintained stable MHO status. Additionally, there was a clear
dose-response relationship observed between the duration of MetS and the risk
of CVD: individuals with MetS detected during 1, 2, and 3 or more visits had
odds ratios (ORs) of 1.62 (95% CI 1.272.07), 1.92 (95% CI 1.482.49), and 2.33
(95% CI 1.892.87), respectively, indicating a progressively higher risk with
longer duration of MetS. This underscores the importance of considering the
stability of MHO status and the duration of MetS in assessing the risk of CVD
CONCLUSION
This research emphasizes that while obesity is linked to
cardiovascular disease (CVD) risk, this relationship is influenced by various
factors beyond BMI alone. Genetic predisposition, physical activity levels,
metabolic disorders, prior heart disease history, nutritional status, fat
distribution, and changes in BMI all play significant roles in determining the
prognosis of heart disease. BMI alone is insufficient to reliably predict CVD
risk due to its inability to differentiate between muscle mass and fat
accumulation. Studies underscore that metrics such as fat distribution
indicators (waist circumference, waist-to-height ratio, log-transformed body
shape index [LBSIZ], ratio of visceral adipose tissue [VAT] to subcutaneous
adipose tissue [SAT]) provide better predictive value for CVD risk in
individuals with obesity compared to BMI alone. Moreover, there remains a need
for further research to explore the specific cardiovascular risks associated
with obesity, particularly given the frequent co-occurrence of metabolic
disorders in obese individuals.
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