Asian Journal of Cardiology Research

6(4): 5-10, 2022; Article no.AJCR.85867

Short Chain Fatty Acids Level are Associated with

Lipid Profile in Patients with Coronary Slow Flow
Siti Adewiah a*, Muhammad Diah a, Azhari Gani a, Fauzi Yusuf b
and Azzaki Abubakar b
a
Division of Cardiology, Department of Internal Medicine, School of Medicine, Universitas Syiah
Kuala/ Dr. Zainoel Abidin Centre Hospital, Banda Aceh, Indonesia.
b
Division of Gastroenterology-Hepatology, Department of Internal Medicine, School of Medicine
Universitas Syiah Kuala/ Dr. Zainoel Abidin Centre Hospital, Banda Aceh, Indonesia.

Authors’ contributions

This work was carried out in collaboration among all authors. All authors read and approved the final
manuscript.

Article Information
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Received 28 January 2022

Accepted 07 April 2022
Original Research Article Published 11 April 2022

ABSTRACT
Background: The phenomenon of Coronary Slow Flow (CSF) is an angiographic clinical verity,
which is characterized by late opacification of the distal segments of the coronary artery without
having significant stenosis. However, a definite and reliable mechanism of CSF is still not known.
Short-chain fatty acids (SCFA) such as acetate, butyrate, and propionate are produced as a result
of the fermentation of indigestible dietary fibers in the gut by the microbiota. Many studies have
investigated the role of SCFA as a related signaling pathway in inflammation, glucose metabolism,
and lipid metabolism. In this study, we investigated the correlation between Short Chain Fatty
Acids and Lipid Profile serum in Patients with Slow Flow Coroner.
Materials and Methods: A cross sectional study was conducted at dr. Zainoel Abidin Hospital of
Banda Aceh. All consecutive patients scheduled for coronary angiography between July 2021 to
Desember 2021. CSF was diagnosed based on the Thrombolysis In Myocardial Infarction (TIMI)
frame count (TFC) of coronary flow. Data was obtained through laboratory examination and stool
samples. Stool samples were analyzed for SCFA (acetate, propionate, and butyrate acids) with
gas chromatography.
Results: The results of the present study indicate that SCFA, acetate, propionate, and valerate did
not show a significant correlation with lipid profile (P>0.05). The level of fecal butyrate was
negatively correlated with HDL (p=<0.05; r = -0.532).
Conclusions: Our study indicated that the level of butyrate was a moderate negative correlated
with HDL inpatient with slow flow coroner.
_____________________________________________________________________________________________________

*Corresponding author: Email: [email protected];

 Adewiah et al.; AJCR, 6(4): 5-10, 2022; Article no.AJCR.85867

Keywords: SCFA; lipid profile; coronary slow flow.

1. INTRODUCTION Infarction (TIMI) frame count method, described”

by Gibson et al (7). The whole blood were
“The phenomenon of Coronary Slow Flow (CSF) analyzed for fasting blood sugar (FBS), total
is an angiographic clinical verity, which is cholesterol (TC), triglycerides (TGs), high-density
characterized by late opacification of the distal lipoprotein cholesterol (HDL-C) and low-density
segments of the coronary artery without having a lipoprotein cholesterol (LDL-C).
significant stenosis” (1). Small vessel, diffuse
atherosclerosis, vascular inflammation, 2.2 Gas Chromatography Analysis of
endothelial dysfunction, and platelet aggregation Faecal SCFA Concentration
dysfunctions are some of the theories that have
been proposed to explain the pathophysiology of Stool samples were analysed for SCFA
CSF (2,3). “The gut microbiota has been concentration with gas chromatography (GC) as
demonstrated to have a key role in the described from a previous method (8). The
progression of atherosclerosis, but the exact amounts of acetate, propionate, butyrate and
mechanism remains unknown. Short-chain fatty valerate acids have been reported as mg/ml
acids (SCFAs), such as acetate, propionate, and and %.
butyrate, are metabolites created by bacterial
fermentation in the colon from otherwise 2.3 Statistical Analysis
indigestible polysaccharides (fibres)” (4). In
rodents and humans, SCFAs have been found to The results of the statistical analysis were
reduce plasma concentrations of cholesterol. presented as mean standard deviation or median
Propionate is being considered as a possible (interquartile range) for normally and non-
contender for decreasing plasma cholesterol normally distributed continuous variables, and
levels; however, the outcomes of trials evaluating number (percentages) for nominal variables,
are controversial (5,6). respectively. The Shapiro-Wilk test was
employed to determine whether the variable
2. MATERIALS AND METHODS distributions were normal. The intensity and
correlation between the two quantitative
2.1 Patients and Study Design variables were investigated using the Pearson
correlation test (in the case of a normal
This is a cross-sectional study that included fifty distribution) and Spearman's correlation test (in
patients from July 2021 to Desember 2021 in the the event of a non-normal distribution). All of the
Division of Cardiology, Internal Medicine tests were carried out at a 0.05 significance level.
Department, Faculty of Medicine, University of
Syiah Kuala, Banda Aceh and Cardiac 3. RESULTS
Catheterization Laboratory at dr. Zainoel Abidin
Hospital of Banda Aceh. Exertional chest pain A total of 50 patients joined in the study. Table 1
suggestive of stable angina pectoris or positive demonstrated the characteristics of the patients.
or inconclusive results of non-invasive screening Of these, 24 (48%) were male and the mean age
tests for myocardial ischemia had all led to of the studied population was 44.9 years old.
referral to coronary angiography. Among them, The mean of fecal concentrations of acetate,
the patients who had no coronary plaque disease propionate, butyrate, valerate, absolute butyrate
and having delayed coronary flow rate were and total SCFA were 58.13 %, propionate is
selected for the study. Individuals who had 21.67 %, valerate is 2.34%, absolute butyrate is
active antibiotic treatment or within the month 2.34 mg/ml, and total SCFAs is 15.40 mg/dl,
prior to angiography, yogurt consumption or respectively.
laxative medicine for the last four weeks or who
had undergone surgery for intestinal tumors were Table 2 presents the association between short-
excluded from the study. “All angiographic chain fatty acids (SCFAs) with Lipid Profile. TC,
examinations were conducted by two cardiologist LDL and TG not significantly correlated with
who were blinded to the clinical characteristics of SCFA but Pearson’s correlation revealed a
the patients assessed the flow in coronary significant inverse correlation between HDL and
arteries using the Thrombolysis in the Myocardial butyrate acids (r = -0.532; p=<0.05) (Fig. 1).

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Table 1. Characteristics of Subjects

Variable CSF (n=50)

Age (years) 44.93 ± 11.13
Sex, male female 24 (48%)/26 (52%)
2
BMI (kg/m ) 23,24±2,86
SBP (mmHg) 140 (109 – 191)
DBP (mmHg) 86 (63 – 148)
Hemoglobin (g/dl) 14.30 (10.5 – 16.6)
WBC (ul) 9900±2600
3
Platelet (10 /ul) 301 (150 – 406)
Neutrophil-lymphocyte count ratio 1.78 (0.81 – 7.3)
Total Cholesterol (mg/dl) 164 (117 – 297)
LDL cholesterol (mg/dl) 107.27 ± 27.79
HDL cholesterol (mg/dl) 47 ( 16 – 77)
Triglyceride (mg/dl) 91 (72 – 269)
Urea (mg/dl) 26.20 ± 10.4
Creatinin ( mg/dl) 1 (0.5 – 1.20)
Random blood glucose (mg/dl) 93.60 ± 17.43
Short Chain Fatty Acids (SCFA)
Acetate Acids (%) 58.13 ± 7.29
Propionate Acids (%) 21.67 ± 6.58
Butyrate Acids (%) 12.2 ± 3.7
Valerate Acids (%) 2.34 ± 0.98
Absolute Butyrate Acids (mg/dl) 2.34 ± 1.26
Total SCFAs (mg/dl) 15.40 ± 5.6
TIMI Frame Count
LAD (frame) 53,07±10,35
LCX (frame) 50,20±9,6
RCA (frame) 60,73±12,30
Data were presented as mean±SD, median (minimum-maximum) or n (%). BMI: Body Mass Index; SBP: Systolic
Blood Pressure; DBP: Diastolic Blood Pressure; ESR: Erythrocyte Sedimentation Rate; LDL: Low-density
Lipoprotein; HDL, High-density Lipoprotein. RCA: Right Coronary Artery; LCx: Left Circumflex Artery; LAD: Left
Anterior Descending Artery; TIMI: Thrombolysis in Myocardial Infarction Frame Count

Fig. 1. A negative correlation between butyrate acids with High-density Lipoprotein (HDL)

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 Adewiah et al.; AJCR, 6(4): 5-10, 2022; Article no.AJCR.85867

Table 2. The associations between short-chain fatty acids (SCFAs) with Lipid Profile

TC LDL HDL TG
r (P value) r (P value) r (P value) r (P value)
Acetate Acids 0.063(0.823) 0.168(0.55) 0.325(0.237) 0.331(0.228)
Propionate Acids 0.081(0.773) -0.327(0.234) 0.003(0.992) -0.472(0.076)
Butyrate Acids -0,230 (0.410) -0.188(0.503) -0.532(0.041)* -0.033(0.907)
Valerate Acids -0.135(0.631) -0.026(0.926) -0.275(0.321) 0.409(0.130)
Absolute Butyrate Acids -0.280(0.312) -0.437(0.103) -0.1(0.722) -0.394(0.146)
Total SCFAs -0.108(0.701) -0.354(0.196) 0.379(0.163) -0.506(0.055)
*: p value correlation is significant at 0.05 level, r: Pearson’s correlation coefficient

4. DISCUSSION (16,17). In rat colonic epithelial cells that convert

SCFAs to acetyl-CoA, Zambell et al. discovered
The gut microbiome is a growing topic of that acetate and butyrate are the predominant
“
research in metabolic health and its link to CVD synthetic lipid substrates (18). Finally, acetate,
risk (9). “SCFAs are produced by the microbiota propionate, and butyrate appear to promote
through the fermentation of ingestible hepatic cholesterol uptake from the circulation,
polysaccharides and proteins, and are thought to decreasing plasma cholesterol in model animal
represent the link between the microorganisms experiments. Furthermore, propionate inhibits
and the host. Individual SCFAs have also been cholesterol production effectively” (19).
shown to play a role in metabolism; for example,
acetic acid supplementation reduces weight gain According to Granado-Serrano et al., participants
and improves glucose tolerance in obese people with hypercholesterolemia had higher
and diabetic rats” (10), “butyric acid protects abundances of Odoribacter (Bacteroidetes) and
against obesity and increases thermogenesis in Ruminococcus (Firmicutes) and lower
mice” (11), and “propionic and butyric acids abundances of Anaeroplasma (Tenericutes) and
improve glucose homeostasis in mice” (12). “By Haemophilus influenzae (Proteobacteria) (20).
interacting with the diet, changes in the gut Fu et al. found a negative connection between
microbiota disrupt not only metabolism but also TG levels and the Pasteurellaceae genus (21).
the composition of the host's lipids” (13). Anaeroplasma abundance was also linked to an
Dyslipidaemia has changed with SCFA, unfavorable lipid profile (IDL-C, TG-related
especially HDL. According to our findings, HDL biomarkers and the ratio Total-C to HDL-C
is negatively correlated with butyrate acid in a among others) (20). The level of acetic acid in
patient with slow flow coroner. the feces was linked to IDL-C levels, which are
linked to a more unfavorable lipid profile, but not
“Gut dysbiosis is generally characterized by a propionic acid. Although there were no significant
decrease in microbial population diversity and differences in serum levels of acetic and
stability, and blooms in certain harmful bacteria” propionic acids between groups,
(14). “Insulin resistance and abnormal level of hypercholesterolemia showed a profile with
short chain fatty acids (SCFAs) can occur from higher and lower abundance of acetic and
the metabolic network within the host harboring propionic acids, respectively, than
dysbiotic microorganisms being altered in situ” normocholesterolemia. “These findings are in line
(11). The phylum Firmicutes produces butyric with prior research that found that circulating
acid, the phylum Bacteroidetes produces acetic acid stimulated "de novo" lipogenesis and
propionic acid, and the majority of anaerobic cholesterogenesis in the liver, while propionic
bacteria make acetate (15). acid inhibited it” (20-23). There was no significant
link between the lipid profile and the examined
Short-chain fatty acids appear to play a role in SCFA, acetate, propionate, and valerate in our
the regulation of fatty acid, glucose, and study.
cholesterol metabolism in cells. SCFAs have the
ability to control lipolysis and adipogenesis. A study by Granado-Serrano et al reported that
Endogenous lipolysis is inhibited by acetate and “there was no difference in the abundance of
propionate, whilst extracellular lipolysis is butyrate in feces between hypercholesterolemia
regulated by propionate via a rise in lipoprotein and normocholesterolemia,and there was no
lipase production, resulting in a decrease of the association with any of the lipid biomarkers
circulating lipid plasma levels and body weight studied. However, in normocholesterolemia, its

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 Adewiah et al.; AJCR, 6(4): 5-10, 2022; Article no.AJCR.85867

serum levels were greater, indicating a negative COMPETING INTERESTS

relationship with lipids associated with a worst
profile, such as LDL-C, Total-C, LDL-TG, LDL-P Authors have declared that no competing
(large and small), and Total-C to HDL-C ratio interests exist.
among others” (20). Butyrate has been shown to
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