Received: 31 March 2023 | Revised: 17 July 2023 | Accepted: 17 August 2023
DOI: 10.1002/hsr2.1535
OR I G I NA L R E S E A R CH
Blood C‐peptide concentration as a proxy marker
of cardiovascular disease: An observational
cross‐sectional study
Laurinda Adusu‐Donkor1,2 | Emmanuel Kwaku Ofori1 | Fleischer C. N. Kotey3,4 |
Francis Kwaku Dogodzi1 | Wormenor Dziedzorm1 | Alfred Buabeng1 |
Segla Kwame Bernard1 | Seth K. Amponsah5 | Henry Asare‐Anane1
1Department of Chemical Pathology, U.G.M.S,
University of Ghana, Accra, Ghana Abstract
2Department of Chemical Pathology, Background and Aims: Cardiovascular diseases (CVDs) are among the leading causes
37 Military Hospital, Accra, Ghana
of disability and early death in sub‐Saharan Africa. Most of the current blood tests
3Department of Medical Microbiology,
U.G.M.S, University of Ghana, Accra, Ghana for CVD diagnosis involve performing about three test profiles; often at additional
4FleRhoLife Research Consult, Accra, Ghana cost to patients. C‐peptide, a cleavage product of proinsulin, is a promising marker
5Department of Medical Pharmacology, that has the potential to serve as a proxy marker for diagnosing CVDs in resource‐
U.G.M.S, University of Ghana, Accra, Ghana poor settings.
Correspondence Methodology: The study was an observational cross‐sectional one and involved
Emmanuel Kwaku Ofori, Department of 127 consenting persons diagnosed with CVD and 127 individuals without CVD.
Chemical Pathology, U.G.M.S, University of
The socio‐demographic and clinical characteristics of participants were obtained.
Ghana, Accra, Ghana.
Email: ekofori1@ug.edu.gh Blood levels of C‐peptide, fasting plasma glucose (FPG), total creatinine kinase
(CK), creatine kinase myocardial bound (CKMB), lactate dehydrogenase (LDH),
propeptide of brain natriuretic peptide (PBNP), Troponin T, lipids, and biomarkers
of kidney and liver function were analyzed using ELISA and an automated analyzer.
Insulin resistance was computed using the modified homeostatic model assess-
ment (HOMA‐IR).
Results: The CVD Group had significantly higher levels of C‐peptide, CK, CKMB,
troponin T, PBNP, FPG, HOMA‐IR, and several selected kidney, liver, and lipid
parameters compared to the non‐CVD Group (p < 0.05 for all). TroponinT recorded
a positive correlation (r = 0.34, p < 0.001) with C‐peptide among the CVD Group.
The sensitivity and specificity of C‐peptide in identifying CVD were 96.1% and
91.3% respectively (area under the curve = 0.938, p < 0.001).
Conclusion: C‐peptide levels were higher in the CVD Group and appeared to be a
valuable (high sensitivity and specificity) biomarker in detecting CVD.
K E YWORD S
cardiovascular disease, C‐peptide, diabetes, inflammation, insulin resistance
This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License, which permits use, distribution and reproduction in any
medium, provided the original work is properly cited and is not used for commercial purposes.
© 2023 The Authors. Health Science Reports published by Wiley Periodicals LLC.
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https://doi.org/10.1002/hsr2.1535
2 of 9 | ADUSU‐DONKOR ET AL.
1 | INTRODUCTION
Key points
Cardiovascular diseases (CVDs) are a group of disorders of the
• Cardiovascular diseases (CVDs) are primary contributors
heart and blood vessels and comprise both atherosclerotic (such
to both disability and early death in sub‐Saharan Africa.
as coronary artery disease [CAD], cerebrovascular disease, and
Most of the current blood tests for CVD diagnosis
peripheral artery disease) and non‐atherosclerotic disorders (e.g.,
involve performing about three test profiles often at
venous thromboembolism, valvular, rheumatic, and congenital
additional cost to patients.
heart diseases [CHD]).1,2 CVDs are a major cause of death in both
• C‐peptide, a product of proinsulin, could potentially
industrialized and developing countries.3,4 Mortality attributed to
serve as a proxy marker for diagnosing CVDs in
CVDs, which was estimated to be 17.9 million in 2015, is
resource‐poor settings.
projected to rise to more than 23.6 million by the year 2030.5
• The sensitivity and specificity of C‐peptide in identifying
Aside from contributing to early mortality, CVDs are responsible
CVD in this study were 96.1% and 91.3%, respectively
for incapacitation to work, decreased family income, and dimin-
(area under the curve = 0.938, p < 0.001).
ished productivity.6 Over the years, the prevalence, morbidity,
and mortality associated with CVDs have risen in Sub‐Saharan
African.7 More than 60% of CVD‐related deaths in Africa occur in
adults aged 30–65 years old, which is about 10 years younger 2 | MATERIALS AND METHODS
than the average bracket age of mortality for people in the
industrialized world.7,8 2.1 | Study design, site, and participants
The incidence of CVD tends to increase with age, and several
modifiable risk factors, including alcohol misuse, sedentariness, This was an observational cross‐sectional study conducted at the
excessive weight gain, and tobacco use continue to be associated 37 Military Hospital, Accra, Ghana. A total of 354 consenting
with CVD development and progression.9 The growing incidence volunteers, comprising 127 with CVD and 127 without CVD, were
of CVDs in sub‐Saharan Africa highlights the importance of recruited. The Ethical and Protocol Review Committee (EPRC) of the
investigating potential markers that could assist in early diagnosis. College of Health Sciences at the University of Ghana approved this
The majority of the currently available blood diagnostic tests for study (ID: CHS‐Et/M.4‐5.6/2020‐2021). Additionally, permission
CVD diagnosis include at least three test profiles. These tests are was obtained from the Management at the 37 Military Hospital.
not readily available, costly, and out of reach for most people in Clinicians at the hospital referred potential participants to the
resource‐poor settings. research team, after which the objectives, rationale, and outcomes
Connecting peptide (C‐peptide) is a 31‐amino‐acid cleavage of the study were explained. Those willing to participate in the study
precursor of the production of insulin. C‐peptide was previously were offered appointment dates and times. Those who refused to
thought to be a physiologically inactive molecule.10 It is released participate in the experiment or expressed reservations were
into the bloodstream at the same concentration as insulin, but in allowed to continue receiving their customary care at the hospital.
contrast to insulin, it undergoes only a tiny amount of first‐pass Patients who had a severe condition that required immediate
metabolism in the liver.11,12 Importantly, C‐peptide has been medical attention, such as severe chest pain, altered mental status,
associated with inflammation and is touted to have a protective breathing difficulties, and persistent bleeding, were excluded from
role in blood glucose metabolic disorders in both humans and the study. The volunteers were to fast for 8–12 h overnight.
rats.13–15 This peptide and related inflammatory mechanisms Participants in the Control Group were seemingly healthy, between
have also been implicated in conditions such as obesity,16 the ages of 18 and 65, and free of any CVD, diabetes, or any severe
metabolic syndrome,17 hypertension,18 and hepatosteatosis.15,19 condition that required immediate medical attention. The partici-
This has led to an increase in the clinical usefulness of C‐peptide, pants were instructed to complete a questionnaire that had
as it may readily exhibit hormone‐like properties and offer information on socio‐demographic and clinical information; age,
promise as a diagnostic marker in pathologies such as CVDs. gender, weight and height, educational level, lifestyle (degree of
Although data shows that there is some relationship between cigarette usage, alcohol intake), and medical history (personal or
C‐peptide and CVDs in the Caucasian population, there is sparse family history of CVD). A minimum sample size of 100 participants
data among sub‐Saharan Africans. Furthermore, the majority was adequate for this study.
of the existing data supporting C‐peptide as a possible CVD
marker have been derived from diabetic patients. These data
are insufficient to validate the use of C‐peptide as a diagnostic 2.2 | Clinical assessment and laboratory
marker for CVD. This study, therefore, aimed to evaluate the procedures
role of blood C‐peptide in the detection of CVDs among
Ghanaians and to elucidate factors that contribute to the Blood pressure was measured with an OMRON digital sphygmo-
incidence of CVDs. manometer (OMRON HEALTHCARE Company Limited). Height
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ADUSU‐DONKOR ET AL. | 3 of 9
and weight were assessed using a digital stadiometer and an TABLE 1 Socio‐demographic and clinical (categorical)
electronic digitized scale (both from SECA). Venous blood characteristics of the study participants.
samples (5 mL) were taken from each study participant, after CVD group Control group
which 3 mL was placed in a serum separator tube and 2 mL in a Features Number % Number % p value
sodium fluoride tube. Samples in the serum separator tubes were
Gender
allowed to clot for 10–20 min before centrifugation at 3000 rpm
for 10 min (at room temperature) together with the samples in the Female 58 45.7 58 45.7 0.71
sodium fluoride tubes. The sera and plasma were aliquoted into Male 69 54.3 69 54.3
0.5 mL Eppendorf tubes and stored at −20°C until analysis. The Marital status
plasma was used to determine fasting blood glucose (FPG)
Single 35 27.6 105 82.7 <0.001
whereas the serum was used to assess liver function [aspartate
Married 72 56.7 22 17.3
aminotransferase (AST), alanine aminotransferase (ALT), alkaline
phosphatase (ALP), gamma‐glutamyl transferase (GGT), total Widowed 10 7.9 0 0.0
bilirubin (TBIL), direct bilirubin (DBIL), total proteins, and Divorced 10 7.9 0 0.0
albumin], kidney function (sodium, potassium, chloride, urea,
Educational level
creatinine), lipids [total cholesterol, triglycerides and high‐density
None 5 3.9 0 0.0 0.01
lipoproteins cholesterol (HDL)], total creatinine kinase (CK),
creatine kinase myocardial bound (CKMB) and lactate dehy- Basic 19 15.0 3 2.4
drogenase (LDH) concentrations using dry reagent slides from the Secondary 37 29.1 45 35.4
VITROS 5.1FS Chemistry Autoanalyser (Ortho Clinical Diagnos-
Tertiary 66 52.0 79 62.2
tics, Neckargemünd, Germany). The Sandwich enzyme‐linked
Occupation
immunosorbent assay (ELISA) method was used to analyze serum
concentrations of C‐peptide, troponin T, and propeptide of brain Unemployed 7 5.5 2 1.6 0.79
natriuretic peptide (PBNP) on a micro‐ELISA strip‐plate analyzer Student 1 0.8 3 2.4
(SUNLONG BIOTECH Company Limited) pre‐coated with an National service 0 0.0 5 3.9
antibody specific to these tests. The modified homeostasis model personnel
assessment for insulin resistance (HOMA‐IR) formula was used to Retired 28 22.0 5 3.9
measure insulin resistance (IR) as previously described.20 Low‐
Military personnel 13 10.2 92 72.4
density lipoprotein cholesterol (LDL) was derived using Frielde-
wald's equation.21 The coronary risk was computed as a ratio of Trader 41 32.3 8 6.3
total cholesterol and HDL cholesterol. Finance officer 4 3.1 5 3.9
Healthcare worker 4 3.1 0 0.0
Artisan 9 7.1 0 0.0
2.3 | Statistical analysis
Civil servant 5 3.9 2 1.6
Teacher 15 1.8 5 3.9
STATA, version 14, was used to analyze the data. The biodata of
the participants was summarized using descriptive statistics and Monthly family income (in Ghana cedis)
the normality of the data determined by the Shapiro–Wilk test. ≤500 45 35.4 51 40.2 0.18
The biochemical parameters of the participants with CVD were
501–1000 35 27.6 30 23.6
compared to those without CVD using independent‐sample
1001–2000 4 3.1 7 5.5
t tests. Associations between these biochemical parameters and
C‐peptide levels were determined separately for the CVD and >2000 43 33.9 39 30.7
control participants using Pearson's product‐moment correlation. Family history of CVD
Furthermore, the sensitivity, specificity, accuracy, positive predic-
No 31 24.4 55 43.3 <0.001
tive value, and negative predictive value of C‐peptide in
Yes 86 67.7 33 26.0
distinguishing between CVD and non‐CVD participants were
determined, as previously described.22 These analyses were Unsure 10 7.9 39 30.7
bolstered by plotting a receiver operating characteristic (ROC) Smoking status
curve and computing Kappa's measure of agreement between the
No 120 94.5 125 98.4 0.09
C‐peptide‐based diagnosis and the reference CVD diagnosis of
Yes 7 5.5 2 1.6
the participants. All inferential statistics were performed at a 0.05
alpha level. (Continues)
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4 of 9 | ADUSU‐DONKOR ET AL.
TABLE 1 (Continued) 3 | RESULTS
CVD group Control group
3.1 | Sociodemographic and clinical (categorical)
Features Number % Number % p value
features of the study participants
Alcohol consumption status
No 105 82.7 114 89.8 0.10 The socio‐demographic and clinical (categorical) characteristics of the
Yes 22 17.6 13 10.2 participants are shown inTable 1. In this study, 127 individuals with CVD
(Case Group) and 127 individuals without CVD (Control Group) were
Note: The sociodemographic and clinical (categorical) characteristics of the
study participants. % = percentages. recruited. Each of these Groups had identical distributions for males
Abbreviation: CVD, cardiovascular diseases. (54.3%, n=69) and females (45.7%, n=58) respectively. In both Groups,
TABLE 2 Comparison of clinical (continuous) and biochemical parameters of the study participants.
CVD group Control group
Features x̄ ± SD x̄ ± SD 95% CI p value
Clinical/metabolic
Age (years) 57.18 ± 14.74 56.20 ± 13.60 −2.52 to 4.49 0.58
BMI (Kg/m2) 37.59 ± 8.58 24.83 ± 3.28 11.15 to 14.37 <0.001
Systolic blood 131.71 ± 23.87 98.54 ± 11.00 28.57 to 37.76 <0.001
pressure (mmHg)
Diastolic blood 89.27 ± 14.04 74.96 ± 10.79 11.21 to 17.40 <0.001
pressure (mmHg)
Insulin resistance 1.74 ± 0.20 1.55 ± 0.02 0.16 to 0.23 <0.001
C peptide (ng/mL) 6.75 ± 4.57 1.56 ± 0.69 4.39 to 6.00 <0.001
FPG (mmol/L) 5.44 ± 2.58 4.41 ± 0.49 0.57 to 1.49 <0.001
Cardiac parameters
Total Creatine kinase (U/L) 141.06 ± 86.56 51.21 ± 26.40 74.04 to 105.72 <0.001
CKMB (U/L) 66.95 ± 30.60 14.09 ± 5.60 47.40 to 58.30 <0.001
LDH (U/L) 56.30 ± 11.85 51.32 ± 29.98 −0.67 to 10.62 0.08
Troponin T (ng/L) 1.06a ± 0.73 0.31 ± 0.08 0.62 to 0.88 <0.001
PBNP (pg/mL) 176.42 ± 136.84 103.22 ± 23.84 18.66 to 54.17 <0.001
Coronary risk 4.25 ± 1.17 3.28 ± 0.59 0.75 to 1.21 <0.001
Liver parameters
AST (U/L) 27.23 ± 14.93 23.47 ± 11.06 0.51 to 7.00 0.02
ALT (U/L) 27.58 ± 15.89 20.20 ± 10.63 4.04 to10.72 <0.001
GGT (U/L) 55.26 ± 36.69 28.96 ± 11.27 19.59 to 33.07 <0.001
TBIL (mg/dL) 12.92 ± 8.13 13.15 ± 7.15 −2.12 to 1.66 0.81
DBIL (µmol/L) 5.47 ± 3.48 4.85 ± 2.12 −0.09 to 1.33 0.09
Total protein (g/L) 71.16 ± 15.33 77.21 ± 6.08 −8.94 to −3.17 <0.001
ALP (U/L) 81.39 ± 34.88 63.29 ± 18.07 11.23 to 24.96 <0.001
Albumin (g/L) 40.73 ± 5.08 46.08 ± 2.57 −6.34 to −4.35 <0.001
Kidney parameters
Sodium (mmol/L) 140.44 ± 5.34 140.26 ± 4.54 −1.04 to 1.41 0.77
Potassium (mmol/L) 3.97 ± 0.59 4.33 ± 0.64 −0.51 to −0.20 <0.001
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ADUSU‐DONKOR ET AL. | 5 of 9
TABLE 2 (Continued)
CVD group Control group
Features x̄ ± SD x̄ ± SD 95% CI p value
Chloride (mmol/L) 102.57 ± 6.09 106.46 ± 2.00 −5.01 to −2.77 <0.001
Urea (mmol/L) 7.03 ± 5.29 3.81 ± 0.09 2.28 to 4.15 <0.001
Creatinine (µmol/L) 123.02 ± 69.88 94.87 ± 16.43 15.55 to 40.74 <0.001
Lipid parameters
Total cholesterol (mmol/L) 5.41 ± 1.11 4.47 ± 0.52 0.73 to 1.15 <0.001
Triglycerides (mmol/L) 1.56 ± 0.71 0.75 ± 0.27 0.68 to 0.94 <0.001
HDL (mmol/L) 1.43 ± 0.36 1.40 ± 0.21 −0.04 to 0.10 0.42
LDL (mmol/L) 3.28 ± 1.19 2.74 ± 0.52 0.32 to 0.77 <0.001
VLDL (mmol/L) 0.71 ± 0.32 0.34 ± 0.13 0.31 to 0.43 <0.001
Note: A comparison of levels of C‐peptide and other biochemical and clinical (continuous) parameters of the study participants. Data presented as mean
(x̄), SD = standard deviation.
Abbreviations: ALT, alanine aminotransferase; AP, alkaline phosphatase; AST, aspartate aminotransferase; BMI, body mass index; CI, confidence interval;
CKMB, creatinine kinase myocardial bound; DBIL, direct bilirubin; FPG, fasting plasma glucose; GGT, gamma glutamyl transferase; HDL, high‐density
lipoprotein cholesterol; LDH, lactate dehydrogenase; LDL, low‐density lipoprotein cholesterol; PNBP, propeptide of brain natriuretic peptide; TBIL, total
bilirubin; VLDL, very low‐density lipoprotein.
aSignificant at 0.05 alpha level.
the majority of the participants had tertiary education [CVD Group cardiac, liver, kidney, and lipid biomarkers among individuals with or
(52.0%); Control Group (62.2%)]. In the CVD Group, retired individuals without CVDs. The levels of troponinT in the CVD Group were found
and traders, as a composite, made up the highest proportion (54.3%) with to be associated with C‐peptide levels (r = 0.34, p < 0.001). In the
regard to participant occupation, whereas in the Control Group, it was Control Group, GGT showed a weak relationship with C‐peptide
military personnel who dominated (72.4%). Again, 67.7% of the participa- levels (r = 0.19, p = 0.04). The correlation analysis is shown inTable 3.
nts in the CVD Group reported having a family history of CVD, compared
to 26% in the Control Group. Majority of the participants were non‐
smokers [CVDGroup=94.5%; Control Group =98.4%)] and did not cons- 3.4 | Performance of the C‐peptide as a CVD
ume alcohol [CVD Group=82.7%; Control Group =89.8%)] (Table 1). diagnostic marker
As observed inTable 4, the sensitivity, specificity, accuracy, positive
3.2 | Clinical (continuous) and biochemical predictive value, and negative predictive value of C‐peptide in
parameters of study participants distinguishing between CVD and non‐CVD participants ranged
between 91.3% and 96.1%. The ROC curve (Figure 1) showed high
The independent‐sample t test conducted to compare the clinical sensitivity and specificity. The area under the curve (AUC) for the
(continuous) and biochemical parameters of the study participants is model was large (AUC = 0.938, p < 0.001; SE = 0.017; 95% confi-
shown in Table 2. C‐peptide, FPG, HOMA‐IR, urea, creatinine, total dence interval = 0.90–0.97). Furthermore, the Kappa measure
CK, CKMB, troponin T, PBNP, ALT, ALP, total cholesterol, triglycer- (k = 0.874, p < 0.001) indicated a high degree of agreement between
ides, LDL, very low‐density lipoprotein cholesterol (VLDL), coronary the C‐peptide assay and the reference CVD diagnosis.
risk, systolic, and diastolic blood pressure levels were higher
(p < 0.001, respectively) whereas potassium, chloride, total protein
and albumin were lower (p < 0.001 for all) in the CVD Group when 4 | DISCUSSION
compared with the Control group.
The present investigation sought, among others, to compare the
levels of C‐peptide in individuals with and without CVD. Participants
3.3 | Associations between levels of C‐peptide and in the CVD Group had considerably higher C‐peptide levels (Table 2),
other biochemical markers corroborating the findings of Li et al.,23 where C‐peptide was strongly
associated with cardiovascular risk factors. Further, Harnishsingh and
The Pearson product‐moment correlation was conducted to deter- colleagues found a relationship between C‐peptide levels, disease
mine associations between the levels of C‐peptide and several severity, and the existence of CAD.24 Other studies have found
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6 of 9 | ADUSU‐DONKOR ET AL.
TABLE 3 Associations between levels of C‐peptide and other TABLE 4 Performance of the C‐peptide assay as a CVD
biochemical markers. diagnostic marker.
CVD group Control group Metric Score (%)
Features r p r p Sensitivity 96.1
Cardiac parameters Specificity 91.3
Total creatine kinase 0.02 0.80 −0.09 0.33 Accuracy 93.7
Creatine kinase myocardial −0.16 0.86 −0.12 0.20 Positive predictive value 91.7
bound
Negative predictive value 95.9
Lactate dehydrogenase −0.03 0.73 0.04 0.67
Note: The performance of C‐peptide as a diagnostic marker of CVD.
Troponin T 0.34 0.001 0.07 0.41 The Kappa (k) measure was 0.874 (p < 0.001).
Propeptide of brain −0.10 0.25 0.10 0.26 Abbreviation: CVD, cardiovascular diseases.
natriuretic peptide
Coronary risk −0.14 0.12 0.13 0.14
contributes to the expanding body of knowledge supporting the use
Liver parameters of C‐peptide as a stand‐in biomarker for CVD. In this study,
Aspartate aminotransferase 0.05 0.57 0.01 0.87 C‐peptide had high specificity (96.1%) and sensitivity (91.3%),
Alanine aminotransferase −0.07 0.43 0.06 0.49 indicating its potential as a CVD diagnostic marker. Any good
biomarker for any disease should be simple to assess and must have
Gamma‐glutamyl transferase −0.10 0.25 0.19 0.04
high precision and accuracy. A prior study used C‐peptide with a
Total bilirubin −0.16 0.08 −0.09 0.31 sensitivity of 83% and specificity of 89% to discriminate T1DM from
Direct bilirubin −0.17 0.06 −0.12 0.18 T2DM in pediatric diabetes typology.30
Total protein −0.02 0.82 −0.03 0.72 This study also evaluated the levels of various cardiac, lipids, liver
and kidney biomarkers between the two study groups, as well as their
Alkaline phosphatase 0.01 0.94 0.01 0.95
relationship with C‐peptide. Participants with CVD exhibited signifi-
Albumin −0.06 0.51 0.07 0.43
cantly higher levels of cardiac biomarkers in this study and
Kidney parameters corroborated previous studies,31,32 lending credence to the fact that
Sodium 0.03 0.75 0.13 0.13 our Case Group was indeed persons with CVD. Importantly, troponin
T showed a significant association with C‐peptide levels in the CVD
Potassium 0.07 0.45 −0.10 0.27
Group. Cardiac troponins are key diagnostic markers for CVD.33 The
Chloride 0.07 0.42 0.08 0.38
observation of a positive association between troponin T (considered
Urea −0.07 0.45 −0.13 0.16 a key marker of MI and by extension, CVD) and C‐peptide levels are
Creatinine −0.01 0.91 −0.04 0.63 further evidence of the potential appropriateness of C‐peptide in
CVD. However, C‐peptide levels did not correlate with the other
Lipid parameters
established CVD diagnostic markers like CK, CKMB, and PBNP.
Total cholesterol −0.11 0.23 0.11 0.23
In the current study, the findings that patients with CVD had
Triglycerides −0.02 0.83 0.04 0.66 higher levels of total cholesterol, triglycerides, and LDL confirms
High‐density lipoprotein 0.13 0.14 −0.08 0.39 earlier observations.34–36 The combined action of these lipid
cholesterol biomarkers has been linked to plaque development and CVD
Low‐density lipoprotein −0.13 0.13 0.12 0.19 progression.37,38 Indeed, whiles raised HDL levels are connected
cholesterol to lower CVD risks, high levels of LDL have long been linked to
Very low‐density lipoprotein −0.02 0.85 0.03 0.70 increased CVD risk. HDL is known to create an enabling environ-
cholesterol ment for endothelial repair and function improvement, as well as
Note: Associations between levels of C‐peptide and other biochemical decrease inflammation, vascular thrombosis, and oxidation.
39,40
parameters of the study participants; significant at 0.05 alpha level, Among the liver function biomarkers ALT, AST, ALP, and GGT
r = Pearson's correlation coefficient. were higher in the CVD Group than in the Control Group, and these
results were consistent with other studies.41,42 Wannamethee et al.43
for instance, investigated the link between ALP and CVD as well as
significant relationships between C‐peptides, cardiovascular events, total mortality in older adults. In that study, a retrospective
and mortality.25,26 assessment was performed on a total of 3381 patients who had
Basal C‐peptide levels have also been linked with carotid artery stable angina pectoris. During their hospitalization, their ALP levels
intima‐media thickness in T2DM patients27,28 and myocardial infarc- were measured by an automated analyzer. A link was found by the
tion (MI) in the general population.29 As such, the current study researchers between ALP levels versus systolic blood pressure and
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ADUSU‐DONKOR ET AL. | 7 of 9
F IGURE 1 ROC curve for C‐peptide in
detecting CVD. CVD, cardiovascular diseases;
ROC, receiver operating characteristic curve.
DM.43 The CVD group had higher urea and creatinine levels could, thus, potentially be a cost‐effective CVD diagnostic‐cum‐
compared with the control Group. Indeed, CVD and kidney disease prognostic tool, particularly, in resource‐limited settings. None-
are inexorably intertwined. Instability in one organ encourages theless, further research is needed to understand the role
dysfunction in the other, eventually leading to the loss of both C‐peptide plays in health and disease.
organs.
This study does have some limitations. The fact that this research AUTHOR CONTRIBUTIONS
was conducted using a cross‐sectional methodology places restric- Laurinda Adusu‐Donkor: Conceptualization; Data curation; Funding
tions on the degree to which C‐peptide could be considered a acquisition; Investigation; Writing—original draft. Emmanuel Kwaku
potential contributor to the observed relationships seen. To deter- Ofori: Conceptualization; Supervision; Validation; Writing—original
mine whether or not our findings are the product of causal draft; Writing—review & editing. Fleischer C N Kotey: Formal
connections, follow‐up data will be extremely helpful. Because of analysis; Software; Writing—review & editing. Francis Kwaku
time constraints as well as the specific characteristics of the CVD Dogodzi: Data curation; Methodology. Wormenor Dziedzorm: Data
Group that were being targeted, it was not possible to sample a larger curation; Investigation; Methodology. Alfred Buabeng: Data curation;
number of study participants. In this particular study, dietary habits Investigation; Methodology. Segla Kwame Bernard: Data curation;
and overall levels of physical activity were not taken into considera- Investigation; Methodology. Seth K Amponsah: Validation; Writing—
tion and could be incorporated in the design of future studies. The review & editing. Henry Asare‐Anane: Conceptualization; Supervi-
procedure called a hyperinsulinemic‐euglycaemic clamp, which is sion; Writing—original draft.
used to determine glucose disposal rates, is the ideal measure of
insulin sensitivity rather than the calculated HOMA‐IR used. ACKNOWLEDGMENTS
These limitations notwithstanding, it is noteworthy that this We are grateful to all who volunteered to participate in the research.
study is among the few to have evaluated the diagnostic potential of The authors would like to also appreciate the staff of the Chemical
C‐peptide among sub‐Saharan Africans, and its findings fill important Pathology Unit, 37 Military Hospital, Accra Ghana. In addition, we
epidemiological gaps. express our gratitude to the Department of Chemical Pathology,
In conclusion, the Group that had CVD had higher circulating University of Ghana for the institutional assistance provided.
levels of C‐peptide, and this peptide was demonstrated to be a
good biomarker in cardiovascular illnesses, with sensitivity and CONFLICT OF INTEREST STATEMENT
specificity scores of 96.1% and 91.3%, respectively. C‐peptide The authors declare no conflicts of interest.
 23988835, 2023, 9, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/hsr2.1535 by University of Ghana - Accra, Wiley Online Library on [02/10/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
8 of 9 | ADUSU‐DONKOR ET AL.
DATA AVAILABILITY STATEMENT 14. Flynn ER, Lee J, Hutchens Jr. ZM, Chade AR, Maric‐Bilkan C.
Emmanuel Kwaku Ofori and Fleischer C. N. Kotey have full access to C‐peptide preserves the renal microvascular architecture in the
streptozotocin‐induced diabetic rat. J Diabetes Complications.
the data and will make the datasets that were used throughout this
2013;27(6):538‐547.
study available to the interested party upon reasonable request. 15. Wang N, Wang Y, Zhang W, et al. C‐peptide is associated with
NAFLD inflammatory and fibrotic progression in type 2 diabetes.
ETHICS STATEMENT Diabetes Metab Res Rev. 2020;36(2):e3210.
16. Kurpiewska E, Ciężki S, Jamiołkowska‐Sztabkowska M, et al.
All participants provided written informed consent.
Excessive BMI is associated with higher C‐peptide level at
recognition but also with its greater loss in two years clinical
TRANSPARENCY STATEMENT observation in children with new onset type 1 diabetes. Front
The lead author Emmanuel Kwaku Ofori affirms that this manuscript Immunol. 2023;14:1176403.
is an honest, accurate, and transparent account of the study being 17. Gonzalez‐Mejia ME, Porchia LM, Torres‐Rasgado E, et al. C‐peptide
is a sensitive indicator for the diagnosis of metabolic syndrome in
reported; that no important aspects of the study have been omitted; subjects from Central Mexico. Metab Syndr Relat Disord. 2016;14(4):
and that any discrepancies from the study as planned (and, if relevant, 210‐216.
registered) have been explained. 18. Aktas G, Khalid A, Kurtkulagi O, et al. Poorly controlled hypertension
is associated with elevated serum uric acid to HDL‐cholesterol ratio:
a cross‐sectional cohort study. Postgrad Med. 2022;134(3):297‐302.
ORCID
19. Atsawarungruangkit A, Chenbhanich J, Dickstein G. C‐peptide as a
Emmanuel Kwaku Ofori http://orcid.org/0000-0001-7375-8830 key risk factor for non‐alcoholic fatty liver disease in the United
Fleischer C. N. Kotey http://orcid.org/0000-0003-0286-3638 States population. World J Gastroenterol. 2018;24(32):3663‐3670.
20. Li X, Zhou Z‐G, Qi H‐Y, Chen X‐Y, Huang G. Replacement of insulin
by fasting C‐peptide in modified homeostasis model assessment to
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