Cardiovascular Journal of Africa: Vol 29 No 5 (September/October 2018)

CARDIOVASCULAR JOURNAL OF AFRICA • Volume 29, No 5, September/October 2018

AFRICA

299

response of neutrophils and monocytes was similar although the

magnitude of NADPH oxidase activity was significantly higher

in neutrophils than in monocytes of patients with ARF.

In recent years, there has been a focus on WBC subtypes,

such as neutrophils, lymphocytes, and NLR as predictors

of cardiovascular risk. Many studies have shown that high

ratios are associated with increased inflammation in various

cardiovascular diseases. Öztürk

et al

. reported that higher

NLR was associated with spontaneous echocardiographic

contrast in rheumatic mitral valve stenosis.

Increased

neutrophil count was found to be associated with infarct size

and adverse angiographic outcomes in patients with myocardial

infarction,

while low lymphocyte count was related to adverse

outcomes in patients with myocardial infarction and chronic

heart failure.

Akboga

et al

. evaluated adult patients with rheumatic mitral

valve stenosis (RMS) and found median NLRs to be significantly

higher in patients with RMS compared with the control group.

Moreover, they also showed NLRs to increase with the severity

of mitral stenosis.

Baysal

et al

. revealed that high levels of

NLR were an independent predictor of severe RMS.

In a

recent study, it was reported that patients with severe RMS had

significantly higher NLRs than those with mild-to-moderate

RMS.

In addition, higher NLRs were associated with an

increased risk of long-term mortality in patients admitted with

acute decompensated heart failure.

In our study, we found that there was a significant positive

correlation between CRP, ESR and NLR in ARC, indicating

that NLR was associated with inflammation in this group of

patients. Kucuk

et al.

demonstrated a strong association of CRP

and ESR levels in children with ARC.

Similarly, Ozdemir

et al.

showed higher CRP and ESR levels in ARF.

The NLR may be the more preferable marker owing to three

factors. First, although some conditions such as exercise and

dehydration may increase the absolute number of neutrophils

and lymphocytes, NLR is less commonly affected.

Second,

NLR is calculated from the counts of products of two different

but complementary immune pathways.

Third, the reason for

the increased NLR was probably increased apoptosis of the

lymphocytes, associated with the increased inflammatory status

in ARF.

We also discovered increasing platelet counts and decreasing

MPV values in patients with ARC, which reflect the inverse

relationship between changes in platelet count and size. The

mechanism of increase in platelet volume is thought to be

that inflammatory cytokines stimulate the production of large,

reactive platelets, which have a shorter life span.

Sert

et al

. showed lower MPV levels in ARF patients.

They

speculated that lower MPV values during ARF may be related to

the effect of interleukin 6 (IL-6). In a previously reported study,

administration of IL-6 was shown to cause an increase in platelet

number as well as a decrease in MPV values.

Previous studies

showed that serum IL-6 levels were significantly elevated during

attacks of ARF.

Regarding the effect of IL-6 on thrombocytes,

low MPV values during ARF may be related to the effect of

IL-6. Similarly, in a prospective study, MPV values significantly

decreased together with CRP and IL-6 values and platelet counts

in response to two-year anti-rheumatic treatment, questioning

the inverse correlation between MPV and thrombocytosis.

Since 2015, there have been changes in the diagnosis of ARF

due to the revised Jones criteria. Changing the criteria may have

led to an increase in our patient numbers. However, at least one

extra major criterion or at least two minor criteria were definitely

identified besides clinical carditis in the patient group prior to

2015. Therefore none of the ARC patients were excluded from

the study.

Although conducted with a relatively large ARC patient

cohort, the retrospective design represents this study’s main

limitation. Also we could not find follow-up full blood count

values for the majority of patients due to their lack of adherence.

Therefore the study was conducted using pre-treatment blood

values.

Conclusion

NLR and MPV are simple, rapid and easily accessible

inflammatory markers that could be prognostic parameters

associated with the severity of valvular involvement in ARC.

However, prospective studies with larger numbers of patients are

needed to evaluate the role of NLR and MPV values in ARC.

References

Carapetis JR, Steer AC, Mulholland EK, Weber M. The global burden

of group A streptococcal diseases.

Lancet Infect Dis

2005;

(11):

685–694.

Sika-Paotonu D, Beaton A, Raghu A, Steer A, Carapetis J. Acute

rheumatic fever and rheumatic heart disease. In: Ferretti JJ, Stevens

DL, Fischetti VA, eds.

Streptococcus pyogenes

: Basic Biology to

Clinical Manifestations [Internet]. Oklahoma City (OK): University of

Oklahoma Health Sciences Center; 2016–2017 Mar 10 [updated 2017

Apr 3].

Cunningham MW. Pathogenesis of group A streptococcal infections.

Clin Microbiol Rev

2000;

(3): 470–511.

Guilherme L, Kalil J, Cunningham M. Molecular mimicry in the auto-

immune pathogenesis of rheumatic heart disease.

Autoimmunity

2006;

(1): 31–39.

Zahorec R. Ratio of neutrophil to lymphocyte counts-rapid and

simple parameter of systemic inflammation and stress in critically ill.

Bratislavske Lekarske Listy

2001;

102

(1): 5–14.

Azab B, Zaher M, Weiserbs KF, Torbey E, Lacossiere K, Gaddam S,

Table 2. Independent predictors of severity of valve regurgitation

Independent variables

Univariate logistic

regression

Multiple logistic

regression

OR (95% CI)

-value OR (95% CI)

-value

WBC count

(×10

cells/mm

)

0.79 (0.53–2.86)

0.034

Haemoglobin (g/dl)

1.53 (1.26–1.87)

0.042

ESR (mm/h)

0.38 (0.21–0.76)

0.50

CRP (mg/l)

0.92 (0.88–0.97)

0.22

Platelet count

(× 10

cells/mm

)

0.26 (0.18–0.52)

0.035

MPV (fl)

0.44 (0.24–0.94)

0.001 0.78 (0.72–0.98)

0.008

Neutrophil count

(× 10

cells/mm

)

0.85 (0.54–1.89)

0.042

NLR

0.42 (0.27–0.66)

0.001 0.51 (0.32–0.68)

0.006

MCV

0.36 (0.26–0.64)

0.024

Dependent variable: severe valve regurgitation cases with or without two-valve

regurgitation (

38).

OR: odds ratio, CI: confidence interval, WBC: white blood cell, ESR: erythro-

cyte sedimentation rate, CRP: C-reactive protein, MPV: mean platelet volume,

NLR: neutrophil-to-lymphocyte ratio, MCV: mean corpuscular volume (fl).