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Sakinah Baharun
30101407318

dr. H. M. Saugi Abduh, Sp.PD, KKV, FINASIM

 C-reactive Protein, Inflammation and C
oronary Heart Disease
Journal
Identity Amit Kumar Shrivastava, Harsh Vardhan Singh, Arun
Raizada, Sanjeev Kumar Singh

The Egyptian Heart Journal (2014)

ABSTRACT
Inflammation is widely considered to be an important contributing factor of
the pathophysiology of coronary heart disease (CHD), and the inflammatory
cascade is particularly important in the atherosclerotic process.

Recent work has been focused on whether biomarkers of inflammation

may help to improve risk stratification and identify patient.
C-reactive protein (CRP) has emerged as one of the most important novel
inflammatory markers.

CRP strongly and independently predicts adverse cardiovascular events,

including myocardial infarction, ischemic stroke, and sudden cardiac death
in individuals both with and without overt CHD.

CRP is believed to be both a marker and a mediator of atherosclerosis and

CHD.
CRP high sensitive assays has made screening for this marker simple,
reliable, and reproducible and can be used as a clinical guide to diagnosis,
management, and prognosis of CHD.
INTRODUCTION
Cardiovascular diseases (CVDs) are Age (older than 40 years for men, 45 years
the leading cause of mortality and for women), male sex, family history of CHD,
morbidity all over the world. CVD smoking, hypertension, diabetes, obesity,
encompasses coronary heart disease high total cholesterol, low high density
(CHD), as well as congestive heart lipoprotein cholesterol (HDL-C), high low
failure, stroke, peripheral artery density lipoprotein cholesterol (LDLC), high
disease, carotid artery disease, and triglycerides, low physical activity, and
aortoiliac disease. accumulation of abdominal fat are some of
the major risk factors.
WHO estimates, 17.3 million people
died from CVDs in 2008, representing Up to half of all events associated with CHD
are reported to occur in apparently healthy
30% of all global deaths. Of these
individuals who have few or none of the
deaths, an estimated 7.3 million were traditional risk factors, including
due to CHD and 6.2 million were due dyslipidemia.
to stroke.
Atherosclerosis, is an inflammatory disease, and is associated with an increase level in
markers of inflammation (play in determining plaque stability). Recent work has focused on
whether biomarkers of inflammation and among them, C-reactive protein (CRP) is the most
studied both as a causal factor and in the prediction of CHD.

CRP levels are stable over long periods, have no diurnal variation, can be measured
inexpensively with available high-sensitivity assays, and have shown specificity in terms of
predicting the risk of CHD.

Prospective cohort studies have established that increased CRP levels are associated with
increased CHD risk in both genders, different populations with diverse ethnic backgrounds.

CRP levels have also been shown to predict risk of both recurrent ischemia and death among
those with stable and unstable angina
 INFLAMMATION
AND
ATHEROSCLEROSIS
 A formation of atherosclerotic plaques consisting of necrotic cores, calcified
regions, accumulated modified lipids, inflamed smooth muscle cells (SMCs), ECs,
leukocytes, and foam cells
Histologically, atheromatous plaques demonstrated the presence of inflammatory
mononuclear cells with foci of monocytes, macrophages and T lymphocytes in the
arterial wall.
All stages of the atherosclerotic process, from its initiation to plaque rupture,
might be considered an inflammatory response to injury and endothelial dysfunction

Damage to the Modulates the Recruitment of Rise of Initiate

endothelial inflammatory white blood cells
into the blood abnormal atherosclerotic
wall response vessel wall foam cells lesions
Pathophysiology of ath
erosclerosis
Under normal conditions, the ECs of the arterial wall resist adhesion and aggregation of
leukocytes and promote fibrinolysis.
Stimuli : hypertension, smoking, an unhealthy diet, obesity, insulin resistance, inflammation or
other types of injuries

Activated by Monocytes adhere to the

dysfunctional endothelial
Proinflammatory proteins
(chemokines) provide a
stimuli surface
chemotactic stimulus that induces
to enter the intima

Monocytes Express scavenger receptors Appearance of the

Cytoplasm becomes
that allow macrophages to foam cells found in
mature into engulf modified lipoprotein engorged with lipid
atherosclerotic
macrophages particles particles
lesions
 Other inflammatory release of additional mediators,
mediators, activated T cells like adhesion molecules, Formation of the
and mast cells, also attach to cytokines, chemokines, and
growth factors
atheromatous lesion
the endothelium

Over time the Decreased NO Giving the macrophages the

Endothelium-derived NO typical microscopic frothy
production  the
plaque attract is reduced at the site of
clinical course of
appearance of the foam
vascular injury cells found in atherosclerotic
deposits of calcium CVD lesions
 progressive The internalization
LDL particles
trapped in an
oxidation and be leads to the Formation of
artery
internalized by formation of lipid foam cells
macrophages peroxides

Patients MIs occur as a result of erosion or uneven thinning and rupture of the fibrous
cap, often at the shoulders of the lesion where macrophages enter, accumulate, and
are activated and where apoptosis may occur.

The results may be either coronary or cerebral infarction, depending on the duration of
the thrombosis and the location of the associated vasoconstriction.
C-reactive protein (CR
P)
 Structure of CRP

CRP belongs to the pentraxin family of calcium dependent ligand-binding

plasma proteins.

In human, the CRP gene is located on chromosome 1q23, which codes for
proteins important for immune system as well as cell to cell communication.

The major part of the CRP present in the plasma comes from the liver,
where the synthesis of CRP is mainly regulated by interleukin-6 (IL-6), which in
turn is up-regulated by other inflammatory cytokines such as IL-1 and tumor
necrosis factor (TNF)-a. CRP also produced locally in atherosclerotic lesions by
SMCs lymphocytes and monocytic cells.
 Biological functions of CRP

CRP provides the first line of defense of pathogen. Despite structural differences
with immunoglobulin molecule, CRP shares similar functional properties with the
immunoglobulins, such as, the ability to promote agglutination, activation of the
classical complement pathway, bacterial capsular swelling, phagocytosis and
precipitation of polycationic and polyanionic compounds.

By analogy with antibodies, it is therefore possible that CRP might contribute both
to host defence against infection and enhancement of inflammatory tissue
damage.
 Clinical utility of CRP

CRP is very stable in serum or plasma with very marginal fluctuations, more cost
effective than the emerging risk markers and has been proven to orchestrate
atherosclerosis.

Although CRP is a nonspecific inflammatory marker, it is a strong independent

predictor for CHD risk and events. Epidemiological studies and clinical trials have
found that CRP is a strong independent predictor of future CHD risk. In addition,
elevation of hs-CRP levels predicts a poor cardiovascular prognosis.

It may be used in conjunction with troponin I or T levels to identify high-risk patients

for more aggressive management with antiplatelet agents and statins.
Components of the metabolic syndrome (i.e., central obesity, increased plasma
triglyceride concentrations, low plasma concentrations of HDL-C, hypertension,
and increased concentrations of blood glucose) correlate with increased plasma
CRP concentrations.

Concerning hs-CRP level and CHD risk :

• <1 mg/L : lower risk,
• 1 - 3 mg/L : moderate risk and
• >3 mg/L indicates a higher risk,
• 5–10, 10–20, >20 mg/L : very highest risk
 Your Picture Here

hs-CRP is the same In the mid of 1990s, a new

exquisitely sensitive and method enzyme-linked
entirely nonspecific systemic immunosorbent assay
marker of infection, High sensitive CRP (ELISA) was established to
inflammation, tissue damage (hs-CRP) evaluate the level of hs-CRP,
and/or almost any form of which has much higher
adverse non-physiological sensitivity (to quantify CRP
stress as the CRP, which has throughout its normal range)
been extensively studied and then classic methods used
used clinically for over 75 previously
years.
Atherosclerosis, inflammation, and CRP
CRP and coronary hear
t disease
Elevated CRP has been associated with many non-communicable diseases
such as CHD, ischemic stroke, insulin resistance, hypertension, metabolic
syndrome and peripheral artery disease.

Several landmark large prospective clinical case-control studies on middle-

aged men, postmenopausal women, and elderly men and women have
identified CRP as a strong, independent risk factor for CHD
 In patients with ACS, an increase in the CRP level at admission is associated with a
poorer short-term and longterm prognosis. Patients with ACS and higher CRP may
represent a group with hyper-responsiveness of the inflammatory system, which may in
turn mediate myocardial damage and promote cardiac complications.

This may be more pronounced in patients with nonSTEMI than in those with STEMI, due
to a higher atherosclerotic burden. As reported by several studies, elevated CRP levels
after MI are associated with adverse clinical outcome, including cardiac rupture, heart
failure, and cardiac death. The higher the maximum CRP recorded, the more severe the
infarction suffered, the greater the likelihood of ventricular remodeling, the lower the
ejection fraction, and the greater the risk of heart failure, heart rupture, and death
Conclusion
CHD is the leading cause of death and disability in developed nations and is
increasing rapidly in the developing world. Up to half of all events associated with
CHD are reported to occur in apparently healthy individuals who have few or none
of risk factors.

Recent observations suggest that the atherosclerotic process is characterized by

a low-grade inflammation altering the endothelium of the coronary arteries and is
associated with an increase level in markers of inflammation. In an attempt to
improve global cardiovascular risk prediction, considerable interest has focused
on CRP. CRP is not only an excellent biomarker of inflammation, but it is also a
direct participant in atherogenesis.

Many studies have demonstrated that increased CRP concentrations are

associated with an increased risk of MI, stroke, peripheral arterial disease, and
sudden cardiac death. Unlike other markers of inflammation, CRP levels are
stable over long periods, have no diurnal variation, can be measured
inexpensively with available high-sensitivity assays, and have shown specificity in
terms of predicting the risk of cardiovascular disease.
THANKYOU
 CRITICAL
APPRAISAL
 PEMBAHASAN IDENTITAS JURNAL
C-reactive Protein, Inflammation and
Coronary Heart Disease
Amit Kumar Shrivastava, Harsh Vardhan Singh,
Arun Raizada, Sanjeev Kumar Singh
Ya (+), Tidak
No Kriteria (-), TR (Tidak
relevan)

Judul Jurnal

1 Tidak terlalu panjang atau terlalu pendek +

•Nama Penulis
tanpa gelar akademis atau indikasi jabatan dan
2 Menggambarkan isi utama penelitian +
kepangkatan
3 Cukup menarik + •Penulis sudah sesuai dengan bidangnya.
•Tidak terdapat erdapat alamat email
4 Tanpa singkatan, selain yang baku +

Pengarang dan Institusi

Nama-nama dituliskan sesuai dengan

5 +
aturan jurnal
 ABSTRACT
Ya (+), Tidak (-),
No Kriteria TR (Tidak
relevan)
ABSTRAK
Abstrak satu paragraph atau
6 terstruktur (beri tanda yang +
sesuai)

7 Mencakup komponen IMRAD -

8 Secara keseluruhan informatif +

9 Tanpa singkatan selain yang baku +

10 Kurang dari 250 kata + (219 kata)
 Ya (+), Tidak
(-), TR
PENDAHULUAN
No Kriteria
(Tidak
relevan) Ya (+),
PENDAHULUAN Tidak (-),
No Kriteria
TR (Tidak
 - relevan)
Ringkasan, terdiri
11 (ada 4
atas 2-3 paragraf
paragraf)
Paragraf pertama 14
Didukung oleh
+
mengemukakan pustaka yang relevan
12 +
alasan dilakukan
penelitian
Paragraf berikutnya Kurang dari satu
15  -
menyatakan halaman
13 -
hipotesis atau tujuan
penelitian
 Ya (+), Tidak Ya (+), Tidak
No Kriteria (-), TR (Tidak No Kriteria (-), TR (Tidak
relevan) relevan)
METODE METODE
Disebutkan desain, tempat dan waktu Ditulis rujukan bila teknik pengukuran
16
penelitian  - 24
tidak dirinci -
Disebutkan populasi sumber (populasi
17
terjangkau  - 25 Pengukuran dilakukan secara tersamar - 
18 Dijelaskan criteria inklusi eksklusi  -
Dilakukan uji keandalan pengukuran
19
Disebutkan cara pemilihan subyek (teknik
- 26
(Kappa)  -
sampling)
Disebutkan perkiraan besar sampel dan Definisi istilah dan variabel penting
20
alasannya - 27
dikemukakan  -
21
Besar sampel dihitung dengan rumus
 - 28 Ethical clearance diperoleh  -
yang sesuai
29 Persetujuan subyek diperoleh  -
Komponen-komponen rumus besar
22
sampel masuk akal - Disebut rencana analisis, batas
30
kemaknaan, dan power penelitian  -
Observasi , pengukuran serta intervensi
23 dirinci sehingga orang lain dapat  - 31
Disebutkan program computer yang
 -
mengulanginya dipakai
 Ya (+), Tidak (-),
 No HASIL TR (Tidak
relevan)

32 Disertakan tabel karakteristik subyek penelitian -

33 Karakteristik subyek sebelum intervensi dideskripsi -
34 Tidak dilakukan uji hipotesis untuk kesetaraan pra-intervensi -
35 Disebutkan jumlah subyek yang diteliti -
36 Dijelaskan subyek yang drop out dengan alasannya -
37 Ketepatan numerik dinyatakan dengan benar -
38 Penulisan tabel dilakukan dengan tepat -
39 Tabel dan ilustrasi informatif & memang diperlukan -
40 Tidak semua hasil di dalam tabel disebutkan pada naskah -
41 Semua outcome yg penting disebutkan dalam hasil -
42 Subyek yg drop out disebutkan dalam analisis -
43 Analisis dilakukan dengan uji yg sesuai -
44 Ditulis hasil uji statistika, degree of freedom & nilai p -
45 Tidak dilakukan analisis yang semula tidak direncanakan -
46 Disertakan interval kepercayaan -
47 Dalam hasil tidak disertakan komentar atau pendapat -
 Ya (+), Tidak (-),
 No. DISKUSI TR (Tidak
relevan)

48 Semua hal yg relevan dibahas +

49 Tidak sering diulang hal yg dikemukakan pada hasil +
50 Dibahas keterbatasan penelitian, dan dampak terhadap hasil +
51 Disebut penyimpangan protokol dan dampaknya terhadap hasil -
52 Diskusi dihubungkan dengan pertanyaan penelitian +
53 Dibahas hubungan hasil dengan teori/peneliti terdahulu +
54 Dibahas hubungan hasil dengan praktek klinis -
55 Efek samping dikemukakan dan dibahas -
56 Disebutkan hasil tambahan selama observasi -
57 Hasil tambahan tersebut tidak dianalisis secara statistika +
58 Disertakan simpulan utama penelitian +
59 Simpulan didasarkan pada data penelitian +
60 Simpulan tersebut sahih +
61 Disebutkan generalisasi hasil penelitian -
62 Disertakan saran dari penelitian selanjutnya +
 Ya (+),
Tidak (-),
UCAPAN TERIMAKASIH
TR (Tidak
Relevan)

Ucapan terimakasih dapat

63 ditujukan pada orang yang +
tepat

Ucapan terimakasih
64 +
dinyatakan secara wajar
 DAFTAR PUSTAKA

Ya (+), Tidak (-),

DAFTAR PUSTAKA TR (Tidak
Relevan)

65 Daftar pustaka disusun sesuai dengan aturan journal +

66 Kesesuaian sitasi pada naskah dan daftar pustaka +

Ya (+), Tidak (-),

LAIN-LAIN TR (Tidak
Relevan)

Bahasa yang baik dan benar, mudah dibaca,

67 +
informatif dan efektif

68 Makalah ditulis dengan ejaan yang taat asas +

DESKRIPSI UMUM
No Kriteria Hasil
1 Desain Penelitian Cohort

2 Populasi Target Pasien Diabetes

Pasien Diabetes di Tertiary care diabetes clinic in

Populasi
3 Golestan Hospital, a university hospital in Ahvaz (south-
Terjangkau
west of Iran)
4 Sampel 566 pasien
Cara Pemilihan
5 Nonprobabilistic convenience sampling
Sampel
6 Variabel Bebas Incidence and Risk Factors

7 Variabel Terikat Diabetic Foot Ulcer

The average annual DFU incidence to be about 2.8%.
Independent risk factors of DFU development were
Hasil Utama
8 history of previous DFU or amputation, insulin usage,
Penelitian
gender, distal neuropathy, and foot deformity. This finding
provides support for a multifactorial etiology of DFU
Validity Importancy Applicability
 VALIDITAS INTERNA HUBUNGAN NON KAUSAL

No Kriteria Hasil

Ya
1 Apakah hasil dipengaruhi oleh bias?
(bias seleksi)

Apakah hasil dipengaruhi oleh faktor

2 Ya
peluang?

Apakah observasi dipengaruhi oleh

3 Tidak
faktor perancu?
 VALIDITAS INTERNA HUBUNGAN KAUSAL
No Kriteria Hasil
1. Apakah hubungan waktu benar? Ya
2. Apakah asosiasi kuat? Ya

3. Apakah ada hubungan dosis? Tidak relevan

(Bukan merupakan penelitian eksperimental)

4. Apakah hasil konsisten dalam penelitian ini? Ya

Apakah ada koherensi hasil studi dengan fakta di

5. Ya
masyarakat?
6. Apakah hasil biologically plausible? Ya
Apakah hubungan bersifat spesifik (hubungan sebab
7. akibat semakin nyata bila hanya disebabkan satu Ya
sebab?
 VALIDITAS EKSTERNA

No. Kriteria Hasil

1. Apakah hasil dapat diterapkan pada sampel terpilih? Ya

Apakah hasil dapat diterapkan pada populasi

2. Ya
terjangkau?

3. Apakah hasil dapat diterapkan pada populasi target? Ya

 IMPORTANCY
No. Kriteria Hasil

Apakah alokasi sampel pada penelitian ini

1. Tidak
dilakukan secara acak?

Apakah pengamatan sampel dilakukan secara

2. Ya
cukup panjang dan lengkap?

Apakah semua sampel dalam kelompok yang

3. Ya
diacak, dianalisis?

Apakah sampel dan peneliti tetap blind dalam

4. TR
melakukan terapi?

5. Apakah kelompok terapi dan kontrol sama? TR

 APPLICABILITY
The average annual DFU incidence to be about 2.8%.
Independent risk factors of DFU development were history
of previous DFU or amputation, insulin usage, gender,
distal neuropathy, and foot deformity. This finding
provides support for a multifactorial etiology of DFU.
VALIDITY, IMPORTANCY, APPLICABILITY

NO KRITERIA +/-
1 VALIDITY
Validitas Interna Hubungan Kausal +
Validitas Interna Hubungan Non
+
Kausal
Validitas Eksterna +
2. IMPORTANCY +
3. APPLICABILITY +
VALIDITY IMPORTANCY APPLICABILITY