Download MYOCARDIAL INFARCTION IN A YOUNG AFRICAN MALE USING

MYOCARDIAL INFARCTION IN A YOUNG AFRICAN MALE USING PROTEIN
SUPPLEMENTS RICH IN BRANCHED CHAIN AMINO ACIDS & CREATINE
A Case Report and Review of the Literature
Salem Abujalalaa, Adeel Arshadb, Nisrine Assal El Muabbyc, Jassim Zaheen Shahd, Shaban
Fathy Kamel Mohammedc
aConsultant
Cardiology, Heart Hospital, Hamad Medical Corporation/Weil-Cornell Medical
College in Doha, Doha, Qatar
bResident,
Internal Medicine, Hamad Medical Corporation/Weil-Cornell Medical College in
Doha, Doha, Qatar
cClinical
Pharmacist, Heart Hospital, Hamad Medical Corporation/Weil-Cornell Medical
College in Doha, Doha, Qatar
dFellow
Cardiology, Heart Hospital, Hamad Medical Corporation/Weil-Cornell Medical College
in Doha, Doha, Qatar
Abstract:
Myocardial Infarction is one of the leading causes of mortality which is more likely to inflict
patients with major cardiovascular risk factors like old age, diabetes mellitus, hypertension,
smoking and hyperlipidemia. Sometimes during our clinical encounters, we come across a few
patients with myocardial infarction who doesn’t have any of the typical risk factors for
cardiovascular morbidity. Such patients give us an insight to explore other unidentified
predisposing factors which can lead to the development of this catastrophic disease.
We hereby present a case of 41 years old African man, with no cardiovascular risk factors, who
presented with ST-elevation MI. Patient was taking protein supplements rich in branched chain
amino acids and creatine which we hypothesize to be the culprit for his intracoronary thrombosis.
Such cases bring out the active debate about the safety of these widely-available nutritional
products and give us a thought to broaden our spectrum for the factors responsible for
development of prothrombotic disease.
Introduction
According to Consumer Reports, $2.7 billion are spent per annum on sports nutritional
products in the US. These supplements are used to improve athletic performance by enhancing
muscle mass. The Joint Commission, which is responsible for hospital accreditation in the US,
requires that all these supplements, because of their many pharmacologically-active ingredients,
should be scrutinized as drugs. In contrast, FDA doesn’t work on the same principle, which
makes this market largely unregulated. These products aren’t monitored for their efficacy and
safety before and after they are brought out for public use which naturally raises a lot of
questions. With no support from the FDA, the doctors---and the consumers---are on their own.
This is an interesting case of a young guy taking protein supplements for muscle-building who
developed intracoronary thrombosis.
Keywords: body-building, coronary thrombosis, protein supplements, leucine, valine,
myocardial infarction, creatine monohydrate, branched chain amino acids
Case Report
41 years old male, without any chronic medical illness, presented to the ER with sudden onset of
retrosternal chest pain, radiating to neck and right arm. It occurred when he reached home after
doing his routine workout for approximately 1 hour that day. It was associated with sweating,
nausea, vomiting and mild shortness of breath. He denied dizziness, palpitations, chest trauma
or fever. Patient did not have any risk factor for coronary artery disease like diabetes mellitus,
hypertension, hyperlipidemia or cigarette smoking. He had no family history of premature
coronary artery disease or sudden death. He denied the use of alcohol, cocaine, amphetamines or
other illicit drugs.
He is a professional gym-trainer. He exercises for 1-2 hours 5 times a week involving
predominantly weight-lifting. He has been using multiple protein supplements for the last 1-2
years which include branched chain amino acids (1g leucine, 3g isoleucine, 2g valine per serving
daily). He never used anabolic steroids. On the day when he had chest pain, he took creatine
monohydrate for the first time in his life before the workout. He took 2 scoops (10g) of it on the
very first day in the morning--double the dose recommended by the manufacturer (Suggested
Usage: Loading dose of 1 rounded teaspoon with morning, afternoon, and evening meals and 1
additional rounded teaspoon before going to bed for 4-5 days, followed by daily 1 scoop as
maintenance).
At presentation, his blood pressure was 140/80 mmHg, pulse rate 80 per minute, temperature
36.8C and respiratory rate was 19 per minute. Patient was a well-built muscular man, with a
height of 173cm and weight of 104kg. He was in mild distress due to his pain. Both heart sounds
were audible on cardiac auscultation. There was no added sound or murmur. Carotid upstroke
was normal without any bruit. Estimated central venous pressure was normal. There was no
chest tenderness. Chest auscultation revealed normal vesicular breathing, equal on both sides,
without any rhonchi or crepitation. Abdominal and nervous system examination was also
unremarkable. 12-lead electrocardiogram (Figure 1) revealed >1 mm ST-segment elevation in
inferior leads (lead II, III and aVF) and 2mm ST-segment elevation in V5-V6.
Fig. 1 : 12-Lead Electrocardiogram at presentation showing >1 small square ST Segment
elevation in Lead II, III, aVF and V5, V6.
Trop T was 3467 nanogram per litre ( 0-14 nanogram per litre) . Blood glucose was 6.2 (3.5-6
millimoles per litre), BUN 5.1(1.7-8.7 millimoles per litre), creatinine 164(53-184 millimoles per
litre), phosphate 0.66 (0.87-1.45 millimoles per litre), potassium 3.6(3.6-5.1 millimoles per litre),
triglycerides 1.29 (0.45-1.81 millimoles per litre) ,total Cholesterol 6.40 (<5.18 millimoles per
litre), LDL-Cholesterol 4.62 (<3.36 millimoles per litre) and HDL Cholesterol 1.16 (>1
millimoles per litre). CBC was within normal range. Procoagulant state work-up revealed
antithrombin activity 89.9% (71-116%), lupus anticoagulant screening 40.1 (31-44), fibrinogen
level 3.7 (1.8-3.5 gram per litre),protein C chromogenic 74.4 (70-140%), protein S clotting
activity 61.3 (60->130%),homocysteine 10.2 (4-12 micromole per litre),ANA screening
negative, anticardiolipin IgM <9 ( negative <12.5 IgM Phospholipid Units),anticardiolipin IgG
<9 ( Negative <15 IgG Phospholipid Units),beta-2 glycoprotein IgM <9 (negative 0-20 standard
IgM beta-2 glycoprotein unit),Beta 2 glycoprotein IgG <9 (negative 0-20 standard IgG beta-2
glycoprotein unit). Factor V Leyden was negative.
Chest X-ray was normal. Patient was given aspirin, clopidogrel, nitrates and beta-blockers. He
was immediately taken to the hospital’s coronary catheterization lab. Coronary angiography
revealed a large thrombus in left coronary artery main stem (Fig. 2).
Fig 2: Big thrombus in Left Main (at presentation)
Fig 3: Partial Dissolution of Thrombus after 2 days of IV Heparin and Eptifibatide + IVUS
Picture
Fig 4: Disappearance of thrombus angiographcally after 5 days of IV heparin and integrillin
Thrombus was aspirated. Intravenous eptifibatide was given and anticoagulation was initiated.
Relook angiography twice in the 5 days showed remnant of thrombus at distal left coronary
artery main stem causing 30% stenosis (Fig. 3, 4). Echocardiography showed ejection fraction of
45-50%, mild global hypokinesia of left ventricle, more prominent over inferior wall and inferior
septum.
Hospital course was uneventful. Patient showed good recovery and was discharged home a few
days later. He is now being followed up regularly in the outpatient clinics.
Discussion
Myocardial infarction is the irreversible necrosis of the myocardium owing to the mismatch
between the demand and supply of oxygen to the heart. Approximately 1.5 million new cases of
acute MI occur annually in the US alone with mortality encroaching approximately 30%. It’s a
disease of the elderly with most patients being older than 60 years. 7Many patients have wellrecognized risk factors like old age, diabetes mellitus, hypertension, dyslipidemia, smoking and a
strong family history. With time, increasing numbers of young patients with MI without
significant risk factors are being recognized. 6 This has raised questions over the existence of
other factors which may contribute towards the development of this catastrophic illness.
This healthy, athletic man experienced an acute myocardial infarction in the absence of any
identifiable inciting factors. Coronary angiography revealed an obstructing thrombus in the left
main stem. Laboratory investigations ruled out any pro-coagulant state or disease predisposing
the patient to thromboembolism. He is a non-smoker. Although we don’t have toxicological
screen evidence to rely upon, but the patient denied use of alcohol or any recreational drug.
Patient is a user of protein supplements including branched chain amino acids. On the day of
infarction, he took more-than-recommended dose of micronized creatine hydrate on that
particular time. This was the first time he ever used this supplement to enhance his muscle mass.
We have a hypothetical idea that the supplements that he was heavily dependent on might be the
culprit in his case which may have worked via any of three components of Virchow’s triad
(hypercoagulability, stasis or endothelial injury). We don’t have any ‘evidence’ to prove it but
it’s a proposal worth noticing which brings into question the safety of these nutritional aids
which are used by the thousands of consumers.
Leucine, valine and isoleucine, the branched chain amino acids, constitute 40% of the preformed
amino acids required by the mammals.18 These are ‘essential’ in the synthesis of proteins,
especially muscle proteins of which they make 40% part. 18 They have been studied in various
studies to define their therapeutic significance. On the contrary, it’s also a known fact that the
catabolism of these amino acids leads to production of some toxic metabolites like branched chain
alpha-ketoacids (BCKAs)9 which can be detrimental for health. De Brandt et al concluded that
leucine-supplemented nutrition may bring about an improvement in the nutritional status and
outcome of patients with burns, sepsis and trauma. 5 Similarly their role in hepatic
encephalopathy1, 3, 10, 12, 20, mania16, tardive dyskinesias,14, 15 spinocerebellar degeneration13 and
in certain cancers4 has also been studied. Though most of the studies showed no untoward effects
of BCCAs supplementation, but it was found to enhance mortality in patients with Amyotrophic
Lateral Sclerosis (ALS), explained possibly by impairment of neutral amino acid availability in
the brain.2
Moreover, in a study involving 118696 subjects, higher consumption of branched amino acids
was associated with moderately increased risk of CHD in women & men but the association is
partly explained by obesity and diabetes status.
Creatine is a nitrogenous organic acid that helps to supply energy to all cells in the body,
primarily muscle. Creatine is most commonly used for improving exercise performance and
increasing muscle mass in athletes and older adults. It is claimed that creatine is a safe product;
however this product was associated with harmful adverse events. Cases of acute kidney injury,
atrial fibrillation, and ischemic stroke were reported in people using creatine alone or with other
energy products. 8, 11
Moreover, case reports of venous thrombotic events in previously healthy adults were also
reported in the literature due to creatine use. The cause may be attributed to creatine causing
dehydration since creatine can draw water into the muscles by osmotic effect, and dehydration is
a known precipitating factor for venous thromboembolism.19. A study was designed to assess the
risk of creatine with the dose ingested. It indicated that the evidence of safety is strong at intakes
up to 5 g/d for chronic supplementation, and although much higher levels have been tested under
acute conditions without adverse effects and may be safe, the data for intakes above 5 g/d are not
sufficient for a confident conclusion of long-term safety.17
It’s too early to say whether it was the chronic supplementation of BCCAs or the acute
intoxication of creatine which led to the development of thrombosis in an otherwise healthy male.
But it certainly has raised some concerns. This needs further investigations and more
sophisticated studies to highlight the health implications of such supplements, whose use has
become quite frequent these days.
Conflict of Interests
The authors declare that there is no conflict of interests regarding the publication of this paper.
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