Double Trouble-Hyperhomocysteinemia and Lipoprotein(a) Induced Myocardial Infarction in Very Young - A Case Report

doi:10.21203/rs.3.rs-4934523/v1

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Case Report

Double Trouble-Hyperhomocysteinemia and Lipoprotein(a) Induced Myocardial Infarction in Very Young - A Case Report

https://doi.org/10.21203/rs.3.rs-4934523/v1

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Background

Acute coronary syndrome is a category that includes unstable angina, non-ST-elevation myocardial infarction (NSTEMI), and ST-elevation myocardial infarction (STEMI). Currently, the most significant cause of death globally is coronary artery disease. It is generally not suspected in a young person, especially without a significant family history. Hyperhomocysteinemia and high lipoprotein(a) are important risk factors and can be used in screening tools.

Case presentation

A 23-year-old male presented with an evolved anterior wall myocardial infarction, which was confirmed by ECG findings and Echocardiography findings. Subsequent coronary angiography was suggestive of a Single vessel with branch vessel disease, which was successfully revascularised with bifurcation stenting. OCT study of the lesion was suggestive of fibro atheromatous lesion with thrombosis. On workup, high lipoprotein(a) and hyperhomocysteinemia were found to be the risk factors for his disease.

Conclusion

Thus, Lipoprotein(a) and familial hyperhomocysteinemia may not always be associated with a family history of young ASCVD and are important risk factors for screening Intracoronary imaging should be used liberally to understand pathophysiology of the disease and also optimising interventions in such cases

CAD

AWMI

OCT

IVUS

LIPOPROTEIN(A)

HOMOCYSTEINE

Acute myocardial infarction (AMI), sudden cardiac death, stable angina, and unstable angina are all symptoms of coronary artery disease, an atherosclerotic cardiovascular disease. Acute coronary syndrome is a category that includes unstable angina, non-ST-elevation myocardial infarction (NSTEMI), and ST-elevation myocardial infarction (STEMI). Currently, the most significant cause of death globally is CAD. Over 80% of the world's CVD cases are found in low- and middle-income nations. Eight low- or lower-middle-income nations comprise the South Asian region: Bangladesh, Bhutan, Sri Lanka, India, Nepal, Afghanistan, Pakistan, and the Maldives. The ethnicity of South Asians has been linked to an increased risk of developing CAD and other non-communicable diseases.(1)

We are presenting a 23-year-old gentleman shopkeeper by occupation, presented with a history of sudden onset severe compressive chest pain, which lasted for five hours ten days before. The pain was reduced with medications from the local hospital but persisted with heavy exertion. He also complained of dyspnoea on mild exertion. A detailed family history didn’t reveal any risk factors, nor did he have any addictions to suggest a cause. On physical examination, he had tachycardia. His BMI was 21.4 kg/sq m. He was admitted from our OPD after admission, and ECG was suggestive of Wellens pattern type A (Fig. 1).

(Fig. 1)

2D Echocardiography revealed anterior and anterolateral wall hypokinesia with an estimated ejection fraction of 35–40%. He was started on parenteral anticoagulation and goal-directed medical therapy for heart failure with reduced ejection fraction. Immediately, he was taken for angiography, which was suggestive of single vessel disease of Proximal to mid-diffuse LAD disease with early D1 ostial 100% occlusion. (Fig. 2)

(Fig. 2)

A blood workup revealed an elevated homocysteine level of 28.52 micromol/l with a Vitamin B12 level of 996 pmol/l and an elevated lipoprotein(a) level of 105 mg/dl. His Lipid profile was otherwise borderline, with Triglycerides of 131 mg/dl and LDL cholesterol of 101 mg/dl, HDL of 31 mg/dl, and Total cholesterol of 158 mg/dl. His RPR for syphilis was negative. He was subsequently taken up for percutaneous angioplasty under OCT guidance. OCT revealed a fibro atheromatous lesion in proximal to mid-LAD unto D2 with red thrombus with a dense lipid-rich plaque with underlying necrosis and calcium at the ostium of D1 (Fig. 3).

(Fig. 3)

Bifurcation stenting was done under IVUS guidance from LAD to D1. Post angioplasty, TIMI III flow was achieved ( Fig. 4).

(Fig. 4)

Post-procedure ECG changes reverted to deep QS complexes in anterior leads with inverted T waves in V3-V4 (Fig. 5).

(Fig. 5)

The patient was started on double antiplatelets and statin and ezetimibe as the patient was not affordable for other lipid-lowering therapies. Genetic workup for hyperhomocysteinemia could not be done due to financial constraints. The patient was symptomatically better with adequate cardiovascular rehabilitation. He was discharged and followed up for two weeks to be symptomatically better with a reduction of dyspnoea. He is planned for re-evaluation of lipid profile and lipoprotein(a) on further follow-up.

Increased homocysteine levels and lipoprotein(a) are known to be associated with coronary artery diseases(2, 3). Lp(a) is the most common monogenetic lipid pathology in the world; around 1.4 billion persons are predicted to have a prevalence of Lp(a) > 50 mg/dL.(4) Increased Lp(a) levels are linked to an increased risk of atherothrombosis, and patients may exhibit a variety of clinical manifestations, such as stroke in younger age groups, ST-segment elevation myocardial infarction in young men, or calcific aortic valvular disease in older adults. In the absence of conventional risk factors, Asian Indians have been shown to have extremely high prevalence rates of coronary artery disease (CAD). In migratory Asian Indians, elevated levels of lipoprotein (a) have been linked to premature CAD. (3) Still, there is a shortage of information about Lp(a) in individuals with CAD from the Indian subcontinent. The most prevalent causes of hyperhomocysteinemia, which increases the risk of atherosclerosis, include genetic abnormalities, some medications, renal impairment, and B-vitamin deficiencies, particularly folic acid, B(6), and B(12). Elevated homocysteine contributes to atherosclerosis through heightened oxidative stress, compromised endothelial function, and thrombosis induction. According to prospective studies, there is a twofold increase in the risk of cardiovascular disease and a less significant rise in the risk of cerebrovascular disease with elevated plasma homocysteine concentrations. (5) In our patient, vitamin b12 levels were normal, thus pointing towards inherited hyperhomocysteinemia as the culprit. South Asians present with their first AMI at a younger age than people from other regions, even though CAD is typically seen in adults over 60. Generally, research has found that a patient with CAD who is 45 years of age or under meets this definition. Young CAD is frequently associated with risk factors, including smoking, hypertension, diabetes, dyslipidemia, obesity, and family history. However, there is also evidence linking less frequent risk factors such as coagulation disorders, drug addiction, and vasculitis. (6) However, despite not having any significant family history of young CAD, our patient most likely suffers from a genetic predisposition of hyperhomocysteinemia and high lipoprotein(a), thus leading to such diseased coronaries

Study points

Lipoprotein(a) and familial hyperhomocysteinemia may not always be associated with a family history of young ASCVD
In our Indian population, it is always advisable to screen out these parameters in the absence of traditional risk factors
Awareness about coronary artery disease and its severity should be spread to the young population as well
Intracoronary imaging helps us to understand the pathophysiology of coronary artery disease and should be used whenever CAD is suspected in a not-so-usual population

Patient perspective

He was surprised to be diagnosed with such a condition despite living a healthy lifestyle and with no significant family history. He was symptomatically better after proper cardiac rehabilitation and went back to his usual occupation after two weeks of discharge.

Thus, Familial hyperhomocysteinemia and high lipoprotein(a) levels can lead to fatal coronary artery disease even in healthy individuals with a healthy lifestyle. Therefore, one should be on the lookout for these traits.

AMI

Acute Myocardial Infarction

NSTEMI

Non-ST elevated Myocardial Infarction

STEMI

ST elevated Myocardial infarction

CAD

coronary artery disease

Lp(a)

lipoprotein(a)

BMI

Body Mass Index

OCT

Optical coherence tomography

LDL

low density lipoprotein

HDL

high density lipoprotein

ECG

Electrocardiogram

LAD

Left anterior descending artery

1st Diagonal branch

IVUS

Intravascular Ultrasound

Ethical statement

The Cardiology Departmental Ethics Committee of AIIMS Rishikesh approved the project. In addition, we confirm that all applicable rules and guidelines are executed in all processes. Informed consent was obtained from all subjects. All data was collected following sound clinical practice principles and the Declaration of Helsinki.

Informed consent

Informed consent was taken from the patient

Consent for publication

We confirm that the manuscript has been read and approved by all named authors and that no other persons have satisfied the criteria for authorship but are not listed. We further confirm that all have approved the order of authors noted in the manuscript. We confirm that we have given that there are no objections to publication, including the timing of publication, concerning intellectual property.

Data availability statement

The data supporting this study's findings are not openly available due to reasons of sensitivity and are available from the corresponding author upon reasonable request. Data are located in controlled access data storage at the Cardiology Department of AIIMS Rishikesh.

Yusuf S, Hawken S, Ounpuu S, et al. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study. Lancet 2004; 364: 937–952. 2004/09/15. DOI: 10.1016/s0140-6736(04)17018-9.
Tripathi R, Tewari S, Singh PK, Agarwal S. Association of homocysteine and methylene tetrahydrofolate reductase (MTHFR C677T) gene polymorphism with coronary artery disease (CAD) in the population of North India. Genet Mol Biol. 2010;33(2):224–8. doi: 10.1590/S1415-47572010005000026. Epub 2010 Jun 1. PMID: 21637473; PMCID: PMC3036870.
Mohan V, Deepa R, Haranath SP, Premalatha G, Rema M, Sastry NG, Enas EA. Lipoprotein(a) is an independent risk factor for coronary artery disease in NIDDM patients in South India. Diabetes Care. 1998;21(11):1819-23. doi: 10.2337/diacare.21.11.1819. PMID: 9802727.
Tsimikas S, Stroes ESG. The dedicated “Lp(a) clinic”: A concept whose time has arrived? Atherosclerosis. 2020;300:1–9. doi: 10.1016/j.atherosclerosis.2020.03.003. Epub 2020 Mar 13. PMID: 32234580.
Guthikonda S, Haynes WG. Homocysteine: role and implications in atherosclerosis. Curr Atheroscler Rep. 2006;8(2):100-6. doi: 10.1007/s11883-006-0046-4. PMID: 16510043.
Agrawal A, Lamichhane P, Eghbali M, Xavier R, Cook DE, Elsherbiny RM, Jhajj LK, Khanal R. Risk factors, lab parameters, angiographic characteristics and outcomes of coronary artery disease in young South Asian patients: a systematic review. J Int Med Res. 2023;51(8):3000605231187806. doi: 10.1177/03000605231187806. PMID: 37555333; PMCID: PMC10413899.

No competing interests reported.

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Version 1

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You are reading this latest preprint version

Double Trouble-Hyperhomocysteinemia and Lipoprotein(a) Induced Myocardial Infarction in Very Young - A Case Report

Status:

Version 1

Abstract

Background

Case presentation

Conclusion

Figures

Background

Case presentation

(Fig. 1)

(Fig. 2)

(Fig. 4)

(Fig. 5)

Discussion

Study points

Patient perspective

Conclusion

Abbreviations

Declarations

References

Additional Declarations

Status:

Version 1