Study to Evaluate Serum Homocysteine Levels as Marker of Peripheral Arterial Disease in a Tertiary Care Hospital in India

ABSTRACT


INTRODUCTION
Peripheral arterial disease (PAD) is the most common condition affecting the arteries of lower extremity.Compromise of arterial flow due to stenosis and occlusion can result in limb ischemia, which may manifest as claudication, rest pain, local tissue loss (ulceration) and even loss of limb due to amputation.
It adversely affects the functional status of the limb and is associated with poor quality of life.Patients with PAD may also be asymptomatic.These patients have an increased risk of myocardial infarction and stroke.
The most common cause in the lower limb arterial occlusive disease is atherosclerosis. 1 Atherosclerosis is a systemic disease affecting the medium and large arteries.The pathophysiology of this disease involves the accumulation of fibrin and lipid between the tunica intima and media of the blood vessel leading to narrowing of the vessel lumen.This results in decreased blood flow which may lead to ischemia.It is called disease 3 , especially of the systemic type.
Atherosclerosis, inflammation and thrombosis are the most common causes of decreased peripheral blood flow. 420% -50% Peripheral Arterial Disease (PAD) cases are asymptomatic while 10% -35% present with claudication pain and another 20% present with nonspecific local symptoms 5 .
Diagnosis of PAD is critical because people with PAD have 4-5 times the risk of a heart attack or a stroke than the age-matched population. 6These asymptomatic patients realize their predicament too late, even for secondary prevention.They continue to smoke and are non-compliant with medications for diabetes mellitus as they are asymptomatic and lead a comfortable life, therefore not needing to change their current lifestyle.It is a known fact and proven by studies that prevalence of PAD is associated with diabetes Homocysteine is prothrombotic, atherogenic agent, it promotes endothelial cell damage, platelet hyperactivity, and the production of abnormal clotting factors leading to the development of thromboembolic plaques in the coronary, carotid, and peripheral vascular systems and confers an independent risk of vascular disease similar to that of smoking or hyperlipidemia. 11,12The association is independent of other factors, is consistent across many studies is strong and dose-related, and is biologically plausible.However, the evidence needs to be strengthened by a systematic review of all comparable studies and the demonstration, in randomized trials, that lowering serum homocysteine is followed by a significant reduction in athero thrombotic vascular disease. 13perhomocysteinaemia can be shown in 30% of patients with premature peripheral vascular disease (PVD). 12Long-term survival in patients with lower extremity PVD is greatly diminished as a result of atherosclerotic complications in the coronary and cerebrovascular beds, hence primary therapy should be directed at treating the generalized atherosclerotic process i.e. the management of lipids, blood sugar, and blood pressure and therefore monitoring of homocysteine (Hcy) levels in such patients and primary treatment to lower the raised titers along with early referrals aid in improving the prognosis of those with PVD. 14,15

Study Design
Hospital based; single center prospective observational study.

Study population
All the cases PVD admitting in hospital in the one year period meeting the inclusion and exclusion criteria.

Study area
Department of Surgery in a tertiary care government hospital in West India with attached Medical College.

Sample size
Sample size was established as 84 patients was calculated at 95% confidence at 80% power to predict the severity of PAD patients at 67.75 predictability.

Inclusion Criteria
• All diagnosis of peripheral vascular disease of upper and/or lower limbs in which Doppler ultrasound was done.

Exclusion Criteria
• Ongoing or previously treated for hyperhomocysteinemia.

Procedure
The patients were identified with symptoms and/or signs of peripheral arterial disease visiting OPD and Emergency Department were included in study.Serum homocysteine was sent in these patients along with preliminary Doppler USG.

STATISTICAL ANALYSIS
Descriptive statistics was done measuring mean and proportions.
Kruskal-Wallis test were done for logistic regression analysis.All statistical calculations documented in this report were done using SPSS (Online free version).For statistical calculations a p value of <0.5 considered as significant.

RESULTS
The study included 84 patients.However its role as marker of severity of PVD is yet to be tested and this study aimed to assess and establish Hcy as a reliable predictor of severity in PVD so that lowering homocysteine levels with multivitamin therapy becomes an additional established protocol in the treatment of PAD and may also be used as an effective screening tool in suspected subsets of population.Homocysteine is prothrombotic, atherogenic agent, it promotes endothelial cell damage, platelet hyperactivity, and the production of abnormal clotting factors leading to the development of thromboembolic plaques in the coronary, carotid, and peripheral vascular systems and thereby confers an independent risk of vascular disease similar to that of smoking or hyperlipidaemia. 17

Study to
Homocysteine levels were not specifically raised in smokers or in those with co-morbid status of diabetes or hypertension.
Hyperhomocysteinaemia can be shown in up to 30% of patients with premature PVD as demonstrated by this population-based survey on the prevalence of diabetes and associated diseases conducted in Japanese-Brazilians which reported men in particular with PAD had higher prevalence rates of hyper-homocysteinemia as compared to women (22.7% vs 7.6%). 18 Hence the need to evaluate Hcy as an effective marker and screening tool in mild to moderate cases of PAD in order to diminish the long-term complications in lower extremity PVD as a result of atherosclerotic complications in the coronary and cerebrovascular beds.Highly prevalent in the Indian Subcontinent, vascular occlusive disease is a leading contributor to overall cause of death as a result of myocardial infarction or stroke, significant disability and loss of function which result in an enormous cost in impaired quality of life for our aging population and hence implementation of newer management; diagnostic and treatment protocols will aid is better prevention of PVD related morbidity and mortality.
We recommend more studies with larger sample for greater insights into the subject for confirming the association between homocysteine levels and severity of PVD for effective management of the patient.
Hcy with severity of PVDThis study showed a significant association of Serum homocyteine levels with moderate severity of PVD but Hcy levels did not correlate with mild and severe cases of PVD probably due to rampant use of multivitamins and necessitates further clinical trials on a larger population and preferably in different regions.DISCUSSIONRaised Homocystien levels is a well-established risk factor for coronary and peripheral vascular disease and it should be suspected especially in young patients in whom other risk factors are absent and with a gene frequency between one in 70 and one in 200 this condition may be more common than previously thought.16A study was done in Department of General Surgery, tertiary care government hospital in western India showed that patients with hyper-homocysteinemia had a four-fold increase in risk of PVD relative to patients with a normal Homocysteine level.These observations were in spite of no significant difference between the two groups with respect to various other factors such as patient demographics, biochemical risk factors, and disease pattern and severity etc.
Primary therapy should be directed at treating the generalized atherosclerotic process i.e. the management of lipids, blood sugar, and blood pressure and monitoring of homocysteine levels in such patients 15 and primary treatment to lower the raised titers along with early referrals aid in improving the prognosis of those diagnosed with PVD and in those in whom clinical presentations are yet to manifest.Folic acid and multivitamin drugs are the recommended treatment for raised homocysteine levels and can be included in the standard treatment regimen of PAD once high levels are detected. 1Compared with nonusers of vitamin supplements, the small number of subjects taking such vitamins appeared to have a substantially lower risk of vascular disease, a proportion of which was attributable to lower plasma homocysteine levels as per Case-control study published as The European Concerted Action Project,1995 where a total of 750 cases of atherosclerotic vascular disease (cardiac, cerebral, and peripheral) and 800 controls of both sexes younger than 60 years were studied across nineteen centres in 9 European countries.

to Evaluate Serum Homocysteine Levels as Marker of Peripheral Arterial Disease in a Tertiary Care Hospital in India 2174 Volume 03 Issue 10 October 2023 Corresponding Author: Dr Gaurav Gupta
The prevalence of peripheral arteries disease increases with age affecting up to 65% of patients over the age of 41 years.The age and sex distribution are in accordance with the general demographics of peripheral arteries disease, the incidence of which increases with age, from approximately 0.3%/year for Study