|Year : 2020 | Volume
| Issue : 2 | Page : 42-46
Clinical and angiographic profile of premature heart attack in patients with family history of premature coronary heart disease: A substudy of the PCAD registry (Registered under the Clinical Trials Registry of India [CTRI/2018/03/012544])
Rahul S Patil, CM Satvic, Laxmi H Shetty, HS Natraj Setty, Spandana Komma, Anesh Rajesh Jain, TR Raghu, CN Manjunath
Department of Cardiology, Sri Jayadeva Institute of Cardiovascular Sciences and Research, Bengaluru, Karnataka, India
|Date of Submission||13-May-2020|
|Date of Acceptance||10-Jun-2020|
|Date of Web Publication||27-Jul-2020|
Dr. Rahul S Patil
Consultant Cardiologist and Head, Project P.C.A.D Room, 7th floor North Block, Jayadeva institute of Cardiovascular Sciences, Jayanagar, Bangalore - 560 069, Karnataka
Source of Support: None, Conflict of Interest: None
Aim: The aim is to study the clinical, social, biochemical, and angiographic profile of youth (under 35 years) with familial premature coronary artery disease (PCAD). Subjects and Methods: The PCAD registry is a prospective ongoing descriptive observational study of Indians aged below 40 years with coronary artery disease (CAD) which was started on April 1, 2017. Of 3450 patients registered in the PCAD registry till date, 1628 patients were aged 35 years or younger. Of these 1628 patients, 218 satisfied entry criteria. The entire clinical and angiographic profile of these patients was documented. The distribution of different lipid profile parameters was visualized by nonparametric density plot. The data were analyzed by statistical software R version 3.5.0. Results: Of 3450 patients registered in the PCAD registry till date, 1628 patients were aged ≤ 35 years. Two hundred and eighteen out of these 1628 patients (13.39%) belonged to the study group for this particular study. The mean age of all patients under the PCAD registry was 30.44 years, and 201 (92.2%) were males. 106 (48.62%) were smokers. Twenty-nine patients (13.33%) of them were diabetic. The most common index presentation of CAD in familial PCAD was with ST-elevation myocardial infarction (STEMI; 112 patients – 51.37%) and unstable angina/non-STEMI (58 patients – 26.6%). Forty-eight patients (22.01%) presented with evolved MI. Conclusions: Almost 14% of coronary events in younger age (under 35 years) were attributable to family history of CAD. Family history of CAD can be used as a criterion to select younger age population to perform targeted screening for cardiovascular diseases.
Keywords: Family history of cardiovascular diseases, premature coronary artery disease, prospective observational study
|How to cite this article:|
Patil RS, Satvic C M, Shetty LH, Natraj Setty H S, Komma S, Jain AR, Raghu T R, Manjunath C N. Clinical and angiographic profile of premature heart attack in patients with family history of premature coronary heart disease: A substudy of the PCAD registry (Registered under the Clinical Trials Registry of India [CTRI/2018/03/012544]). Res Cardiovasc Med 2020;9:42-6
|How to cite this URL:|
Patil RS, Satvic C M, Shetty LH, Natraj Setty H S, Komma S, Jain AR, Raghu T R, Manjunath C N. Clinical and angiographic profile of premature heart attack in patients with family history of premature coronary heart disease: A substudy of the PCAD registry (Registered under the Clinical Trials Registry of India [CTRI/2018/03/012544]). Res Cardiovasc Med [serial online] 2020 [cited 2020 Oct 24];9:42-6. Available from: https://www.rcvmonline.com/text.asp?2020/9/2/42/290865
| Introduction|| |
Family history of premature coronary heart disease (CHD) (<55 years in first-degree male relatives and <65 years in female relatives) is a traditional risk factor for future coronary artery disease (CAD). Depending on the definition used, family history confers a relative risk for developing CAD that ranges from 2–12 times that in the general population. A positive family history was considered if there was presence of angina, myocardial infarction (MI), angioplasty, or coronary artery bypass surgery.
In a large, prospective study, Andresdottir et al. reported that 15% of coronary events were attributable to family history of CAD when they used a history of MI at any age (not premature coronary artery disease [PCAD]) in first-degree relatives.
The long-recognized familial clustering of CAD suggests that genetics plays a central role in its development, with the heritability of CAD and MI estimated at approximately 50%–60%. Understanding the genetic architecture of CAD and MI has proven to be difficult and costly due to the heterogeneity of clinical CAD and the underlying multidecade complex pathophysiological processes that involve both genetic and environmental interactions.
The “common soil” hypothesis  suggests that a family history of cardiovascular disease (CVD) increases the risk of type 2 diabetes through the common predispositions of obesity,, hypertension, metabolic syndrome, and other pathways, whereas several studies  have shown that a family history of diabetes can increase cardiovascular risk, including subclinical atherosclerosis.
Studies suggest that having a family history of CHD confers additional type 2 diabetes risk among those with a parental history of diabetes. They also indicate that genetic predisposition to type 2 diabetes mellitus is associated with elevated risk of severe CAD.
An association between family history of premature CHD and the presence of any coronary artery calcification (CAC), as well as advanced CAC, was observed in the population-based multiethnic study. The relationship was independent of other risk factors and Framingham Risk Score.
Atherosclerosis is a chronic inflammatory condition which starts from young age itself  and depends on many factors; the most important one is dyslipoproteinemia, i.e., lipid metabolism disturbance. Studies have shown that atherosclerotic plaques or their precursors could be seen in children younger than 10 years. During later life, effect of sedentary lifestyle, coupled with unhealthy nutrition, smoking, alcohol consumption, obesity, and family history of CVD accelerates atherosclerotic disease. Atherosclerosis is a prerequisite for different diseases such as acute MI, stroke, peripheral vascular disease, and many others.
PCAD by definition occurs at a younger age (before the age of 55 years in men and 65 years in women). In its severe form, PCAD occurs below the age of 40 years. CVD is the leading cause (28%) of death in India. The annual CVD mortality in India was predicted to rise to 4.77 million  making India the CVD capital of the world by 2020. The risk of CAD in Asian Indians is 4 times Caucasians, 6 times Chinese, and 20 times Japanese. Indians are prone to CAD at a much younger age. Approximately 50% of first heart attacks occur before 55 years and 25% occur before 40 years of age.
| Subjects and Methods|| |
The PCAD registry is a prospective multisite descriptive observational study examining a cohort of young Indian adults aged ≤40 years with CAD from the point of index admission till a period of 5 years. This is registered under the Clinical Trials Registry of India (CTRI/2018/03/012544). This study proposal was fully accepted and cleared by the Institutional ethical committee of Sri. Jayadeva institute of cardiovascular sciences.
This registry included all patients with index admission for ischemic heart disease, as proven by (1) documented episode of acute coronary syndrome and (2) chronic stable angina with documented evidence of CAD. Moreover, patients (1) with myocarditis, cardiomyopathies, and pulmonary embolism; (2) who previously diagnosed case of CAD or on medications such as antiplatelets and statins; and (3) with chronic kidney disease, liver failure, consumption of oral contraceptives, and steroids were excluded from the study.
Once admitted into the hospital, patients who satisfied the entry criteria for age group were selected. Demographic factors such as age, gender, and address; socioeconomic factors such as occupation, income, marital history, and religion; and risk factor profiles such as the presence of smoking, diabetes, hypertension, and family history were all recorded.
Presentation to hospital, window period from onset of symptoms to arrival in hospital, primary method of management, course in hospital, and echo on admission were all documented.
Biochemical and hematological profile was documented. About 5 ml of patients' venous blood sample was collected in plain vacutainers even before the first dose of cardiac drugs was administered and sent for assessment. The blood was subjected to centrifugation at 3500 rpm for 10 min, and the separated serum was used for the estimation of routine lipid profile. Total cholesterol and triglycerides (TGs) were estimated using commercially available kits (Accurex Biomedical Pvt. Ltd., Mumbai, Maharashtra, India). Measurement of direct low-density lipoprotein cholesterol (LDL-C) was done by enzymatic homogeneous colorimetric assay using Cobas Gen3. C502 analyzer.
Body mass was measured using a portable electronic scale to the nearest 0.1 kg. Height was measured to the nearest 0.1 cm using a portable wall-mounted stadiometer. Waist (just above the iliac crest) and hip (the widest part of the hips at the middle of the pelvis) circumferences were measured to the nearest 0.1 cm. Body mass index (BMI) was calculated as body weight (kg) divided by height squared (m).
Coronary angiographic profile and mode of intervention (if any) were all documented.
The qualitative data were summarized by count and percentage, whereas quantitative data were tabulated by descriptive statistics such as mean, median, standard deviation, interquartile range, minimum, and maximum. Some extreme values of lipid profile were excluded (above the 99th percentile) to prevent the data from asymmetric shape.
The data were analyzed by R statistical analysis and computing language version 3.5.1 (R core team, 2018, R Foundation for Statistical Computing, Vienna, Austria), which are released under the GNU General Public License, version 2, published by the free software foundation.
| Results|| |
A total of 3450 patients were registered under the PCAD registry during the 3 years (2017–2020). Two hundred and eighteen out of a total of 1628 patients (13.39%) under 35 years of age registered under the PCAD registry belonged to the study group for this particular study. The mean age of all patients under the PCAD registry was 30.44 years. [Figure 1] shows graph of age distribution of patients. Two patients (0.9%) were aged <20 years, 16 patients (7.33%) in 20–25 years' age group, 68 patients (31.19%) in 25–30 years' age group, and 132 patients (60.55%) in 30–35 years' age group.
A majority of 201 (92.2%) of the patients were males. One hundred and six (48.62%) were smokers. [Table 1] shows table of risk factor distribution of patients. Twenty-nine patients (13.33%) of them were diabetic and 27 patients (12.33%) was hypertensive. Twenty-six (11.92%) were previously diagnosed with dyslipidemia. Eighty-two patients (37.16%) gave a history of alcohol consumption.
The most common index presentation of CAD in familial PCAD was with ST-elevation MI (STEMI; 112 patients – 51.37%) and unstable angina/non-STEMI (58 patients – 26.6%). Forty-eight patients (22.01%) presented with evolved MI.
The mean total cholesterol of the entire study population was 178.51 ± 47.11, LDL was 126.02 ± 84.81 mg/dl, high-density lipoprotein (HDL) was 29.11 ± 9.64, and TG was 201.57 ± 87.11. The predominant form of dyslipidemia was low HDL cholesterol (HDL-C) and high total with LDL-C.
One hundred eighty-nine patients (87%) underwent coronary angiogram. One hundred and five (55.5%) had CAD, 10 patients (4.58%) had normal coronaries, 42 (19.26%) had recanalized coronaries, and 32 (14.67%) had mild nonflow-limiting atherosclerotic plaques.
Ultimately, 153 out of 218 patients (70.18%) were discharged and continued on optimal medical therapy and follow-up, whereas 65 patients (29.81%) had significant CAD requiring percutaneous coronary intervention (62) or coronary artery bypass grafting (3 patients).
Seventy-two patients (33.02%) were from rural side. Forty-nine patients (22.47%) of patients belonged to Muslim community. Seventy-six patients (34.86%) had polycythemia, whereas 25 patients (11.47%) had mild anemia.
The most common profession among all the patients was driving (61 patients, 27.98%), followed by agriculture (20 patients, 9.17%) and manual laborer (19 patients, 8.71%).
Fifty-one patients (23.39%) were graduates, whereas 34 (15.59%) were educated up to 12th standard and 66 (30.27%) up to 10th standard.
One hundred and twenty-nine patients (59.17%) were covered under the government social security schemes and belonged to below poverty line category. Fourteen patients (6.4%) were vegetarians.
Physical parameters showed that 97 patients (44.49%) had normal BMI, whereas 82 patients (37.61%) had high BMI (47 – overweight and 35 – obese), and 39 patients (17.89%) had BMI which according to the revised BMI classification for south Asian Indians comes under the category of overweight.
Going by waist–hip ratio definition, 176 patients (80.73%) had abdominal obesity, 73 patients (33.48%) had elevated total cholesterol levels, 40 patients (18.34%) had elevated LDL-C, 147 patients (67.43%) had low HDL-C levels, and 75 patients (34.44%) had elevated TG levels.
Among patients presenting with STEMI, 88% were thrombolysed with streptokinase, whereas 12% were thrombolysed with tenecteplase. [Figure 2] shows angiographic profile PCAD patients. [Table 2] shows ultimate mode of management of all PCAD patients.
|Figure 2: Angiographic profile of premature coronary artery disease patients with family history of coronary artery disease|
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|Table 2: Ultimate mode of management of premature coronary artery disease|
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Left ventricular ejection fraction recorded for each of patients showed adequate systolic function (>50%) in 76 patients (34.86%) and moderate LV systolic dysfunction (40%–50%) in 126 patients (57.79%), whereas it was severe LV dysfunction (<40%) in 16 patients (7.34%).
| Discussion|| |
In a large, prospective study, Andresdottir et al. reported that 15% of coronary events were attributable to family history of CAD when they used a history of MI at any age (not PCAD) in first-degree relatives.
Asian Indians have the highest risk of PCAD and diabetes. When compared with Western population, Asian Indians have double the risk of CAD and triple the risk of diabetes mellitus. A cause of concern to developing countries such as India is the incomplete detection, treatment, and control of CAD risk factors. The nonavailability of guidelines for various risk factors with particular reference to Indians hampers treatment.
Although definitions vary, it is well established that the strength of the association between family history and CHD is greatest with earlier age of presentation of CHD in the family member (i.e., premature family history ).
A family history of CHD is associated with an approximately 1.5–2.0-fold higher risk of CHD independent of conventional risk factors, highlighting the contribution of genetic factors to disease susceptibility. PCAD generally makes up to 30%–40% of the total ischemic heart disease population.
Studies suggest that having a family history of CHD confers additional type 2 diabetes risk among those with a parental history of diabetes  and that genetic predisposition to T2D is associated with elevated risk of severe CAD.
A total of 3450 patients were registered under the PCAD registry during the 3 years (2017–2020). One thousand six hundred and twenty-eight patients (47.28%) were under 35 years of age registered under the PCAD registry. Two hundred and eighteen of these 1628 (13.38%) belonged to the study group for this particular study. The mean age of all patients under the PCAD registry was 30.44 years.
A majority of 201 (92.2%) patients were males. The most common risk factor was smoking 106 (48.62%). The presence of diabetes (13.33%), hypertension (12.33%), and dyslipidemia (11.92%) was relatively high among this group compared to nonfamily history PCAD.
The most common index presentation of CAD in familial PCAD was with transmural MI including STEMI (51.37%) and evolved MI (22.01%). Presentation with chronic stable angina was almost negligible.
The predominant form of dyslipidemia was low HDL-C with high total cholesterol and LDL-C. The proportion of Muslim patients in this study group (22.47%) makes it an interesting topic for further research. Hematological derangements (34.86%) had polycythemia, whereas 25 patients (11.47%) had mild anemia and also need to be further studied.
Physical parameters showed that a higher proportion (37.61%) of patients had high BMI (47 – overweight and 35 – obese) and further 39 patients (17.89%) had BMI which according to the revised BMI classification for south Asian Indians comes under the category of overweight.
Going by waist–hip ratio definition, 176 patients (80.73%) had abdominal obesity, 73 patients (33.48%) had elevated total cholesterol levels, 40 patients (18.34%) had elevated LDL-C, and 147 patients (67.43%) had low HDL-C levels. Moreover, 75 patients (34.44%) had elevated TG levels.
Compared to PCAD patients without family history, the incidence of established CAD (55.5%) was higher, and 32 (14.67%) had mild nonflow limiting atherosclerotic plaques.
The proportion of patients requiring coronary revascularization (29.81%) due to significant CAD was higher compared to PCAD patients without family history.
The angiographic profile showed that 55.55% had atherosclerotic CAD, of which 29.81% required intervention which is unusually high compared to other PCAD populations without family history which has predominant thrombus burden responding to antithrombotics ± thrombolysis.
Conventional lipid parameters fail to explain the higher occurrence or severity of CAD in the young Indian population. With respect to the entire study population as a whole, LDL as an independent entity did not seem to be a strong risk factor. Hence, among all the conventional lipid parameters, low HDL-C along with high TGs seems to be the main contributing factor for premature coronary artery in Indians.
Furthermore, risk assessment that considers the entire lipid profile will identify more high-risk individuals than evaluating LDL-C alone. Some epidemiologic data suggest that instead of measuring the cholesterol in LDL or HDL, measuring their respective apolipoproteins, apoB-100, and apoA-I, ratios of lipids and/or apolipoproteins have been better predictors of CHD risk.
Many studies, among them YUSAD study  and Bogalusa study, indicate a close relationship between lipid and nonlipid atherogenic risk factors in early childhood and atherosclerosis development in later life. Identification of the risk factors and their limitation lead to a significant decrease of the possibility of CVD development.
Nevertheless, accumulating evidence from longitudinal studies indicates the early identification of risk in children, particularly for body fat percentage, blood lipids, hypertension, cigarette smoking, and cardiorespiratory fitness. Family history of CAD can be used as a criterion to select a younger age population to perform targeted screening.
We would like to thank Research Coordinator, Mrs. Rani B J, and Research Assistant, Mr. Prateesh, for technical help.
Financial support and sponsorship
This study was financially supported by Sri Jayadeva Institute of Cardiovascular Sciences and Research.
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2]
[Table 1], [Table 2]