CORONARY ARTERY DISEASE – in the Indian—Sitting on the volcano
There is a strong possibility of a genetic risk factor with a high prevalence of CAD and CVD in Indians and South Asians. The incidence, prevalence, and mortality, from premature CAD, in Indians and other South Asians have been among the highest reported for any ethnic group in different countries. The prevalence of CAD is 89% – 300% higher among Indian men than among whites in the US. The CAD mortality rates have been declining in the Indian diasporas, but the rate of decline is slower than the rates for those born in the UK, Many studies confirm a higher morbidity and mortality in South Asians than in whites following AMI, percutaneous coronary intervention (PCI), or coronary artery bypass graft(CABG) surgery.
India is experiencing an escalating epidemic of CAD and CVD. The contribution of CVD to total deaths and disease burden in India has almost doubled since 1990. In 2016, an estimated 2.8 million Indians died from CVD. Overall, CVD contributed to 28% of the total deaths in India in 2016, compared to 15% in 1990. The burden of CVD varies markedly within India, with Kerala, Punjab, and Tamil Nadu having the highest prevalence of CAD, high cholesterol, and high blood pressure. CVD has now become the leading cause of mortality in all parts of India, including the poorer states and rural areas. The prevalence of CAD has increased seven-fold in urban India and fourfold in rural areas between 1970 and 2013. Current prevalence of 14% in the urban and 7% in the rural populations. The number of patients with CAD also increased to 24 million in2016. CAD was the leading cause of deaths (18% of all deaths) while stroke was the fifth leading cause (7% of total deaths) in India in2016.
India currently has the highest burden of acute coronary syndrome (ACS) and ST-elevation MI (STEMI) in the world. ST-elevation MI is the common form of presentation accounting for two-thirds of all Acute MI in India Recent estimates from the global burden of disease (GBD) study shows that between1990 and 2010, CAD mortality in South Asia increased by 88%compared to a 35% decline globally. The number of CAD deaths in South Asia is predicted to increase by another 50% by 2030, unless aggressive preventive efforts are undertaken.
Premature CVD deaths in Indians
The GBD (global burden disease ) task force has defined premature CVD mortality as CVD deaths occurring in people aged<70 years. In the Million Death Study, 62% of all CVD deaths in India were premature deaths.
Malignant CAD in young Indians
Indians are particularly susceptible to premature CAD leading to AMI at an earlier age. In a study of 877 patients with angiographically documented CAD in India, more than one-half of patients were <55 years and one-third were <45 years, with a mean age of 48 years. Despite the young age, multivessel disease (MVD) which includes double-vessel disease (DVD), three-vessel disease (TVD), and left main disease was found in 79% of patients. Additionally, coronary atherosclerosis was generally diffuse with multiple sites of obstruction in most vessels. In another large Indian study, the median age of CABG surgery was 60 years; 6% of CABG was performed in those aged <45 years. Extreme premature ‘Malignant CAD’ is a term coined by Enas and Mehta in 1995, wherein they highlighted the unique features of CAD in young Indians. The 3 hallmarks of malignant CAD in Indians are (1) extreme prematurity, (2) extreme severity, and (3) high mortality at a young age. A notable element, that can be considered the fourth feature of malignant CAD, is that established risk factors are at low levels or absent.
CAD in young people (aged <45 years in men and <50 years in women) is strikingly more common in Indians – 10% to 15% of all CAD – compared to 2% – 5% reported in Western populations.
In a large single-centre study of patients with ACS (n = 8268) in India, 820 (10%) were aged <40 years (with a mean age of 35years). Strikingly, 611 (75%) of those aged <40 years had STEMI.
In Western countries, angiographic studies of young patients with AMI reveal less extensive and less severe coronary atherosclerosis, often limited to single-vessel disease, or no disease at all, resulting in relatively good short-term and long-term prognosis. In sharp contrast, coronary atherosclerosis in young Indians is clinically aggressive, severe, extensive, diffuse, and malignant, often resembling the disease pattern of older individuals. These features are typically found in patients with diabetes but are also common in young Indians without diabetes. This phenomenon may be termed diabetic-like coronary arteries in the absence of diabetes. Overall, TVD is found in nearly half of all young Indians and one-third of premenopausal women undergoing coronary angiography for clinical indications. Epidemiologic data suggest a complex relationship between risk factors, CAD severity, and CAD events. Contrary to the commonly held notion, Indians, in general, do not have small coronary arteries; only Indians with a smaller body habitus have smaller coronary arteries. Coronary artery size, when indexed to the body surface area, is not statistically different in Indian men and women and compared to Caucasians. However, many South Asians have extensive and diffuse atherosclerosis and greater plaque burden throughout the arteries, which may masquerade and get misinterpreted as small coronary arteries on angiography.
High CAD mortality rates
Diabetes and established risk factors insufficient to explain malignant CAD
Although the modifiable established risk factors (dyslipidemia, hypertension, smoking, and diabetes) are undoubtedly major contributors to CAD, they do not fully explain malignant CAD in young Indians and point to the presence of other drivers. Approximately 25 – 30% of Indian patients with CAD have total cholesterol <150 mg/dl and/or LDL<100 mg/dl. Cholesterol and LDL-C levels in Indians with and without CAD are 20 – 30 mg/dl lower than those in their Western counterparts. The prevalence of diabetes in Indians of all ages is 3 – 4 times higher than that in whites in the UK and the US. Although diabetes is a major contributor to CAD in the middle-aged individuals, its prevalence is low, in the range of 5 – 15% in young Indians. In the INTERHEART study, the prevalence of diabetes in South Asians aged <40 years was <1%.
Strikingly, Indians develop more metabolic abnormalities and metabolic syndrome at a lower BMI. But high prevalence of insulin resistance, metabolic syndrome, and diabetes have failed to explain the heightened incidence of CAD in Indians and other South Asians in prospective studies in Trinidad and the UK. Compared to whites, all minorities in the US have higher rates of diabetes but lower rates of CAD, except for Indians.
In view of such a high incidence of cardiovascular disease we require intense screening for primary prevention.
Assessment of cardiovascular risk can be done by taking the following parameters into consideration. There are risk enhancing factors for clinician-patient risk calculation –
Family history of premature CAD (males, age <55y; females, age <65 y)
Primary hypercholesterolemia (LDL -C, 160-189 mg/dL [4.1-4.8 mmol/L]; non-HDL-C 190-219 mg/dL [4.9-5.6 mmol/L]
Metabolic syndrome (increased waist circumference [by ethnically appropriate cutpoints], elevated triglycerides [>150 mg/dL, nonfasting], elevated blood pressure, elevated glucose, and low HDL-C [<40 mg/dL in men, <50mg/dL in women] are factors, a tally of 3 makes the diagnosis)
Chronic kidney disease (estimated glomerular filtration rate 15-59 mL/min/1.73 m2 with our without albuminuria; not treated with dialysis or kidney transplantation)
Chronic inflammatory conditions such as psoriasis, rheumatoid arthritis, lupus or HIV/AIDS
History of premature menopause (before age 40 years) and history of pregnancy-associated conditions that increase later CAD risk, such as preeclampsia
High – risk race/ethnicity (e.g South Asian ancestry)
Lipids/biomarkers: associated with increased CAD risk
- Ankle-brachial indices (<0.9)
Dr. Anand Pandey, Director & Senior – Cardiology, Dharamshila Narayana Superspeciality Hospital, Delhi