Indian Heart Journal 76 (2024) S20–S28

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Indian Heart Journal

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Review Article

Trends in epidemiology of dyslipidemias in India

Sonali Sharma a, Kiran Gaur b, Rajeev Gupta c, *
a
Department of Biochemistry, RUHS College of Medical Sciences, Rajasthan University of Health Sciences, Jaipur, Rajasthan, India
b
Department of Statistics, Mathematics and Computer Science, Government SKN Agriculture University, Jobner, Jaipur, Rajasthan, India
c
Department of Preventive Cardiology & Medicine, Eternal Heart Care Centre & Research Institute, Jaipur, Rajasthan, India

A R T I C L E I N F O A B S T R A C T

Keywords: Dyslipidemias are the most important coronary artery disease (CAD) risk factor. High total cholesterol and its
Dyslipidemias principal subtypes: low-density lipoprotein (LDL) cholesterol and non-high-density lipoprotein (NHDL) choles­
Epidemiology terol are the most important. Epidemiological and Mendelian randomization studies have confirmed role of
Cholesterol
raised triglycerides and lipoprotein(a). INTERHEART study reported a significant association of raised ApoB/
LDL cholesterol
ApoA1, total-, LDL-, and NHDL-cholesterol in South Asians. Prospective Urban Rural Epidemiology (PURE) study
identified raised NHDL cholesterol as the most important risk factor. Regional and multisite epidemiological
studies in India have reported increasing population levels of total-, LDL-, and NHDL cholesterol and tri­
glycerides. India Heart Watch reported higher prevalence of total and LDL cholesterol in northern and western
Indian cities. ICMR-INDIAB study reported regional variations in hypercholesterolemia (≥200 mg/dl) from 4.6 %
to 50.3 %, with greater prevalence in northern states, Kerala, Goa, and West Bengal. Non-Communicable Disease
Risk Factor Collaboration and Global Burden of Diseases Studies have reported increasing LDL- and NHDL-
cholesterol in India. Studies among emigrant Indians in UK and USA have reported higher triglycerides in
compared to Caucasians. Identification of regional variations and trends in dyslipidemias need more nationwide
surveys. Prospective studies are needed to assess quantum of risk with CAD incidence.

1. Introduction
Importance of cholesterol lipoproteins in pathogenesis of athero­
sclerosis has been known for a long time. Hundreds of thousands of
studies have confirmed their role in the initiation, progression and
perpetuation of atherosclerosis and in etiopathogenesis of acute and
chronic coronary artery disease (CAD).1 High total cholesterol and its
principal subtype low-density lipoprotein cholesterol (LDL-C) are the
most important risk factors for atherosclerosis and scientific statements
from most learned international and national cardiovascular societies
have repeatedly confirmed their importance.2–4 There is a plethora of
evidence of significant direct epidemiological and genetic association of
raised total and LDL-C with the incidence of CAD events.4,5 Moreover,
strong clinical trial evidence exists for the benefits of reduction of total
and LDL-C by lifestyle or drugs with decreased CAD incidence.5 These
studies, thus, fulfil the Bradford–Hill criteria of causality (strength of
association, consistency, specificity, temporality, biological gradient,
plausibility, coherence, experiment and analogy) and confirm their
importance in CAD.6 In addition to raised LDL-C, recent epidemiological
and Mendelian randomization (genetic) studies and clinical trials have
reported the emerging importance of raised non-high-density lipopro­
tein (NHDL) cholesterol, triglycerides and lipoprotein(a) in atheroscle­
rosis and CAD.7 These studies have also reported a lack of clinical trial
evidence of the importance of high-density lipoprotein (HDL) choles­
terol in CAD, therefore, this has been relegated to a risk-marker and not
a causal risk factor.
Coronary artery disease epidemic was rampant in most developed
countries in the middle of the last century. Better risk factor control
(especially total and LDL cholesterol) and high-quality disease man­
agement have led to its decline by 60–90 % in most of these developed
countries of Western Europe and North America in the last 50–60 years.
On the other hand, in India and many developing countries, CAD is
increasing both in terms of mortality and disease burden. Risk factors for
the epidemic of CAD are well known and include multiple lifestyle and
metabolic factors.6 The case–control INTERHEART study in 52 countries
reported that nine standard risk factors explained more than 90 % of
acute myocardial infarctions (Table 1).8 More recently, Prospective
Urban Rural Epidemiology (PURE) study reported that a dozen

* Corresponding author. Department of Preventive Cardiology and Medicine, Eternal Heart Care Centre & Research Institute, Jawahar Circle, Jaipur, Rajasthan,
India.
E-mail addresses: rajeevgg@gmail.com, drrajeev.gupta@eternmalheart.org (R. Gupta).

https://doi.org/10.1016/j.ihj.2023.11.266
Received 8 October 2023; Received in revised form 16 November 2023; Accepted 24 November 2023
Available online 12 February 2024
0019-4832/© 2023 Cardiological Society of India. Published by Elsevier, a division of RELX India, Pvt. Ltd. This is an open access article under the CC BY-NC-ND
license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
S. Sharma et al. Indian Heart Journal 76 (2024) S20–S28

Table 1 Table 2
Important CAD risk factors: Evidence from cross-sectional INTERHEART and Prevalence of hypercholesterolemia (≥200 mg/dl) in multisite Indian studies.
prospective PURE studies.8,9 Study and Sites Reference Year Sample Prevalence (%)
Risk Factors INTERHEART PURE reported size
Men Women
Lifestyle ● Smoking and tobacco use ● Smoking and tobacco use
Indian Industrial 14 2006 10,442 25.1a b
factors ● Unhealthy diet ● Unhealthy diet, Sodium
Population
● Physical inactivity intake
Surveillance Study:
● Alcohola ● Physical inactivity
Urban
● Household air pollution
India Migration Study: 15 2010 1983 21.1 27.8
Metabolic ● Abnormal lipids (ApoB/ ● NHDL cholesterol
Rural
factors ApoA1) ● Hypertension
ICMR Integrated 16 2010 15,223 31.7 32.8
● Hypertension ● Diabetes
Disease Surveillance
● Abdominal obesity ● Abdominal obesity
Project: Urban
● Diabetes ● Grip strength
ICMR Integrated 16 2010 13,517 19.5 26.4
Social factors ● Psychosocial stress ● Low education
Disease Surveillance
● Depression ● Psychosocial stress
Project: Rural
● Depression
ICMR Integrated 16 2010 15,751 18.1 23.4
a
Alcohol protective in global populations, harmful in South Asians.Apo: Disease Surveillance
apolipoprotein; NHDL: non-high-density lipoprotein. Project: Periurban/
Urban Slum
Indian Women’s Health 17 2013 2008 c 27.7
well-known risk factors explained more than 65–70 % of incident car­ Study: Urban
diovascular and CAD events in low, middle, and high-income countries Indian Women’s Health 17 2013 2616 c 13.5
Study: Rural
(Table 1).9
India Heart Watch: 18 2014 6123 25.1 24.9
A comparative chart shows that cardiometabolic factors such as Urban
abnormal lipids (NHDL cholesterol), hypertension and diabetes and a ICMR INDIAB Study: 19 2014 2042 13.9 a
b
few lifestyle factors (smoking, pollution and low education) are the most Rural & Urban
important factors of risk and confer the highest population-attributable ICMR INDIAB Study: 21 2023 18,492 23.2 24.8
Rural & Urban
risk. In this article, we shall focus on the epidemiology of various forms
a
of dyslipidemias that have been identified as important in CAD (total Prevalence for men and women combined.
b
cholesterol, LDL cholesterol, NHDL cholesterol and triglycerides), Sex-specific data not available.
c
particularly with reference to India. We shall describe the epidemiology Only women participated in this study.
of each of these dyslipidemias in Indian studies and contextualize this
with the global prevalence using data from Global Burden of Disease 11.8 %.19 A study that utilized hospital administrative database at Jai­
(GBD) study,10 and Non-Communicable Risk Factor Collaboration pur of more than 67,000 participants reported prevalence of various
(NCDRisC).11 dyslipidaemias.20 In this cohort of mostly middle class men and women,
prevalence of various dyslipidemias was total cholesterol ≥200 mg/dl in
2. Total cholesterol 30.5 % and high LDL-C (>130 mg/dl) in 31.8 %. These prevalence rates
are much lower than in studies from the US and other developed
Epidemiological studies in first half of the last century evaluated role countries. In the recent nationwide ICMR-INDIAB study,21 which is the
of total cholesterol in CAD following pathological observations of most comprehensive cardiovascular risk factor assessment study in the
cholesterol-rich atheroma and cholesterol-laden macrophages in the country, the prevalence of various dyslipidemias has been reported as:
atherosclerotic plaque. Measurement of total cholesterol is simple and hypercholesterolemia ≥200 mg/dl 24.0 %, high LDL cholesterol >130
widely available, and it is the measurement of choice in most parts of the mg/dl 20.9 %, low HDL cholesterol 66.9 %, and hypertriglyceridemia
world. Prospective data from the Framingham and many other studies 32.1 %.21
reported a strong correlation of raised cholesterol with greater CAD There are regional differences in the prevalence of hypercholester­
incidence and mortality.12 olemia in India.13 In the India Heart Watch study, cities were classified
into tertiles of Human Development Index (HDI). Developed states had
greater prevalence of cholesterol-related dyslipidemias such as hyper­
2.1. Indian studies
cholesterolemia and high LDL cholesterol (Fig. 1).22 This is similar to the
greater prevalence of cardiometabolic risk factors—hypertension, dia­
In India, only limited studies exist on epidemiology of cholesterol
betes, and obesity in more developed states of India in National Family
and other lipoprotein lipids on large samples in the last 30 years.13 We
Health Surveys.23 Data from the recent ICMR-INDIAB study (2023) re­
reviewed recent population-based epidemiological studies that focused
ported large interstate and inter-regional variability regarding hyper­
on cardiovascular risk factors including cholesterol levels and found that
cholesterolemia and other dyslipidemias (Fig. 2). The highest
there were only six multisite studies with sample size ranging from 2000
prevalence of high toral cholesterol was in Kerala (50.3 %), Goa (45.6
to 16,000.14–19 None of these studies is nationally representative.
%), and Himachal (39.6 %) while the lowest was in Jharkhand (4.6 %),
Studies with a large sample size are shown in Table 2. Prevalence of
Assam (7.9 %) and Bihar (9.7 %).21 A detailed description of the prev­
hypercholesterolemia in these studies varies from 10 to 15 % in rural to
alence of various dyslipidemias (raised total and LDL cholesterol and
25–30 % in urban populations. In the India Heart Watch study among
triglycerides and low HDL cholesterol) in all the large Indian states is
urban middle class subjects in 11 cities of India,18 the prevalence of
provided in Table 3.
various cholesterol lipoprotein abnormalities after age-adjustment in
Changing trends in prevalence of hypercholesterolemia have been
men and women were: raised total cholesterol ≥200 mg/dl in 25.1 %
studied in only a few cross-sectional studies. In Jaipur Heart Watch, we
and 24.9 %; raised LDL-C ≥130 mg/dl in 16.3 % and 15.1 % and ≥100
conducted a series of cross-sectional studies over 25-year period from
mg/dl in 49.5 % and 49.7 %; raised NHDL cholesterol ≥160 mg/dl in
1991 to 2015 to identify trends in various cardiovascular risk factors in
23.6 % and 22.2 % and ≥130 mg/dl in 54.6 % and 55.1 %, respec­
urban Indian population.24,25 Prevalence of hypercholesterolemia
tively.18 The prevalence rates of various dyslipidemia in the first phase
(≥200 mg/dl) over this period is shown in Fig. 3 and shows a slightly
of ICMR-INDIAB study restricted to urban and rural populations in four
increasing trend. Time-interrupted cross-sectional studies from other
states in India was hypercholesterolemia in 13.9 % and high LDL-C in

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Fig. 1. Geographic variations in prevalence of various dyslipidemias in different regions of India in the India Heart Watch. Definitions are-hypercholesterolemia
≥200 mg/dl, high LDL cholesterol ≥130 mg/dl, low HDL cholesterol <40 mg/dl in men and <50 mg/dl in women, and hypertriglyceridemia ≥150 mg/dl. Data
source: India Heart Watch.18,22

Fig. 2. State-level variation in the prevalence of various dyslipidemias in India. Definitions are-hypercholesterolemia ≥200 mg/dl, hypertriglyceridemia ≥150 mg/
dl, high LDL cholesterol ≥130 mg/dl, low HDL cholesterol <40 mg/dl in men/<50 mg/dl in women. Data Source: ICMR-INDIAB study.21

regions of India (Delhi, Punjab, Vellore, etc.), also reported similar
trends.26–28
NCDRisC investigators has reported secular trends in mean total
cholesterol levels and other lipid parameters in almost all countries
across the globe.29 In contrast to the GBD study where data are sum­
marized based on many sociodemographic variables using artificial in­
telligence technology and advanced statistical software, in the NCDRisC
the investigators collate available regional and national studies and
perform Bayesian analyses to arrive at conclusions.30 Trends for India
are shown in Fig. 4 and reveal that mean cholesterol levels have slightly
increased from the year 1980–2018. These are similar to data from the
JHW studies shown in Fig. 3 and highlight the fact that there is no
macrolevel correlation of total cholesterol level with increasing trends in
CAD in India.13 This is in contrast to the decrease of total cholesterol
levels in USA and other developed countries where declining cholesterol
levels correlate well with the reducing CAD incidence.29
2.2. Global scenario
Global Burden of Metabolic Risk Factors Collaboration reported
trends in mean cholesterol levels in various regions and countries of the
world from 1994 to 2009.30 During this period, the mean cholesterol
levels declined in high-income countries in North America and Western
Europe, remained static in Central and Eastern Europe and Latin
America and increased in South Asia and Africa.30 Trends in total
cholesterol levels in 10 most populous countries show a similar pattern:
Levels are declining in USA and Russia, static in Brazil and China and
either static or increasing in most developing countries.10,11,31 NCDRisC
collaboration has reported that the hub of high cholesterol has shifted
away from Europe and North America to South and Southeast Asia.29
The collaborators evaluated trends in population total cholesterol levels
from the year 1990–2019 and reported that while cholesterol levels are
declining in developed countries, these are increasing in developing
countries of Southeast, South and Central Asia.29

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Table 3 risk factor for CAD that fulfills the Bradford–Hill criteria.6 However, it is
Prevalence (percent, 95 % confidence intervals) of various dyslipidemia in India: only in the past couple of decades that epidemiological studies in India
ICMR-INDIAB Study.21 have focused on LDL-C.
States High total High LDL High Low HDL
cholesterol cholesterol triglycerides cholesterol 3.1. Indian studies
(>200 mg/ (>130 mg/ (>150 mg/dl) (<40/50 mg/
dl) dl) dl men/
women)
Only a limited number of population-based studies from India have
evaluated epidemiology of LDL-C. In the multisite India Heart Watch (n
Andhra 21.6 17.9 39.3 64.2
= 6100), we reported raised LDL-C (>130 mg/dl) in 16.3 % men and
Pradesh (6.3–38.7) (4.3–33.7) (17.5–61.6) (42.8–84.9)
Arunachal 9.6 6.2 32.7 66.7 15.1 % women.18 This was lower than data from a large hospital-based
Pradesh (1.9–17.7) (0.3–12.9) (18.9–46.5) (52.3–80.9) cohort at Jaipur (n = 67395), where raised LDL-C was in 28.1 % men and
Assam 7.9 4.6 (0–12.0) 28 71.1 35.1 % women.21 With the present understanding of harmful effects of
(0.2–18.0) (12.2–44.4) (53.7–87.4) raised LDL-C of >100 mg/dl, a high prevalence in almost half of men
Bihar 9.7 6.2 26.9 73.1
(1.5–18.9) (0.4–13.7) (13.9–40.2) (58.8–87.0)
(49.5 %) and women (49.7 %) was observed in India Heart Watch.18
Chandigarh 26.3 20.0 41.8 65.0 ICMR-INDIAB study has also reported prevalence of low LDL cholesterol
(7.9–46.1) (5.0–36.8) (20.0–66.2) (40.9–86.7) ≥130 mg/dl in 20.9 % of the study population (IQR 17.3–24.5 %) with
Chhattisgarh 17.4 18.0 21.2 74.3 significant state-level variation (Fig. 2). The highest prevalence was in
(5.1–30.5) (5.8–30.8) (8.4–34.4) (59.8–88.3)
Kerala (52.1 %) and Goa (46.8 %) and the lowest in Jharkhand (3.2 %)
Delhi 31.2 26.9 32.8 51.8
(9.5–52.9) (6.3–47.9) (11.8–54.7) (28.0–75.4) and Assam (4.6 %).21 Secular trends in raised LDL-C have been reported
Goa 45.6 46.8 31.6 69.2 in Jaipur Heart Watch studies from 1991 to 2015 (Fig. 3) and show a
(26.7–64.7) (28.3–65.5) (16.1–47.8) (51.2–86.5) high prevalence (40–80 %) of age- and sex-adjusted raised LDL-C (≥100
Gujarat 18.1 16.0 26.9 56.4 mg/dl) in various studies. The observed fluctuating trends could be due
(5.0–31.8) (3.4–29.4) (9.9–44.6) (37.5–74.8)
Haryana 28.1 24.1 32.5 64.5
to differences in indirect (Friedewald-formula based) vs direct estima­
(13.3–43.1) (10.1–38.5) (15.3–50.0) (47.6–81.1) tion of LDL cholesterol. Secular trends in mean LDL-C levels have also
Himachal 39.6 33.6 34.8 61.2 been reported in NCDRisC report (Fig. 4).11 This shows that LDL-C levels
Pradesh (23.0–56.8) (17.8–50.0) (19.7–50.3) (45.2–77.4) have not changed in India over this period, which is similar to the data
Jharkhand 4.6 3.2 (0–8.1) 26.9 75.1
from other Indian studies.13,24,25
(0.2–10.8) (9.8–43.4) (56.4–91.8)
Karnataka 17.1 11.5 41.9 71.1 An important consideration in LDL-C epidemiological studies, espe­
(3.9–31.3) (1.6–23.1) (24.2–59.8) (54.6–87.3) cially relevant to South Asian populations is the absence of data on the
Kerala 50.3 52.1 33.2 67.6 small-dense LDL component. Studies among the emigrant South Asians
(30.3–70.3) (31.9–72.7) (13.6–53.6) (48.4–85.6) in the USA have reported a distinct atherogenic dyslipidemia charac­
Madhya 21.9 23.9 23.7 68.7
Pradesh (7.7–36.5) (9.0–39.2) (10.5–37.8) (51.9–85.1)
terized by high levels of qualitatively abnormal LDL-C particles of
Maharashtra 14.0 13.9 27.9 67.7 smaller size and lower density.32 Other components of this atherogenic
(3.3–25.6) (2.7–26.9) (8.4–47.9) (49.4–84.9) dyslipidemia are low HDL cholesterol and raised triglycerides. More
Manipur 25.8 19.3 43.2 59.9 studies are required in India to identify LDL-C subfractions of impor­
(9.6–42) (5.6–33.4) (26.5–60.3) (42.7–76.7)
tance in CAD pathogenesis.
Meghalaya 10.2 7.6 28.9 80.4
(1.6–19.8) (0.6–16.2) (14.2–44.1) (67.6–92.4)
Mizoram 21.2 12.9 36.7 64.1 3.2. Global scenario
(5.8–37.1) (1.0–26.0) (16.5–57.5) (43.3–84.0)
Nagaland 20.0 15.5 32.5 67.7 The GBD Study reported on the importance of LDL-C in the burden of
(6.1–34.4) (3.4–29.1) (14.8–50.8) (47.9–86.6)
Odisha 24.0 24.2 23.4 67.1
CAD as determined by calculating disability-adjusted life years
(8.9–39.9) (8.6–40.9) (8.5–38.9) (49.4–84.7) (DALYs).10 According to the study, while hypertension and tobacco use
Puducherry 28.9 28.5 43.4 83.1 are the most important risk factors for DALYs in India (2760/100,000
(8.7–50.5) (8.1–50.1) (22.4–65.1) (67.6–95.8) and 2252/100,000, respectively in 2019), those lost due to high LDL-C
Punjab 28.7 19.0 47.9 66.3
(1342/100,000) are also high. Globally, the total number of DALYs
(10.4–48.8) (3.5–36.4) (28.4–68.6) (46.4–84.5)
Rajasthan 36.8 34.8 23.2 52.3 due to high LDL-C has steadily increased since 1990, reaching 98.6
(21.3–52.4) (19.8–50.1) (8.5–38.5) (35.5–68.9) million (95 % confidence intervals, UI 80.3–119.0) in 2019. The number
Sikkim 22.1 19.4 35.3 61.7 of deaths from high LDL-C is estimated to be 4.40 million (UI 3.30–5.65)
(8.2–36.9) (6.4–34.3) (18.5–53.2) (42.5–78.7) in 2019. According to these findings, there is an increasing global trend
Tamil Nadu 22.1 19.8 33.4 71.4
(5.2–39.3) (4.5–35.5) (14.5–53.1) (53.5–87.5)
of deaths from high LDL-C, mainly fueled by increased deaths from CAD
Telangana 23.1 18.1 27.4 58.1 in South Asia. Global rates for DALYs, deaths, and years of life lost (YLLs)
(4.5–42.9) (2.5–37.1) (4.6–52.0) (33.3–82.0) have remained relatively stable between 1990 and 2019, but years lost
Tripura 10.6 6.5 42.3 72.4 with disability (YLDs) have increased. On the other hand,
(1.6–20.7) (0.1–14.9) (25.1–59.4) (56.8–87.5)
age-standardized rates for all of these measures have decreased during
Uttar 23.5 18.9 31.9 65.1
Pradesh (7.0–40.2) (4.1–34.5) (12.8–51.6) (47.0–82.9) this time period. This disparity between all-age rates and
Uttarakhand 33.4 31.3 31.4 67.6 age-standardized rates suggests that while the global burden of
(17.4–49.8) (14.5–48.3) (15.3–47.8) (51.1–83.6) LDL-related disease remains unacceptable, observed increases in the
West Bengal 27.9 25.0 22.7 61.1 burden of DALYs in places such as China and India are driven primarily
(10.3–46.3) (8.1–42.6) (7.0–39.6) (39.0–82.3)
by population growth and ageing. This trend is significant for global
health because it indicates that there has been, at least, some progress in
3. Low-density lipoprotein cholesterol reducing the global burden of LDL-cholesterol-related disease.
Age-standardized DALY rates attributable to high LDL-C are expected to
Low-density lipoprotein-cholesterol (LDL-C) has emerged as the most rise in some regions, including South and West Asia. Presently the
important atherosclerosis risk factor.5,7 A plethora of epidemiological, age-standardized DALYs due to high LDL-C in the GBD study are the
pathophysiological, clinical studies and trials have confirmed LDL-C as a highest in Eastern Europe, North Africa, the Middle East, and Central
Asia. High-income Asia Pacific, Australasia, Western Europe, and

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Fig. 3. 25-year trends in prevalence (percent) of various dyslipidemias in an urban Indian population in the Jaipur Heart Watch (JHW) studies. JHW-1 to JHW-6
from 1991 to 2015. Data source: Jaipur Heart Watch.24,25

Fig. 4. Secular trends in mean total cholesterol, LDL cholesterol and NHDL cholesterol (in mmol/L) among men and women in India from 1980 to 2018. Data source:
NCDRisC Report.11

Andean Latin America have the lowest levels.10 Low physical activity, a
high BMI, dietary patterns, and increased tobacco use are all possible
explanations for these regional differences.
3.3. High density lipoprotein cholesterol
High density lipoprotein cholesterol (HDL-C) has long been regarded
as a protective lipid factor.1,13 This association was first reported in
prospective studies conducted in North America and Europe, but has
now been reported from all over the world.1,33 However, recent clinical
trials have reported that there is a neutral and possibly harmful effect on
cardiovascular events and mortality in trials with various
CETP-inhibitors (torcetrapib, anacetrapib, etc.) where HDL cholesterol
increased by more than 100 %.7 As a result of failing to meet the
Bradford–Hill criteria, HDL cholesterol has been relegated to the status
of a risk-marker rather than a risk factor.34 However, the HDL-C story
appears to be far from over as shown by the results of the cross-sectional
population-based survey, Indian Council of Medical Research-India

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Diabetes (ICMR-INDIAB) study.21 In this study, the most important Table 5

dyslipidemia was low HDL cholesterol and present in more than
two-third of the study population (66.9 %, IQR 62.9–70.9 %). Low HDL
is widely prevalent in all the states of the country (Fig. 2) with smaller
state-level differences as compared to other dyslipidemias. Further
studies are needed to evaluate the contribution of low HDL-C levels to
CVD risk in Indians.
4. Non-high density lipoprotein cholesterol
As NHDL-C is the sum of all atherogenic lipid particles—low density,
intermediate density, and remnant—NHDL cholesterol has now
emerged as an important CAD risk factor.7 NHDL is a poor man’s
apolipoprotein B (apoB) molecule which has now emerged as more
important than the cholesterol fractions.35 The ratio of apoB:apoA1 has
emerged as an important risk factor in multiple ethnic groups in the
INTERHEART study and predicted CAD better than total or HDL
cholesterol (Table 4).36 The Prospective Urban Rural Epidemiology
(PURE) study found NHDL cholesterol to be the most important CAD risk
factor (Table 5).9 While reporting its global epidemiology, NCDRisC also
emphasised the importance of NHDL cholesterol as a global CAD risk
factor.29 NHDL cholesterol has an advantage over LDL-C because it in­
cludes remnant cholesterol and is not affected by triglyceride variability,
which is a major risk factor in Indians.37,38
4.1. Indian studies
The importance of NHDL cholesterol as an important cardiovascular
risk factor was reported in the PURE study in high-, middle-, and low-
income countries (Table 5).9 Indeed, it is the most important risk fac­
tor for CAD, with a population attributable fraction of 17 %, signifi­
cantly higher than risk factors such as hypertension, smoking, and
diabetes. The population attributable risk fraction from elevated NHDL
cholesterol is 14.2 % among South Asians, which is comparable to hy­
pertension (14.3 %) but significantly higher than other important risk
factors such as indoor air pollution (11.9 %), diabetes (10.4 %), and poor
diet (10.1 %) (Fig. 5).9
The study also reported increasing cardiovascular risk with
increasing NHDL cholesterol in groups with value < 125, 125–155 and
> 155 mg/dl for CVD incidence and mortality as well as IHD incidence
and mortality.9 Other than PURE, multiple studies across the globe have
reported that NHDL cholesterol is one of the more important CAD risk
factors.33,37,38
Only limited epidemiological studies from India have reported NHDL
cholesterol. In Jaipur Heart Watch studies (1–5) from 1991 to 2010, we
reported prevalence of raised NHDL >160 mg/dl in about a quarter of
the population while ≥130 mg/dl is observed in more than half
(Table 6).24 The prevalence was higher in the Jaipur Heart Watch-5
study (47.5 %) among middle-class urban participants.39 In the much
larger multicentric India Heart Watch study, prevalence of raised NHDL
cholesterol >160 mg/dl was in 23.0 % (men 23.6, women 22.2) while
that of >130 mg/dl was in 54.9 % (men 54.8 %, women 55.1 %).18 The
large Kerala Cardiovascular Risk Prevalence (CRP) Study reported
prevalence of various dyslipidemias among 5167 adults.40 Raised total
cholesterol was in 52.3 % and low HDL cholesterol in 38.5 %. Data on
Non-HDL Cholesterol as an Important Cardiovascular Risk Factor in the PURE
study.9
Rank Cardiovascular disease incidence & Ischaemic heart disease
mortality (global) incidence (global)
1. Hypertension (22 %) High NHDL cholesterol (17 %)
2. High NHDL cholesterol (8 %) Hypertension (13 %)
3. Household air pollution (7 %) Tobacco use (12 %)
4. Tobacco use (6 %) Abdominal obesity (11 %)
5. Poor diet (6.1) Diabetes (8 %)
6. Low education (6 %) Low education (7 %)
Percentages in parentheses are population attributable fractions (PAF).
NHDL cholesterol were not reported. Secular trends in raised NHDL
cholesterol in India have been reported in the NCDRisC study (Fig. 4).11
Trends show that the mean levels of NHDL cholesterol are increasing
slowly similar to raised LDL-C and Jaipur Heart Watch studies. More
cross-sectional as well as prospective studies are required in India to
identify regional variation, secular trends and association with CAD risk.
4.2. Global studies
According to the NCDRisC report,29 the global age-standardized
mean NHDL cholesterol for women was 128.0 mg/dl and 127.7 mg/dl
for men in 2018; the global age-standardized mean HDL cholesterol for
women was 50.3 mg/dl and 42.7 mg/dl for men. From 1980 to 2018,
global age-standardized mean NHDL cholesterol remained nearly un­
changed, decreasing by only 0.77 mg/dl in women and 0.39 mg/dl in
men per decade.29 Regionally, NHDL cholesterol levels have dropped
significantly in developed Western countries as well as Central and
Eastern Europe. Northwestern Europe experienced the greatest decrease
(11.6 mg/dl per decade). It increased in East, Southeast, and South Asia,
as well as parts of Sub-Saharan Africa. Southeast Asia experienced the
greatest increase, increasing by approximately 7.7 mg/dl per decade.
Belgium, Finland, Greenland, Iceland, Norway, Sweden, Switzerland,
and Malta had some of the highest NHDL cholesterol levels in 1980
(>174 mg/dl in women and >182 mg/dl in men), but have seen some of
the steepest drops. At the extreme, mean NHDL cholesterol decreased by
17.4 mg/dl or more per decade in Belgian and Icelandic people, moving
them from the top 10 countries in terms of NHDL cholesterol in 1980 to
the lower half of the countries in 2018. East Asian countries (for
example, China) and Southeast Asian countries saw the greatest in­
creases. Age-standardized mean NHDL cholesterol increased by up to
8.9 mg/dl per decade in these countries. As a result of these opposing
trends, the countries with the highest age-standardized mean NHDL
cholesterol levels outside of northwestern Europe in 2018 were
Malaysia, the Philippines, and Thailand, all of which had mean NHDL
cholesterol levels >155 mg/dl. High-income countries not only
benefitted from lower NHDL cholesterol levels, but they also had higher
mean HDL cholesterol levels than low- and middle-income countries.
These could be attributed to healthier lifestyles and increased use of
lipid-lowering medications.41

Table 4
Relative risk (95 % confidence intervals) for acute myocardial infarction for 1 SD change in various dyslipidaemias in INTERHEART study.36
South Asians European Chinese Latin American Overall

Total cholesterol 1.23 (1.14–1.31) 1.08 (1.02–1.15) 1.16 (1.09–1.23) 1.05 (0.97–1.14) 1.16 (1.13–1.19)
HDL cholesterol 0.97 (0.90–1.05) 0.78 (0.73–0.83) 0.83 (0.78–0.88) 1.03 (0.94–1.13) 0.85 (0.83–0.88)
NHDL cholesterol 1.23 (1.15–1.31) 1.17 (1.10–1.24) 1.24 (1.18–1.31) 1.04 (0.96–1.28) 1.21 (1.17–1.24)
Apolipoprotein A-1 0.72 (0.66–0.78) 0.70 (0.66–0.75) 0.67 (0.63–0.71) 0.67 (0.61–0.74) 0.67 (0.65–0.70)
Apolipoprotein B 1.38 (1.29–1.48) 1.24 (1.16–1.32) 1.28 (1.20–1.36) 1.18 (1.09–1.28) 1.32 (1.28–1.36)
Total:HDL cholesterol ratio 1.10 (1.04–1.17) 1.31 (1.21–1.42) 1.34 (1.24–1.45) 0.97 (0.90–1.05) 1.17 (1.13–1.20)
Apo B:ApoA-1 ratio 1.53 (1.42–1.64) 1.47 (1.37–1.59) 1.77 (1.63–1.92) 1.27 (1.17–1.38) 1.59 (1.52–1.64)

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S. Sharma et al. Indian Heart Journal 76 (2024) S20–S28

Fig. 5. Population attributable fractions (percent) for various cardiovascular risk factors in the Prospective Urban Rural Epidemiology study shows raised NHDL
cholesterol as the most important cardiovascular risk factor among South Asians. Data source: PURE Study.9

5.1. Indian studies

Table 6
Prevalence of raised Non-HDL cholesterol in Selected Indian studies.
There are limited population-based studies on prevalence of hyper­
Reference Year Sample NHDL NHDL triglyceridemia in India.13,32 When compared with the western pop­
Reported size cholesterol cholesterol
ulations, Indians and migrant South Asians have been reported to have
≥130 mg/dl ≥160 mg/dl
(%) (%) higher triglyceride levels while total cholesterol levels are lower than in
UK and Europeans.44 Low HDL cholesterol and hypertriglyceridemia are
Jaipur 24 1994 276 NA 23.0
Heart
metabolically interlinked and their combination has been termed as
Watch-1 atherogenic dyslipidaemia.45 This is also associated with increased
Jaipur 24 2002 926 66.1 33.5 levels of small-dense LDL particles and insulin resistance. Atherogenic
Heart dyslipidaemia is particularly common in South Asians and has been
Watch-2
shown to have a strong association with type 2 diabetes mellitus,
Jaipur 24 2005 374 58.3 27.4
Heart metabolic syndrome, and CAD.32,45 This could be related to
Watch-3 high-carbohydrate diets in South Asian populations.44,45 In the Jaipur
Jaipur 24 2007 500 60.1 26.6 Heart (JHW) studies we reported a significant increase in prevalence of
Heart hypertriglyceridemia (Fig. 3). In interrupted time-series cross-sectional
Watch-4
Jaipur 25 2012 739 75.2 47.5
studies, we also reported that this was associated with increasing
Heart overweight, obesity and abdominal adiposity.24,25 Prognostic implica­
Watch-5 tions of higher triglyceride levels or increasing trends in its prevalence
India 18 2014 6123 54.8 23.0 have not been studied well in India in a large prospective study. The
Heart
ICMR-INDIAB also found hypertriglyceridemia to be significantly higher
Watch
in both males and females in urban vs rural populations in the country:
NA: not available. mean levels 149 ± 2.05 vs 136 ± 1.07 mg/dl and hypertriglyceridemia
36.4 vs 30.0 %.21 The prevalence is much more than that of
5. Triglycerides hypercholesterolemia.

According to epidemiologic and clinical research, high triglyceride
levels are a biomarker of cardiovascular (CV) risk.7,33,42 However, the
Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention
Trial (REDUCE-IT) trial with icosapent ethyl (highly purified eicosa­
pantenoic acid) has demonstrated its importance as a CAD risk factor.43
This study reported that in individuals with raised triglyceride levels
(>200 mg/dl), long-term use of icosapent ethyl was associated with
reduced risk of subsequent CV events (mechanisms of this benefit are
debated).42 Triglycerides play a role in CAD pathogenesis through a
variety of direct and indirect mechanisms, including effects on the
metabolism of other lipoproteins, transport proteins, enzymes, coagu­
lation, and endothelial dysfunction.42 Triglyceride levels can be affected
by a variety of factors including diet, age, lifestyle, and a variety of
medical conditions, drug therapy, and metabolic disorders. It has been
recommended that the non-fasting triglyceride levels may be a better
predictor of CAD events than fasting levels.42 A normal fasting triglyc­
eride level >150 mg/dl is usually defined. However, because there is no
accepted cut-point for non-fasting triglyceride concentration, deter­
mining hypertriglyceridemia prevalence is more difficult. However, in
normolipidemic subjects, post-prandial triglyceride values rarely exceed
400 mg/dl even post-fat challenge.42
5.2. Global scenario
In European countries prevalence of hypertriglyceridemia has been
reported in about 10 % with large regional variations, much lower than
in India.42,46 The prevalence of mild-to-moderate hypertriglyceridemia
parallels that of obesity and type 2 diabetes. Severe hyper­
triglyceridemia, defined as plasma triglyceride >10 mmol/L (>885
mg/dl) is less common, with prevalence ranging from 0.1 % to 0.2 %,
while very severe hypertriglyceridemia, defined at triglyceride >1770
mg/dl) is rarer still (prevalence 0.014 %).42 In South America, The
Venezuelan Metabolic Syndrome, Obesity and Lifestyle Study (VEM­
SOLS) study determined the prevalence of dyslipidemia in five pop­
ulations from three regions of Venezuela. The prevalence of lipid
abnormalities related to the metabolic syndrome (low HDL cholesterol
in 58.6 %; elevated triglycerides in 39.7 %) were the most prevalent.47
The Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) verified
the differences in lipid profile of racially mixed populations. Elevated
concentrations in LDL-C and triglycerides and low HDL-C had a lower
prevalence in black populations compared with whites after multivar­
iate adjustment.48 In Nigeria, data from four population-based cross-­
sectional studies on 2447 apparently healthy individuals from 18 to 89

S26
S. Sharma et al.
years were analysed.49 It was reported that hypertriglyceridemia was an
important risk factor among impaired fasting
glucose-normocholesterolemic overweight or obese individuals.49 The
prevalence of hypertriglyceridemia in Asia–Pacific region has been re­
ported to be in Taiwan 15.3 % (men 19.5 %, women 11.6 %); Japan 18.0
% (men 25.1 %, women 13.0 %); Korea 13.2 % (men 12.6 %, women
14.9 %); China 15.1 %; Malaysia 44.9 %; Singapore 17.4 %; Australia
32.8 %; Philippines 46.9 %; and Indonesia 35.8 % (men 22.1 %, women
38.2 %).50 These rates of prevalence of hypertriglyceridemia in other
countries in Asia are similar to studies in India. Prevalence of high tri­
glycerides was found to be 13.8 % in a nationally representative survey
in mainland China which recruited 163,641 adults aged >18 years be­
tween 2013 and 2014.51 In USA, an estimated 53 % adults have lipid
abnormalities and 30 % have high triglycerides.52
Older studies reported an increasing prevalence of hyper­
triglyceridemia in Europe and USA.2,3,42 This has coincided with
increasing incidence of obesity and the metabolic syndrome.42 More
recently, the National Health and Nutrition Examination Surveys
(NHANES) evaluated trends in population triglyceride levels in 8
cross-sectional cycles between 1999 and 2014.53 Age-adjusted geo­
metric mean triglyceride levels decreased from 123 mg/dl (95 % CI,
118–129 mg/dl) in 1999 to 97 mg/dl (95 % CI, 92–102 mg/dl) in 2014
(p = 0.02 for quadratic trend). It has been speculated that this is due to a
healthier diet with control of carbohydrates and trans fats. This is in
contrast to India and most developing countries where the levels are
increasing.
6. Conclusion
Lipid abnormalities are a common clinical condition that results in
the overproduction of potentially atherogenic lipids and lipoproteins
and is the most important determinant of CAD. Raised total cholesterol,
LDL cholesterol, NHDL cholesterol, and triglycerides are important
dyslipidemias that meet the Bradford Hill criteria for CAD causality.6
The epidemiology of lipoprotein(a), an emerging risk factor, is not
covered in this article and is reviewed elsewhere.33,54 Dyslipidemia
prevalence varies with age, gender, residence region, and socioeco­
nomic status. There are geographic variations in the prevalence of
various dyslipidemias in India. India Heart Watch study in 11 cities
across India reported variable prevalence of various dyslipidaemias in
different geographic regions.22 While the prevalence of raised total and
LDL-C was higher in northern and western Indian cities that of raised
triglycerides was more in eastern and southern states (Fig. 1). Cities with
better human development index had higher total and LDL-C while
those with lower development index had more hypertriglyceridemia.
Significant state-level variation in various dyslipidemias has been re­
ported by the ICMR-INDIAB study (Fig. 2, Table 3).21 This study shows
that the highest prevalence of raised total and LDL cholesterol in in more
developed states of the country (Kerala, Goa, Delhi, etc.) while hyper­
triglyceridemia and low HDL are widely prevalent.21 Dietary factors
could be important but need more studies. Because India has the world’s
highest number of CAD patients, evaluation of dyslipidemias through
more national representative survey studies must begin here. Efforts to
raise awareness, screen for lipid abnormalities, stratify risk, and initiate
appropriate treatment should be stepped up.55 Adherence to
well-structured population-based and individual-level interventions to
reduce dyslipidemia, as suggested by the World Heart Federation,56
shall result in a decrease in cardiovascular mortality and morbidity in
our country.
Declaration of competing interest
The authors declare that they have no known competing financial
interests or personal relationships that could have appeared to influence
the work reported in this paper.
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Indian Heart Journal 76 (2024) S20–S28
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