A Retrospective, Observational Study Comparing Dyslipidemia Patterns in Asian Indians with Whites

INTRODUCTION

Cardiovascular disease (CVD) is the leading global cause of morbidity and mortality worldwide [Figure 1]. As per the World Health Organization data (2021), ischemic heart disease was the leading cause of death globally.^[1,2] While CVD deaths related to causes such as ischemia, stroke, and cardiomyopathy in high-income countries have decreased from 1990 to 2021, the numbers for South Asians (SAs) have spiked.^[3] CVD events occur almost a decade earlier in Asian Indians: Mean age of 52 years versus the global average of 62 years.^[4]

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Figure 1:

Incidence rate of cardiovascular disease, 2021

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The prevalence of CVDs in India exceeds the global average considerably (282 deaths/100,000 vs. 233 deaths/100,000, respectively).^[5] Asian Indians are particularly vulnerable due to a genetic combination, environmental, and lifestyle factors, as well as a unique dyslipidemia profile that includes high triglycerides (TG), low high-density lipoprotein (HDL) cholesterol, elevated Lipoprotein-A levels, and higher atherogenic particles.^[6-8] Being Indian seems to blunt the cardioprotective effects of HDL, attributed to the smaller, dysfunctional, and proatherogenic HDL particles. These peculiarities of HDL particles reduce their efficiency in reverse cholesterol transport, which is crucial for cholesterol clearance.^[9] These factors contribute to the elevated risk of premature CVD, even in the absence of traditional risk factors, a phenomenon often referred to as the “South Asian Paradox”.^[10] Hence, the primary prevention guidelines of the American College of Cardiology/American Heart Association (2019) list SA ancestry as a risk-enhancing factor for atherosclerotic CVD.^[11] Since SAs are a broader phenotype, this study will focus on Asian Indians, and any further reference to “South Asians” or “Indians” is synonymous to “Asian Indians”.

Aging, along with genetic and lifestyle factors, plays a critical role in exacerbating CVD risk. Aging is associated with disruptions in lipid metabolism and a chronic inflammatory state, both of which contribute to the development of atherosclerotic CVD. [11] Studies indicate that women experience higher mortality rates and poorer outcomes following acute cardiovascular events compared to men as they age, given their hormonal changes.^[12,13]

In addition, Indians exhibit higher visceral adiposity and body fat percentage at the same body mass index (BMI) compared to Whites, which contributes to greater insulin resistance and metabolic syndrome.^[14] Since Indians face an elevated risk, lower BMI cutoffs have been recommended.^[8]

The rapid acculturation and dietary shifts towards Western habits among Indian migrants have further exacerbated these health risks, reflecting the complex interplay of traditional practices and modern lifestyle factors.^[9] Despite the growing recognition of CVD risk within this population, clinical data remains limited, and existing cardiovascular risk models-largely based on Western data-fail to accurately predict the risk for Indians.^[15]

MATERIAL AND METHODS

Study population and data collection

As shown in Figure 2, we studied a total of 190 patients comprising 110 males (56 Whites, 54 Indians) and 80 females (54 Whites, 26 Indians), all presenting with dyslipidemia or CVD. Demographics, BMI, and laboratory values (TC, TG, LDL, HDL, non-HDL cholesterol, TC/HDL ratio) were collected from the Cerna electronic medical record system.

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Figure 2:

Study Population Flowchart

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RESULTS

Effect of race

Indians showed higher TG levels (160 ± 75.71 vs. 130 ± 64.80 mg/Ld.; P = 0.004) [Table 1]. Indians consistently displayed trends of elevated TC, LDL, and non-HDL cholesterol, coupled with lower HDL levels [Table 1 and Figure 3a]. Indians also showed trends of higher TC, TG, and LDL across all BMI categories, including within the healthy BMI range [Figure 3b-d]. Whites had a significantly higher BMI (31.0 ± 6.41) compared to Indians (26.6 ± 4.95; P < 0.001) [Table 1], and a higher trend of BMI was seen across healthy, overweight, and obese categories [Figure 3e].

Table 1: Patient characteristics by race

Variables	Units	Race (across birth sex and age group)
		Indians	Whites	Statistical significance
		Mean ± Std. deviation	Mean ± Std. deviation	(p)
Weight	Pounds	164 ± 37.47	201 ± 54.06	NS
Height	Inches	65.9 ± 4.06	67.2 ± 4.28	NS
BMI	Kg/m2	26.6 ± 4.95	31.0 ± 6.41	<0.001
Total Cholesterol	mg/dL	182.4 ± 48.70	176 ± 41.33	NS
Triglycerides	mg/dL	160 ± 75.71	130 ± 64.80	0.004
LDL	mg/dL	103 ± 42.25	99.8 ± 36.22	NS
HDL	mg/dL	52.1 ± 11.90	54.78 ± 15.13	NS
CHOL./HDLC		3.66 ± 1.20	3.39 ± 1.02	NS
NON-HDL CHOL.	mg/dL	130 ± 48.36	122 ± 38.30	NS

Analysis was done using Mann Whitney test at P0.05 except cholesterol, n=190 (Indians 80, Whites 110) BMI: Body mass index, LDL: Low density lipoprotein, HDL: High density lipoprotein, Chol: Cholesterol, HDLC: HDL cholesterol, NS: Non-significant.

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Figure 3:

(a) Means of total cholesterol (TC), triglyceride, low density lipoprotein (LDL), high density lipoprotein (HDL), non-HDL Cholesterol across race. (* = refers to significant different ≤0.05). (b) Means of triglycerides (TG) across race for the BMI groups. (c) Means of total cholesterol (TC) across race for the BMI groups. (d) Means of low-density lipoprotein (LDL) across race. (e) Means of BMI across race within BMI groups. BMI: Body mass index.

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Indian women exhibited significantly higher TG levels compared to White women, along with trends toward elevated TC, LDL, and non-HDL cholesterol, and lower levels of HDL [Figure 4]. Similarly, Indian men showed trends of higher levels of TC, TG, LDL, and non-HDL cholesterol, and lower HDL levels compared to White men [Figure 5].

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Figure 4:

Means of total cholesterol (TC), triglyceride, low density lipoprotein (LDL), high density lipoprotein (HDL), non HDL Cholesterol for Asian Indian females vs. White females. (* = refers to significant different ≤0.05).

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Figure 5:

Means of total cholesterol (TC), triglyceride, low density lipoprotein (LDL), high density lipoprotein (HDL), non HDL Cholesterol for Asian Indian males vs. White males.

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Effect of gender

Across sexes, females, despite a lower weight (but similar BMI) exhibited higher TC (190 ± 44 vs. 171 ± 43.3 mg/dL; P = 0.003), LDL, and HDL levels compared to males [Table 2 and Figure 6]. Older females had significantly higher TC, LDL, HDL, and non-HDL cholesterol than older males [Figure 7]. Females generally showed higher TC and LDL levels than males, indicating higher cardiovascular risk across ages [Table 2]. They also showed higher HDL cholesterol levels compared to males.

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Figure 6:

Means plot for total cholesterol (TC), triglyceride, low density lipoprotein (LDL), high density lipoprotein (HDL), non HDL Cholesterol across Birth-sex, (* = refers to significant difference ≤ 0.05).

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Figure 7:

Means plot for total cholesterol (TC), triglyceride, low density lipoprotein (LDL), high density lipoprotein (HDL), non HDL Cholesterol across birth-sex, age > 50 years, (* = refers to significant difference ≤ 0.05).

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Table 2: Patient characteristics by birth sex

Variables	Units	Birth sex (across race and age groups)
		Males	Females	Statistical significance
		Mean ± Std. deviation	Mean ± Std. deviation	(p)
Weight	Pounds	201 ± 54.3	164 ± 37	<0.001
Height	Inches	68.8 ± 3.68	63.7 ± 3	<0.001
BMI	Kg/m2	29.8 ± 6.65	28.4 ± 5.6	NS
Total Cholesterol	mg/dL	171 ± 43.3	190 ± 44	0.003
Triglycerides	mg/dL	142 ± 72.6	144 ± 69.2	NS
LDL	mg/dL	95.3 ± 39	109 ± 38	0.025
HDL	mg/dL	50.7 ± 13.5	57.7 ± 13.5	<0.001
CHOL./HDLC		3.56 ± 1.21	3.43 ± 0.95	NS
NON-HDL CHOL.	mg/dL	120 ± 43.3	133 ± 42	NS

Analysis was done using Mann Whitney test at P=0.05 except cholesterol, n=190 (Males 110, females 80) BMI: Body mass index, LDL: Low density lipoprotein, HDL: High density lipoprotein, Chol.: Cholesterol, HDLC: HDL cholesterol

Effect of age

Age-stratified analysis indicated higher TC, LDL, TC/HDL ratio, and non-HDL cholesterol in individuals under 50, while older individuals showed a trend for higher TG levels [Table 3 and Figure 8]. Younger males, irrespective of race, had elevated TC, LDL, and non-HDL cholesterol. Younger males showed trends of higher TG and lower HDL-C compared to older males [Figure 9]. Older Indian females had higher TG, while younger Indian females showed trends for higher TC, LDL, and non-HDL cholesterol compared to their older counterparts, with smaller differences seen in White females [Figure 10].

Table 3: Patient characteristics by age-group

Variables	Units	Age groups (across race and birth sex)
		< 50 Years	> 50 Years	Statistical Significance
		Mean ± Std. deviation	Mean ± Std. deviation	(p)
Weight	Pounds	197 ± 57.3	174 ± 41	0.002
Height	Inches	67 ± 4.4	66.5 ± 4.1	NS
BMI	Kg/m2	31 ± 7	27.5 ± 4.8	NS
Total Cholesterol	mg/dL	186 ± 35.2	172 ± 51.6	0.026
Triglycerides	mg/dL	142 ± 65	143 ± 77.1	NS
LDL	mg/dL	108 ± 30	93.8 ± 45.3	<0.001
HDL	mg/dL	52.7 ± 15	54.6 ± 13	NS
CHOL./HDLC		3.77 ± 1.14	3.24 ± 1.01	<0.001
NON-HDL CHOL.	mg/dL	133 ± 34.3	117 ± 49	<0.001

Analysis was done using Mann Whitney test at P 0.05 except cholesterol (n<50 years=96, n>50 years=94) BMI-Body mass index, LDL-Low density lipoprotein, HDL: High density lipoprotein, Chol.: Cholesterol, HDLC: HDL cholesterol

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Figure 8:

Means plot for total cholesterol (TC), triglyceride, low density lipoprotein (LDL), high density lipoprotein (HDL), non HDL cholesterol across age-groups. (* = refers to significant different ≤0.05).

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Figure 9:

Means plot for total cholesterol (TC), triglyceride, low density lipoprotein (LDL), high density lipoprotein (HDL), non HDL Cholesterol across age groups, Asian Indian and White Males. (* = refers to significant different ≤0.05).

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Figure 10:

Means plot for total cholesterol (TC), triglyceride, low density lipoprotein (LDL), high density lipoprotein (HDL), non HDL Cholesterol across age groups, Indians and White females. (* = refers to significant different ≤0.05).

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Correlation analysis highlighted that BMI, TC, LDL, and nonHDL cholesterol decreased significantly with age, suggesting a lower lipid-related CVD risk in those over 50 years of age [Table 4]. Analysis across race showed that though Indians had lower BMI than Whites, their TG were significantly higher, giving further credence to the SA paradox. Analysis across sex showed females to have significantly higher TC and LDL than males, underlining their higher CVD risk. Females also had higher levels of HDL cholesterol compared to males, consistent with data from other studies.^[18,19]

Table 4: Correlation analysis of variables

	Age 1= <50y, 2= >50y	Race 1=Indians, 2=Whites	Birth-sex 1=Males, 2=Females
BMI	-0.264**	0.373**	-
Total Chol.	-0.196**	-	0.204**
TG	-	-0.209**	-
LDL	-0.240**	-	0.163*
HDL	-	-	0.270**
Non-HDL	-0.232**	-	-

**. Correlation is significant at the 0.01 level (2-tailed). *. Correlation is significant at the 0.05 level (2-tailed). Non-parametric variables (birth sex, age, race, LDL, HDL) assessed with Spearman coefficient. Pearson coefficient used to assess parametric variable (cholesterol), BMI-Body mass index, Chol.: Cholesterol, TG: Triglyceride, LDL: Low density lipoprotein, HDL: High density lipoprotein

DISCUSSION

This study highlights the distinctive lipid profiles among Indians, revealing significantly higher CVD risk compared to Whites. Indians, both men and women, have a more atherogenic lipid profile than Whites, characterized by higher TG and lower HDL levels, alongside elevated atherogenic lipoproteins. The same was emphasized by Kalra et al., who noted high hypertriglyceridemia and complex dyslipidemia in this population.^[20] While HDL levels may appear similar across ethnicities, Dodi et al. pointed out that HDL particles in SAs may be dysfunctional, reducing their protective effect and highlighting the need for tailored lipid management.^[21]

Women were found to have more elevated TC and LDL markers than males, putting them at an equal or higher risk. A study by Feng et al. observed that in the age group of 51–65, women surpassed men’s TC, TG, and LDL-C levels.^[22] These differences are linked to hormonal fluctuations and variations between men and women.^[8] The impact of aging is further amplified in post-menopausal women, whose CVD risk increases significantly due to combined dyslipidemias resulting from aging and estrogen decline. Menopause itself is an independent predictor of CVD, with women facing a higher risk of nonobstructive CVD compared to men.^[12,13] Despite CVD being the leading cause of death in women, this study also found far fewer women seeking cardiology care, as evidenced by the huge disparity in the number of Indian men and women visiting the clinic.

Age-based stratification shows concerning TC and LDL levels in younger Indian males, echoing the findings by Joseph et al. They observed a higher CVD risk among SA men under 50 years, underscoring the importance of early intervention.^[22] In older women, lipid profile irregularities increase post-menopause as HDL cholesterol’s protective effects diminish. This trend, noted by Feng et al., shows that women surpassed men’s TC, TG, and LDL-C levels in the 51–65 year of age group.^[23]

Our study also found that Indians have lower BMI than Whites, irrespective of the age group or birth sex. As studied by Deshpande et al., SAs were found to have a higher risk of developing metabolic syndrome at a relatively lower BMI and a normal body weight.^[24]

The unique adiposity pattern in Indians, marked by lower BMI but high serum lipid levels, adds to their CVD risk. Even normal HDL-C levels may be insufficient in Indians due to potential HDL dysfunction, emphasizing that traditional lipid measures may not fully capture their risk.^[21] The Indian Consensus Group of Physicians recommends lower BMI cut-offs and lipid intervention thresholds tailored for SAs to better address their risk.^[24]

It is also of concern that guidelines suggesting statins for moderate-risk SAs may not accurately reflect the unique risk profiles of this population and underestimate their actual risk, as these are often based on non-SA data. The multi-ethnic study of atherosclerosis indicates a higher predisposition to subclinical atherosclerosis in SAs, advocating for ethnicity-specific CVD risk models.^[25] Physiological variations of SAs have been highlighted in recent studies by Parke et al. and Krishnaraj et al.^[26,27] Collectively, this study, along with other findings, emphasizes the importance of an individualized approach, incorporating Indian-specific lipid, BMI, and metabolic parameters to effectively manage and mitigate CVD risk in this high-risk population.

CONCLUSION

This study underscores the higher CVD risk for younger males and all females irrespective of their ethnicity. The multifactorial nature of CVD necessitates the use of comprehensive risk assessment and early screening programs. Despite lower levels of adiposity (BMI), Indians (both males and females) are at a greater risk for dyslipidemias as compared to Whites. The pronounced lipid abnormalities in young Indian males (<50 years) underline the higher risk they face and suggest an urgent need for early screening programs. High dyslipidemia patterns are seen in Indians in “healthy” and “obese” BMI categories. Initiating educational initiatives to promote awareness about CVD and the benefits of early lifestyle interventions are crucial. Females are an a elevated risk than males for CVD. Healthcare systems should prioritize hormonal and metabolic evaluations as part of routine CVD risk assessments, especially for post-menopausal women. Increasing social awareness and advocacy of women’s cardiovascular health would aid in early detection and treatment. Noted disparity in the utilization of healthcare services among Indian women might arise from cultural factors. Hence, ethno-specific education programs and fostering peer networking could be powerful tools to eradicate these disparities. Social determinants of health may affect ethnic groups differently within a country itself, necessitating addressing these issues with tailored therapeutic strategies emphasizing sex-sensitive, person-centered care, more utilization of rehabilitative programs, and enhanced psychological support for women. Developing advanced diagnostic tools and biomarkers to predict/monitor dyslipidemia more accurately could uncover further nuances in CVD risk among diverse populations. Supportive biotechnological innovations such as genomics and proteomics could deepen the understanding of the molecular basis of these racial variations in lipid metabolism, highlighting novel therapeutic pathways. Continued research is warranted to deepen our understanding of the complex interplay of factors contributing to CVD risk and inform more targeted and personalized approaches to cardiovascular care.