The Double-Dare of Cholesterol: Why Indian Patients Need Both LDL and ApoB to Outwit Heart & Kidney Risk

Authors

  • Dr. Ashutosh Mishra MBBS, MD (Medicine), IMS BHU Fellowship in Diabetes (DFID), CMC Vellore DMSc (Endocrinology), University of South Wales, UK Consultant Endocrinologist, Panacea Hospital English Author

Keywords:

Apolipoprotein B, LDL cholesterol, Lipid discordance, South Asian dyslipidaemia, Cardiovascular risk, Chronic kidney disease

Abstract

Abstract


India faces a disproportionate burden of premature cardiovascular disease (CVD) and chronic kidney disease (CKD), driven by a distinct dyslipidaemic profile known as “South Asian dyslipidaemia.” This phenotype—characterized by elevated triglycerides, low high-density lipoprotein cholesterol, and a predominance of small, dense low-density lipoprotein (LDL) particles—frequently results in discordance between LDL cholesterol (LDL-C) and apolipoprotein B (ApoB). Reliance on LDL-C alone may therefore underestimate true atherogenic risk in Indian patients.

The Double-Dare of Cholesterol: Why Indian Patients Need Both LDL and ApoB to Outwit Heart & Kidney Risk Dr. Ashutosh Mishra MBBS, MD (Medicine), IMS BHU Fellowship in Diabetes (DFID), CMC Vellore DMSc (Endocrinology), University of South Wales, UK Consultant Endocrinologist, Panacea Hospital India’s Unique Cardiometabolic Challenge and the Lipid Complexity In clinics across metropolitan hubs and rural corners of India, cholesterol readings are often the starting point in evaluating cardiovascular risk. However, Indians carry a distinctive lipid fingerprint, vastly different from many global populations, which requires a more precise interpretation. The traditional reliance on LDL cholesterol (LDL-C) as the "bad cholesterol" marker for cardiovascular risk is insufficient for India’s diverse and dynamic population. Indians are disproportionately affected by a severe cardiometabolic crisis marked by elevated triglycerides, reduced HDL cholesterol, and notably, elevated apolipoprotein B (ApoB) levels. ApoB reflects the total number of atherogenic lipoprotein particles—including very-low-density lipoproteins (VLDL), intermediate-density lipoprotein (IDL), LDL particles, and lipoprotein(a)—responsible for vascular plaque formation. This lipoprotein count is especially crucial given the predominance of small, dense LDL particles in Indians, which are more atherogenic and frequently not reflected adequately by LDL-C measurements. This “South Asian dyslipidaemia” occurs in the context of an epidemic of insulin resistance, type 2 diabetes, chronic kidney disease, and premature cardiovascular disease (CVD). Recent research shows that up to 50% of Indians, including those with diabetes and CKD, have discordant LDL-C and ApoB levels, meaning that LDL-C targets may appear met, but ApoB—and thus actual atherogenic particle burden—remains dangerously high. This discordance masks true cardiovascular and renal risk. The epidemiological and genetic factors compounded by rapid lifestyle and dietary shifts present a “perfect storm”—increasing the necessity to measure both LDL-C and ApoB or at least non-HDL cholesterol to fully capture risk. National and international guidelines now acknowledge this paradigm shift, advocating for ApoB assessment particularly in South Asians, diabetic populations, and those with high triglycerides or metabolic syndrome. Given the insidiousness of this risk profile, failing to incorporate ApoB into routine clinical practice is akin to reading only half the story—a dangerous oversight in a population already grappling with one of the highest cardiovascular death rates globally. The Phenomenon of Lipid Discordance: Understanding Why ApoB Complements LDL-C For decades, LDL cholesterol has been the cornerstone lipid marker in assessing atherosclerotic cardiovascular disease (ASCVD) risk. However, LDL-C measures cholesterol mass within LDL particles, which can vary widely in number and size. Each ApoB molecule marks one atherogenic particle, directly counting particles that contribute to plaque formation, regardless of cholesterol content. Among Indians, this discordance is particularly pronounced due to the predominance of small, dense LDL particles carrying less cholesterol per particle but causing disproportional vascular damage. While LDL-C may appear normal or low, ApoB levels can be elevated, indicating a high number of atherogenic particles “firing” at arterial walls. Conversely, some individuals may have elevated LDL-C but normal ApoB—a scenario often involving larger, less harmful LDL particles. The clinical importance of this discordance is profound. Numerous studies, including Indian cohorts, demonstrate that ApoB outperforms LDL-C in predicting myocardial infarction, stroke, and CKD progression, especially in patients with diabetes and metabolic syndrome. Approximately half of the adult Indian population exhibits such discordance, reinforcing the need for dual assessment to avoid underestimating risk. This discordance challenges clinicians familiar with traditional LDL-centric approaches to shift towards integrated lipid evaluation. Recognizing ApoB’s superior predictive value, particularly in South Asians, elevates the opportunity to initiate appropriate preventive strategies earlier, personalized to individual lipid particle burden rather than cholesterol mass alone. Epidemiology and Impact of Dyslipidemia and ApoB-LDL-C Discordance in India India faces an unprecedented cardiometabolic crisis with premature cardiovascular mortality at younger ages compared to Western countries. Urban epidemiological studies reveal that nearly seven out of ten urban Indians carry some form of dyslipidaemia, frequently featuring the pattern of low HDL, high triglycerides, and elevated ApoB despite near-normal LDL-C values. Among Indian patients with diabetes and CKD—two major risk amplifiers—high ApoB levels are independently linked to accelerated renal function decline and adverse cardiovascular outcomes, even when LDL-C meets guideline targets. This potentiated risk translates into earlier onset of myocardial infarction and kidney disease progression, placing an enormous burden on healthcare systems. Recent consensus and expert panels, including those from the Lipid Association of India, have embraced this reality, updating lipid management guidelines to emphasize aggressive dual metric targets with clear ApoB and non-HDL cholesterol goals across risk strata. These reflect growing global recognition from European and American cardiovascular societies, particularly underscoring South Asian populations’ increased vulnerability. This solid epidemiological foundation underpins the urgent call for broader adoption of ApoB testing and aggressive lipid management in Indian clinical practice, integral to reducing premature morbidity and mortality. Clinical Guidelines and Target Lipid Levels for Indian Patients Reflecting evidence and population-specific needs, current Indian guidelines recommend aggressive lipid targets that are considerably lower for high and very high-risk patients than Western standards. For instance, extreme risk individuals—such as those with recent acute coronary syndromes (ACS), diabetes, or CKD—are advised to achieve LDL-C below 30–50 mg/dL and ApoB below 60–65 mg/dL. Very high-risk patients should aim for LDL-C under 50 mg/dL and ApoB under 65 mg/dL, while high-risk patients, including those with uncomplicated diabetes or familial hypercholesterolemia, are targeted for LDL-C below 70 mg/dL and ApoB less than 80 mg/dL. Non-HDL cholesterol serves as a practical alternative where ApoB measurement may be unavailable. Global guidelines such as from the European Society of Cardiology and American Association of Clinical Endocrinologists have echoed this inclusive lipid assessment strategy. India’s tailored targets respond to local epidemiology, with a focus on implementing these aggressive goals in real-world clinical settings for maximal impact. Why is ApoB-LDL-C Discordance Particularly Risky in Indians? The South Asian metabolic milieu is characterized by multiple synergistic factors that amplify the risk of ApoB-LDL-C discordance: higher baseline insulin resistance even at normal BMI ranges, frequent elevation of triglycerides, reduced HDL particle functionality, and the accumulation of small, dense, highly atherogenic LDL particles. This unique dyslipidaemia variably manifests as normal LDL-C reporting misleadingly reassuring physicians and patients while elevated numbers of ApoB-containing atherogenic particles exert outsized influence in promoting endothelial damage, plaque instability, and microvascular injury affecting vital organs including the kidneys. This partly explains the notably high rates of premature cardiovascular events and chronic kidney injury seen in Indians at younger ages. The metabolic “perfect storm” presents hidden dangers: therapeutic complacency based on LDL-C alone can leave atherogenic lipid particles unchecked, fueling the progression of arterial and renal pathology with devastating consequences. Personalized Clinical Vignettes: The Importance of Dual-Metric Lipid Measurement Consider a middle-aged Indian diabetic named Mr. Sharma. Despite achieving an LDL-C of 70 mg/dL on standard statin therapy, his ApoB remains elevated at 105 mg/dL—indicating ongoing atherogenic particle burden and cardiovascular risk. For such a patient, intensifying therapy by adding ezetimibe or a PCSK9 inhibitor is warranted to reduce the hidden risk better. Ms. Meena, a patient with stage 3 CKD, exhibits borderline LDL-C at 80 mg/dL but increased ApoB and non-HDL cholesterol with hypertriglyceridemia. Her elevated ApoB signals residual risk not captured by LDL-C alone, prompting adjustment of lifestyle, glycemic control, and lipid-lowering strategies targeting comprehensive lipid improvement. These cases exemplify the critical role of dual-factor lipid assessment as a clinical decision aid enabling individualized treatment escalation. Conclusion: Cardiovascular disease and chronic kidney disease impose a disproportionate risk on the Indian population, fueled by a unique interplay of metabolic, genetic, and lifestyle factors. Conventional lipid parameters such as LDL cholesterol have long guided cardiovascular risk stratification and treatment, but mounting evidence reveals significant limitations when LDL-C is considered in isolation, especially in Indians. The high prevalence of “South Asian dyslipidaemia”—characterized by elevated triglycerides, low HDL cholesterol, and the predominance of small, dense LDL particles—renders LDL-C alone an incomplete marker, often underestimating true atherogenic burden. Apolipoprotein B (ApoB), representing the total number of atherogenic lipoprotein particles, has emerged as a superior risk predictor across global and Indian populations. Discordance between LDL-C and ApoB is frequent, noted in nearly half of Indian adults affected by metabolic syndrome, diabetes, and kidney disease. This discordance signifies a “hidden” risk environment wherein normal LDL-C masks continued elevated atherogenic particle number, accelerating premature coronary artery disease, stroke, and renal impairment. Such a scenario makes a compelling case for dual lipid profiling—measuring both LDL-C and ApoB or, alternatively, non-HDL cholesterol—as routine practice in India, especially for high-risk groups. National guidelines from the Lipid Association of India now recommend aggressive lipid targets tailored to levels of cardiovascular and renal risk, with ApoB-guided therapy intensification alongside LDL-C lowering. Targets as low as LDL-C below 30–50 mg/dL and ApoB below 60–65 mg/dL for extreme-risk patients underscore the urgency in addressing this dual risk with precision. Combination therapies including high-intensity statins, ezetimibe, and PCSK9 inhibitors, with adjunctive use of high-dose pure EPA fish oils, provide a robust pharmacologic armamentarium. These treatments, grounded in trials such as VESALIUS-CV and supported by international cardiology consensus, have proven efficacy and safety relevant to the Indian context. Lifestyle modification remains foundational, focusing on dietary carbohydrate restriction, increased physical activity, tobacco cessation, and sustained patient education tailored to cultural contexts. Early and repeated dual lipid assessment allows clinicians to escalate therapy proactively, circumventing the atherogenic particle excess characteristic of Indian patients and thereby preventing premature cardiovascular mortality and kidney disease progression. Ultimately, embracing a dual-lipid strategy transforms the management paradigm from reactive to proactive care—turning partial lipid information into a full narrative of risk. This comprehensive approach empowers clinicians and patients alike to make fully informed, personalized therapeutic decisions, fostering improved clinical outcomes across India’s immense cardiometabolic disease burden. References: 1. Natesan S, et al. South Asian dyslipidaemia: The India difference. Natl Med J India. 2020. 2. Enas EA, et al. Unique lipid risk factors in South Asians. J Clin Lipidol. 2021. 3. Mazidi M, et al. Discordance between LDL-C and ApoB in diabetic and CKD populations. PubMed. 2022. 4. Kriemler L, et al. Lipid discordance and implications for risk. SAGE Journals. 2024. 5. Lipid Association of India. 2023/24 Dyslipidemia Guidelines. SciDirect. 2024. 6. De Oliveira-Gomes D, et al. Global lipid guidelines and ApoB. PMC. 2024. 7. PACE-CME. ApoB and LDL-C discordance impact on cardiovascular risk. 2025.

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Published

2025-11-15

Issue

Vol. 3 No. 2 (2025): The Double-Dare of Cholesterol: Why Indian Patients Need Both LDL and ApoB to Outwit Heart & Kidney Risk

Section

Articles

How to Cite

The Double-Dare of Cholesterol: Why Indian Patients Need Both LDL and ApoB to Outwit Heart & Kidney Risk . (2025). Diabzen, 3(2), 35-38. https://www.thediabzen.com/index.php/d/article/view/17

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