Are Current Lipid Guidelines Adequate for South Asian Patients? A Narrative Review

2.1 Atherogenic dyslipidaemia and ApoB discordance

South Asians exhibit a distinct atherogenic dyslipidaemia characterised by hypertriglyceridaemia, reduced HDL-C, elevated ApoB, and an increased proportion of sdLDL particles, a pattern that persists even when LDL-C remains within the normal range (Table 1) (4, 5). This discordance between LDL-C and atherogenic particle burden has important clinical implications: a substantial proportion of South Asian patients present with ASCVD at LDL-C concentrations below 100 mg/dL (2.6 mmol/L), a threshold at which standard risk calculators would otherwise offer reassurance (1, 2).

The discordance between LDL-C and true atherogenic particle burden is explained by ApoB, which represents one particle per molecule regardless of cholesterol content. ApoB and the ApoB/ApoA-1 ratio have demonstrated stronger associations with ASCVD risk than LDL-C in several South Asian cohorts (5, 12, 13, 14), yet routine ApoB reporting and population-specific decision thresholds remain absent from most clinical guidelines and healthcare systems (5, 15). Non-HDL-C, calculable from a standard fasting lipid panel, provides a practical surrogate where ApoB is unavailable (16). The discordance between LDL-C and atherogenic particle burden in South Asians is illustrated in Figure 1.

Figure 1

2.2 Lipoprotein(a) and residual risk

Lp(a) warrants particular emphasis. A substantial proportion of South Asians, often approaching one quarter in some cohorts, have Lp(a) concentrations exceeding 50 mg/dL (125 nmol/L), conferring independent and additive cardiovascular risk beyond LDL-C (17, 18). Data from the Mediators of Atherosclerosis in South Asians Living in America (MASALA) cohort and the UK Biobank demonstrate associations with aortic valve calcification and a steeper risk gradient than observed in European comparators at equivalent concentrations (19). Population-specific reference ranges have not been established, no harmonised screening pathway exists across major guideline frameworks, and South Asian representation in late-phase Lp(a)-targeted therapy trials (pelacarsen, olpasiran, lepodisiran) remains minimal (20). Measurement of Lp(a) at least once in adulthood is supported by the LAI 2023 Consensus Statement IV for risk refinement in Indian patients and by the National Lipid Association (NLA) clinical perspective, and it is now recommended as a Class I indication for all adults in the 2026 ACC/AHA/Multisociety Dyslipidemia Guideline (1, 6, 10).

2.3 Heterogeneity within South Asian populations

The term ‘South Asian’ encompasses populations with diverse genetic ancestry, dietary patterns, and cardiovascular risk trajectories (1, 5, 10). Despite this diversity, Indian, Pakistani, Bangladeshi, Sri Lankan, and Nepali populations are commonly analysed as a single ethnic category in epidemiological studies and guideline frameworks (1, 10). Evidence from South Asian and diasporic cohorts demonstrate variation in lipid profiles and cardiometabolic risk according to sex, urbanisation, and ancestral origin, suggesting that a uniform approach to risk assessment may overlook clinically relevant subgroup differences (21, 22). The under-representation of Bhutanese, Maldivian, and Afghan populations in contemporary lipid research further limits understanding of intra-regional variation and remains an important knowledge gap (5).

This heterogeneity has practical implications for clinicians navigating the absence of population-specific risk equations. The existing evidence base is disproportionately Indian and Indian-diasporic in origin, drawn heavily from cohorts such as MASALA (13) and the INTERHEART case-control study (12, 14) and consolidated in India-specific frameworks such as the LAI Consensus Statement (10); dedicated evidence for Pakistani, Bangladeshi, Sri Lankan, and Nepali populations is comparatively sparse, and virtually absent for Bhutanese, Maldivian, and Afghan populations. Country-of-origin-specific guidance, where it exists, should take precedence over generic ‘South Asian’ extrapolation. Where it does not exist, clinicians should apply the same risk-enhancing assumptions used for the best-studied group as a precautionary default rather than assume equivalence, while remaining alert that unmeasured differences in diet, urbanicity, and migration generation may shift true risk in either direction.

A related limitation concerns the provenance of the evidence itself. Much of the data most frequently cited to characterise the South Asian lipid phenotype and its cardiovascular consequences, including the MASALA cohort and UK Biobank (19), derives from diaspora populations resident in the US and the UK rather than from South Asians living in South Asia. Diaspora and native populations differ systematically in dietary patterns, environmental exposures, healthcare access, and socioeconomic profile, and diaspora cohorts are additionally subject to a ‘healthy migrant’ selection effect that may not generalise to the broader native population. Because the central argument of this review is precisely the absence of validated risk data in native South Asian populations, caution is warranted in extrapolating diaspora-derived findings, including lipid-phenotype characterisation and Lp(a) prevalence estimates, directly to clinical decision-making in South Asia itself.

2.4 Early ASCVD and familial hypercholesterolaemia

The early onset of ASCVD in South Asians, occurring 5–10 years earlier than in European populations, implies that atherogenic dyslipidaemia accumulates during decades that standard screening programmes do not address (2, 23). Evidence on screening thresholds in South Asian children and adolescents remains sparse. The co-occurrence of premature coronary artery disease and familial hypercholesterolaemia (FH) in young South Asians is of particular concern, given an estimated burden of approximately five million affected individuals in India alone, the majority undiagnosed, and a mutation spectrum that diverges from Western reference panels (23, 24).

3.1 Failure of standard risk calculators

Accurate cardiovascular risk stratification is the gateway to appropriate lipid-lowering therapy. Historically, the PCE (ACC/AHA), QRISK3 (NICE), and SCORE2 (ESC/EAS) have been the principal tools used to estimate cardiovascular risk. Developed predominantly in European-origin populations, their performance in South Asians is inconsistent and, in clinically important subgroups, demonstrably inadequate (27, 28). Although the PCE has now been replaced by the PREVENT equations in the 2026 ACC/AHA guideline, dedicated validation of PREVENT in South Asian populations is currently lacking (6).

The PCE has been shown both to over- and underestimate 10-year ASCVD risk in South Asian cohorts, with underestimation most pronounced in low- and borderline-risk individuals, precisely the patients in whom a risk-calculator result is most likely to influence the decision to initiate therapy (28). In a large US integrated healthcare cohort, the PCE substantially underestimated absolute 10-year ASCVD risk among South Asians classified as low risk, with observed risk nearly three-fold higher than predicted (4.9% observed versus 1.8% predicted, p < 0.0001); underestimation was more pronounced among those already receiving statin therapy, among whom observed risk exceeded predicted risk by more than five percentage points (e.g., 8.43% observed versus 2.58% predicted) (28). QRISK3 incorporates ethnicity-specific adjustment factors for South Asian groups, although residual miscalibration remains evident in validation studies. In the Southall And Brent REvisited (SABRE) cohort, an earlier ethnicity-stratified validation of QRISK2 found that only around half of observed 10-year cardiovascular risk in South Asian women was captured by the score (predicted-to-observed risk ratio 0.52), compared with closer calibration in European-origin women (ratio 0.73); a gap of similar magnitude was seen with the Framingham score (0.43 versus 0.73) (27). By contrast, an independent validation of QRISK3 in the broader UK Biobank cohort found the score to overpredict risk overall, particularly among older participants, underscoring that population-level and ethnicity-specific calibration are not necessarily aligned and that subgroup-specific validation remains essential (29).

SCORE2 Asia-Pacific has begun recalibration for East and Southeast Asian populations, but India, Pakistan, Bangladesh, Sri Lanka, and Nepal lack contemporary locally validated equations (30, 31). Although the 2019 WHO cardiovascular risk charts remain widely used in some South Asian primary-care settings, they are regionally calibrated public-health tools rather than ethnicity-specific lipid-management frameworks and are therefore not discussed further (32).

3.2 The 2026 ACC/AHA PREVENT equations and South Asian implications

The 2026 ACC/AHA/Multisociety Dyslipidemia Guideline replaces the PCE with the AHA PREVENT equations for 10- and 30-year risk assessment in adults aged 30–79 years. PREVENT generally generates lower estimated cardiovascular risk than the PCE in derivation and validation cohorts. Whether this improves calibration or instead increases the underestimation of risk among South Asians remains unknown, because dedicated validation studies in South Asian cohorts have not yet been performed (6). Given the consistently lower estimates that PREVENT produces relative to the PCE, prospective validation in South Asian populations is urgently required. Pending such studies, clinicians should apply explicit South Asian risk-enhancer classification under the 2026 framework and maintain a low threshold for coronary artery calcium (CAC) scoring in South Asian patients reclassified downward by PREVENT, relative to their previous PCE estimate. In this context, CAC scoring assumes particular importance as an objective reclassification tool that is independent of risk-equation choice, as discussed below.

3.3 Coronary artery calcium scoring

CAC scoring has emerged as the most validated imaging tool for reclassifying South Asians at borderline or intermediate estimated risk. Data from the MASALA cohort demonstrate that CAC scoring meaningfully reclassifies a substantial proportion of South Asian individuals initially categorised as borderline or intermediate risk by conventional calculators. A CAC score of zero identifies a lower-risk subgroup with very low short-term ASCVD event rates, supporting individualised decisions regarding statin initiation (33, 34). Guideline uptake of CAC in the South Asian context remains inconsistent across frameworks (Table 2) (8, 9, 16, 35).

3.4 Emerging risk markers

Beyond traditional lipid parameters, several biomarkers may improve cardiovascular risk stratification in South Asians. Lp(a) is elevated in approximately one-quarter of South Asians and functions as an independent ASCVD risk enhancer across contemporary guideline frameworks. Current ACC/AHA, ESC/EAS, and LAI recommendations support at least one lifetime measurement, although no South Asian-specific threshold has been established (5).

ApoB may provide a more accurate estimate of atherogenic particle burden than LDL-C in South Asians, because discordance between LDL-C and ApoB is common in insulin-resistant states characterised by hypertriglyceridaemia and increased concentrations of sdLDL. At any given LDL-C concentration, South Asians frequently exhibit higher ApoB and greater atherogenic particle burden than European populations. Therefore, elevated ApoB despite apparently acceptable LDL-C may identify individuals whose cardiovascular risk is underestimated by conventional assessment (5, 17, 36).

High-sensitivity C-reactive protein (hsCRP) reflects the systemic inflammation associated with the South Asian metabolic phenotype and is recognised as a risk-enhancing factor in ACC/AHA guidance. Evidence from primary-prevention studies, including the Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) trial, suggests that elevated hsCRP identifies individuals at increased cardiovascular risk despite relatively normal LDL-C and may help refine risk assessment in selected patients (35, 37). Polygenic risk scores remain investigational and require validation in large South Asian cohorts before routine clinical implementation. At present, no major framework recommends their routine use in this population (24, 38).

3.5 The case for lifetime risk

All four contemporary frameworks are anchored to 10-year risk horizons. Given that South Asians experience their first ASCVD event 5–10 years earlier than their European counterparts, this approach systematically deprioritises young South Asian patients whose short-term calculated risk remains low despite a high lifetime atherogenic burden (2). The LAI 2023 Consensus Statement IV explicitly endorses lifetime-risk framing as a supplementary stratification tool in South Asians under 50 years of age, a position now partially addressed by the 2026 ACC/AHA guideline’s incorporation of 30-year risk estimation via PREVENT (6, 10). NICE NG238 similarly allows consideration of lifetime risk to support risk communication and lifestyle counselling, although it is not used to determine statin eligibility (9). ESC/EAS has not formally incorporated lifetime-risk estimation into routine treatment algorithms (16, 39).

3.6 Statin pharmacokinetics and dosing considerations

Even where risk stratification correctly identifies a South Asian patient as requiring statin therapy, none of the frameworks compared in this review address a population-specific consideration in treatment itself. Rosuvastatin plasma exposure (area under the curve) is approximately two-fold higher in Asian subjects than in white subjects of similar age and renal function, independent of body weight, diet, or environment, with Asian Indian subjects specifically shown to have around 60% greater exposure than white subjects in direct comparison (43, 44). This elevated exposure is not matched by a proportionally greater LDL-C-lowering effect, so Asian patients achieve comparable percentage reductions in LDL-C at lower doses while experiencing higher systemic drug exposure, and by extension, a plausibly greater risk of dose-dependent myopathy, at doses considered standard in European-origin populations. On this basis, regulatory labelling recommends that Asian patients initiate rosuvastatin at 5 mg once daily rather than the 10–20 mg starting doses used elsewhere (45). A randomised trial conducted specifically in South Asian patients found rosuvastatin to be an effective and generally well-tolerated alternative to atorvastatin in this population, although it was not designed to test dose-adjusted safety outcomes (46). This dosing consideration is one of the few areas in South Asian lipid management where a specific, actionable, and already regulator-endorsed practice change exists today, independent of any future validation of risk equations or treatment targets, yet it is absent from all four major frameworks compared in this review.

4.1 Points of convergence

Despite differences in architecture and target populations, the contemporary frameworks share several areas of agreement. All endorse high-intensity statin therapy as the first-line treatment in established ASCVD. All recognise South Asian ethnicity as a cardiovascular risk modifier, most explicitly in the 2026 ACC/AHA guideline, which, for the first time, names South Asian and Filipino ancestry as risk-enhancing factors. All support the addition of non-statin agents, principally ezetimibe and PCSK9 inhibitors, when LDL-C targets are not achieved on maximally tolerated statin therapy (6, 7, 8, 9, 10, 16, 39). These areas of convergence provide a clinically stable foundation regardless of which framework a practitioner follows.

4.2 Points of divergence

Meaningful divergence exists across five clinically actionable domains, summarised in Table 3.

LDL-C targets. The most consequential divergence concerns numerical LDL-C goals. ESC/EAS (2019 and 2025 Focused Update) endorses <55 mg/dL (<1.4 mmol/L) for very high-risk patients, with consideration of <40 mg/dL (<1.0 mmol/L) in selected patients at extreme risk (16, 39). The LAI 2023 Consensus Statement IV is more intensive still, recommending LDL-C <50 mg/dL (1.3 mmol/L) for very high-risk South Asian individuals and ≤30 mg/dL (≤0.8 mmol/L) for those at extreme risk, reflecting earlier onset and greater ASCVD burden (10). The 2026 ACC/AHA guideline reintroduced numerical goals, recommending <55 mg/dL (<1.4 mmol/L) for very high-risk and <70 mg/dL (<1.8 mmol/L) for high-risk patients, substantially converging with ESC/EAS and LAI (6, 8). NICE NG238 differs in retaining a percentage-based primary-prevention target (>40% non-HDL-C reduction) but introducing absolute secondary-prevention targets (LDL-C ≤77 mg/dL (≤2.0 mmol/L) or non-HDL-C ≤100 mg/dL (≤2.6 mmol/L)) in 2023 (9). Consequently, South Asian patients managed in different healthcare systems may receive substantially different treatment goals despite identical risk profiles.

Operationalisation of South Asian ethnicity. ACC/AHA identifies South Asian ancestry as a risk-enhancing factor without a quantitative adjustment (7, 8, 35). ESC/EAS recognises South Asian ethnicity as a risk modifier but does not incorporate it directly into prediction algorithms (16). NICE embeds ethnicity within QRISK3, whereas the LAI framework embeds Indian-population-focused stratification throughout (9, 10). As a result, clinicians applying different national guidelines to the same patient may arrive at different risk estimates and treatment thresholds.

Screening age and Lp(a). No consensus exists on the optimal age for lipid screening in otherwise healthy South Asian adults. The LAI and NLA clinical perspectives support earlier assessment because of the high prevalence of premature ASCVD, whereas ACC/AHA, ESC/EAS, and NICE generally follow population-based strategies (1, 10). Once-in-a-lifetime Lp(a) measurement is now strongly recommended by ACC/AHA and ESC/EAS and supported by the LAI and NLA, while NICE NG238 remains comparatively less prescriptive (6, 9, 16, 39).

CAC. The 2026 ACC/AHA guideline retains CAC as a Class IIa recommendation and adds sex-specific age thresholds (men ≥40 years, women ≥45 years), providing more actionable guidance than the 2018 framework (6). ESC/EAS gives CAC a Class IIa recommendation in its 2025 Focused Update (39). NICE does not embed CAC in the NG238 pathway (9) and the LAI acknowledges it as a potentially useful adjunct without a defined implementation pathway (10). Given the MASALA evidence of reclassification benefit specifically in South Asians, the absence of a harmonised CAC pathway represents a missed opportunity for this population.

Lifestyle and dietary guidance. All frameworks endorse a ‘heart-healthy diet’ without addressing the specific dietary exposures prevalent in South Asian populations, including ghee, trans fats, refined grains, high-carbohydrate staples, and vegetarian patterns with suboptimal omega-3 to omega-6 ratios. A more substantive alternative would extend the WHO recommendation to replace saturated and trans fats with unsaturated alternatives (40) into region-specific substitutions: favouring mustard or soybean oil, both comparatively rich in alpha-linolenic acid, over ghee and palm-based cooking fats, shifting the carbohydrate base from refined grains and polished rice towards the whole grains, legumes, and pulses that are already regional staples, and directly addressing the omega-3 deficit common in vegetarian South Asians through plant-based alpha-linolenic acid sources such as flaxseed and walnuts, given limited regional access to marine omega-3. Regional precedents exist on which such guidance could build: the LAI has previously issued consensus dietary guidelines for Asian Indians addressing comparable substitutions (41), and India’s regulatory cap on industrial trans fats at 2% of total fat, recognised by the WHO as a best-practice policy and mirrored by comparable action in Bangladesh, demonstrates that population-level implementation of at least one of these exposures is achievable within the region (42). Extending and harmonising such frameworks across South Asian guideline bodies, rather than defaulting to generic dietary language, would substantially strengthen the practical value of lipid guidance for this population.

4.3 Practical implications: which framework to apply?

For clinicians managing South Asian patients, the practical answer is context-dependent (Box 1). In native South Asian settings, LAI 2023 Statement IV provides the most population-appropriate framework and should be the primary reference—though for patients from countries other than India, this remains the best available proxy rather than a validated national framework, consistent with the heterogeneity caveat in Section 2.3. In the UK, NICE NG238 with QRISK3 remains the regulatory standard, but its known limitations in South Asian women and its absence of Lp(a) and CAC pathways should prompt supplementary assessment using LAI or NLA guidance. In the US, the 2026 ACC/AHA framework should be applied, noting three South Asian-specific considerations: South Asian ancestry is now explicitly named as a risk enhancer, PREVENT equations may be used for risk estimation but have not been validated in South Asians and may underestimate risk at borderline and intermediate categories, and Lp(a) measurement is now a Class I recommendation for all patients. In all settings, the more aggressive LDL-C targets of ESC/EAS and LAI are biologically justifiable given the South Asian lipid phenotype, and clinicians should consider adopting them even where national guidance does not mandate them. For resource-limited native South Asian settings, these recommendations are condensed into a stepwise, low-cost-first sequence in Box 2.