Table 1
Typical lipid phenotype in South Asian versus European-ancestry populations.
| LIPID PARAMETER | TYPICAL SOUTH ASIAN PHENOTYPE | TYPICAL EUROPEAN-ANCESTRY PHENOTYPE | CLINICAL IMPLICATION |
|---|---|---|---|
| LDL-C | Often similar despite higher ASCVD risk | Variable | LDL-C alone may underestimate risk |
| ApoB | Disproportionately elevated relative to LDL-C | More closely aligned with LDL-C | Greater atherogenic particle burden |
| Triglycerides | Elevated | Lower | Reflects insulin resistance and remnant lipoprotein excess |
| HDL-C | Lower | Higher | Associated with impaired reverse cholesterol transport |
| sdLDL proportion | Increased | Lower | Greater arterial-wall penetrance and oxidisability |
| Lp(a) >50 mg/dL (125 nmol/L) | Frequently elevated | Variable | Independent ASCVD risk; not statin-responsive |
| Non-HDL-C | Often elevated relative to LDL-C | More concordant with LDL-C | Practical ApoB surrogate on a standard panel |
Figure 1
The South Asian lipid paradox. Two patients with identical LDL-C (135 mg/dL, 3.5 mmol/L) have substantially different atherogenic particle burdens. The South Asian phenotype is characterised by a predominance of sdLDL particles and elevated Lp(a), reflected in a higher ApoB concentration despite equivalent LDL-C. Standard cardiovascular risk calculators anchored to LDL-C systematically underestimate risk in this context. ApoB = apolipoprotein B; HDL-C = high-density lipoprotein cholesterol; LDL-C = low-density lipoprotein cholesterol; Lp(a) = lipoprotein(a); TG = triglycerides.
Table 2
Performance and applicability of cardiovascular risk-stratification tools in South Asian populations.
| TOOL | DEVELOPED IN | SA-SPECIFIC ADJUSTMENT | KNOWN LIMITATION IN SOUTH ASIANS | CAC INTEGRATION | LIFETIME RISK |
|---|---|---|---|---|---|
| ATP III (National Cholesterol Education Program Adult Treatment Panel III) | US | None | No ethnicity modifier; outdated lipid targets | Not included | Not included |
| PCE (ACC/AHA 2018) (8) | US multi-ethnic | SA listed as risk enhancer; no quantitative adjustment | Over- and underestimation reported; underprediction at borderline risk | Class IIa recommendation | Not incorporated |
| PREVENT-ASCVD (ACC/AHA 2026) (6) | US contemporary multi-ethnic cohorts | No quantitative adjustment; SA ancestry treated as a risk-enhancing factor | Not validated in South Asians; generally lower estimates than PCE, risking downward reclassification near thresholds | Recommended for risk refinement when uncertainty persists | 10- and 30-year estimates |
| QRISK3 (NICE NG238) (9) | UK population | Includes SA ethnicity within the model | Performance varies by subgroup; NICE advises clinical judgement as risk may be underestimated | Not embedded in pathway | Optional tool for communication; not used to guide statin initiation |
| SCORE2 (ESC/EAS) (16, 39) | European | None for South Asia | No validated equation for native SA populations | Class IIa | Not incorporated |
| SCORE2 Asia-Pacific (16, 39) | East/SE Asian | Recalibrated for East/SE Asia | Not validated for the SA subcontinent | Not included | Not incorporated |
| LAI Consensus IV (10) | Indian populations | India-specific stratification; supports ApoB, non-HDL-C, Lp(a) | Limited prospective external validation outside India | Considered a useful adjunct | Emphasises early/lifetime risk in younger adults |
[i] CAC = coronary artery calcium; PCE = Pooled Cohort Equations; SA = South Asian.
Table 3
Comparison of major lipid guideline frameworks and their applicability to South Asian populations.
| DOMAIN | ATP III | ACC/AHA 2018 (7, 8) | ACC/AHA 2026 (6) | ESC/EAS 2019 (16) | ESC/EAS 2025 (39) | NICE NG238 (9) | LAI 2023 IV (10) |
|---|---|---|---|---|---|---|---|
| Primary treatment target | LDL-C (numerical) | % LDL-C reduction | Numerical LDL-C and non-HDL-C restored | LDL-C numerical | Unchanged | ≥40% non-HDL-C reduction (primary prevention) | LDL-C numerical goals |
| Very high-risk LDL-C goal | <70 mg/dL (<1.8 mmol/L) | ≥50% reduction + <70 mg/dL (<1.8 mmol/L) optional | <55 mg/dL (1.4 mmol/L) | <55 mg/dL (<1.4 mmol/L) + ≥50% reduction | Unchanged | Secondary prevention LDL-C ≤77 mg/dL (≤2.0 mmol/L) or non-HDL-C ≤100 mg/dL (≤2.6 mmol/L) | <50 mg/dL (<1.3 mmol/L) |
| Extreme-risk LDL-C goal | Not defined | Not defined | Not defined | <40 mg/dL (<1.0 mmol/L) (IIb) | Added polyvascular disease | Not defined | ≤30 mg/dL (≤0.8 mmol/L) (selected) |
| High-risk LDL-C goal | <100 mg/dL (<2.6 mmol/L) | ≥50% reduction | ≥50% reduction ± <70 mg/dL (<1.8 mmol/L) | <70 mg/dL (<1.8 mmol/L) + ≥50% reduction | Unchanged | Not specifically defined | <70 mg/dL (<1.8 mmol/L) |
| Borderline/lower-risk LDL-C goal | <130 mg/dL (<3.4 mmol/L) | Not specified | <100 mg/dL (<2.6 mmol/L) | Moderate <100 mg/dL (<2.6 mmol/L); low <116 mg/dL (< 3.0 mmol/L) | Unchanged | Focus on >40% non-HDL-C reduction | <100 mg/dL (<2.6 mmol/L) |
| Risk calculator | Framingham | PCE | PREVENT-ASCVD | SCORE | SCORE2 /SCORE2-OP | QRISK3 | Indian framework |
| SA ethnicity adjustment | None | Risk enhancer | Risk enhancer | Not named | Explicitly named high-risk modifier | Incorporated in QRISK3 | India-focused framework |
| Lp(a) screening | Not included | Optional; once-in-lifetime | Class I once-in-lifetime, all adults | Once-in-lifetime (IIa) | >50 mg/dL (125 nmol/L) risk enhancer (IIa, B) | Not routinely recommended | Recommended in SA adults |
| ApoB as target | Not included | Optional secondary | Reasonable for intensification (ASCVD, diabetes, CKM, hypertriglyceridaemia) | Endorsed secondary | Unchanged | No | Secondary target endorsed |
| hsCRP | Not included | Not specified | Risk enhancer; may guide statin initiation | No formal class | >2 mg/L risk modifier (IIa, B) | Not incorporated | Adjunctive marker |
| CAC recommendation | Not included | Class IIa (intermediate risk) | Risk-refinement pathway when uncertain | Class IIb | Upgraded to IIa, B | Not routinely recommended | Adjunctive refinement |
| Non-statin trigger | LDL-C ≥130 on statin | Goal not met on max statin | Expanded: ezetimibe, PCSK9i, inclisiran, bempedoic acid | Ezetimibe + PCSK9i if goal not met | Added bempedoic acid (I); evinacumab (IIa) | Goal not met in secondary prevention | Goal not met; lower thresholds in very high/extreme risk |
| Culturally tailored diet | None | None | None | None | None | None | Partial; SA diet addressed |
| Lifetime-risk framing | Not incorporated | Not incorporated | 30-year estimation incorporated | Not incorporated | Acknowledged as gap | QRISK3 lifetime available | Emphasised, especially younger adults |
| Familial hypercholesterolaemia | Not specified | Not specified | Expanded pathway including genetic testing | Comprehensive; cascade Class I | Added evinacumab HoFH (IIa) | Dedicated referral pathway | Strong emphasis on cascade screening |
| South Asian evidence base | None | None | Limited; PREVENT not validated in SA | None | SA named but not validated | Limited UK SA representation via QRISK3 | India-focused; limited external validation |
[i] The 2025 ESC/EAS Focused Update names South Asian ethnicity (Box 1) as a high-risk modifier beyond SCORE2/SCORE2-OP, which may support reclassifying an individual to a higher risk category and thereby guide LDL-C goals and intervention thresholds. ApoB = apolipoprotein B; CAC = coronary artery calcium; CKM = cardiovascular-kidney-metabolic; HoFH = homozygous familial hypercholesterolaemia; PCE = Pooled Cohort Equations; PCSK9i = PCSK9 inhibitor; SA = South Asian.
Box 1
Practical framework selection for lipid risk assessment and management in South Asian populations.
| Clinical setting | Primary framework | Additional considerations for South Asian patients |
|---|---|---|
| South Asian countries | LAI Expert Consensus Statement IV (2023) | Measure ApoB, non-HDL-C, and Lp(a) where available; apply intensive risk-factor modification in high-risk individuals. LAI Statement IV is India-derived; for Pakistani, Bangladeshi, Sri Lankan, and Nepali patients, it is the best available proxy, not a validated national framework, and should be applied with the same caution urged in Section 2.3. |
| United Kingdom | NICE NG238 with QRISK3 | QRISK3 incorporates South Asian ethnicity, but risk may still be underestimated in some subgroups. Consider supplementary Lp(a), ApoB, or CAC when treatment decisions remain uncertain. |
| United States | ACC/AHA 2026 Dyslipidemia Guideline | South Asian ancestry explicitly named a risk enhancer. Use PREVENT with awareness of the lack of SA validation—maintain a low threshold for CAC in patients reclassified downward. Once-in-lifetime Lp(a) measurement is now a Class I recommendation for all adults. Numerical LDL-C targets restored: <55 mg/dL (<1.4 mmol/L) very high-risk, <70 mg/dL (<1.8 mmol/L) high-risk. |
| Europe (excluding UK) | ESC/EAS guidelines with SCORE2 | Risk tools are not specifically calibrated for South Asians. Additional stratification using ApoB, Lp(a), or CAC may help in selected patients. |
| South Asian diaspora | National guideline of country of residence | Follow local recommendations while recognising the higher cardiometabolic risk profile; incorporate South Asian-specific risk enhancers and targets where appropriate. |
[i] ApoB = apolipoprotein B; CAC = coronary artery calcium; LAI = Lipid Association of India; Lp(a) = lipoprotein(a); SA = South Asian.
Box 2
A pragmatic point-of-care sequence for lipid management in resource-limited South Asian settings.
| The following sequence synthesises the recommendations made throughout this review into an ordered, low-cost-first pathway. It is offered as a starting point for local adaptation and clinical judgement, not as a validated clinical algorithm. |
| 1. Assess conventional risk factors and apply South Asian ethnicity as an automatic risk enhancer, regardless of which calculator is used; treat a ‘low-risk’ result with caution, given the systematic underestimation documented in this review (Section 3.1). |
| 2. Order a standard fasting lipid panel and calculate non-HDL-C at no additional cost; add a one-time Lp(a) and ApoB where accessible (Section 5). |
| 3. Initiate a statin if LDL-C or non-HDL-C exceeds the intensive LAI/ESC-EAS thresholds for the patient’s risk category, even when the calculated 10-year risk is ‘low’, given the underestimation documented in Section 3.1; start rosuvastatin at 5 mg or atorvastatin at 10 mg, consistent with the pharmacokinetic considerations in Section 3.6, rather than at doses standard for European-origin patients. |
| 4. If LDL-C targets are not met on maximally tolerated statin therapy, add ezetimibe as the realistic first-line escalation option; reserve PCSK9 inhibitors, inclisiran, or bempedoic acid for patients who can access them (Section 5). |
| 5. Where risk remains borderline after the above, and CT infrastructure is accessible through tertiary referral, obtain a CAC score to support the decision to intensify or de-escalate therapy (Section 3.3). |