What is the atherogenic plasma index (API), what are the abnormal cutoff values, and how should an elevated API be evaluated and managed?

Atherogenic Plasma Index (AIP)

Definition and Calculation

The atherogenic index of plasma (AIP) is calculated as the logarithm (base 10) of the molar ratio of triglycerides to HDL-cholesterol: AIP = log₁₀(TG/HDL-C), where both lipids are expressed in molar concentrations (mmol/L). 1, 2

• AIP strongly correlates with LDL particle size (r = 0.8) and cholesterol esterification rate (r = 0.9), making it a sensitive marker of atherogenic lipoprotein profile 2
• The index can be calculated from standard lipid panels available in any clinical setting 1
• AIP reflects the balance between atherogenic (triglyceride-rich) and protective (HDL-C) lipoproteins 2

Abnormal Cutoff Values and Risk Stratification

Based on population studies of 8,394 subjects, AIP values are stratified as follows: low cardiovascular risk (AIP -0.3 to 0.1), medium risk (AIP 0.1 to 0.24), and high risk (AIP >0.24). 1

• Non-risk populations (umbilical cord blood, young children, healthy women) typically have AIP values ≤0 or below 0.1 1, 2
• Men and individuals with cardiovascular risk factors (hypertension, diabetes, dyslipidemia) demonstrate progressively increasing values up to 0.4 1
• High-risk groups (diabetic patients, those with documented CAD, positive angiography, or prior myocardial infarction) consistently show high positive AIP values 2
• Women consistently demonstrate lower AIP values compared to men across all age groups 1, 2

Prognostic Value and Clinical Significance

In patients with established coronary artery disease, elevated AIP independently predicts major adverse cardiovascular events (MACE) with a 63% increased risk in the highest versus lowest AIP quartile (RR 1.63,95% CI 1.44-1.85). 3

• Each 1-standard deviation increment in AIP confers a 2.10-fold increased odds of CAD (95% CI 1.51-2.93) after adjusting for traditional risk factors 4
• In a nationwide Korean cohort of 514,866 participants, multivariate-adjusted hazard ratios for MACE increased progressively across AIP quartiles: Q2 HR 1.113, Q3 HR 1.175, Q4 HR 1.278 5
• Elevated AIP specifically predicts cardiovascular death (RR 1.79), myocardial infarction (RR 2.21), revascularization (RR 1.62), no-reflow phenomenon (RR 3.12), and stent thrombosis (RR 13.46) 3
• The association between AIP and cardiovascular events is particularly pronounced in patients with diabetes 5

Evaluation of Elevated AIP

When AIP is elevated (>0.24), perform the following assessment:

• Obtain fasting lipid panel to confirm triglyceride and HDL-C values, as fasting state is essential for accurate triglyceride measurement 6
• Calculate non-HDL-cholesterol (total cholesterol minus HDL-C) to estimate total atherogenic particle burden 6
• Assess for secondary causes of dyslipidemia: uncontrolled diabetes (measure HbA1c and fasting glucose), hypothyroidism (TSH), chronic kidney disease (creatinine, eGFR), nephrotic syndrome (urinalysis for proteinuria), and medication effects 6
• Screen for metabolic syndrome components: measure waist circumference (abnormal if >102 cm in men, >88 cm in women), blood pressure, and fasting glucose 6
• Evaluate for familial dyslipidemia if AIP remains elevated despite lifestyle modification and triglycerides are persistently >400 mg/dL 6
• Consider measuring apolipoprotein B, which provides superior risk estimation in patients with hypertriglyceridemia combined with diabetes or metabolic syndrome 6

Management of Elevated AIP

The primary management strategy is aggressive LDL-cholesterol reduction to <70 mg/dL (1.8 mmol/L) using high-intensity statin therapy, as this reduces cardiovascular events even when AIP is elevated. 6, 7

Pharmacological Interventions

• Initiate high-intensity statin therapy (atorvastatin 40-80 mg or rosuvastatin 20-40 mg daily) as the foundation of treatment 7, 8
• Add ezetimibe 10 mg daily if LDL-C remains ≥70 mg/dL on maximal statin therapy, providing an additional 15-20% LDL-C reduction 7
• Consider fibrate therapy (ciprofibrate or gemfibrozil) for direct triglyceride reduction, which can dramatically decrease AIP values 1, 2
• Niacin (immediate- or extended-release) titrated up to 2000 mg/day reduces triglycerides and raises HDL-C, with documented efficacy in lowering AIP 7, 1
• PCSK9 inhibitors (evolocumab or alirocumab) provide 50-60% LDL-C reduction and should be considered for high-risk patients with AIP >0.24 and additional cardiovascular risk factors 7, 8

Lifestyle Modifications

• Target blood pressure <130/80 mmHg in patients with elevated AIP and hypertension 6
• Achieve HbA1c <7% (or individualized target) in diabetic patients, as glycemic control improves AIP 7, 1
• Prescribe at least 150 minutes of moderate-intensity aerobic exercise weekly 7
• Implement weight management to achieve BMI 18.5-24.9 kg/m² 7
• Enforce smoking cessation, as smoking independently elevates cardiovascular risk 6

Monitoring Strategy

• Re-measure fasting lipid panel (including calculation of AIP) 4-12 weeks after initiating or changing lipid-lowering therapy 7, 8
• Assess medication adherence and lifestyle compliance at each follow-up visit 7, 8
• Schedule lipid monitoring every 3-12 months once therapeutic targets are achieved and adherence is established 7, 8

Common Pitfalls to Avoid

• Do not calculate AIP from non-fasting samples, as triglyceride levels vary significantly with recent food intake 6
• Do not assume achieving LDL-C targets eliminates cardiovascular risk when AIP remains elevated, as residual risk persists 7, 5
• Do not use the Friedewald formula to calculate LDL-C when triglycerides exceed 400 mg/dL (4.5 mmol/L), as it becomes inaccurate; instead, use non-HDL-cholesterol or direct LDL-C measurement 6
• Recognize that AIP adds predictive value beyond individual lipid parameters and the total cholesterol/HDL-C ratio, particularly in identifying small dense LDL particles 1, 2
• In patients with chronic kidney disease, AIP may be particularly elevated and warrants aggressive management, as these patients face substantially increased cardiovascular risk 7, 5