What is the atherogenic plasma index, how is it calculated, and how should an adult with an elevated atherogenic plasma index be evaluated and managed?

Atherogenic Plasma Index: Definition, Calculation, and Clinical Management

What is the Atherogenic Index of Plasma?

The atherogenic index of plasma (AIP) is a logarithmically transformed ratio of triglycerides to HDL-cholesterol that serves as a marker of lipoprotein particle size and cardiovascular risk, calculated as log₁₀(TG/HDL-C) using molar concentrations. 1

• AIP correlates strongly with the presence of small, dense LDL particles, which are highly atherogenic 1
• Values below 0.1 indicate low cardiovascular risk, 0.1 to 0.24 indicate medium risk, and above 0.24 indicate high cardiovascular risk 1
• AIP adds predictive value beyond traditional lipid measurements and the TC/HDL-C ratio 1

How to Calculate AIP

Calculate AIP by taking the base-10 logarithm of the ratio of triglycerides (in mmol/L) to HDL-cholesterol (in mmol/L): AIP = log₁₀(TG/HDL-C). 1

Critical Calculation Requirements:

• Blood must be obtained after 12 hours of fasting because triglyceride levels are markedly altered by recent food intake 2
• Convert triglycerides and HDL-cholesterol to molar concentrations (mmol/L) before calculating the ratio 1
• Do not attempt to calculate AIP from non-fasting samples, as this produces unreliable results 2

Evaluation of an Adult with Elevated AIP

Initial Laboratory Assessment

Obtain a fasting lipid panel to confirm triglyceride and HDL-cholesterol concentrations and calculate non-HDL cholesterol (total cholesterol minus HDL-C) to estimate total atherogenic particle burden. 2

• Measure apolipoprotein B in patients with hypertriglyceridemia combined with diabetes or metabolic syndrome, as it provides superior risk estimation compared to LDL-C alone 2
• Calculate LDL-cholesterol using the Friedewald formula only if triglycerides are <400 mg/dL (<4.5 mmol/L); otherwise use direct LDL-C measurement or non-HDL-C 3

Screen for Secondary Causes

Evaluate for poorly controlled diabetes (HbA1c), hypothyroidism (TSH), chronic kidney disease (creatinine, eGFR), nephrotic syndrome (urinalysis for proteinuria), and medication effects (beta-blockers, thiazide diuretics, corticosteroids). 2

Assess Metabolic Syndrome Components

Measure waist circumference, blood pressure, and fasting glucose to identify metabolic syndrome, which frequently accompanies elevated AIP. 2

• Men with metabolic syndrome typically have higher AIP values than women 1
• Patients with diabetes, hypertension, or dyslipidemia show progressively increasing AIP values up to 0.4 1

Consider Familial Dyslipidemia

Suspect familial dyslipidemia when AIP remains elevated despite aggressive lifestyle modifications and triglycerides stay at very high levels (>500 mg/dL). 2

Management of Elevated AIP

Primary Therapeutic Target

Aggressively lower LDL-cholesterol to <70 mg/dL using high-intensity statin therapy (atorvastatin 40-80 mg or rosuvastatin 20-40 mg daily), as this reduces cardiovascular mortality even when AIP is elevated. 3, 2, 4

• TC and LDL-C remain the primary targets supported by major clinical trial evidence demonstrating statistically and clinically significant reductions in cardiovascular mortality 3
• While AIP provides additional risk stratification, treatment decisions should prioritize proven LDL-C targets 3

Pharmacological Interventions

Initiate high-intensity statin therapy as first-line treatment for all patients with elevated AIP and cardiovascular risk factors. 2, 4

• Add ezetimibe 10 mg daily if LDL-C remains ≥70 mg/dL despite maximal statin therapy, providing an additional 15-20% LDL-C reduction 2, 4
• Consider PCSK9-inhibitor therapy (evolocumab or alirocumab) for very high-risk individuals with AIP >0.24 and additional cardiovascular risk factors, delivering 50-60% LDL-C reduction 2, 4
• For patients with triglycerides ≥200 mg/dL, consider adding fibrates or nicotinic acid, with non-HDL-C target set 30 mg/dL above the LDL-C goal 3, 4
• Treatment with ciprofibrate or combination of statin and niacin dramatically decreases AIP 1

Lifestyle Modifications

Implement comprehensive lifestyle changes including blood pressure control to <130/80 mmHg, optimal glycemic control (HbA1c <7%), ≥150 minutes of moderate-intensity aerobic exercise weekly, healthy body weight (BMI 18.5-24.9 kg/m²), and smoking cessation. 2

• Reduce saturated fat to <7% of total daily calories and limit dietary cholesterol to <200 mg/day 4
• Reduce simple carbohydrate intake to help lower triglycerides 4
• In patients with type 2 diabetes, combination therapy including pioglitazone decreases AIP 1

Monitoring Strategy

Re-measure fasting lipid panel (including AIP calculation) 4-12 weeks after initiating or changing lipid-lowering therapy to assess response. 2

• Evaluate medication adherence and lifestyle compliance at each follow-up visit 2
• Schedule routine lipid monitoring every 3-12 months once therapeutic targets are achieved and adherence is confirmed 2

Common Pitfalls and How to Avoid Them

Do not calculate AIP from non-fasting samples, as recent food intake markedly alters triglyceride levels and produces unreliable results. 2

Do not rely solely on LDL-C target achievement; residual cardiovascular risk persists if AIP remains elevated, particularly in patients with metabolic syndrome or diabetes. 2, 5

• The association of AIP with major adverse cardiovascular events is particularly outstanding in patients with diabetes 5
• Elevated AIP is independently associated with increased risk of cardiovascular death (RR 1.79), myocardial infarction (RR 2.21), revascularization (RR 1.62), and no-reflow phenomenon (RR 3.12) in patients with coronary artery disease 6

Avoid using the Friedewald formula when triglycerides are ≥400 mg/dL (≥4.5 mmol/L); instead use non-HDL-C or direct LDL-C measurement for accurate assessment. 3, 2

Do not overlook apolipoprotein B measurement in high-risk patients with elevated AIP, as it provides superior risk estimation and does not require fasting. 3, 2, 7

• Non-HDL-C or apo B may give a better estimate of atherogenic particle concentration, especially in high-risk patients with diabetes or metabolic syndrome 3
• Apo B measurement has less laboratory error than LDL-C determination, particularly in patients with hypertriglyceridemia 7