What is the diagnosis for a patient with elevated triglycerides, LDL cholesterol, non-HDL cholesterol, and mildly elevated liver enzymes?

Diagnosis: Mixed Dyslipidemia with Metabolic Syndrome Features and Mild Hepatic Steatosis

This patient has mixed dyslipidemia characterized by elevated triglycerides (165 mg/dL), low HDL cholesterol (39 mg/dL), borderline elevated LDL cholesterol (108 mg/dL), and mildly elevated liver enzymes (ALT 51), consistent with metabolic syndrome and likely non-alcoholic fatty liver disease (NAFLD).

Lipid Profile Analysis

Triglyceride Classification

• The triglyceride level of 165 mg/dL falls into the mild hypertriglyceridemia category (150-199 mg/dL), which is classified as a cardiovascular risk-enhancing factor 1
• This level does not pose immediate pancreatitis risk, which occurs at ≥500 mg/dL, but does increase long-term atherosclerotic cardiovascular disease (ASCVD) risk 1

HDL Cholesterol Assessment

• The HDL cholesterol of 39 mg/dL is below the threshold of <40 mg/dL that defines low HDL as a major cardiovascular risk factor 2
• Low HDL cholesterol in the context of elevated triglycerides represents the atherogenic lipid triad, consisting of increased VLDL remnants, small dense LDL particles, and reduced HDL-C 2
• This pattern is strongly associated with metabolic syndrome and insulin resistance 3

LDL and Non-HDL Cholesterol

• The LDL cholesterol of 108 mg/dL is borderline elevated but below the 130 mg/dL threshold where therapeutic lifestyle changes are typically initiated for patients with 0-1 risk factors 2
• The non-HDL cholesterol of 137 mg/dL (calculated as total cholesterol minus HDL) is **above the optimal target of <130 mg/dL** for patients with triglycerides >150 mg/dL 2, 1
• Non-HDL cholesterol represents all atherogenic lipoproteins (LDL, VLDL, IDL, and lipoprotein[a]) and is an independent predictor of cardiovascular events 2

Cholesterol/HDL Ratio

• The cholesterol/HDL ratio of 4.6 indicates moderate cardiovascular risk, as ratios >4.5 in men or >4.0 in women suggest increased atherosclerotic risk 2

Hepatic Component

Liver Enzyme Elevation

• The ALT of 51 U/L represents mild transaminitis, likely reflecting non-alcoholic fatty liver disease (NAFLD), which commonly coexists with metabolic syndrome and dyslipidemia 1
• NAFLD is present in approximately 70% of patients with metabolic syndrome and is both a consequence and contributor to dyslipidemia 1
• The liver enzyme elevation is mild enough that lipid-lowering therapy is not contraindicated, though monitoring is warranted 1

Metabolic Syndrome Diagnosis

Diagnostic Criteria Met

This patient likely meets criteria for metabolic syndrome, which requires ≥3 of the following components 2:

• Elevated triglycerides ≥150 mg/dL (present: 165 mg/dL)
• Low HDL cholesterol <40 mg/dL in men or <50 mg/dL in women (present: 39 mg/dL)
• Additional criteria to assess: waist circumference (≥102 cm in men, ≥88 cm in women), blood pressure (≥130/85 mmHg or on antihypertensive medication), and fasting glucose (≥100 mg/dL or on diabetes medication) 2

Clinical Significance

• Metabolic syndrome increases cardiovascular disease risk 2-3 fold and type 2 diabetes risk 5-fold 2
• The presence of metabolic syndrome makes this patient a secondary target for intervention beyond LDL cholesterol lowering 2

Cardiovascular Risk Assessment

Risk Factor Counting

To determine appropriate treatment intensity, count the following major risk factors 2:

• Cigarette smoking (assess)
• Hypertension (blood pressure ≥140/90 mmHg or on antihypertensive medication) (assess)
• Low HDL cholesterol <40 mg/dL (present)
• Family history of premature CHD (male first-degree relative <55 years or female <65 years) (assess)
• Age (>45 years for men, >55 years for women) (assess)

Treatment Implications

• If the patient has ≥2 risk factors, calculate 10-year ASCVD risk to determine LDL cholesterol goals 2
• For patients with 10-year ASCVD risk ≥7.5%, statin therapy should be considered as first-line pharmacologic intervention 1
• The non-HDL cholesterol goal should be 30 mg/dL higher than the LDL cholesterol goal, making it <160 mg/dL for patients with 0-1 risk factors or <130 mg/dL for those with ≥2 risk factors 2

Secondary Causes to Exclude

Essential Screening

Before initiating treatment, evaluate for secondary causes of dyslipidemia 1, 4:

• Uncontrolled diabetes mellitus (check HbA1c, fasting glucose)
• Hypothyroidism (check TSH)
• Chronic kidney disease (check creatinine, eGFR, urinalysis)
• Nephrotic syndrome (check urine protein)
• Obstructive liver disease (check alkaline phosphatase, bilirubin)
• Medications that raise triglycerides: thiazide diuretics, beta-blockers, estrogen therapy, corticosteroids, antiretrovirals, antipsychotics 1
• Excessive alcohol intake (assess consumption history) 1

Common Pitfalls to Avoid

• Do not focus solely on LDL cholesterol in patients with metabolic syndrome, as the atherogenic lipid triad (elevated triglycerides, low HDL, small dense LDL) contributes significantly to cardiovascular risk even when LDL is only borderline elevated 2, 3
• Do not ignore the mildly elevated liver enzymes, as they likely indicate NAFLD, which requires lifestyle intervention and may influence medication choices 1
• Do not delay lifestyle modifications while waiting to initiate pharmacotherapy, as weight loss of 5-10% can reduce triglycerides by 20% and significantly improve all lipid parameters 1
• Do not use LDL cholesterol alone to assess cardiovascular risk in patients with triglycerides >150 mg/dL; non-HDL cholesterol is a better predictor in this population 2
• Do not overlook insulin resistance as the underlying driver of this lipid pattern, which requires addressing through weight loss, dietary modification, and increased physical activity 2, 3