Dyslipidemia in the General Practitioner's Office – Featuring LDL Cholesterol
Monitoring LDL cholesterol (LDL-c) levels is crucial in diagnosing hypercholesterolemia as it is directly linked to increased cardiovascular risk. What other tests should be performed upon detecting hypercholesterolemia and which medications can effectively help reduce LDL-c levels?
Introduction
LDL-c is a lipid particle that circulates in the blood, transporting water-insoluble cholesterol throughout the body. LDL receptors are found in most tissues. One of the clinically significant properties of LDL-c is its ability to deposit cholesterol into the artery walls. Elevated LDL-c levels thus correlate with the development of atherosclerosis and an increase in cardiovascular disease risk.
Associated Morbidity
Hypercholesterolemia generally results from an excess of cholesterol from diet, bile, or intestines. Levels of total cholesterol > 5.2 mmol/l and LDL-c > 3.4 mmol/l are considered abnormal. Elevated LDL-c levels are commonly associated with the following conditions:
- diabetes mellitus
- arterial hypertension
- atherosclerosis
- hypertriglyceridemia
- metabolic syndrome
It is crucial to monitor LDL-c values, especially in patients with arterial hypertension and diabetes.
Laboratory Diagnostics
In addition to a fasting lipid profile, further laboratory tests are required to rule out secondary causes of hypercholesterolemia:
- fasting glucose and glycated hemoglobin levels to rule out glucose metabolism disorders
- thyroid hormones to rule out thyroid disease
- ALP levels as a marker for cholestasis
- urine analysis to rule out proteinuria accompanied by hyperlipidemia
Treatment Options
Lifestyle Modification?
Measures including diets low in saturated fats and aerobic exercise can help reduce LDL-c levels. Lifestyle modifications, including weight reduction, should therefore be the foundation of hypercholesterolemia treatment.
HMG-CoA Reductase Inhibitors
HMG-CoA reductase is a key enzyme in cholesterol synthesis. Statins inhibit the conversion of HMG-CoA to mevalonate, a precursor of cholesterol, significantly reducing LDL-c levels through this mechanism.
PCSK9 Inhibitors
Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) inactivate the degradation of LDL receptors in target tissues. Increased numbers of LDL receptors on cell membranes lead to increased internalization of LDL-c into cells, reducing plasma LDL-c concentration. One PCSK9i released into clinical practice is alirocumab, a specific antibody against PCSK9 obtained through recombinant technology. Its beneficial effect on atherogenic lipoproteins and LDL-c reduction of > 50% is documented both in monotherapy and combination with statins or other lipid-lowering drugs. The ODYSSEY OUTCOMES study showed that adding alirocumab to intensive statin therapy significantly reduced cardiovascular events in patients with acute coronary syndrome, and subsequent analyses indicated a reduction in overall mortality. Its administration in clinical studies was safe, with minimal adverse events.
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Source:
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3. Ryšavá R. Nephrotic Syndrome. Internal Medicine for Practice 2005; 3: 131–134.
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