Increased Levels of Pregnancy-Associated Plasma Protein-A
Increased Levels of Pregnancy-Associated Plasma Protein-A
Background: Serum levels of pregnancy-associated plasma protein-A (PAPP-A) have recently been linked to plaque instability and are increased in acute coronary syndromes. The relation between PAPP-A levels and coronary risk factors, namely blood lipids, has not been studied to date. We have therefore investigated whether serum PAPP-A levels are increased in asymptomatic hypercholesterolemic subjects and whether PAPP-A levels are influenced by atorvastatin therapy.
Methods: We examined 27 subjects with isolated hypercholesterolemia free of manifest vascular disease and 29 age-matched healthy control subjects. Patients were examined at baseline and after 10 weeks of atorvastatin treatment (20 mg/d).
Results: In untreated hypercholesterolemic subjects, PAPP-A levels were significantly higher than in control subjects (8.02 ± 1.86 mU/L vs 6.50 ± 2.54 mU/L, P = .018). There was no correlation between PAPP-A levels and serum lipid levels. Atorvastatin treatment reduced total and LDL-cholesterol by 31% and 40%, respectively. Despite this profound lipid lowering, there was no significant change in the serum PAPP-A levels.
Conclusions: PAPP-A levels are elevated in hypercholesterolemic subjects without clinical signs of atherosclerosis. PAPP-A may therefore not only reflect plaque instability but also serve as a marker of total atherosclerotic burden in asymptomatic subjects with hyperlipidemia. However, PAPP-A levels are not influenced by atorvastatin treatment.
Conventional risk factors often fail to identify patients who eventually develop premature atherosclerosis. New markers of atherosclerotic plaque development and activity are therefore sought to identify patients at highest risk of clinical events. Various inflammatory mediators such as C-reactive protein (CRP) and endothelium or monocyte-derived molecules have been linked to both atheroslerosis and acute coronary syndromes.
Quite recently it has been demonstrated that circulating levels of pregnancy-associated plasma protein A (PAPP-A) are elevated in patients with unstable angina and acute myocardial infarction. PAPP-A, a zinc-binding metalloproteinase, has been detected in vascular smooth muscle cells in unstable and eroded atherosclerotic lesions and in the arteries after experimental injury. It was therefore hypothesized that increased plasma levels of PAPP-A may reflect the instability of atherosclerotic plaques and that PAPP-A might be a novel marker of acute coronary syndromes.
Hypercholesterolemia is a strong risk factor for premature atherosclerosis, and it is associated with increased serum levels of inflammatory markers. Cholesterol lowering is critical treatment in reducing the risk of acute cardiac events; event reduction is accompanied by a decrease of serum inflammatory markers. However, the relation between circulating PAPP-A levels and hyperlipidemia has not been studied to date. We have therefore investigated whether serum PAPP-A levels are increased in asymptomatic middle-aged hypercholesterolemic subjects compared with normolipidemic control subjects and whether PAPP-A levels are influenced by atorvastatin therapy.
Abstract and Introduction
Abstract
Background: Serum levels of pregnancy-associated plasma protein-A (PAPP-A) have recently been linked to plaque instability and are increased in acute coronary syndromes. The relation between PAPP-A levels and coronary risk factors, namely blood lipids, has not been studied to date. We have therefore investigated whether serum PAPP-A levels are increased in asymptomatic hypercholesterolemic subjects and whether PAPP-A levels are influenced by atorvastatin therapy.
Methods: We examined 27 subjects with isolated hypercholesterolemia free of manifest vascular disease and 29 age-matched healthy control subjects. Patients were examined at baseline and after 10 weeks of atorvastatin treatment (20 mg/d).
Results: In untreated hypercholesterolemic subjects, PAPP-A levels were significantly higher than in control subjects (8.02 ± 1.86 mU/L vs 6.50 ± 2.54 mU/L, P = .018). There was no correlation between PAPP-A levels and serum lipid levels. Atorvastatin treatment reduced total and LDL-cholesterol by 31% and 40%, respectively. Despite this profound lipid lowering, there was no significant change in the serum PAPP-A levels.
Conclusions: PAPP-A levels are elevated in hypercholesterolemic subjects without clinical signs of atherosclerosis. PAPP-A may therefore not only reflect plaque instability but also serve as a marker of total atherosclerotic burden in asymptomatic subjects with hyperlipidemia. However, PAPP-A levels are not influenced by atorvastatin treatment.
Introduction
Conventional risk factors often fail to identify patients who eventually develop premature atherosclerosis. New markers of atherosclerotic plaque development and activity are therefore sought to identify patients at highest risk of clinical events. Various inflammatory mediators such as C-reactive protein (CRP) and endothelium or monocyte-derived molecules have been linked to both atheroslerosis and acute coronary syndromes.
Quite recently it has been demonstrated that circulating levels of pregnancy-associated plasma protein A (PAPP-A) are elevated in patients with unstable angina and acute myocardial infarction. PAPP-A, a zinc-binding metalloproteinase, has been detected in vascular smooth muscle cells in unstable and eroded atherosclerotic lesions and in the arteries after experimental injury. It was therefore hypothesized that increased plasma levels of PAPP-A may reflect the instability of atherosclerotic plaques and that PAPP-A might be a novel marker of acute coronary syndromes.
Hypercholesterolemia is a strong risk factor for premature atherosclerosis, and it is associated with increased serum levels of inflammatory markers. Cholesterol lowering is critical treatment in reducing the risk of acute cardiac events; event reduction is accompanied by a decrease of serum inflammatory markers. However, the relation between circulating PAPP-A levels and hyperlipidemia has not been studied to date. We have therefore investigated whether serum PAPP-A levels are increased in asymptomatic middle-aged hypercholesterolemic subjects compared with normolipidemic control subjects and whether PAPP-A levels are influenced by atorvastatin therapy.
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