Relation of Serum Lipoprotein(a) Concentration and Apolipoprotein(a) Phenotype to Coronary Heart Disease in Patients with Familial Hypercholesterolemia

Seed, Mary; Hoppichler, Fritz; Reaveley, D. A.; McCarthy, Susan; Thompson, Gilbert R.; Boerwinkle, Eric; Utermann, Gerd

doi:10.1056/nejm199005243222104

Cited by 573 publications

(205 citation statements)

References 34 publications

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“…Thus, an earlier study showed an increased prevalence of those genetic isoforms of apo(a) that are associated with high serum Lp(a) concentrations in FH patients with CHD compared with those without CHD. 17 In our own study family membership continued to operate as an independent influence on serum Lp(a) concentration, as it does in the general population. 23 However, it is clearly not the case that genetic effects unrelated to the FH gene defect can be the major explanation for the increase in Lp(a) in patients with FH because the presence of the gene still doubles the mean Lp(a) level even when family membership was controlled for, as in the present investigation.…”

Section: Discussionmentioning

confidence: 98%

“…We did not demonstrate any association between Lp(a) level and clinically overt CHD in our patients with FH. Both Seed and her coworkers 17 and Wiklund and colleagues 16 have recently reported that Lp(a) concentrations are higher in FH heterozygotes who have developed CHD than in those who have not. In both studies the criteria for identifying patients with CHD were similar to those in the present investigation.…”

Section: Discussionmentioning

confidence: 99%

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Serum lipoprotein(a) in patients heterozygous for familial hypercholesterolemia, their relatives, and unrelated control populations.

Mbewu

Bhatnagar

Durrington

et al. 1991

Arterioscler Thromb

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Serum lipoprotein(a) (Lp[a]) levels were significantly higher in 89 patients with heterozygous familial hypercholesterolemia (FH) (geometric mean, 22.7 mg/dl) than in 109 normocholesterolemic controls (10.0 mg/dl, p<0.05) and 40 controls (9.1 mg/dl, /?<0.05) with similarly elevated low density lipoprotein cholesterol levels due to other primary hypercholesterolemias. To provide further evidence that the increased serum Lp(a) concentration was due to inheritance of the FH gene, 24 unaffected first-degree relatives were compared with their FH probands. Serum Lp(a) in affected individuals was significantly greater than in unaffected relatives (geometric means, 26.5 versus 13.7 mg/dl, respectively; p<0.05). Family membership exerted an effect on serum Lp(a) concentrations, indicating that other genetic influences were also operating, as is known to be the case in general populations. Serum Lp(a) in 30 of the FH patients, who had coronary heart disease, was not significantly different from 30 age-and sex-matched controls with FH but without coronary heart disease (geometric means, 23.6 versus 24.7 mg/dl, respectively). FH is associated with an increase in serum Lp(a). Elevated serum Lp(a) concentrations should probably now be regarded as a component of the clinical syndrome of FH. However, within our FH population Lp(a) did not distinguish those with clinically overt coronary heart disease from those without the disease. (Arteriosclerosis and Thrombosis 1991;ll:940-946)

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Serum lipoprotein(a) in patients heterozygous for familial hypercholesterolemia, their relatives, and unrelated control populations.

Mbewu

Bhatnagar

Durrington

et al. 1991

Arterioscler Thromb

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“…Step OR 95% CL independent correlate for the presence of coronary heart disease among whites and Japanese Americans Seed et al 1990), and it has also been identified as an independent risk factor for myocardial infarction (Rhoads et al 1986), as well as for atherogenesis and thromboembolytic events (Scott 1989). Levels of Lp(a) in serum are genetically determined, and these levels do not correlate in general with other plasma lipids (Utermann 1989).…”

Section: Discussionmentioning

confidence: 99%

The association of hyperlipidemia with retinopathy in diabetic patients aged 15‐50 years in the county of Umeå

Alm

Lithner

et al. 1999

Acta Ophthalmologica Scandinavica

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ABSTRACT.Purpose: To study possible associations between serum lipid levels and degree of retinopathy in a population-based study on a specific age-group of patients with diabetes mellitus in the county of Umeå, Sweden. Methods: All patients with diabetes mellitus aged 15-50 years living in the county of Umeå were invited to the study. The participating subjects had a standard clinical examination and an eye examination performed. Seven-field stereoscopic photographs were taken of each eye, and the photos were sent to Grading Center, Hammersmith Hospital, London, U.K. for grading of the retinopathy. Blood samples were drawn for analysis of lipoprotein(a), high density lipoprotein (HDL) cholesterol, cholesterol and triglycerides. Univariate and multivariate statistical analyses were performed. Results: In the present study only patients with type 1 diabetes mellitus were included, and 285 of the invited 308 diabetic subjects (93%) took part. When univariate analysis was applied we found statistically significant associations between higher lipoprotein(a) levels, higher triglyceride levels, higher cholesterol levels, lower HDL cholesterol/total cholesterol ratios and increasing severeness of retinopathy. However, in the multivariate analysis triglyceride levels lost their importance while all other significant associations were still present. Conclusion: Associations were found between higher levels of serum total cholesterol, declining ratios of high density lipoprotein (HDL) cholesterol/total cholesterol, higher levels of serum lipoprotein(a) and more severe retinopathy in diabetes mellitus type 1. No such association was found between serum triglycerides and degree of retinopathy.

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“…A variation of apoA-I (delta K107) was associated with this syndrome. Increases of lipoprotein(a) (Lp(a)) 75 , of fibrinogen 76 and plasma homocysteine [77][78][79][80][81] may contribute to some cases of CAD. The relationship of homocysteine and atherosclerosis was first reported in 1969, when McCully 82 demonstrated precocious atherosclerosis in children with homocystinuria.…”

Section: Risk Factorsmentioning

confidence: 99%

Chronic Coronary Artery Disease

Thelen¹,

Erbel²,

Kreitner³

et al. 2009

Cardiac Imaging

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State of the ArtCoronary insufficiency (CI) is the state in which an imbalance occurs between the supply and demand of oxygen, which prevents adequate maintenance of the metabolic needs of the myocardium, resulting in ischemia of several degrees of intensity.CI has numerous causes among which are cardiac valvular diseases (aortic stenosis), hypertrophic cardiomyopathy, microvasculature diseases (diabetes mellitus, syndrome X), anomalous origin of coronary arteries, and coronary fistulas. However, the most important cause, because of its frequency and the resulting morbidity and mortality, is atherosclerotic obstructive CI. Therefore, this discussion will be specifically about coronary atherosclerosis. The main objective is not to suggest practical applications for specific situations, but to outline concepts, based on critical analysis of data in the literature, which may provide a basis for conducting further investigation and for providing treatment of coronary artery disease (CAD). PathophysiologyHuman atherosclerosis is a chronic, progressive and systemic process characterized by an inflammatory and fibroproliferative response of the arterial wall caused by aggression against the arterial surface. As a systemic process, it frequently attacks all arterial beds, including the aorta and its main branches: carotid, renal, iliac and femoral arteries. Among the risk factors (RF) for arterial lesions are hypercholesterolemia, arterial hypertension (AH), diabetes, smoking, immunological and inflammatory reactions, and individual genetic susceptibility 1 .The coronary vascular alterations present in atherosclerosis derive from three fundamental components: 1) endothelial dysfunction, which starts early, altering the reactivity of the vessel and causing paradoxical vasoconstriction following stimuli with acetylcholine, and exacerbation of reactivity to epinephrine and angiotensin; endothelial dysfunction also leads to loss of the natural antithrombotic properties and of the selective permeability of the endothelium; 2) obstruction of the lumen of the vessel by the atherosclerotic plaque and 3) thrombosis at the location of the lesion. Any of these could individually trigger CI, but they often occur at the same time. Response of the arterial wall to aggressive agentsEndothelial cells play several physiological roles in maintaining the integrity of the arterial wall and constitute a permeable barrier through which diffusion and exchanges or active transportation of several substances occur. They provide a non-thrombogenic and non-adhesive surface for platelets and leukocytes; they operate to maintain vascular tonus by releasing nitric oxide (NO), prostacyclin (PGI 2 ) and endothelin-1; they produce and discharge growth factors and cytokines and maintain the integrity of the basal membrane rich in collagen and proteoglycans on which they are supported 2 . Alterations in one or more of these functions represent initial manifestations of endothelial dysfunctions and may trigger cellular interactions with monocytes, platele...

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Relation of Serum Lipoprotein(a) Concentration and Apolipoprotein(a) Phenotype to Coronary Heart Disease in Patients with Familial Hypercholesterolemia

Cited by 573 publications

References 34 publications

Serum lipoprotein(a) in patients heterozygous for familial hypercholesterolemia, their relatives, and unrelated control populations.

Serum lipoprotein(a) in patients heterozygous for familial hypercholesterolemia, their relatives, and unrelated control populations.

The association of hyperlipidemia with retinopathy in diabetic patients aged 15‐50 years in the county of Umeå

Chronic Coronary Artery Disease

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