Prospective Study of Lipoprotein(a) as a Risk Factor for Atherosclerotic Cardiovascular Disease in Patients With Diabetes

Hiraga, Takaki; Kobayashi, Tetsuro; Okubo, Minoru; Nakanishi, Kohji; Sugimoto, Tadao; Ohashi, Yasuo; Murase, Toshio

doi:10.2337/diacare.18.2.241

Cited by 64 publications

(42 citation statements)

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“…An elevated level of serum Lp(a), primarily genetically determined (11), is a significant risk factor for atherothrombogenesis in both diabetic and nondiabetic subjects (12)(13)(14)(15)(16)(17). Renal dysfunction in particular has been associated with elevated Lp(a) levels, which partly explains the increased susceptibility to vascular disease in patients with renal disease, including diabetic nephropathy (18 -24).…”

Section: Diabetes Care 28:1718 -1723 2005mentioning

confidence: 99%

Prospective Study of Lipoprotein(a) as a Risk Factor for Deteriorating Renal Function in Type 2 Diabetic Patients With Overt Proteinuria

Song

Kim

et al. 2005

Diabetes Care

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OBJECTIVE -The effect of lipoprotein(a) [Lp(a)] on the progression of diabetic nephropathy has not been evaluated yet. The aim of this study was to determine whether Lp(a) is an independent risk factor for deteriorating renal function in type 2 diabetic patients with nephropathy.RESEARCH DESIGN AND METHODS -We conducted this prospective study in type 2 diabetic patients with overt proteinuria. Patients were divided into two groups according to their baseline serum Lp(a) level. Group 1 had Lp(a) levels Յ30 mg/dl (n ϭ 40) and group 2 had Lp(a) levels Ͼ30 mg/dl (n ϭ 41). Patients were followed for 2 years. Progression of diabetic nephropathy was defined as a greater than twofold increase of follow-up serum creatinine concentration from the baseline value.RESULTS -At baseline and during the follow-up, there was no difference in HbA 1c and lipid profile between groups 1 and 2. However, serum creatinine was significantly higher in group 2 than in group 1 after 1 year (148.3 Ϯ 78.0 vs. 108.1 Ϯ 34.9 mol/l, P ϭ 0.004) and after 2 years (216.9 Ϯ 144.5 vs. 131.3 Ϯ 47.3 mol/l, P ϭ 0.001), although baseline serum creatinine did not differ significantly between groups. In all, 13 of 14 patients with progression of diabetic nephropathy (progressors) were from group 2. Baseline Lp(a) levels were higher in the progressors than in the nonprogressors (62.9 Ϯ 26.7 vs. 33.5 Ϯ 27.5 mg/dl, P Ͻ 0.001). Multiple logistic regression showed that baseline Lp(a) level was a significant and independent predictor of the progression of diabetic nephropathy.CONCLUSIONS -Our study demonstrated that Lp(a) is an independent risk factor for the progression of diabetic nephropathy in type 2 diabetic patients with overt proteinuria. Diabetes Care 28:1718 -1723, 2005D iabetic nephropathy is characterized by proteinuria, hypertension, progressive loss of renal function, and a high incidence of cardiovascular morbidity and mortality (1). Of patients with type 2 diabetes, 20 -40% develop diabetic nephropathy over a period of 15-20 years after the onset of diabetes (2). It is noteworthy that the prevalence of diabetic nephropathy in type 2 diabetes appears to be higher in the Asian population than in the white population, although the underlying mechanisms for this difference are not clear (3,4). Because diabetic nephropathy is the leading cause of end-stage renal disease in many countries including Korea (5,6), it is critical to slow the loss of renal function in diabetic patients at the stage of overt proteinuria or macroalbuminuria (established diabetic nephropathy).Hyperglycemia, hypertension, hypercholesterolemia, and proteinuria are the most significant risk factors or markers for the development and progression of diabetic nephropathy in type 2 diabetic patients (1,2,7-9). Nevertheless, in type 2 diabetic patients with overt proteinuria, postponing end-stage renal disease remains an elusive goal in the clinical setting. Therefore, it is still important to explore other risk factors with possible therapeutic applications in these patients.Lipoprotei...

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Section: Diabetes Care 28:1718 -1723 2005mentioning

confidence: 99%

Prospective Study of Lipoprotein(a) as a Risk Factor for Deteriorating Renal Function in Type 2 Diabetic Patients With Overt Proteinuria

Song

Kim

et al. 2005

Diabetes Care

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“…Nonetheless, these non-genetic parameters could be subject to therapeutic intervention in attempts to modify Lp(a) concentrations. 9 Suggested mechanisms for the effects of Lp(a) in modulating vascular disease risk include: (1) anti®brinolytic and prothrombotic effects based on the structural similarity between Lp(a) and plasminogen 10,11 and the described in¯uence of Lp(a) in regulating the endothelial cell synthesis of tissue plasminogen activator inhibitor PAI-1; 12 (2) signi®-cant uptake of Lp(a) with low-density lipoprotein (LDL) by the LDL native and scavenger receptorsÐ indeed, both lipoproteins co-determine atherosclerotic disease risk. However, these different mechanisms remain controversial 13 and do not always satisfactorily account for the striking atherogenicity of Lp(a).…”

Section: Introductionmentioning

confidence: 99%

Metabolic and anthropometric determinants of serum Lp(a) concentrations and Apo(a) polymorphism in a healthy Arab population

1999

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BACKGROUND: Blood lipoprotein(a) Lp(a) concentrations are an important risk factor for atherosclerosis. The basis for this atherogenic property of Lp(a) and the factors that in¯uence its cross-population levels, however, remain poorly understood. OBJECTIVES: To investigate the relationship between serum Lp(a) and metabolic and anthropometric parameters in a healthy Kuwaiti population. DESIGN: Cross-sectional study. SUBJECTS: 177 (72 male, 105 female) randomly recruited healthy Kuwait Arabs aged 17 ± 60 y MEASUREMENTS: Metabolic parameters in serum: Lp(a), apo(a) phenotypes, lipids and lipoproteins, glucose and urate. Anthropometric parameters: body mass index (BMI) and waist:hip-ratio (WHR). RESULTS: The distribution of Lp(a) concentrations was positively skewed (median 153 mgal, range 0 ± 1086). Women had higher concentrations ± (194, 0 ± 1086) than men (117, 0 ± 779), P 0.069. Lp(a) and insulin concentrations were signi®cantly higher when the men and women were obese. In all subjects, there were signi®cant correlations between Lp(a) and BMI (r 0.23), total cholesterol (TC) (r 0. Multivariate analyses con®rmed BMI and low-density lipoprotein (LDL) as the signi®cant determinants of serum Lp(a).On apo (a) phenotyping, 114 (67%), 51 (30%) and 6 (4%) had single, double and null phenotypes respectively. The isoforms and their corresponding kringle IV repeat numbers were: F (14 repeats in 3%, mean Lp(a) 497 mgal); S1 (19 repeats in 14%, mean 245 mgal); S2 (23 repeats in 16%, mean 264 mgal); S3 (27 repeats in 35%, mean 236 mgal); and S4 (35 repeats in 28%, mean 235 mgal). DISCUSSION AND CONCLUSION: The results from the Kuwaiti population studied suggest that: (1) serum Lp(a) concentrations and distribution are similar to the pattern in Caucasians and Asians but not African ± Americans or Africans; (2) serum Lp(a) is variably in¯uenced by BMI and LDL ± the impact of either factor differs between the sexes; (3) there is a high frequency of the single-banded phenotype; (4) contrary to reports in some Caucasian and Asian populations, there is no simple relationship between kringle IV repeat numbers and plasma Lp(a) concentrations.

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“…Several investigations are available in type 2 diabetic patients, including four prospective studies (22)(23)(24)(25). With the exception of one study (24), the other three showed positive associations (22,23,25).…”

Section: Research Design and Methods -mentioning

confidence: 99%

Lipoprotein(a) as a Predictor of Cardiovascular Disease in a Prospectively Followed Cohort of Patients With Type 1 Diabetes

Kollerits

Auinger

Reisig³

et al. 2006

Diabetes Care

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Prospective Study of Lipoprotein(a) as a Risk Factor for Atherosclerotic Cardiovascular Disease in Patients With Diabetes

Abstract: Lp(a) is a significant risk factor for atherosclerotic cardiovascular disease in NIDDM.

Cited by 64 publications

References 6 publications

Prospective Study of Lipoprotein(a) as a Risk Factor for Deteriorating Renal Function in Type 2 Diabetic Patients With Overt Proteinuria

Prospective Study of Lipoprotein(a) as a Risk Factor for Deteriorating Renal Function in Type 2 Diabetic Patients With Overt Proteinuria

Metabolic and anthropometric determinants of serum Lp(a) concentrations and Apo(a) polymorphism in a healthy Arab population

Lipoprotein(a) as a Predictor of Cardiovascular Disease in a Prospectively Followed Cohort of Patients With Type 1 Diabetes

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