Impact of markedly elevated serum lipoprotein(a) levels (> or = 100 mg/dL) on the risk of coronary heart disease

The serum lipoprotein(a) [Lp(a)] concentration is under genetic control, and most humans have values lower than 30 mg/dL. Subjects with markedly elevated serum Lp(a) concentrations, that is, > or =100 mg/dL, are rarely encountered, and these subjects have not yet been fully characterized from the clinical point of view. In the present investigation, we studied a total of 223 subjects, comprising 123 males and 100 females, with serum Lp(a) values of more than 100 mg/dL. Many of these subjects had a variety of underlying diseases, including metabolic disorders, renal diseases, and hypertension. We focused our attention on the patients with metabolic disorders, namely, familial hypercholesterolemia (FH), primary non-FH hypercholesterolemia (HC), and type 2 diabetes mellitus (DM), and conducted a comparative study of the patients of these 3 disease groups with the corresponding disease controls with serum Lp(a) levels of less than 30 mg/dL, a presumed high normal value. The frequency of markedly elevated serum Lp(a) levels in the general population has not been reported previously. We determined the frequencies in a consecutive series of patients at our Diabetes and Lipid Outpatient Clinic; the results revealed that the frequencies were 6.4% (8/125), 2.6% (6/232), and 0.9% (3/352) in patients with FH, HC, and type 2 DM, respectively. In an attempt to further demonstrate the impact of markedly elevated serum Lp(a) concentrations on the risk of coronary heart disease (CHD), we compared the prevalence of CHD among the study subjects with that among the corresponding disease controls. The results revealed a significantly higher CHD prevalence in the study subjects of all the 3 groups as compared with that in the corresponding disease controls: the odds ratios of a markedly elevated serum Lp(a) level were 5.429 (95% confidence interval [CI], 1.353-21.782), 8.243 (95% CI, 2.793-24.327), and 5.981 (95% CI, 2.530-14.139) for FH, HC, and type 2 DM, respectively. In the present study, we examined some characteristics of this rare population of subjects with markedly elevated serum Lp(a) levels and demonstrated a very high prevalence of CHD among these patients with FH, HC, and type 2 DM, strongly suggesting the significance of Lp(a) as a risk factor for CHD.     

Lipids and lipoprotein(a) concentrations in Tunisian type 2 diabetic patients; Relationship to glycemic control and coronary heart disease

The aim of this study was to evaluate plasma lipoprotein(a) [Lp(a)] concentrations in Tunisian patients with type 2 diabetes mellitus (DM), to correlate the values with other lipid parameters, and to examine the relationship to glycemic control and coronary heart disease (CHD). Diabetic patients with and without CHD (n=200) had significantly higher levels of Lp(a) (327.94+/-239.93 mg/l) and a greater proportion of elevated (>300 mg/l) Lp(a) concentrations (46%) compared with 100 healthy nondiabetic controls (269.83+/-225.6 mg/l, P<.01, and 26%, P<.01), while there were no statistically significant difference between diabetics without CHD (n=100) and controls. No significant association of Lp(a) with glycemic control (HbAlc or fasting blood glucose) was noted in diabetic patients. Positive correlations were observed between Lp(a) levels and total cholesterol and LDL-C in all diabetic patients and particularly in diabetic men. Male patients with CHD showed significantly higher plasma Lp(a) levels than those without CHD (P=.023), and 57.3% of patients with CHD showed increase (>300 mg/l) Lp(a) compared with 33.3% of patients without CHD. Elevated levels of Lp (a) and abnormal lipid profile in diabetic men suggest their involvement in atherogenesis and subsequent development of CHD.     

脂蛋白（a）浓度变化与急性冠脉综合征患者预后的关系

目的探讨血清脂蛋白（a）[1ipoprotein（a）,Lp（a）]浓度以及Lp（a）浓度的变化对经皮冠状动脉介入（percutaneous coronary intervention,PCI）治疗完全血运重建后的急性冠脉综合征（acute coronary syndrome,ACS）患者预后的影响。方法选取240例因ACS行冠状动脉支架植入术并予常规药物治疗的患者,临床随访一年。检测基线及随访半年时Lp（a）浓度,并收集传统的心血管危险因素以及主要心血管事件（major adverse cardiac events,MACE）的资料。通过多因素Logistic回归的方法评价血清Lp（a）浓度的变化（基线水平至随访半年的变化）是否与ACS患者预后相关。结果基线血清Lp（a）浓度与冠状动脉Gensini评分呈正相关（r=0．142,P=O．027）,与糖尿病的发生（r=-0．182,P=0．005）以及三酰甘油浓度（r=-0．156,P=O．016）呈负相关。在MACE发生的患者中,Lp（a）浓度平均升高了50mg／L,而在非MACE患者中平均下降了40mg／L。单因素Logistic回归分析发现基线Lp（a）浓度与MACE的发生无明显关系（OR=1．123,P=O．753）,并筛选年龄（OR=1．03,P=O．060）,Gensini评分（OR=1．010,P=0．015）,原发性高血压（OR=1．696,P=O．069）,糖尿病（OR=1．818,P=O．060）以及血清Lp（a）浓度变化的差值（OR=0．027,P=O．027）进入多因素Logistic逐步回归分析,发现Lp（a）浓度的变化（OR=3．119,95％CI=1．112～8．746,P=O．031）以及Gensini评分（OR=I．010,95％CI=1．002～1．018,P=O．016）可能是影响ACS预后的独立危险因素。结论基线血清Lp（a）浓度与ACS的预后无明显相关,与糖尿病的发生以及三酰甘油浓度呈负相关一存晡访讨程申向洁Tp（a）浓度的变化可能是ACS不良预后的独立危险因素.     

Urinary excretion of apolipoprotein(a) fragments in type 1 diabetes mellitus patients

High levels of plasma lipoprotein(a) [Lp(a)] represent an independent risk factor for cardiovascular morbidity; however, Lp(a) has not yet been identified as a risk factor for type 1 diabetic patients. Results from the limited number of available studies on plasma Lp(a) levels in relation to renal function in type 1 diabetes mellitus are inconclusive. We hypothesized that only type 1 diabetes mellitus patients with impaired renal function show increased plasma Lp(a) levels, due to decreased urinary apolipoprotein(a) [apo(a)] excretion. We therefore measured urinary apo(a) levels in 52 type 1 diabetes mellitus patients and 52 matched controls, and related the urinary apo(a) concentration to the plasma Lp(a) level, kidney function, and metabolic control. Our findings indicate that patients with incipient diabetic nephropathy as evidenced by microalbuminuria (20 to 200 microg/min) exhibit significantly higher plasma Lp(a) levels (median, 15.6 mg/dL) in comparison to normoalbuminuric patients (median, 10.3 mg/dL) and healthy controls (median, 12.0 mg/dL). Urinary apo(a) normalized to creatinine excretion was significantly elevated in both normoalbuminuric (median, 22.3 microg/dL) and microalbuminuric type 1 diabetic patients (median, 29.1 microg/dL) compared with healthy subjects (median, 16.0 microg/dL) and correlated significantly with Lp(a) plasma levels in both patient and control groups (P < .003). No correlation existed between the Lp(a) plasma level or urinary apo(a) concentration and metabolic control in type 1 diabetes mellitus patients. From these studies, we conclude that urinary apo(a) excretion is significantly increased in type 1 diabetic patients and correlates with plasma Lp(a) levels, and only type 1 diabetic patients with microalbuminuria have higher plasma levels of Lp(a) compared with patients with normoalbuminuria and healthy controls.     

Lack of change of lipoprotein (a) concentration with improved glycemic control in subjects with type II diabetes.

Recently, lipoprotein (a) [Lp(a)] has been identified as a major risk factor for coronary heart disease. No data are available on the effect of improved metabolic control on plasma Lp(a) concentrations in subjects with type II diabetes mellitus, a group at high risk for coronary heart disease. We examined the effects of improved metabolic control on plasma lipid and lipoproteins and Lp(a) concentrations in 12 subjects before and after 21 days of tight metabolic control. Glycosylated hemoglobin declined from 8.9% to 6.9% (P less than .002). Lp(a) increased slightly from 21.4 to 25.8 mg/dL (P = .119) with improved metabolic control. There were no significant differences in total, low-density, or high-density cholesterol values, although the decline in triglyceride concentrations was statistically significant. The distribution of apolipoprotein (a) [apo (a)] isoforms in subjects with type II diabetes mellitus was not unusual and the apo (a) isoform patterns did not change with improved metabolic control. Although the number of subjects was small, there was no decline in Lp(a) concentrations with improved control and thus the effect of glycemic control on Lp(a) concentrations may be much smaller in type II than in type I diabetes. These results suggest that diabetic subjects with elevated Lp(a) concentrations should have intensive management of conventional cardiovascular risk factors such as high-density lipoprotein cholesterol (HDLC), low-density lipoprotein cholesterol (LDLC), and blood pressure.     

Relation of lipoprotein(a) as coronary risk factor to type 2 diabetes mellitus and low-density lipoprotein cholesterol in patients > or =65 years of age (The Italian Longitudinal Study on Aging)

High levels of serum lipoprotein(a) [Lp(a)] have been associated with increased risk of coronary artery disease (CAD), but this association apparently is not confirmed in elderly people. We evaluated the interactions of Lp(a) with lipid and nonlipid CAD risk factors in a sample of subjects enrolled in the prevalence survey (1992 to 1993) of the Italian Longitudinal Study on Aging (ILSA). The entire population consisted of 5,632 elderly people, aged 65 to 84 years, randomly selected in 8 Italian municipalities. The present cross-sectional study included 400 free-living elderly subjects (74 +/- 6 years) from the randomized cohort of Casamassima (Bari, Southern Italy) (n = 704). The results showed that in the elderly population, high serum Lp(a) is a CAD risk factor dependent on type 2 diabetes mellitus and elevated low-density lipoprotein (LDL) cholesterol levels. In particular, the combined effect of high Lp(a) (> or =20 mg/dl) and high LDL cholesterol (> or =3.63 mmol/L [> or =140 mg/dl]), increases coronary risk by 2.75 (95% confidence interval 7.70 to 0.99); finally, the effect of Lp(a) > or =20 mg/dl and LDL cholesterol > or =3.63 mmol/L (> or =140 mg/dl), combined with type 2 diabetes mellitus, increases risk of CAD by 6.65 (95% confidence interval 35.40 to 1.25). In the elderly, elevated Lp(a) levels appear not to be an independent predictor of CAD, but this lipoprotein is a risk factor only in subjects with type 2 diabetes mellitus and elevated LDL cholesterol.     

Lipoprotein (a) and coronary heart disease among women: beyond a cholesterol carrier?

AIMS: With its homology with plasminogen, lipoprotein(a) [Lp(a)] may be related to thrombosis and inflammation. We assessed the role of Lp(a) in coronary heart diseases (CHD) by a recently developed assay that is not affected by the plasminogen-like Kringle-type-2 repeats. METHODS AND RESULTS: Of 32 826 women from the Nurses' Health Study, who provided blood at baseline, we documented 228 CHD events during 8 years of follow-up. Each case was compared with two matched controls. In a multivariable model adjusted for body mass index, family history, hypertension, diabetes, post-menopausal hormone use, physical activity, blood drawing characteristics, and alcohol intake, the odd ratio (OR) for Lp(a) levels > or =30 mg/dL was 1.9(95% CI: 1.3-3.0) when compared with those with Lp(a)<30 mg/dL. Women with high levels of both Lp(a) (> or =30 mg/dL) and fibrinogen (> or =400 mg/dL) had an OR of 3.2(95% CI: 1.6-6.5) for CHD, when compared with the combination of low levels (P interaction=0.05). Women with high levels of both Lp(a) and C-reactive protein (> or =3 mg/L) had an OR of 3.67(95% CI: 2.03-6.64) for CHD, when compared with the combination of low levels (P interaction=0.06). CONCLUSION: Lp(a) levels >30 mg/dL are associated with twice the risk of CHD events among women and may be related to thrombosis and inflammation.     

Lipoprotein (a) levels in diabetes mellitus: relationship to metabolic control.

OBJECTIVE: To determine the influence of diabetes control on serum lipoprotein (a) concentrations. SETTING: Diabetes clinic of a large metropolitan public hospital, with primary- and secondary-care patients. DESIGN: A cross-sectional study. Comparisons of lipoprotein (a) concentrations were made between a normal control group, a group of diabetic patients with glycated hemoglobin (HbA1c) less than 8.0%, and a group of diabetic patients with HbA1c of 8.0% or higher. PATIENTS: Ninety-five normal controls and 93 diabetic subjects (49 with insulin-dependent diabetes mellitus and 44 with noninsulin-dependent diabetes mellitus). RESULTS: Sixty diabetic subjects with HbA1c levels of 8.0% or higher had higher (25 mg/dL) median levels of lipoprotein (a) when compared with either 93 normal controls (8.8 mg/dL) or 33 diabetic patients with HbA1c less than 8.0% (7.5 mg/dL) (P = 0.008 and P = 0.012, respectively). A similar pattern of distribution of lipoprotein (a) levels according to degree of metabolic control was seen in patients with insulin-dependent diabetes mellitus and noninsulin-dependent diabetes mellitus. No difference in the lipoprotein (a) distribution was noted between diabetic men and women. No correlation was observed between lipoprotein (a) levels and total cholesterol, low-density lipoprotein cholesterol, and triglyceride levels. CONCLUSION: Lipoprotein (a) levels are elevated in poorly controlled diabetic patients. Increased levels of lipoprotein (a) may be a contributing factor to the high risk for atherosclerosis observed in diabetic patients.     

A cross-sectional evaluation of cardiovascular risk factors in coronary heart disease associated with type 1 (insulin-dependent) diabetes mellitus.

The contribution from lipoproteins, blood pressure, albuminuria and demographic variables to coronary heart disease in 90 adult subjects with and 172 without Type 1 diabetes mellitus was examined in order to investigate whether risk factors were of equivalent importance in diabetic and non-diabetic coronary heart disease. Coronary heart disease (CHD) was present in roughly 25% of subjects in each group. In Type 1 diabetes those with CHD had significantly higher levels of systolic blood pressure, albumin excretion, serum creatinine, triglycerides, VLDL cholesterol and C-peptide, and reductions in serum concentrations of HDL and HDL2 cholesterol, in comparison to those without. However, the prevalence of smokers, and concentrations of Lp(a), ApoB and fibrinogen were comparable. Blood pressure and HDL cholesterol were higher in the CHD group with Type 1 diabetes in comparison to the nondiabetic group with CHD, although LDL concentrations and the prevalence of Lp(a) concentrations > 200 mg/l were lower. Logistic regression analysis revealed the strongest independent predictors of CHD in Type 1 diabetes were serum triglycerides, systolic blood pressure, age, serum LDL cholesterol, and the daily insulin dosage, whereas in the non-diabetic control group HDL2 cholesterol, Lp(a), ApoA1 and ApoB, total serum cholesterol and body mass index were additional predictors. CHD in Type 1 diabetes appears to be most closely associated with increasing age and levels of blood pressure and total serum lipids. Apolipoproteins and albuminuria did not seem to be important independent predictors of CHD in Type 1 diabetes, whereas the former were more clearly associated with CHD in non-diabetic controls.     

绝经后女性冠心病患者血清脂蛋白(a)的研究

目的 :研究脂蛋白 (a) [L p(a) ]与绝经后女性冠心病 (CH D)的关系 ,并初步探讨内源性雌激素对血清 L p(a)水平的影响。方法 :采用 EL ISA法测定 5 2例绝经后女性 CHD患者及 48例健康者的血清 L p(a)浓度 ,并测定了其中 40例 CHD患者和 30例健康者的雌激素水平。结果 :CHD组平均 L p(a)浓度显著高于对照组 [(2 5 2 .9± 31.5 )∶ (12 9.2± 2 0 .0 ) mg/L ,P <0 .0 1],且与冠状动脉病变支数相关 ,r =0 .398,P <0 .0 0 1;而血清 L p(a)浓度与雌二醇水平未见显著关联。结论 :血清 L p(a)水平的增加是 CHD的独立危险因子 ,也是冠状动脉病变严重程度的一个预测因素 ,其浓度与内源性雌激素水平无关。     

The effect of rosiglitazone on serum lipoprotein(a) levels in Korean patients with type 2 diabetes mellitus

The aim of the study was to determine if rosiglitazone increases serum levels of lipoprotein(a) [Lp(a)] in Korean patients with type 2 diabetes mellitus. A total of 118 patients were divided into 2 groups: those with rosiglitazone (rosiglitazone group, n = 49) and those without rosiglitazone (control group, n = 69). The rosiglitazone group was given rosiglitazone (4 mg/d) with previous treatment, insulin, or sulfonylurea, for 12 weeks, whereas the control group continued previous treatment with some dose modification for glycemic control. The patients had their blood glucose, lipid levels, as well as Lp(a) levels assessed to obtain a baseline, which were remeasured 12 weeks later. The fasting blood glucose and glycosylated hemoglobin (HbA(1c)) levels decreased significantly in both groups as compared with the baseline. The fasting glucose and HbA(1c) levels in both groups were similar at 12 weeks. The total cholesterol levels increased significantly in the rosiglitazone group (190.6 +/- 32.4 to 212.2 +/- 47.2 mg/dL, P =.002), while they were unchanged in the control group (185.4 +/- 36.8 to 188.0 +/- 35.8 mg/dL, P =.615). The triglyceride levels did not change in either group. Significant increases in high-density lipoprotein (HDL) cholesterol levels were observed in the rosiglitazone group as compared with the baseline (41.7 +/- 10.6 to 45.9 +/- 11.4 mg/dL, P =.004). The low-density lipoprotein (LDL) cholesterol levels increased significantly in the rosiglitazone group (120.5 +/- 29.9 to 136.3 +/- 40.0 mg/dL, P =.012), while they did not change in the control group (113.0 +/- 29.1 to 118.3 +/- 31.7 mg/dL, P =.234). Significant increases in Lp(a) levels were observed in the rosiglitazone group as compared with the baseline (22.4 +/- 17.4 to 25.7 +/- 20.5 mg/dL, P =.015), approximately a 15% increase in average values. In contrast, there was no change in Lp(a) levels in the control group. There was no correlation between the changes in Lp(a) and changes in fasting blood glucose or HbA(1c) levels in all study subjects. In summary, rosiglitazone increased serum total cholesterol, LDL cholesterol, as well as Lp(a) levels in patients with type 2 diabetes mellitus. Considering that patients with type 2 diabetes mellitus have increased risks for cardiovascular disease, caution should be taken when prescribing rosiglitazone to patients who already have other risk factors, such as hypertension and smoking.     

Efficacy and tolerability of combined treatment with L-carnitine and simvastatin in lowering lipoprotein(a) serum levels in patients with type 2 diabetes mellitus

Lipoprotein(a) [Lp(a)] concentration is generally related to coronary artery disease (CAD) and cerebrovascular disease. However, at present, few interventions are available to lower Lp(a) concentrations. We investigated the effects of l-carnitine, co-administered with simvastatin, on hyper-Lp(a) in patients with type 2 diabetes mellitus. We conducted an open, randomised, parallel-group study, in one investigational center (University hospital). Fifty-two patients with type 2 diabetes mellitus, a triglyceride serum levels <400mg/dL (<4.5 mmol/L), and Lp(a) serum levels >20mg/dL (0.71 mmol/L) were randomised to receive simvastatin alone (n=26) or simvastatin plus l-carnitine (n=26) for 60 days. Simvastatin was administered, in both groups, at a dosage of 20 mg/day, while l-carnitine was administered at a dosage of 2g/day once daily. Both treatments were given orally. Serum levels of triglycerides, total cholesterol, LDL cholesterol, high-density lipoprotein (HDL) cholesterol, non-HDL cholesterol (total cholesterol minus HDL cholesterol), apolipoprotein B, and Lp(a) were measured at baseline and 60 days after starting treatment. No difference in time by groups (simvastatin and simvastatin plus l-carnitine) were observed in the reduction of LDL cholesterol, non-HDL cholesterol, and apoB serum levels. On the other hand, Lp(a) serum levels increase from baseline to 60 days in the simvastatin group alone versus a significant decrease in the combination group. Our findings provide support for a possible role of combined treatment with l-carnitine and simvastatin in lowering Lp(a) serum levels in patients with type 2 diabetes mellitus than with simvastatin alone. Our results strongly suggest that l-carnitine may have a role among lipid-lowering strategies.     

Serum lipoprotein(a) concentration as a cardiovascular risk factor in Kuwaiti type 2 diabetic patients

Serum lipoprotein(a) [Lp(a)], a risk factor for coronary heart disease (CHD) in some nondiabetic populations, is largely under genetic control and varies among ethnic and racial groups. We evaluated serum Lp(a) concentration and its relationship with traditional CHD risk factors (age, sex, smoking, hypertension, dyslipidemia) as well as stage of diabetic nephropathy in 345 type 2 diabetic patients. Lp(a) concentration was skewed with median (2.5th, 97.5th percentiles) of 25.0 (8.1, 75.7) mg/dl. Twenty-three of 55 (41.8%) patients with CHD had increased (>30 mg/dl) Lp(a) compared with 102 of 290 (35.1%) patients without CHD (P=.35). Twelve of 27 (44.4%) female patients with CHD had increased Lp(a) compared to 11 of 28 (39.3%) males (P=.70). Lp(a) was significantly (P<.05) higher in females than males, but the logistic regression analysis showed significant association of Lp(a), LDL-C, and duration of diabetes mellitus (DM) with CHD in male patients only. Although female patients with CHD and macroalbuminuria had significantly (P<.05) higher Lp(a) than normoalbuminuric female patients without CHD, no such association was found in males and no significant association was found between Lp(a) and the degree of albuminuria. Partial correlation analysis controlling for age, sex, and BMI showed significant correlation of Lp(a) with total cholesterol only (P=.03) and no correlation was found with other lipid parameters. Multiple regression analysis did not show significant associations of Lp(a) with standard CHD risk factors, HbA(1c), and plasma creatinine. This study is in agreement with studies in other populations, which showed that Lp(a) may not be an independent risk factor for CHD in patients with DM. However, as Lp(a) could promote atherogenesis via several mechanisms, follow-up studies in our patients will confirm if increased Lp(a) concentration can partly account for the poorer prognosis when diabetic patients develop CHD.     

Lipoprotein(a), homocysteine, and remnantlike particles: emerging risk factors

Although lipoprotein(a) [Lp(a)] was first described more than 35 years ago, adequate prospective data have only recently supported Lp(a) as an independent risk factor for coronary heart disease (CHD). In vitro studies suggest that Lp(a) contributes to atherogenesis directly by cholesterol uptake and indirectly by the inhibition of fibrinolysis. In patients with CHD or a significant risk for CHD, Lp(a) should be measured and treated with either niacin or estrogen if the patient has Lp(a) cholesterol levels of more than 10 mg/dL or an Lp(a) mass of more than 30 mg/dL. In addition, homocysteine and remnantlike lipoprotein cholesterol are strongly supported by prospective or population-based prevalence data as independent risk factors for CHD. Homocysteine levels of more than 14 mumol/L should be treated with vitamin supplements of folate, B6, and B12. Remnantlike lipoprotein cholesterol is the product of a novel immunoassay that separates the partially hydrolyzed triglyceride-rich remnant particles. The association of these particles with CHD risk in women may explain the small independent CHD risk that triglycerides have in women in the Framingham Heart Study. A clear therapeutic intervention has not been documented but may include diet, fibric acid derivatives, or hydroxymethylglutamyl coenzyme A reductase inhibitors.     

Increased lipoprotein (a) levels as an independent risk factor for venous thromboembolism

Elevation of serum lipoprotein (a) (Lp[a]) is a known risk factor predisposing to cardiovascular and cerebrovascular disease. However, little is known about the role of increased Lp(a) in venous thromboembolism (VTE). This study evaluated the role of Lp(a) among a panel of established hereditary thrombogenic defects in patients with VTE. A total of 685 consecutive patients with at least one episode of VTE and 266 sex- and age-matched healthy controls were screened with regard to activated protein C resistance, protein C, protein S, and antithrombin deficiency, elevated serum levels of Lp(a), and the factor V G1691A, MTHFR C677T, and prothrombin G20210A mutations. Elevated Lp(a) levels above 30 mg/dL were found in 20% of all patients, as compared to 7% among healthy controls (P <.001, odds ratio [OR] 3.2, 95% confidence interval [CI], 1.9-5.3). The coexistence of FV G1691A and elevated Lp(a) was significantly more prevalent among patients with VTE than in the control group (7% versus 0.8%; P <.001, OR 9.8, 95% CI, 2.4-40.7). No other established prothrombotic risk factor was found to be significantly combined with increased Lp(a). These data suggest that Lp(a) concentrations greater than 30 mg/dL are a frequent and independent risk factor for VTE. Furthermore, elevated Lp(a) levels might contribute to the penetrance of thromboembolic disease in subjects being affected by other prothrombotic defects, such as FV G1691A mutation.     

2型糖尿病患者血清脂蛋白(a)水平及其与冠心病的关系

目的　探讨 2型糖尿病患者血清脂蛋白 (a) [Lp(a) ]水平及其与冠心病的关系。方法　选择 90例 2型糖尿病及 6 8例健康对照者测定其血清Lp(a)、总胆固醇 (TC)、甘油三酯 (TG)、高密度脂蛋白胆固醇 (HDL C)水平 ;计算低密度脂蛋白胆固醇 (LDL C)水平及TC、TG、LDL C与HDL C比值。结果　 (1)糖尿病组血清Lp(a)水平与对照组比较差异无显著性意义 (P >0 .0 5 )。 (2 )将 2型糖尿病患者分为糖尿病伴冠心病和单纯糖尿病亚组后发现 :①糖尿病伴冠心病亚组血清Lp(a)水平明显高于单纯糖尿病亚组 [(2 3.78± 2 3.73)mg/dlvs (13.31± 10 .6 6 )mg/dl;P <0 .0 1]及对照组 [(2 3.78± 2 3.73)mg/dlvs (16 .2 8± 17.95 )mg/dl;P <0 .0 5 ];②糖尿病伴冠心病亚组血清Lp(a)水平与LDL C呈正相关关系 (r =0 .32 16 ,P <0 .0 5 )。结论　 2型糖尿病患者血清Lp(a)水平增高可能与冠心病发病有密切关系。     

Relation between serum lipoprotein (a) and residual lesion stenosis of coronary artery after myocardial Infarction without reperfusion therapy

Lipoprotein (a) (Lp(a)) is an independent risk factor for myocardial infarction (MI). It may also inhibit the fibrinolysis system, and Lp (a) affects the natural course of MI and the results of thrombolytic therapy. The purpose of this study was to investigate the influence of Lp (a) on the residual lesion stenosis of the infarction-related arteries (residual stenosis) in acute MI patients in whom reperfusion therapy was not performed. We studied 129 MI patients not given reperfusion therapy who underwent coronary angiography in the chronic stage. Morning fasting blood was collected and Lp (a), blood sugar, total cholesterol (TC), triglycerides (TG), and hemoglobin A1c (HbA1c) were measured. Residual stenosis was compared between the low Lp(a) group (< 30 mg/dL) and the high Lp(a) group (> or = 30 mg/dL). It was severe in the high Lp(a) group (85.0 +/- 24.9% vs 94.5 +/- 15.5%, P = 0.0044). We also compared residual stenosis and TIMI classification between younger and older, non-DM and DM, non-HT and HT, low-TC (< 220 mg/dL) and high-TC (> or = 220 mg/dL), low-TG (< 150 mg/dL) and high-TG (> or = 150 mg/dL), and low-Lp (a) and high-Lp (a) patients. Only the serum Lp (a) level affected the residual stenosis and TIMI classification (P < 0.05). CONCLUSION: These findings suggest that elevated Lp (a) levels inhibit fibrinolysis.     

The association between serum Lp(a) concentrations and angiographically assessed coronary atherosclerosis. Dependence on serum LDL levels

Lipoprotein(a) concentrations were measured by radial immunodiffusion in a cohort of 40-60 year males who had been classified by coronary angiography as CAD+ with 50% stenosis of one or more of the major coronary arteries or CAD- with no signs of coronary lesions. Sample odds ratios were calculated as a measure of association between serum Lp(a) values and the presence of coronary artery disease. An odds ratio of 2.706 (P less than 0.001) was derived for elevated (greater than or equal to 30 mg/dl) Lp(a) levels vs low (less than 5 mg/dl) Lp(a) levels indicating a strong association between the presence of coronary artery disease and elevated Lp(a) concentrations. This association was independent of the known risk factors smoking, hypertension and diabetes as well as the serum concentrations of total triglycerides, HDL-cholesterol, alpha-Lp-cholesterol and pre-beta-Lp-cholesterol. In contrast to these variables the association between Lp(a) and coronary artery disease was dependent upon the serum concentrations of LDL-cholesterol, beta-Lp-cholesterol and total cholesterol. At concentrations below the respective median for each variable, odds ratios of between 1.42 and 1.67 were calculated whereas at concentrations above the respective medians the odds ratios ranged from 4.50 to 6.33 (P less than 0.001). Our data, therefore, suggest that increasing LDL concentrations markedly increase the risk of coronary artery disease due to elevated Lp(a) levels.     

Lack of association of serum lipoprotein (a) levels with type-2 diabetes mellitus in patients with angiographically defined coronary artery disease

Multiple studies have demonstrated that elevated serum lipoprotein (a) [Lp(a)] levels are independent predictors for coronary artery disease (CAD) in subjects without diabetes mellitus (DM). However, their contribution in patients with DM is controversial and still requires clarification. We determined serum Lp(a) levels in 355 consecutive Caucasian patients (271 men and 84 women) with angiographically documented CAD, and in 100 control subjects (58 men and 42 women) who were clinically free of cardiovascular disease. In addition, the association of serum Lp(a) levels with type-2 DM in patients with CAD was investigated after reassigning patients according to the diagnosis of type-2 DM (61 men and 40 women with type-2 DM and 210 men and 44 women without). No gender differences in Lp(a) levels were observed between men and women (patients and control subjects). Patients with CAD had higher Lp(a) levels than the control subjects (33 (14-74) vs. 13 (9-29) mg/dl, P<0.001). Elevated Lp(a) levels (defined as >90th percentile of controls) were significantly more prevalent in men and women with CAD (35% and 28%, respectively) than in control subjects (13% and 10%, respectively). Serum Lp(a) levels correlated with LDL cholesterol (r=0.22, P<0.001) and apo B levels (r=0.18, P<0.03) in patients and control subjects. Stepwise discriminant analysis revealed that Lp(a) was an independent risk factor for the presence of CAD, independent of smoking, hypertension, type-2 DM, LDL and HDL cholesterol or apo A1 and B levels. When patients were studied according to the spread of CAD (evaluated as the number of narrowed vessels), no differences in serum Lp(a) levels were observed, nor was there a higher prevalence of elevated Lp(a) levels. Finally, when patients were re-assigned according to the diagnosis of type-2 DM, no effect of apo B and LDL-C levels on Lp(a) was found (r=0.06, P=n.s. and 40.14, P=n.s., respectively) and serum Lp(a) levels neither associated nor contributed to the extent of CAD. Our results showed that serum Lp(a) levels are increased in patients with angiographically documented CAD, but there were no significant differences between diabetic and non-diabetic patients, which indicates that elevated Lp(a) levels are specifically associated with CAD but not with type-2 DM.     

新疆巴州地区人群脂蛋白（a）与冠心病相关性研究

目的 探讨新疆巴州地区汉族人群脂蛋白（a）[Lp（a）]与冠心病（CHD）及冠状动脉狭窄程度之间的相关性。方法采用病例对照研究,选择2007年1月至2011年6月在巴州人民医院住院并行冠状动脉造影检查确诊的汉族CHD患者443例;对照组452例,为同期入院行冠状动脉造影检查结果阴性或其他检查排除冠心病者。检测所有纳入对象静脉血清Lp（a）值及其他生物化学指标,探讨高Lp（a）血症及其他因素与CHD的关系,以及Lp（a）血症与冠脉病变程度的关系。结果 CHD组高Lp（a）血症的患病率为23.02%,高于对照组（15.04%）,两组有统计学差异（P〈0.01）;血Lp（a）水平与对照组有比较,差异具有统计学意义（P〈0.01）。多因素Logistic回归分析显示,在校正了年龄、吸烟、高血压、糖尿病、血脂异常等危险因素作用后发现,高Lp（a）血症是CHD的独立危险因素（OR=1.675,95%CI：1.184～3.115;P=0.009）。CHD组中随着病变支数的增加,高Lp（a）血症的患病率也增加,差异具有统计学意义（P=0.026）;血Lp（a）水平也随之增加,差异具有统计学意义（P=0.019）。结论本研究人群高Lp（a）血症是CHD发生的独立危险因素,高Lp（a）血症的患病率及血Lp（a）水平与冠脉狭窄程度呈正相关性,可作为CHD发病及严重程度的预测因子。