Lipoprotein(a): Reloaded

Lipoprotein(a) is a macromolecular complex of enigmatic function in human plasma. Concentrations of Lp(a) constitute a quantitative genetic trait. They are primarily determined by the LPA locus on chromosome 6q26-27, which is characterized by a unique type of copy number variation (CNV), the kringle-IV type 2 (K-IV-2) repeats. Meta-analysis of prospective studies as well as old and new genetic evidence have identified Lp(a) as an independent risk factor for atherothrombotic disease. The K-IV-2 CNV in LPA is the strongest known common genetic variation predicting risk for CHD: small isoforms of this CNV are associated with a doubling of risk for CHD. Together with observations that removal of Lp(a) from plasma may be beneficial in individuals with severe CHD, the strong genetic evidence justifies the consideration of Lp(a) in clinical practice.     

Polymorphism in apolipoprotein(a) kringle IV 37 (Met/Thr): Frequency in a London population and its association with coronary artery disease

Background: A raised concentration of lipoprotein(a) [Lp(a)] in human plasma has been considered as a risk factor for coronary artery disease (CAD). Apolipoprotein(a) and plasminogen genes are exceptionally similar to a variable number of plasminogen-like kringle IV repeats in the apo(a) gene. Polymorphisms have been previously identified in the apolipoprotein(a) kringle IV 37. Hypothesis: In order to determine the frequency of the apolipoprotein(a) kringle IV 37 Met⁶⁶→Thr polymorphism in a London-based population and to assess the relationship of this polymorphism with CAD in Caucasian patients, we geno-typed two groups of people of different ethnic origin (Caucasian and Afro-Caribbean) for the mutation using standard polymerase chain reaction (PCR) techniques. Methods: The first group consisted of 182 unrelated Caucasian patients (107 men and 75 women, mean age 59.7 ± 10.2 years) recruited at St. George's Hospital. They were defined as patients with 0, 1 or ≥ 2 vessel disease patients depending on the degree of stenosis in none, one, or several major epicardial arteries. The second group comprised 64 unrelated patients of Afro-Caribbean origin attending a hypertension clinic at St. George's Hospital. Results: It was shown that the prevalence of the Met⁶⁶→Thr mutation is markedly higher in Caucasians than in Afro-Caribbeans and that this mutation is not associated with either Lp(a) levels or severity of CAD.     

Human Genetics and the Causal Role of Lipoprotein(a) for Various Diseases

Lipoprotein(a) [Lp(a)] is a highly atherogenic lipoprotein that is under strong genetic control by the LPA gene locus. Genetic variants including a highly polymorphic copy number variation of the so called kringle IV repeats at this locus have a pronounced influence on Lp(a) concentrations. High concentrations of Lp(a) as well as genetic variants which are associated with high Lp(a) concentrations are both associated with cardiovascular disease which very strongly supports causality between Lp(a) concetrations and cardiovascular disease. This method of using a genetic variant that has a pronounced influence on a biomarker to support causality with an outcome is called Mendelian randomization approach and was applied for the first time two decades ago with data from Lp(a) and cardiovascular disease. This approach was also used to demonstrate a causal association between high Lp(a) concentrations and aortic valve stenosis, between low concentrations and type-2 diabetes mellitus and to exclude a causal association between Lp(a) concentrations and venous thrombosis. Considering the high frequency of these genetic variants in the population makes Lp(a) the strongest genetic risk factor for cardiovascular disease identified so far. Promising drugs that lower Lp(a) are on the horizon but their efficacy in terms of reducing clinical outcomes still has to be shown.     

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。     

Apolipoprotein(a) size polymorphism is associated with coronary heart disease in polygenic hypercholesterolemia

BACKGROUND AND AIM: In addition to high serum cholesterol levels, various cardiovascular risk factors may be involved in the development of coronary heart disease (CHD) in hypercholesterolemic subjects. As the levels of lipoprotein(a) [Lp(a)], an important and independent cardiovascular risk factor, are high in polygenic hypercholesterolemia (PH), we investigated plasma Lp(a) levels and apolipoprotein(a) [apo(a)] phenotypes in relation to occurrence of CHD events in PH patients. METHODS AND RESULTS: Lp(a) levels and apo(a) isoforms were determined in 191 PH patients, 83 normocholesterolemic subjects with CHD, and 94 normocholesterolemic controls without CHD. Lp(a) levels were similar in the hypercholesterolemic subjects with (n=100) or without CHD (n=91): 21.4 (range 6.6-59.23) vs 18.5 (range 5.25-57.25) mg/dL (p=NS). Low molecular weight apo(a) isoforms were more prevalent (55%) in the PH patients with CHD, whereas high molecular weight apo(a) isoforms were more prevalent (62.6%) in those without CHD: this difference was significant (p<0.05). A stepwise multiple-discriminant analysis made in order to determine the independence of common cardiovascular risk factors, Lp(a) levels and low molecular weight apo(a) isoforms in predicting CHD among hypercholesterolemic subjects showed that the presence of a positive family history of CHD, smoking, age, and the presence of at least one apo(a) isoform of low molecular weight were independently associated with CHD. CONCLUSIONS: Despite high Lp(a) levels, our findings do not support the hypothesis that Lp(a) plays an independent role in determining clinical CHD in PH subjects. However, the presence of at least one low molecular weight apo(a) isoform is an independent genetic predictor of CHD in hypercholesterolemic subjects. Together with other cardiovascular risk factors, apo(a) phenotypes should be assessed to evaluate the overall CHD risk status of all subjects with high serum cholesterol levels.     

冠心病患者血清sdLDL-C、Lp（a）水平变化与冠脉病变的相关性

目的：探讨冠心病（CHD）患者血清小而密低密度脂蛋白胆固醇（sdLDL-C）、脂蛋白（a）（Lp（a））水平变化与CHD临床类型及冠脉病变的相关性。方法：选取因胸痛入院的患者180例,根据冠脉造影结果分为对照组48例,CHD组132例,其中包括稳定型心绞痛（SAP）组41例,不稳定型心绞痛（UAP）组51例,急性心梗（AMI）组40例;根据冠脉造影病变支数又分为对照组48例、单支组44例及多支组88例。分别测定患者血清sdLDL-C、Lp（a）及其它血脂指标。结果：CHD组血清sdLDL-C、Lp（a）水平高于对照组（P<0.05）,CHD各亚组间血清sdLDL-C水平UAP组>SAP组、UAP组>AMI组,血清Lp（a）水平AMI组>UAP组（P<0.05）,两者水平均表现为多支组>单支组＞对照组（P<0.0 5）;Logistic回归分析表明,血清sdLDL-C、Lp（a）是CHD的独立危险因素。结论：血清sdLDL-C、Lp（a）水平变化与CHD的临床类型及冠脉病变程度呈正相关,可作为CHD的独立危险因素。     

The relationship between lipoprotein(a) and the complications of diabetes mellitus

The risk of cardiovascular disease is increased approximately two- to four-fold in patients with diabetes mellitus compared with non-diabetic controls. The nature of this increased risk cannot be completely explained by the contribution of traditional risk factors. As such, there has been a great deal of interest in assessing the role of lipoprotein(a) (Lp(a)), an LDL-like lipoprotein, in the vascular complications of diabetes. Although numerous studies in the non-diabetic population have demonstrated an association between elevated plasma Lp(a) concentration and risk for atherosclerotic disorders, the contribution of Lp(a) to the enhanced risk of vascular disease in the diabetic population is not clearly defined. Herein we review the structure and potential functions of Lp(a), the determination of Lp(a) levels, and the epidemiological evidence supporting its role in coronary heart disease and address the following controversial questions regarding the role of Lp(a) in diabetes mellitus: (1) are plasma Lp(a) levels and phenotype distributions altered in type 1 (insulin-dependent) diabetes mellitus and type 2 (non-insulin-dependent) diabetes mellitus and does the degree of metabolic control influence Lp(a) levels in these patients; (2) what is the relationship between Lp(a) and renal disease in patients with diabetes mellitus; (3) do increased plasma Lp(a) concentrations in patients with diabetes contribute to the vascular complications of this disease; and (4) can the atherogenicity of Lp(a) in diabetes be enhanced in the absence of elevated levels of this lipoprotein due to biochemical modifications. Received: 11 January 2002 / Accepted in revised form: 9 December 2002 Correspondence to S.M. Marcovina     

Association of elevated lipoprotein(a) levels and coronary heart disease in NIDDM patients. Relationship with apolipoprotein(a) phenotypes

Summary Non-insulin-dependent diabetes mellitus (NIDDM) is a strong and independent risk factor for coronary heart disease. We assessed the potential relationship between plasma Lp(a) levels, apo(a) phenotypes and coronary heart disease in a population of NIDDM patients. Seventy-one patients with coronary heart disease, who previously have had transmural myocardial infarction, or significant stenosis on coronary angiography, or positive myocardial thallium scintigraphy, or in combination, were compared with 67 patients without coronary heart disease, who tested negatively upon either coronary angiography, myocardial thallium scintigraphy or a maximal exercise test. The prevalence of plasma Lp(a) levels elevated above the threshold for increased cardiovascular risk (>0.30 g/l) was significantly higher (p=0.005) in patients with coronary heart disease (33.8%) compared to the control group (13.4%). The relative risk (odds ratio) of coronary heart disease among patients with high Lp(a) concentrations was 3.1 (95% confidence interval, 1.31–7.34;p=0.01). The overall frequency distribution of apo(a) phenotypes differed significantly between the two groups (p=0.043). However, the frequency of apo(a) isoforms of low apparent molecular mass (700 kDa) was of borderline significance (p=0.067) between patients with or without coronary heart disease (29.6% and 16.4%, respectively). In this Caucasian population of NIDDM patients, elevated Lp(a) levels were associated with coronary heart disease, an association which was partially accounted for by the higher frequency of apo(a) isoforms of small size. In multivariate analyses, elevated levels of Lp(a) were independently associated with coronary heart disease (odds ratio 3.48, p=0.0233).Abbreviations NIDDM Non-insulin-dependent diabetes mellitus - IDDM insulin-dependent diabetes mellitus - CHD coronary heart disease - Lp(a) lipoprotein(a) - apo(a) apolipoprotein(a) - apoB apolipoprotein B - HMGCoA reductase hydroxymethylglutaryl coenzyme A reductase     

Single nucleotide polymorphisms in the apo(a) kringle IV type 8 domain are not associated with atherothrombotic serum lipoprotein (a) concentration, in a Portuguese paediatric population

Lipoprotein (a) (Lp[a]) is a complex of apolipoprotein (a) (apo[a]) and low-density lipoprotein (LDL), associated with atherothrombotic disease. Most of the interindividual variations in plasma levels of Lp(a) can be attributed to sequence differences linked to the apo(a) gene locus. The aim of this study was to investigate a possible link between single nucleotide polymorphisms (SNPs) in the apo(a) kringle (K) IV type 8 domain and atherothrombotic serum Lp(a) concentrations. Direct sequencing of the two exons and flanking intronic sequences of the apo(a) K IV type 8 domain was performed in a group of 97 paediatric patients, 51 with serum Lp(a) concentration above and 46 with concentration below 30 mg/dl,. We found three SNPs, two in exon 1 (c.66A>C and c.133G>A) and one in intron 1 (c.160+1G>A). The c.66A>C polymorphism was the most common with a heterozygosity frequency of 15.46%. The c.133G>A and c.160+1G>A polymorphisms were found at a frequency of 5.15% and 1.03%, respectively. No statistically significant difference was found in the genotype distribution between the two groups of patients. Our results suggest that these SNPs in the apo(a) K IV 8 domain are not directly associated with atherothrombotic serum Lp(a) concentration in our population.     

Is Lipoprotein (a)—Apheresis Useful?

Numerous epidemiological investigations have shown the importance of cholesterol, and in particular low density lipoprotein (LDL), and of the lipoproteins in the development of coronary sclerosis. A continuing relationship between cholesterol levels and coronary morbidity has been established. The LDL concentration in the blood is, in particular, to be made responsible for the development of arteriosclerosis and especially of coronary heart disease (CHD). Lipoprotein (a) [Lp(a)], as a risk factor for premature cardiovascular and cerebrovascular diseases, can be lowered by LDL-apheresis. Especially in isolated high levels of Lp(a) with CHD or polygenic hypercholesterolemia with elevated Lp(a) levels, LDL-apheresis can be indicated and can be useful to improve endothelium regulation and induce changes in coronary tone by an increase in endothelial derived relaxing factor. Lipoprotein (a) can be dramatically lowered by LDL-apheresis, but clinical improvement especially by low LDL is not still not clarified. Studies with weekly apheresis with statins versus drug therapy alone are necessary. To clarify the controversial discussions of whether lowering Lp(a) may be unnecessary or necessary to arrest progression of CHD, more clinical and randomized studies are needed. Lipoprotein (a) can be also lowered by current LDL-apheresis methods.     

Lipoprotein(a) and atherosclerosis: New perspectives on the mechanism of action of an enigmatic lipoprotein

Although elevated plasma concentrations of lipoprotein(a) (Lp(a)) have been identified as a risk factor for coronary heart disease, the pathophysiologic and physiologic roles of Lp(a) continue to elude basic researchers and clinicians alike. Lp(a) is a challenging lipoprotein to study because it has a complex structure consisting of a low-density lipoprotein-like moiety to which is covalently attached the unique glycoprotein apolipoprotein(a) (apo(a)). Apo(a) contains multiply repeated kringle domains that are similar to a sequence found in the fibrinolytic proenzyme plasminogen; differing numbers of kringle sequences in apo(a) give rise to Lp(a) isoform size heterogeneity. In addition to elevated plasma concentrations of Lp(a), apo(a) isoform size has been identified as a risk factor for coronary heart disease, although studies addressing this relationship have been limited. The similarity of Lp(a) to low-density lipoprotein and plasminogen provides an enticing link between the processes of atherosclerosis and thrombosis, although a clear demonstration of this association in vivo has not been provided. Clearly, Lp(a) is a risk factor for both atherothrombotic and purely thrombotic events; a plethora of mechanisms to explain these clinical findings has been provided by both in vitro studies as well as animal models for Lp(a).     

Genetic basis and pathophysiological implications of high plasma Lp(a) levels.

Lipoprotein(a) or Lp(a) is a genetic variant of plasma low density lipoproteins (LDL) containing apoB100 covalently linked to apolipoprotein(a) or apo(a), the specific marker of Lp(a). Lp(a) is heterogeneous in size and density, accounting in part for the marked size polymorphism of apo(a), 300 to 800 kDa. The apo(a) size polymorphism is related to the different number of kringle repeats which are structurally similar although not identical to the kringle 4 of plasminogen. Recent studies on a genomic level have indicated that the apo(a) gene contains at least 19 different alleles varying in length between 48 and 190 kb, partially impacting on the plasma levels of Lp(a). High plasma levels of Lp(a) have been found to be associated with an increased prevalence of premature atherosclerotic cardiovascular disease by mechanism(s) yet to be established. Both atherogenic and thrombogenic potentials have been postulated and have been related to the LDL-like and plasminogen-like properties of Lp(a), respectively.     

A prospective study of lipoprotein(a) and risk of coronary heart disease among women with type 2 diabetes

Aims We examined the association between lipoprotein (Lp)(a) and CHD among women with type 2 diabetes.Methods Of 32,826 women from the Nurses Health Study who provided blood at baseline, we followed 921 who had a confirmed diagnosis of type 2 diabetes.Results During 10 years of follow-up (6,835 person-years), we documented 122 incident cases of CHD. After adjustment for age, smoking, BMI, glycosylated HbA₁c, triglycerides (TGs), high-density lipoprotein cholesterol, low-density lipoprotein cholesterol and other cardiovascular risk factors, the relative risk (RR) comparing extreme quintiles of Lp(a) was 1.95 (95% CI 1.07–3.56). The association was not appreciably altered after further adjustment for apolipoprotein B₁₀₀ or several inflammatory biomarkers. Increasing levels of Lp(a) were associated with lower levels of TGs. The probability of developing CHD over 10 years was higher among diabetic women with substantially higher levels of both Lp(a) (>1.07 mol/l) and TGs (>2.26 mmol/l) than among diabetic women with lower levels (22 vs 10%, p log-rank test=0.049). Diabetic women with a higher level of only Lp(a) or TGs had a similar (14%) risk. In a multivariate model, diabetic women with higher levels of Lp(a) and TGs had an RR of 2.46 (95% CI 1.21–5.01) for developing CHD, as compared with those with lower levels of both biomarkers (p for interaction=0.413). The RRs for women with a higher level of either Lp(a) (RR=1.22, 95% CI 0.77–1.92) or TGs (RR=1.39, 95% CI 0.78–2.42) were comparable.Conclusions/interpretation Increased levels of Lp(a) were independently associated with risk of CHD among diabetic women.     

Lipoprotein(a) and coronary heart disease risk

Although retrospective case-control studies continue to indicate that plasma lipoprotein(a) [Lp(a)] concentrations are associated with coronary heart disease (CHD), several large population-based prospective studies have failed to confirm that Lp(a) is an independent risk factor. However, evidence exists from several studies to suggest that elevated plasma Lp(a) increases the CHD risk associated with more traditional risk factors. Although identification of the functional role of Lp(a) in atherogenesis has been thwarted by the physical, chemical, and genetic complexity of Lp(a), the structural similarity of Lp(a) to both the fibrinolytic proenzyme plasminogen and low-density lipoprotein (LDL) has suggested a prothrombotic or atherogenic role (or both) for this lipoprotein. Because the clinical determination and application of plasma Lp(a) concentration poses several challenges, we cannot recommend its routine measurement at this time. Rather, plasma Lp(a) determinations should be limited to either patients at high risk for the development of CHD or patients at borderline risk for the development of CHD in whom uncertainty may exist about how aggressively to treat modifiable risk factors such as elevated LDL cholesterol.     

冠心病患者脂蛋白(a)和纤维蛋白原血浓度与冠状动脉狭窄间的关系

为观察血清脂蛋白（ａ）血浆纤维蛋白原浓度与冠心病的冠状动脉狭窄程度的关系，选择了１３７例冠状动脉造影术患者，测定血清脂蛋白和血浆纤维蛋白原水平。结果６１例多支冠状动脉病变的冠心病患者的血清脂蛋白（ａ）水平明显３１例无冠状动脉病变者，冠心病组中的单支及多支病变组血浆纤维蛋白原水平均明显高于无病变组。而脂蛋白（ａ）与纤维蛋白原水平仅在多支病变者中有经度正相关性。     

The Familial Hypercholesterolemia Regression Study: A Randomized Comparison of Therapeutic Reduction of Both Low-Density Lipoprotein and Lipoprotein(a) Versus Low-Density Lipoprotein Alone

Abstract: Lipoprotein (a) [Lp (a)] is a risk factor for coronary heart disease (CHD), especially in the presence of a raised low-density lipoprotein (LDL)-cholesterol (LDL-C). To ascertain whether reduction of both LDL and Lp(a) is more advantageous than reduction of LDL alone, patients with heterozygous FH and CHD were selected randomly to receive either LDL apheresis fortnightly plus simvastatin 40 mg/day or colestipol 20 g plus simvastatin 40 mg/day. Quantitative coronary angiography was undertaken before and after 2.1 years. Changes in serum lipids were similar in both groups except for the greater reduction of LDL-C and Lp(a) by apheresis. There were no significant differences in primary angiographic endpoints, and none of the angiographic changes correlated with Lp(a). Although LDL apheresis plus simvastatin was more effective than colestipol plus simvastatin in reducing LDL-C and Lp(a), it was not more beneficial in influencing coronary atherosclerosis. Decreasing Lp(a) seems unnecessary if LDL-C is reduced below 130 mg/dl.—     

Monitoring of Lipids, Enzymes, and Creatine Kinase in Patients on Lipid-Lowering Drug Therapy

Despite the critical importance of plasma lipoproteins in the development of atherosclerosis, varying degrees of evidence surround the causal associations of lipoproteins with coronary artery disease (CAD). These causal contributions can be assessed by employing genetic variants as unbiased proxies for lipid levels. A relatively large number of low-density lipoprotein cholesterol (LDL-C) variants strongly associate with CAD, confirming the causal impact of this lipoprotein on atherosclerosis. Although not as firmly established, genetic evidence supporting a causal role of triglycerides (TG) in CAD is growing. Conversely, high-density lipoprotein cholesterol (HDL-C) variants not associated with LDL-C or TG have not yet been shown to be convincingly associated with CAD, raising questions about the causality of HDL-C in atherosclerosis. Finally, genetic variants at the LPA locus associated with lipoprotein(a) [Lp(a)] are decisively linked to CAD, indicating a causal role for Lp(a). Translational investigation of CAD-associated lipid variants may identify novel regulatory pathways with therapeutic potential to alter CAD risk.     

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。     

Effect of Nicotinic acid/Laropiprant in the lipoprotein(a) concentration with regard to baseline lipoprotein(a) concentration and LPA genotype

Background

Lipoprotein(a) [Lp(a)] is a lipoprotein in which apolipoproteinB-100 is linked to apolipoprotein(a) [apo(a)]. Significant variation in Lp(a) concentration is specific to LPA gene, which codes for apo(a). Nicotinic acid (NA) is used for treatment of dyslipidemias, and the lowering effect of NA on Lp(a) has been previously reported.

Objective

To evaluate the Lp(a) lowering effect of 1 g/20 mg and 2 g/40 mg day of Nicotinic acid/Laropiprant in subjects with different baseline Lp(a) concentrations and depending on the LPA genotype.

Methods

In an open-label, 10-week study, 1 g/20 mg day of NA/Laropiprant for 4 weeks followed by 6 weeks of 2 g/40 mg day conducted at 3 centers in Spain, 82 subjects were enrolled. Patients were studied at baseline and at the end of both treatment periods and were enrolled in three groups: normal Lp(a) (< 50 mg/dL), high Lp(a) (50–120 mg/dL) and very high Lp(a) (> 120 mg/dL). The LPA genetic polymorphism was analyzed by a real-time PCR.

Results

There was a significant difference in LPA genotypes among Lp(a) concentration groups and an inverse and significant correlation between baseline Lp(a) concentration and LPA genotype was found (R = − 0.372, p < 0.001). There were a significant decrease in total cholesterol, triglycerides, LDL cholesterol, apo B and Lp(a), and a significant increase in HDL cholesterol after NA/Laropiprant treatment, without changes in BMI. However, there were no statistical differences in percentage variation of analyzed variables depending on LPA genotype.

Conclusion

LPA genotype is a major determinant of Lp(a) baseline concentration. However, the lipid lowering effect of NA is not related to LPA genotype.