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Studies on apolipoprotein(a) phenotypes. Part 1. Phenotype frequencies in a healthy Japanese population

Abe A, Noma A

Atherosclerosis, 1992 Sep;96(1):1-8.
PMID: 1418098

The frequency distribution for serum lipoprotein(a) (Lp(a)) concentrations in healthy Japanese was highly skewed, with a mean +/- S.D. of 14.6 +/- 13.6 mg/dl and a median of 11.0 mg/dl. The present study provides the first evidence on the frequencies of Lp(a) phenotypes and alleles in healthy Japanese subjects. There was a strong inverse relationship between the apparent molecular weights of apo(a) isoforms and plasma Lp(a) concentrations, as reported previously. However, because of the considerable overlap between the Lp(a) concentrations of the different phenotypes, it was impossible to predict Lp(a) concentration from Lp(a) phenotypes, or vice versa. The present results suggest that the distribution of Lp(a) concentrations, mean and median values and Lp(a) phenotype and allele frequencies in healthy Japanese are not significantly different from the results for Europeans, whereas they are significantly different from other Asian populations, i.e. Chinese, Indians and Malaysians.
Fulltext Elevated lipoprotein(a) increases risk of subsequent major adverse cardiovascular events (MACE) and coronary revascularisation in incident ASCVD patients: A cohort study from the UK Biobank

Welsh P, Al Zabiby A, Byrne H, Benbow HR, Itani T, Farries G, et al.

Atherosclerosis, 2024 Feb;389:117437.
PMID: 38219651 DOI: 10.1016/j.atherosclerosis.2023.117437

BACKGROUND AND AIMS: Elevated lipoprotein(a) [Lp(a)] is a genetic driver for atherosclerotic cardiovascular disease (ASCVD). We aimed to provide novel insights into the associated risk of elevated versus normal Lp(a) levels on major adverse cardiovascular events (MACE) in an incident ASCVD cohort.
METHODS: This was an observational cohort study of incident ASCVD patients. MACE counts and incidence rates (IRs) per 100-person-years were reported for patients with normal (<65 nmol/L) and elevated (>150 nmol/L) Lp(a) within the first year after incident ASCVD diagnosis and overall follow-up. Cox proportional hazard models quantified the risk of MACE associated with a 100 nmol/L increase in Lp(a).
RESULTS: The study cohort included 32,537 incident ASCVD patients; 5204 with elevated and 22,257 with normal Lp(a). Of those with elevated Lp(a), 41.2% had a subsequent MACE, versus 35.61% with normal Lp(a). Within the first year of follow-up, the IRs of composite MACE and coronary revascularisation were significantly higher (p < 0.001) in patients with elevated versus normal Lp(a) (IR difference 6.79 and 4.66). This trend was also observed in the overall follow-up (median 4.7 years). Using time to first subsequent MACE, a 100 nmol/L increase in Lp(a) was associated with an 8.0% increased risk of composite MACE, and 18.6% increased risk of coronary revascularisation during the overall follow-up period.
CONCLUSIONS: The association of elevated Lp(a) with increased risk of subsequent MACE and coronary revascularisation highlights a population who may benefit from earlier and more targeted intervention for cardiovascular risk including Lp(a), particularly within the first year after ASCVD diagnosis. Proactive Lp(a) testing as part of routine clinical practice can help identify and better manage these higher-risk individuals.
Fulltext Serum lipoprotein(a) levels in patients with atherosclerotic peripheral vascular disease in Hospital Kuala Lumpur

Hakim NA, Hafizan MT, Baizurah MH, Zainal AA

Asian J Surg, 2008 Jan;31(1):11-5.
PMID: 18334463 DOI: 10.1016/S1015-9584(08)60048-2

The objective of this study was to determine the proportion of patients with atherosclerotic peripheral vascular disease (PVD) who had elevated lipoprotein(a) [Lp(a)] levels, as well as to determine the latter's significance as a risk factor for PVD in the local population.
Serum lipoprotein(A) profiles in a Singaporean population

Wong MS, Chew WL, Aw TC

Pathology, 1999 Aug;31(3):225-9.
PMID: 10503268

Lipoprotein(a) [Lp(a)] is formed when apolipoprotein(a) is linked to low density lipoprotein (LDL)-cholesterol via a single disulfide bond. It is an independent risk factor for myocardial infarction and raised concentrations are associated with an increased risk of developing coronary artery disease. Singapore has a multi-racial population of 77% Chinese, 14% Malays and 7% Indians. Studies have shown that the Indians have significantly higher standardised mortality ratios (SMR) compared to the Chinese and the Malays. We measured serum Lp(a) concentrations in 803 healthy individuals recruited from the Multiphasic Health Screening Programme, using the Macra Lp(a) sandwich enzyme immunoassay kit (Strategics Diagnostics, Delaware, USA). Lp(a) concentrations were skewed in all three groups. Our population mean was 9.0 mg/dl, with 50th, 75th and 95th percentile values of 10.2, 19.8 and 43.1 mg/dl, respectively, which are lower than values reported from Caucasian populations (15.0, 29.0 and 60.0 mg/dl, respectively). Males had lower Lp(a) concentrations than females (P < 0.05). The Indian group had significantly higher concentrations (median 12.3 mg/dl) compared to their Chinese (median 9.6 mg/dl) and Malay (median 8.4 mg/dl) counterparts (P < 0.05). This could partly account for the higher SMR seen in the Indian population in Singapore. As serum Lp(a) concentrations are method- and population-dependent, we recommend that laboratories determine their own reference ranges by their method to avoid misclassification of the coronary heart disease (CHD) risk of patients.
Fulltext Serum high-sensitivity C-reactive protein and lipoprotein(a) levels: a comparison between diabetic and non-diabetic patients with coronary artery disease

Shahid HS, Kurdi MI, Zohair AA

Med J Malaysia, 2011 Jun;66(2):113-6.
PMID: 22106689

OBJECTIVE: The aim of this study was to compare high-sensitivity C-reactive protein (hsCRP) and Lipoprotein(a) levels [Lp(a)] levels between diabetic and non-diabetic patients with coronary artery disease (CAD).
STUDY DESIGN: Cross sectional Study.
PLACE AND DURATION OF STUDY: This study was conducted in the department of Physiology of College of Medicine & King Khalid University Hospital, King Saud University, Riyadh between August 2006 and December 2007.
METHODS: One hundred and three individuals with CAD and 30 healthy individuals matched for age and BMI were studied. CAD patients were divided into two groups based on presence (n=62) and absence (n=41) of type 2 diabetes mellitus. Overnight fasting blood samples were collected, and analyzed for total cholesterol (TC), Triglycerides (TG), Low density Lipoprotein (LDL) and High density lipoprotein (HDL), Lp(a) and hsCRP. Data about CAD severity was obtained from medical records.
RESULTS: Both groups of CAD without and with DM had significantly higher levels of Lp(a) [mg/dl] (25.58 +/- 25.99, 25.90 +/- 24.67 respectively) and hsCRP [mg/dl] (0.52 +/- 0.71, 0.82 +/- 0.78 respectively) when compared with healthy control subjects (Lp(a) =16.93 +/- 15.34 & hsCRP=0.27 +/- 0.21) [p<0.05]. Lp(a) levels between the two CAD groups were non significant. While, hsCRP levels were significantly high in CAD with DM compared to those without DM [p<0.05]. Gensini Score of CAD severity was also higher in CAD with DM [67.60 +/- 45.94] than those without DM [52.05 +/- 42.27, p<0.05].
CONCLUSION: Elevated Lp(a) and hsCRP levels are associated specifically with angiographically defined CAD. However, hsCRP elevation but not Lp(a) is also associated with CAD in type 2 diabetes mellitus. Measurement of hsCRP and Lp(a) may be considered optional markers for better prediction of cardiovascular risk.
Fulltext Lipoprotein (A) levels in type 2 diabetic patients with diabetic retinopathy

Ergün UGO, Oztüzün S, Seydaoglu G

Med J Malaysia, 2004 Aug;59(3):406-10.
PMID: 15727389

To examine a possible association between lipoprotein(a) [Lp(a)] levels and diabetic retinopathy in patients with type 2 diabetes mellitus. 100 type 2 diabetic patients were assessed with the following parameters: age, body mass index, duration of diabetes, blood pressure, fasting plasma glucose, total cholesterol, HDL-cholesterol, triglycerides, blood urea nitrogen, creatinine, Lp(a), and albumin excretion rate (AER). Retinopathy was classified as normal retina (NR), non-proliferative diabetic retinopathy (NPDR), and proliferative diabetic retinopathy (PDR) by an ophthalmologist. The PDR group had higher cholesterol (t=-2.24, p<0.05) and creatinine (z=-2.547, p<0.05) levels than the NPDR group. The PDR group had a higher value of AER (z=-2.439, p<0.01) than the NR group. The possibility of developing diabetic retinopathy after 10 years of diabetes was found to be 6.5 fold high (OR; 6.57, 95% CI 1.74-24.79; p<0.05). The Lp(a) levels were similar in the patients with retinopathy and those without retinopathy. In the study, there was no evidence for a relationship between the serum Lp(a) levels and diabetic retinopathy in type 2 diabetic patients.
Study site: diabetic outpatient clinic at Haydarpasa Numune Education and Research Hospital in Istanbul, Turkey.
Type of diabetes and waist-hip ratio are important determinants of serum lipoprotein (a) levels in diabetic patients

Nawawi HM, Muhajir M, Kian YC, Mohamud WN, Yusoff K, Khalid BA

Diabetes Res Clin Pract, 2002 Jun;56(3):221-7.
PMID: 11947970 DOI: 10.1016/s0168-8227(02)00009-8

This cross-sectional study compared serum lipoprotein (a) [Lp(a)] concentrations in type 1 and type 2 diabetic subjects and examined the determinants of Lp(a) concentrations in both types of diabetes. Serum Lp(a) was measured in 26 type 1 and 107 type 2 diabetic patients and 126 non-diabetic controls. HbA(1c), fasting lipids and urinary albumin were also assayed. Lp(a) concentrations were higher in both type 1 and type 2 diabetic patients compared with controls (P<0.0001 and P<0.0001, respectively), and were higher in type 1 than type 2 diabetic patients (P<0.05). Waist-hip ratio (WHR) was an independent determinant of Lp(a) concentrations in both type 1 and type 2 diabetes.
Impact of phytosterol supplementation on plasma lipoprotein(a) and free fatty acid (FFA) concentrations: A systematic review and meta-analysis of randomized controlled trials

Fatahi S, Kord-Varkaneh H, Talaei S, Mardali F, Rahmani J, Ghaedi E, et al.

Nutr Metab Cardiovasc Dis, 2019 11;29(11):1168-1175.
PMID: 31582198 DOI: 10.1016/j.numecd.2019.07.011

BACKGROUND AND AIM: Although some earlier studies have indicated the effect of phytosterol (PS) supplementation on serum lipoprotein(a) (Lp(a)) and free fatty acid (FFA) concentration, findings are still conflicting. We aimed to assess the impact of PS supplementation on serum Lp(a) and FFA concentration through a systematic review and meta-analysis of available RCTs.
METHODS AND RESULTS: We performed a systematic search of all available RCTs conducted up to 21 February 2019 in the following databases: PubMed, Scopus, and Cochrane. The choice of fixed- or random-effect model for analysis was determined according to the I2 statistic. Effect sizes were expressed as weighted mean difference (WMD) and 95% confidence interval (CI). Pooling of 12 effect sizes from seven articles revealed a significant reduction of Lp(a) levels following PS supplementation (MD: -0.025 mg/dl, 95% CI: -0.045, -0.004, p = 0.017) without significant heterogeneity among the studies (I2 = 0.0%, p = 0.599). Also, PS supplementation significantly lowered FFA (MD: -0.138 mg/dl, 95% CI: -0.195, -0.081, p = 0.000) without significant heterogeneity among the studies (I2 = 0.0%, p = 0.911). The results for meta-regression and sensitivity analysis were not significant.
CONCLUSION: The meta-analysis suggests that oral PS supplementation could cause a significant reduction in serum Lp(a) and FFA.
Fulltext Central obesity, insulin resistance, syndrome X, lipoprotein(a), and cardiovascular risk in Indians, Malays, and Chinese in Singapore

Hughes K, Aw TC, Kuperan P, Choo M

J Epidemiol Community Health, 1997 Aug;51(4):394-9.
PMID: 9328546

STUDY OBJECTIVE: To examine the hypothesis that the higher rates of coronary heart disease (CHD) in Indians (South Asians) compared with Malays and Chinese is at least partly explained by central obesity, insulin resistance, and syndrome X (including possible components).
DESIGN: Cross sectional study of the general population.
SETTING: Singapore.
PARTICIPANTS: Random sample of 961 men and women (Indians, Malays, and Chinese) aged 30 to 69 years.
MAIN RESULTS: Fasting serum insulin concentration was correlated directly and strongly with body mass index (BMI), waist-hip ratio (WHR), and abdominal diameter. The fasting insulin concentration was correlated inversely with HDL cholesterol and directly with the fasting triglyceride concentration, blood pressures, plasminogen activator inhibitor 1 (PAI-1), and tissue plasminogen activator (tPA), but it was not correlated with LDL cholesterol, apolipoproteins B and A1, lipoprotein(a), (Lp(a)), fibrinogen, factor VIIc, or prothrombin fragment (F)1 + 2. This indicates that the former but not the latter are part of syndrome X. While Malays had the highest BMI, Indians had a higher WHR (men 0.93 and women 0.84) than Malays (men 0.91 and women 0.82) and Chinese (men 0.91 and women 0.82). In addition, Indians had higher fasting insulin values and more glucose intolerance than Malays and Chinese. Indians had lower HDL cholesterol, and higher PAI-1, tPA, and Lp(a), but not higher LDL cholesterol, fasting triglyceride, blood pressures, fibrinogen, factor VIIc, or prothrombin F1 + 2.
CONCLUSIONS: Indians are more prone than Malays or Chinese to central obesity with insulin resistance and glucose intolerance and there are no apparent environmental reasons for this in Singapore. As a consequence, Indians develop some but not all of the features of syndrome X. They also have higher Lp(a) values. All this puts Indians at increased risk of atherosclerosis and thrombosis and must be at least part of the explanation for their higher rates of CHD.
Trans (elaidic) fatty acids adversely affect the lipoprotein profile relative to specific saturated fatty acids in humans

Sundram K, Ismail A, Hayes KC, Jeyamalar R, Pathmanathan R

J Nutr, 1997 Mar;127(3):514S-520S.
PMID: 9082038

Although dietary trans fatty acids can affect plasma lipoproteins negatively in humans, no direct comparison with specific saturated fatty acids has been reported, even though trans fatty acids were designed to replace saturates in foods and food processing. In this study, dietary trans 18:1 [elaidic acid at 5.5% energy (en)] was specifically exchanged for cis 18:1, 16:0 or 12:0 + 14:0 in 27 male and female subjects consuming moderate fat (31% en), low cholesterol (<225 mg/d) whole food diets during 4-wk diet periods in a crossover design. The trans-rich fat significantly elevated total cholesterol and LDL cholesterol relative to the 16:0-rich and 18:1-rich fats and uniquely depressed HDL cholesterol relative to all of the fats tested. Trans fatty acids also elevated lipoprotein (a) [Lp(a)] values relative to all dietary treatments. Furthermore, identical effects on lipoproteins were elicited by 16:0 and cis 18:1 in these subjects. The current results suggest that elaidic acid, one of the principal trans isomers produced during industrial hydrogenation of edible oils, adversely affects plasma lipoproteins. Thus, the negative effect of elaidic acid on the lipoprotein profile of humans appears to be unmatched by any other natural fatty acid(s).
Modulation of human lipids and lipoproteins by dietary palm oil and palm olein: a review

Sundram K

Asia Pac J Clin Nutr, 1997 Mar;6(1):12-6.
PMID: 24394646

Several human clinical trials have now evaluated palm oil's effects on blood lipids and lipoproteins. These studies suggest that palm oil and palm olein diets do not raise plasma TC and LDL-cholesterol levels to the extent expected from its fatty acid composition. With maximum substitution of palm oil in a Western type diet some coronary heart disease risk factors were beneficially modulated: HDL2-cholesterol was significantly increased while the apolipoprotein B/A1 ratio was beneficially lowered by palm oil. Comparison of palm olein with a variety of monounsaturated edible oils including rapeseed, canola, and olive oils has shown that plasma and LDL-cholesterol were not elevated by palm olein. To focus these findings, specific fatty acid effects have been evaluated. Myristic acid may be the most potent cholesterol raising saturated fatty acid. Palmitic acid effects were largely comparable to the monounsaturated oleic acid in normolipidaemic subjects while trans fatty acids detrimentally increased plasma cholesterol, LDL-cholesterol, lipoprotein Lp(a) and lowered the beneficial HDL-cholesterol. Apart from these fatty acids there is evidence that the tocotrienols in palm oil products may have a hypocholesterolaemic effect. This is mediated by the ability of the tocotrienols to suppress HMG-CoA reductase. These new findings on palm oil merit a scientific reexamination of the classical saturated fat-lipid hypothesis and its role in lipoprotein regulation.

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