Relationship of low-density lipoprotein-cholesterol and lipoprotein(a) to cardiovascular risk: The Multi-Ethnic Study of Atherosclerosis (MESA)

Rikhi, Rishi; Hammoud, Aziz; Ashburn, Nicklaus P.; Snavely, Anna C.; Michos, Erin D.; Chevli, Parag A; Tsai, Michael Y.; Herrington, David M.; Shapiro, Michael D.

doi:10.1016/j.atherosclerosis.2022.10.004

Cited by 18 publications

(14 citation statements)

References 32 publications

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“…Pathophysiologic studies indicate that Lp(a) has proatherogenic effects similar to and independent of those of LDL-cholesterol 8 as well as proinflammatory effects, potentially due to oxidized phospholipids carried by the Lp(a) molecule. Additionally, apo(a) contains a sequence that structurally resembles plasminogen and may therefore have prothrombotic and antifibrinolytic effects.…”

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confidence: 99%

Lipoprotein(a) concentrations in acute myocardial infarction patients are not indicative of levels at six month follow-up

Ziogos

Vavuranakis

Harb

et al. 2023

European Heart Journal Open

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Aims Lipoprotein(a) (Lp(a)) levels are generally constant throughout an individual’s lifetime and current guidelines recommend that a single measurement is sufficient to assess the risk of coronary artery disease (CAD). However, it is unclear whether a single measurement of Lp(a) in individuals with acute myocardial infarction (MI) is indicative of the Lp(a) level six months following the event. Methods and Results Lp(a) levels were obtained from individuals with NSTEMI or STEMI (n = 99) within 24 hours of hospital admission and after six months, who were enrolled in two randomized trials of evolocumab and placebo, and in individuals with NSTEMI or STEMI (n = 9) who enrolled in a small observation arm of the two protocols and did not receive study drug, but whose levels were obtained at the same time points. Median Lp(a) levels increased from 53.5 nmol/L [19,165] during hospital admission to 58.0 nmol/L [14.8, 176.8] six months after the acute infarction (p = 0.02). Subgroup analysis demonstrated no difference in the baseline, six-month, or change between the baseline and six-month Lp(a) values between the STEMI and NSTEMI groups and between the group which received evolocumab and the group that did not. Conclusion This study demonstrated that Lp(a) levels in individuals with acute MI are significantly higher six months after the initial event. Therefore, a single measurement of Lp(a) in the peri-infarction setting is not sufficient to predict the Lp(a)-associated CAD risk in the post-infarction period. Trial registration number Evolocumab in Acute Coronary Syndrome Trial [EVACS I] NCT03515304, Evolocumab in Patients with Acute Myocardial Infarction [EVACS II], NCT04082442

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confidence: 99%

Lipoprotein(a) concentrations in acute myocardial infarction patients are not indicative of levels at six month follow-up

Ziogos

Vavuranakis

Harb

et al. 2023

European Heart Journal Open

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“…The reduced apoA1 protein levels found in all age groups in both FH children and controls suggest a possible lack of protection from LDL R[LGDWLRQ DQG LWV SURLQ˞DPPDWRU\ SURSHUWLHV >@ Lipoprotein (a), which like apoB-containing lipids is known to be atherogenic, was critically elevated in adolescents (10-14 years old) and young adults (15-18 years old) within our FH sample. According to a study by R. Rikhi (2022) [20], a group of patients with LDL-C levels >2.6 mmol/L DQG OLSRSURWHLQ D ! PJG/ VKRZHG D VLJQL˝cantly higher risk of acute coronary syndrome in the next 13.4 years of follow-up compared with patient groups whose LDL-C and lipoprotein (a) OHYHOV ZHUH VLJQL˝FDQWO\ ORZHU ,Q DGGLWLRQ WR GHtermining lipoprotein (a) levels, FH children may also need to be screened for apoE genotype.…”

Section: Discussionmentioning

confidence: 99%

Lipid profile peculiarities and matrix Gla protein concentration in Ukrainian pediatric patients with heterozygous familial hypercholesterolemia

Мarushko¹,

Kurilina²,

Kulchytska³

2022

MPU

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Atherosclerotic changes in the vascular walls begin early in childhood, especially in association with familial hypercholesterolemia (FH). The process may be subclinical, which nevertheless requires therapeutic and preventive measures. Purpose - to evaluate baseline lipid profiles, the thickness of carotid intima-media complexes, blood pressure indices and the association with concentration changes of dephosphorylated-uncarboxylated matrix Gla protein (dp-uc MGP) as a marker of subclinical arterial lesions in different age groups of pediatric patients with FH. Materials and methods. Children with heterozygous FH (n=15), stratified by age and sex, were included in the study. The control group consisted of healthy peers (n=21). Blood samples were analyzed to determine levels of total (TC), low-density (LDL-C), very-low-density (VLDL-C), high-density (HDL-C), remnant (rC) and non-high-density (non-HDL-C) cholesterol, triglycerides (TG), apolipoproteins A1 (apoA1) and B (apoB), lipoprotein (a), and dp-uc MGP. The intima-media complex thickness of the common carotid artery and blood pressure were measured in all study subjects. The obtained data were processed using the accepted methods of medical statistics and SAS® OnDemand for Academics. Results. Lipid profile changes in pediatric patients with FH were characterized by high levels of LDL-C, non-HDL-C and lipoprotein (a) in the 5-9 years age group; in the 10-14 years age group - high levels of LDL-C, TG, rC, non-HDL-C and lipoprotein (a); in the 15-18 years age group - high levels of LDL-C, TG, non-HDL-C and lipoprotein (a). At the same time, the most marked dyslipidemia changes were evident in children aged 10-14 years in the FH group. apoA1 levels were significantly decreased in all FH children. Elevated levels of lipoprotein (a) (>30 mg/dL) in FH children were found in all age groups, suggesting that elevated lipoprotein (a) levels can be used as a factor for cardiovascular risk stratification. Dp-uc MGP levels were significantly elevated in all age groups of FH children compared to healthy peers. Conclusions. A lipid profile examination is necessary to diagnose FH in children, along with family health history and cascade screening. As atherosclerotic changes at 5-18 years of age remain subclinical, and the instrumental tests available in routine medical practice are not sensitive enough to detect them, therefore, preventive or therapeutic measures cannot be initiated promptly. The evaluation of circulating matrix Gla protein in pediatric patients with FH can be used as a marker of vascular wall calcification, which may allow early preventive measures against microcalcification to be developed. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of the participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors.

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“…15 In MESA, Lp(a) was measured from cold storage 10-11 years after sample collection as mass content using an isoform insensitive latex-enhanced turbidimetric immunoassay (Denka Seiken, Tokyo, Japan) by Health Diagnostics Laboratory (Richmond, Virginia). 16,17…”

Section: Methodsmentioning

confidence: 99%

The Impact of Social Determinants of Health and Lifestyle on the Association of Lipoprotein(a) with Myocardial Infarction and Stroke

Brandt,

Kirch,

Patel

et al. 2023

Preprint

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BackgroundIn European cohorts, a higher Mediterranean diet or Life’s Simple 7 (LS7) score abolished or attenuated the risk associated with increasing Lipoprotein(a) [Lp(a)] on cardiovascular outcomes. This is unstudied in US cohorts. The impact of social determinants of health (SDOH) on the association of Lp(a) with cardiovascular outcomes remains unstudied. We sought to test if a SDOH score and LS7 score impacts the association of Lp(a) with myocardial infarction (MI) or stroke.MethodsObservational Cohort of US Adults from the Atherosclerosis Risk in Communities (ARIC) and Multi-Ethnic Study of Atherosclerosis (MESA) cohorts. We performed sequential multivariable Cox proportional hazard analysis, first adjusting for age, gender, non-HDL-C, race and ethnicity, then added SDOH and LS7 scores sequentially. The primary outcomes were time until first fatal or nonfatal MI or stroke.ResultsARIC (n=15,072; median Lp(a)=17.3 mg/dL) had 16.2 years average follow up. MESA (n=6,822; median Lp(a)=18.3 mg/dL had 12.3 years average follow-up. In multivariable analyses adjusted for age, gender, race and ethnicity, and non-HDL-C, Lp(a) was associated (HR, p-value) with MI in ARIC (1.10, <0.001) and MESA (1.09, <0.001), and stroke in ARIC (1.08, <0.001) but not MESA (0.97, 0.50). With SDOH and LS7 added to the model associations remained similar (association of Lp(a) with MI in ARIC 1.09, <0.001 and in MESA 1.10, 0.001, with stroke in ARIC 1.06, <0.003 and in MESA 0.96, 0.39). In models with all covariates, each additional SDOH correlated positively with MI (ARIC 1.13, <0.001; MESA 1.11, <0.001) and stroke (ARIC 1.17, <0.001; HR 1.07, p=0.11) and each additional LS7 score point correlated negatively with MI (ARIC 0.81, <0.001; MESA 0.84, <0.001) and stroke (ARIC 0.82, <0.001; MESA 0.84, <0.001).Conclusions and RelevanceSDOH and lifestyle factors were predictors for MI and stroke that did not impact the association between Lp(a) and cardiovascular events. Our findings support that Lp(a) is an independent risk factor for MI and possibly stroke.

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Relationship of low-density lipoprotein-cholesterol and lipoprotein(a) to cardiovascular risk: The Multi-Ethnic Study of Atherosclerosis (MESA)

Cited by 18 publications

References 32 publications

Lipoprotein(a) concentrations in acute myocardial infarction patients are not indicative of levels at six month follow-up

Lipoprotein(a) concentrations in acute myocardial infarction patients are not indicative of levels at six month follow-up

Lipid profile peculiarities and matrix Gla protein concentration in Ukrainian pediatric patients with heterozygous familial hypercholesterolemia

The Impact of Social Determinants of Health and Lifestyle on the Association of Lipoprotein(a) with Myocardial Infarction and Stroke

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