Absence of High Lipoprotein(a) Levels Is an Independent Predictor of Acute Myocardial Infarction without Coronary Lesions

Abstract

The pathophysiological mechanisms underlying Myocardial Infarction with Non-Obstructive Coronary Artery Disease (MINOCA) are still under debate. Lipoprotein (a) [Lp(a)] has proinflammatory and prothrombotic actions and has been involved in the pathogenesis of atherosclerosis. However, no previous studies have linked Lp(a) levels with the probability of developing MINOCA. Moreover, the relationship between MINOCA and the plasma levels of other proatherogenic and proinflammatory molecules such as Interleukin-18 (IL18) and proprotein convertase subtilisin/kexin type 9 (PCSK9) has not been studied. We conducted a prospective, multicenter study involving 1042 patients with acute myocardial infarction (AMI). Seventy-six patients had no significant coronary lesions. All patients underwent plasma analysis on admission. MINOCA patients were younger (57 (47–68) vs. 61 (52–72) years; p = 0.010), more frequently female (44.7% vs. 21.0%; p < 0.001), and had lower rates of diabetes and of Lp(a) > 60 mg/dL (9.2% vs. 19.8%; p = 0.037) than those with coronary lesions; moreover, High Density Lipoprotein cholesterol (HDL-c) levels were higher in MINOCA patients. The absence of Lp(a) > 60 mg/dL and of diabetes were independent predictors of MINOCA, as well as female sex, high HDL-c levels, and younger age. IL-18 and PCSK9 levels were not predictors of MINOCA. During a follow-up of 5.23 (2.89, 7.37) years, the independent predictors of the primary outcome (acute ischemic events or death) in the whole sample were Lp(a) > 60 mg/dL, older age, low estimated Glomerular Filtration rate (eGFR), hypertension, previous heart failure (HF), coronary artery bypass graft, use of insulin, and no therapy with acetylsalicylic acid. In conclusion, in AMI patients, the absence of high Lp(a) levels, as well high HDL-c levels, were independent predictors of the inexistence of coronary artery disease. High Lp (a) levels were also an independent predictor of ischemic events or death.

Prognostic value of elevated lipoprotein (a) in patients with acute coronary syndromes: a systematic review and meta-analysis

“…The funnel plots and Egger's test examination revealed no significant publication bias, which makes our results more robust. Our evidence-based analysis validated previous studies reporting the different MACE outcomes in high level Lp (a) vs. low level patients with ACS ( 21 , 25 , 28 , 36 – 38 ). More well-designed, large-scale prospective randomized studies with long-term follow-up are needed to further compare the MACE, all-cause mortality in high level vs. low level of Lp (a) patients with ACS.…”

“…For instance, the FORTIAM investigation ( 20 ), a multicenter cohort study in Spain involving 1,371 acute myocardial infarction (AMI) patients across 15 hospitals, revealed a poorer prognosis in those with elevated Lp (a) levels at admission. Consistent findings were reported by Andrea Kallmeyer et al and Si-qi Yang et al ( 21 , 22 ). Conversely, a Vietnam-based observational cohort study ( 23 ) yielded disparate results, suggesting no correlation between Lp (a) levels ≥ 50 mg/dl during AMI and MACE or all-cause mortality.…”

“…Ultimately, 18 full-text articles, encompassing a total of 18,168 patients (13,843 male, 4,325 female), were selected for the comprehensive pooled analysis ( 20 – 23 , 25 – 28 , 33 – 42 ). Of these articles, 5 were prospective cohort studies ( 21 , 23 , 34 , 35 , 40 ), 10 were retrospective cohort studies ( 20 , 22 , 25 , 26 , 28 , 33 , 36 – 39 ), and 3 were observational cohorts ( 4 , 27 , 41 ). The encompassed investigations in this analysis spanned the period from 2009 to 2023.…”

“…The median (range) quality score, indicative of methodological rigor, was determined to be 7 (5–9). Notably, 14 studies were acknowledged for their high quality, indicating the strength of their methodologies and findings within the scope of this comprehensive analysis ( 21 , 23 , 26 – 28 , 33 – 40 , 42 ). The quality assessment details of all eligible are presented in Supplementary Table S3 .…”

The impact of diabetes mellitus on the outcome of troponin-positive patients with non-obstructive coronary arteries

“…Studies demonstrate that compared with patients with myocardial infarction and obstructive coronary artery disease (CAD), MINOCA patients are mostly younger, more often female, not obese, non-smokers, without arterial hypertension or chronic kidney disease, in summary, without traditional cardiovascular risk factors [3] , [4] , [5] , [6] , [7] , [8] , [9] . They also have a significantly higher prevalence of non-ST-segment-elevation myocardial infarction than ST-segment-elevation myocardial infarction [8] , [10] .…”