Reclassification of Low or Intermediate Cardiovascular Risk by Determining Lipoprotein(a) Levels

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

This cross-sectional study effectively demonstrates the role of Lp(a) and highlights the potential benefits of incorporating this test into statin treatment strategies. The authors did an excellent job presenting the data and results while discussing the clinical implications. The findings have significant clinical relevance and contribute to the existing literature on the role of Lp(a).

I do not have any additional comments at this time. However, I recommend that the authors include one or more sentences in the conclusion section to reinforce the clinical recommendation. Specifically, they could reflect this statement: “This result underscores the potential benefits of incorporating Lp(a) screening into routine cardiovascular risk evaluation, enabling the identification of patients who may require lipid-lowering strategies even in the absence of other major risk factors.”

Author Response

Comment 1: I do not have any additional comments at this time. However, I recommend that the authors include one or more sentences in the conclusion section to reinforce the clinical recommendation. Specifically, they could reflect this statement: “This result underscores the potential benefits of incorporating Lp(a) screening into routine cardiovascular risk evaluation, enabling the identification of patients who may require lipid-lowering strategies even in the absence of other major risk factors.”

 

Answer: thanks very much for your kind evaluation. We have added the sentence you proposed that we found very appropriate.

Reviewer 2 Report

Comments and Suggestions for Authors

The authors found some important data that suggests that at least some patients with a low or moderate SCORE2 score should be reclassified as high-risk individuals due to elevated levels of LP(a), and some of these individuals may require statin therapy. The study design is appropriate for publication, but I have one question: how can you explain the difference in the prevalence of low and moderate SCORE2 scores in groups with different levels of LP(a)? (see Table 1). Could you please clarify this in your article?

Author Response

Comment 1: The study design is appropriate for publication, but I have one question: how can you explain the difference in the prevalence of low and moderate SCORE2 scores in groups with different levels of LP(a)? (see Table 1). Could you please clarify this in your article?

 

Answer: thanks very much for your evaluation and for the comment of SCORE2 risk categories. We don´t have a clear explanation for this result rather than just describing that the prevalence of elevated Lp(a) might be even higher in subjects with moderate risk; moreover, the screening might be even more effective in this group. We have added the following sentence at the ending of the third paragraph of the discussion: “Subjects with Lp(a) >50 mg/dl had higher prevalence of moderate cardiovascular risk and, therefore, the screening might be even more effective in this group”.

Reviewer 3 Report

Comments and Suggestions for Authors

1. Materials and methods are described inconsistently. For example, first, what was measured, then the exclusion criteria… It is not clear the purpose of this paragraph “The laboratory is located at San Juan University Hospital, a 395-bed suburban com-77 munity hospital that serves the Department of Health's population of 248.523, including 78 nine different primary care centers. It receives samples from hospitalized, outpatient, and 79 primary care patients, whose samples are transported by couriers from the various collec-80 tion points to the laboratory reception. The laboratory information management system 81 stores and manages the laboratory data for each request in each patient's database. Labor-82 atory requests are made through the patient order entry computer. Laboratory reports are 83 automatically sent to the patient's electronic medical record [13].” Is “395-bed” so important for this study?
2. Incorrect references in the text. For example, this strange paragraph has [13], but if we look at [13] we see that it is reference for: “A recent study performed in Spain showed that 60% of the relatives 149 of patients with premature myocardial infarction and elevated Lp(a) had levels >50 150 mg/dl[16].” So here [16] is also incorrect. Further, “Since early 2023, 62 the SCORE-2 has been automatically calculated for all routine test requests made by pri-63 mary care practitioners in the Health Department of the Hospital de San Juan[11].” Why [11] is here, maybe “according to guideline” must be added or it looks like reference must be about Hospital de San Juan?
3. “3.1. Figures, Tables and Schemes” is very strange name for the subsection. What is the purpose of this subsection? Maybe this version of the manuscript is not last? It is written “All figures and tables should be cited in the main text as Figure 1, Table 1, etc.” But table 1 is not mentioned in the text. In materials and methods it's written very confusingly how quantitative variables are presented. And there is no explanation for the table 1. For example, what does it mean: total cholesterol 203.2 (34.7)? What is 34.7?
4. There is the study with similar design: https://www.atherosclerosis-journal.com/article/S0021-9150(25)01345-0/fulltext. Why do you not discuss it?

Author Response

Comment 1: Materials and methods are described inconsistently. For example, first, what was measured, then the exclusion criteria… It is not clear the purpose of this paragraph “The laboratory is located at San Juan University Hospital, a 395-bed suburban community hospital that serves the Department of Health's population of 248.523, including nine different primary care centers. It receives samples from hospitalized, outpatient, and primary care patients, whose samples are transported by couriers from the various collection points to the laboratory reception. The laboratory information management system 81 stores and manages the laboratory data for each request in each patient's database. Laboratory requests are made through the patient order entry computer. Laboratory reports are automatically sent to the patient's electronic medical record [13].” Is “395-bed” so important for this study?

 

Answer:  we regret that you find that section so inconsistent. We have tried to re-organize it as much as possible. We have also deleted the reference to the number of beds.

 

Comment 2: Incorrect references in the text. For example, this strange paragraph has [13], but if we look at [13] we see that it is reference for: “A recent study performed in Spain showed that 60% of the relatives 149 of patients with premature myocardial infarction and elevated Lp(a) had levels > 150 mg/dl[16].” So here [16] is also incorrect. Further, “Since early 2023, the SCORE-2 has been automatically calculated for all routine test requests made by primary care practitioners in the Health Department of the Hospital de San Juan[11].” Why [11] is here, maybe “according to guideline” must be added or it looks like reference must be about Hospital de San Juan?

 

Answer:  Thanks for the comment. We had a few issues with the references due to the fact that several authors used the same reference manager. We  have solved them and checked that all the references are correctly inserted.  

 

Comment 3: “3.1. Figures, Tables and Schemes” is very strange name for the subsection. What is the purpose of this subsection? Maybe this version of the manuscript is not last? It is written “All figures and tables should be cited in the main text as Figure 1, Table 1, etc.” But table 1 is not mentioned in the text. In materials and methods it's written very confusingly how quantitative variables are presented. And there is no explanation for the table 1. For example, what does it mean: total cholesterol 203.2 (34.7)? What is 34.7?

 

Answer:  We did not submit that section; that might be something with the editorial.

 

 

Comment 4: There is the study with similar design: https://www.atherosclerosis-journal.com/article/S0021-9150(25)01345-0/fulltext. Why do you not discuss it?

 

Answer:  Thanks very much for the reference. This study is actually an estimation on the effect of Lp(a) determinations on cardioprotective therapies (statin plus blood pressure lowering) and, also, the cost-saving by the prevention of cardiovascular events. We have included the following mention in the discussion: “Our results are in concordance with an analysis of  10.000 subjects aged 40-69 years from the UK Biobank that found that 18% of them have Lp(a) >50 mg/dl (>105 nmol/L). That study performed an estimation that revealed that the risk reclassification would induce the initiation of statin and blood pressure lowering therapies that would reduce the cost and burden and cardiovascular disease in this population [23].”