Inclusion Criteria:
1. Understand the specific procedures of the trial, voluntarily participate in this trial, and provide written informed consent;
2. Aged ≥ 18 years on the day of signing the informed consent form;
3. Body mass index (BMI) ranging from 18.5 to 40 kg/m²;
4. High risk of cardiovascular events at screening;
5. Lp(a) ≥ 150 nmol/L as measured by the central laboratory during the screening period;
6. For participants receiving pharmacotherapy per clinical practice, they must have been on a stable treatment regimen for a specified duration prior to screening or randomization and are expected to remain on that regimen through the end of the treatment period;
7. Participants (including their partners) are willing to use effective contraception from the time of signing the informed consent form until 1 month after the last administration of the study drug; female participants must have a negative serum pregnancy test and must not be breastfeeding;
8. Willing and able to comply with all protocol requirements, including demonstrating adherence to study procedures prior to randomization.
Exclusion Criteria:
1. Any of the following occurring within 3 months prior to screening, or between screening and randomization: major cardiac or non-cardiac surgery, coronary, carotid or peripheral arterial revascularization, stroke or transient ischaemic attack, myocardial infarction or unstable angina, acute limb ischaemia; as well as arrhythmias requiring treatment but uncontrolled; or other events deemed clinically unstable by the Investigator;
2. Participants with planned or anticipated cardiac, cerebrovascular, or peripheral arterial surgery, coronary revascularization, or other major surgery during the trial period after randomization;
3. History of haemorrhagic stroke or other major bleeding, or occurrence of haemorrhagic stroke or other major bleeding events between screening visit and randomization visit;
4. Participants with an indication for anticoagulation but not receiving anticoagulant therapy at screening;
5. History of malignancy of any organ system within 5 years prior to screening, or newly diagnosed malignancy of any organ system between screening visit and randomization visit, regardless of signs of local recurrence or metastasis;
6. Prior history of diseases that significantly affect lipid levels, such as nephrotic syndrome, severe liver disease, Cushing's syndrome, etc.;
7. Uncontrolled type 1 or type 2 diabetes within 6 months prior to screening, or HbA1c \>8.0% at screening (a repeat confirmation is allowed);
8. History of acute kidney injury within 12 months prior to screening;
9. Uncontrolled hyperthyroidism or hypothyroidism at screening;
10. Active infection requiring systemic antiviral or antibacterial medication prior to randomization;
11. New York Heart Association (NYHA) functional class III-IV heart failure at screening, or the most recently measured left ventricular ejection fraction (LVEF) \<30%;
12. At screening or prior to randomization, participants suffering from major diseases that are unstable and inadequately controlled, in the judgment of the Investigator;
13. Chronic, continuous, or repeated use of systemic glucocorticoids within 3 months prior to screening;
14. Receipt of lipoprotein apheresis within 3 months prior to screening, or planned lipoprotein apheresis during the study period;
15. Prior receipt of specific antisense or gene therapy;
16. Treatment with oligonucleotides or small interfering ribonucleic acid (siRNA) within 12 months prior to screening;
17. Use of weight-loss medications resulting in significant weight loss, or surgery leading to substantial weight loss within 3 months prior to screening;
18. Known hypersensitivity to the active ingredient or any excipient of HRS-5346;
19. Uncontrolled hypertension prior to randomization;
20. eGFR \< 30 mL/min/1.73 m² at screening or prior to randomization, or participants receiving dialysis;
21. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), or gamma-glutamyl transferase (GGT) \> 2 times the upper limit of normal (ULN), or total bilirubin \>1.5 times ULN at screening or prior to randomization;
22. Human immunodeficiency virus infection (HIV-Ab positive), hepatitis C virus infection (HCV-RNA positive), Treponema pallidum infection (Treponema pallidum antibody positive), hepatitis B virus infection (HBsAg positive) at screening or prior to randomization;
23. Creatine kinase (CK) \> 3 times the upper limit of normal (ULN) prior to randomization;
24. Thyroid-stimulating hormone (TSH) below the lower limit of normal (LLN) or above the upper limit of normal (ULN) during screening;
25. Significant abnormal laboratory parameters at screening or prior to randomization that render the participant unsuitable for this study, as judged by the Investigator;
26. History of drug or alcohol abuse or dependence in the recent past (within 1 year);
27. Pregnant or breastfeeding women;
28. Participation in any clinical trial of investigational drug or medical device within 3 months prior to screening, or still within 5 half-lives of the investigational product at screening, whichever is longer;
29. The Investigator judges that the participant has poor adherence or any other factor rendering participation inappropriate, including but not limited to circumstances where trial participation would expose the participant to unacceptable risk or may confound study results.
