A Study to Assess the Effect of AZD0780 on Ambulatory Blood Pressure

Inclusion Criteria:

1. Participant must be ≥ 18 years of age at the time of signing the informed consent.

2. Participants with a history of ASCVD defined as myocardial infarction, stroke, or symptomatic peripheral arterial disease, or with risk factors hereof.

3. Participants with a fasting serum LDL-C ≥ 70 mg/dL (1.8 mmol/L) at screening.

4. Should be receiving stable SoC therapy for their comorbidities for at least 4 weeks prior to screening. There should be no planned medication or dose changes during study participation.

5. Body mass index ≥ 19.0 kg/m2.

6. Sex: males and females (females of non-childbearing potential).

Exclusion Criteria

1. eGFR < 45 mL/min/1.73m2 using the Chronic Kidney Disease Epidemiology Collaboration creatinine equation (2021) at screening.

2. History or presence of gastrointestinal, hepatic, or renal disease, or any other conditions known to interfere with absorption, distribution, metabolism, or excretion of drugs.

3. Poorly controlled type 2 diabetes mellitus, defined as HbA1c > 10% at screening.

4. Participants with history of coronary artery bypass graft surgery ≤ 6 months prior to screening or percutaneous coronary intervention ≤ 3 months prior to screening.

5. Heart failure with New York Heart Association Class III to IV. 9. Low-density protein or plasma apheresis within 12 months prior to Period 1 Day -1.

6. Uncontrolled hypertension defined as average of triplicate seated SBP > 160 mmHg or DBP > 90 mmHg at screening.

7. Pulse rate after 10 minutes seated rest < 50 or > 100 bpm at screening. 12. Any laboratory values with the following deviations at screening; test may be repeated at the discretion of the investigator if abnormal:

(a) Any positive result on screening for hepatitis B, hepatitis C, or HIV; (b) ALT > 1.5 × ULN; (c) AST > 1.5 × ULN; (d) TBL > ULN; (e) Haemoglobin < 12 g/dL in males or < 11 g/dL in females; (f) Potassium < lower limit of normal. 13. Any clinically important abnormalities in rhythm, conduction, or morphology of the resting ECG and any clinically important abnormalities in the 12-lead ECG as judged by the investigator, including:

1. family history of long QT syndrome;

2. PR interval prolongation > 240 ms;

3. QTcF > 450 ms; (> 470 ms in participants with bundle branch block)

4. any intermittent or persistent high degree atrioventricular-block grade II-III and sinus node dysfunction with significant sinus pause untreated with pacemaker; and cardiac tachyarrhythmias requiring treatment.

5. Lomitapide within 12 months prior to Period 1 Day -1. 19. Current or previous treatment with drugs for reduction or inhibition of PCSK9 (approved or investigational, eg, evolocumab, alirocumab, or inclisiran) within 12 months prior to Period 1 Day -1.

6. Fibrate therapy and derivatives are prohibited. 21. Receiving or has received within 14 days of screening, medication that contains a black box warning for significant QT prolongation. A list of prohibited medications can be found in Appendix G.

7. Nutraceuticals or homeopathic treatments which may have an impact on BP. 26. Participants working 3rd shift or night shifts based on potential changes in circadian rhythm.

8. Participants with sleep disorders that would affect ABPM measurements, in the investigator's opinion.

9. Participant arm circumference not appropriate for available ABPM cuff circumference, or participant has a medical device (eg, continuous glucose monitor) that prevents use of the ABPM device, in the opinion of the investigator.