China Stroke Primary Prevention Trial 2 for Participants with H-type Hypertension and MTHFR 677 CC/CT Genotype (CSPPT2-CC/CT)

Inclusion Criteria:

1. Men and women, aged ≥45 and <75 years;

2. Hypertension: Previously diagnosed with primary hypertension and has been takingantihypertensive medication within the past two weeks; OR has not been takingantihypertensive medications within the last two weeks, but meets the followingcriteria for hypertension: SBP≥140 mmHg and/or DBP≥90 mmHg (average of at least 2measurements each time) at two separate (not on the same day) clinical visits;

3. MTHFR 677 CC or CT genotype (based on the test results from the central laboratoryduring the screening period or a previous official test report from a laboratorywith medical testing qualifications);

4. Plasma total homocysteine ≥10 µmol/L;

5. Serum folate level <12 ng/mL;

6. Has voluntarily agreed to participate and provided signed informed consent.

Randomized-treatment phase inclusion criteria:

1. Good compliance during the run-in period, and unlikely to discontinue treatment;

2. No stroke or cardiovascular events during the run-in period;

3. The participant voluntarily agrees to continue the study.

Exclusion Criteria:

1. Previously diagnosed secondary hypertension;

2. Previously diagnosed stroke;

3. Previously diagnosed myocardial infarction;

4. Previously diagnosed heart failure;

5. Previously diagnosed atrial fibrillation;

6. Cardio-cerebral-kidney revascularization and/or other large arterial stent;

7. Currently on dialysis, or diagnosed with stage 4-5 chronic kidney disease, or eGFR <30 mL/ min/1.73m²;

8. Known to have congenital (such as aortic stenosis) or acquired organic heartdisease;

9. Known to have any of the following severe diseases or conditions:

10. Digestive system: i. Previously diagnosed with any form of viral hepatitis thatis currently still in the active phase; ii. Abnormal liver function test beforeenrollment (any of ALT, AST, GGT, TBIL, DBIL test 3 times higher than normal,or ALB≤30g/L); iii. Subtotal gastrectomy and/or gastrojejunostomy;

11. Respiratory system: previously diagnosed with pulmonary heart disease;

12. Presence of malignant tumors or other severe diseases;

13. Presence of long-term gastrointestinal symptoms such as anorexia, decreasedappetite, nausea, and abdominal bloating;

14. Previously diagnosed with vitamin B12 deficiency and/or its related diseases.

15. Participant, at the investigator's discretion, is assessed to be unsuitable for thestudy, for reasons including but not limited to the presence of abnormal laboratoryresults, or clinical conditions;

16. Prior history of significant intolerance due to adverse reactions resulting fromusage of amlodipine or other CCBs, valsartan or other ARBs, indapamide or othersimilar diuretics, metoprolol tartaric acid or other beta-blockers, or any drugs orhealth products containing folate or folic acid;

17. Regular consumption of folic acid or vitamin B compounds, or other compoundscontaining folic acid in the past 3 months;

18. The presence of any of the following conditions that could negatively influence aparticipant's ability to consent or participate in the trial:

19. Dementia;

20. Severe mental disorders;

21. Inability to express informed consent;

22. Unlikely to complete the study follow-up as specified by the protocol, or plansto relocate outside of the study area in the near future;

23. History of poor compliance when taking antihypertensive medications or isexpected to have poor compliance during the study;

24. Refusal to participate, or inability to modify current drug regimen;

25. Women who are pregnant or breastfeeding; or subjects of childbearing potential whoare unwilling or unable to use effective contraception during the study period.

26. Within one month prior to the first visit, having participated in any clinical trialfor a drug that has not yet been officially approved by the state or is notcurrently approved for sale; or currently participating in any clinical trial thatcould potentially impact the results of this study (medication use, drug efficacy,drug interaction, etc.).