Folic Acid and Intensive Antihypertensive Therapy for Hypertension With CSVD

Inclusion Criteria:

1. Age 35-75 years;
2. Meets any of the following criteria:

1. Lacunar infarction occurring within the period of seven days up to one yearpost-infarction, diagnosed by head MRI/CT (meeting modified Fisher criteria*); 2）Head MRIindicating white matter hyperintensity, 4≥Fazekas score*≥2; 3）Head MRI indicating whitematter hyperintensity, Fazekas=1, combined with old subcortical vascular lacunarinfarction;

• For modified Fisher criteria and Fazekas score, see FAITH main study appendix 1 andappendix 6).

3. Medical recorded history of hypertension. Systolic blood pressure SBP: 130-180 mmHg on 0 or 1 medication SBP: 130-170 mm Hg on up to 2 medications SBP: 130-160 mm Hgon up to 3 medications. 4. mRS score ≤2; 5. Serum Hcy ≥10 µmol/L or MTHFR 677 TTgenotype; 6. Signed informed consent form.

Exclusion Criteria:

1. Patients with secondary hypertension;
2. Symptomatic intracranial and extracranial artery stenosis (stenosis ≥50%), orasymptomatic intracranial and extracranial artery stenosis (stenosis≥70%);
3. Patients who have undergone revascularization of the heart, brain, or kidney, or otheraortic stenting procedures;
4. Any symptoms of orthostatic hypotension when measuring standing blood pressure, or ifstanding SBP <110mmHg;
5. Bilateral renal artery stenosis;
6. Patients who have previously taken candesartan or other angiotensin receptorantagonist (ARB) type medication, indapamide or other similar diuretic typemedication, or any medication or health product containing folic acid, and reportedadverse reactions;
7. Patients who have indicators for specific antihypertensive medications (e.g. β-blockers after acute myocardial infarction, RAS blockers for prevention ofcardiovascular disease, α-blockers for treatment of benign prostate hyperplasia);
8. Within the last three months, regular usage of vitamin supplements containing folicacid, B6, or B12, or usage of folic acid antagonists (e.g. methotrexate);
9. Patients undergoing dialysis or with stage 4-5 chronic kidney disease, or estimatedglomerular filtration rate (eGFR) <30 mL/min/1.73m²;
10. History of epilepsy or currently using anti-epileptic medication;
11. Pregnant and lactating women, or women planning to become pregnant;
12. Life expectancy less than four years;
13. Within the last month, participation in another clinical trial;
14. Any patient determined by the researchers to be unsuitable for the present study.