Folic Acid and Intensive Antihypertensive Therapy for Hypertension With CSVD

Prior treatment

• Patients who have previously taken candesartan or other angiotensin receptor antagonist (ARB) type medication, indapamide or other similar diuretic type medication, or any medication or health product containing folic acid, and reported adverse reactions;
• History of epilepsy or currently using anti-epileptic medication;

Other illness

• Patients with secondary hypertension;
• Patients who have undergone revascularization of the heart, brain, or kidney, or other aortic stenting procedures;
• Patients who have indicators for specific antihypertensive medications (e.g. β-blockers after acute myocardial infarction, RAS blockers for prevention of cardiovascular disease, α-blockers for treatment of benign prostate hyperplasia);

Lab values

• Patients undergoing dialysis or with stage 4-5 chronic kidney disease, or estimated glomerular filtration rate (eGFR) \<30 mL/min/1.73m²;

Other

• Symptomatic intracranial and extracranial artery stenosis (stenosis ≥50%), or asymptomatic intracranial and extracranial artery stenosis (stenosis≥70%);
• Any symptoms of orthostatic hypotension when measuring standing blood pressure, or if standing SBP \<110mmHg;
• Bilateral renal artery stenosis;
• Within the last three months, regular usage of vitamin supplements containing folic acid, B6, or B12, or usage of folic acid antagonists (e.g. methotrexate);
• Pregnant and lactating women, or women planning to become pregnant;
• Life expectancy less than four years;
• Within the last month, participation in another clinical trial;
• Any patient determined by the researchers to be unsuitable for the present study.

• Age 35-75 years;
• Meets any of the following criteria:
  • 1\) Lacunar infarction occurring within the period of seven days up to one year post-infarction, diagnosed by head MRI/CT (meeting modified Fisher criteria\*); 2）Head MRI indicating white matter hyperintensity, 4≥Fazekas score\*≥2; 3）Head MRI indicating white matter hyperintensity, Fazekas=1, combined with old subcortical vascular lacunar infarction;
• For modified Fisher criteria and Fazekas score, see FAITH main study appendix 1 and appendix 6).
  • 3\. Medical recorded history of hypertension. Systolic blood pressure SBP: 130-180 mm Hg on 0 or 1 medication SBP: 130-170 mm Hg on up to 2 medications SBP: 130-160 mm Hg on up to 3 medications. 4. mRS score ≤2; 5. Serum Hcy ≥10 µmol/L or MTHFR 677 TT genotype; 6. Signed informed consent form.