Please select the eligibility criteria that correspond to the clinical trial below.
Title: Effects of Intensive Systolic Blood Pressure Lowering Treatment in Reducing RIsk of Vascular evenTs (ESPRIT) Study
Brief Summary: This trial aims to assess, in patients aged ≥50 years with an average baseline SBP ≥130 mmHg and a previous history of cardiovascular diseases or at high vascular risk, the effects on the incidence of major cardiovascular events during the scheduled treatment period of greater reduction in blood pressure with a SBP target \<120 mmHg versus \<140 mmHg.


Options:
A: Inclusion Criteria:

* Diagnosed with type 2 diabetes mellitus, as determined by the new American Diabetes Association guidelines, which include a fasting plasma glucose level greater than 126 mg/dl (7.0 mmol/l), or a 2-hour postload value in the oral glucose tolerance test of greater than 200 mg/dl, with confirmation by a retest
* For participants aged 40 years or older, history of CVD (heart attack, stroke, history of coronary revascularization, history of peripheral or carotid revascularization, or demonstrated angina)
* For participants aged 55 years or older, a history of CVD is not required, but participant must be considered to be at high risk for experiencing a CVD event due to existing CVD, subclinical disease, or 2+ CVD risk factors
* HbA1c 7.5%-9% (if on more drugs) or 7.5%-11% (if on fewer drugs)
B: Inclusion Criteria:

1. At least ≥50 years old, and
2. Systolic blood pressure (SBP): (having documentation of SBP to meet the criteria below on 2 consecutive visits)

   * SBP: 130-180 mmHg on 0 or 1 medication
   * SBP: 130-170 mmHg on up to 2 medications
   * SBP: 130-160 mmHg on up to 3 medications
   * SBP: 130-150 mmHg on up to 4 medications, and
3. Prior vascular disease or at high vascular risk

   1. Previous myocardial infarction (MI), percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG), at least a 50% diameter stenosis of a coronary, chest pain with objective evidence of myocardial ischemia (load electrocardiogram or load image examination indicated myocardial ischemia)
   2. Previous stroke
   3. Carotid endarterectomy (CE), or carotid stenting
   4. Peripheral artery disease (PAD) with revascularization
   5. Abdominal aortic aneurysm (AAA) ≥5 cm with repair
   6. Combine with no less than two risk factors below

      * ≥60 years old male or ≥65 years old female
      * Diabetes
      * Dyslipidemia (total cholesterol \>200 mg/dL \[5.2 mmol/L\] or LDL-C \>130 mg/dL \[3.4 mmol/L\] or HDL-C \< 40 mg/dL \[1.0 mmol/L\])
      * Current smoking (smoke more than a cigarette every day in the past 12 months)

Exclusion Criteria:

1. Known secondary cause of hypertension
2. An indication for a specific BP lowering medication that the participant is not taking and the participant has not been documented to be intolerant of the medication class
3. One minute standing SBP \<110 mmHg (not applicable if unable to stand)
4. Arm circumference too large or small to allow accurate blood pressure measurement with available devices
5. Proteinuria defined as urine dipstick ≥2+ protein at screening
6. Glomerulonephritis treated with or likely to be treated with immunosuppressive therapy
7. eGFR \<45 ml/min /1.73m2 or end-stage renal disease (ESRD)
8. Previous MI, stroke, or hospitalization for angina, PCI, CABG, CE or carotid stenting, PAD with revascularization, AAA≥5 cm with repair within last 3 months
9. Symptomatic heart failure within the past 6 months or documented left ventricular ejection fraction (by any method) \<35%
10. PCI or CABG planned for the next 6 months
11. A medical condition likely to limit survival to less than 3 years, or a cancer (other than non-melanoma skin cancer) diagnosed and treated within the past two years that, in the judgment of local clinical investigators, would compromise a participant's ability to comply with the protocol and complete the trial
12. Any organ transplant
13. Pregnancy, breast-feeding, or of child-bearing potential and not using adequate contraception
14. Any factors judged by local clinic investigators to be likely to limit adherence to interventions. For example,

    1. Active alcohol or substance abuse within the last 12 months
    2. Plans to move to another place to live for a long time
    3. Clinical diagnosis of dementia or mild cognitive impairment (MCI)
15. Currently participation in a clinical trial with an unlicensed drug or device
16. Living in the same household as an already randomized participant
C: Inclusion Criteria:

Participants include those with essential hypertension and history of stroke who satisfy the following criteria:

* Outpatient
* Onset of stroke(cerebral infarction/cerebral hemorrhage) occurred between 30 days and 3 years prior to the date of consent.
* Drug adherence is ≧80% during the screening period.
* Mean of 2 baseline BP measurements(measured at outpatient clinic) within 30 days prior to the date of consent is either 180 \>SBP ≧130 mmHg or 110 \>DBP ≧80 mmHg (untreated -3 anti hypertensive agents patients).
* Cerebral infarction with severity 3 or less in the modified Rankin scale.

Exclusion Criteria:

Patient who meets any one of the following criteria is excluded from the study.

* Women who are pregnant, are possible pregnant, or are breastfeeding
* Possible secondary hypertension
* Severe hypertension (grade III or greater) with baseline SBP ≧180 mmHg or DBP ≧110 mmHg)
* Myocardial infarction or undergoing angioplasty occurred within 3 months prior to the screening.
* Current or previous heart failure with NYHA classification class III or more, or EF less than 35%
* Severe bilateral carotid stenosis or major cerebral artery occlusion
* Severe paralysis due to stroke (modified Rankin scale ≧ 4 )
* Current renal dysfunction (serum Cr ≧ 2.0 mg/dL right before the date of consent)
* Current hepatic dysfunction with AST or ALT value ≧ 100 IU/mL right before the date of consent
* Refractory hypertension treated with four or more antihypertensive drugs
* Hypersensitivity or allergy to losartan and other angiotensin II receptor blockers, hydrochlorothiazide, amlodipine or sulfonamide derivative
* Major surgery planned during the study period
* Participants of other clinical studies within the last 30 days
* Current malignancy (previous malignancy within 5 years after the end of treatment) excluding squamous-cell skin cancer
* Previous and current subarachnoid hemorrhage
* Definitive dementia 12) (based on a clinical diagnosis)
* Patients who have difficulty in signing consent or who do not agree to the provided consent
* Patients who are judged to be unsuitable for participating the study by the primary investigator or sub-investigator.
D: Inclusion Criteria:

* Qualifying event: stroke or TIA 1 to 6 months previous to randomization.
* All patients should have a CT scan or MRI (preferably MRI) at screening. The CT scan or MRI carried out at the time of the qualifying event, if available, is acceptable. Stroke will be defined as imaging evidence of a recent brain infarction (or haemorrhage) independently of duration of clinical symptoms, or as duration of clinical symptoms \> 24 h even in absence of imaging evidence of lesion
* TIA as clinical symptoms (involving limbs or speech) lasting \< 24 h without imaging evidence of infarction. Enrolling units should avoid enrolling patients with TIA in a proportion greater than 25% of enrolled patients. The general coordinators in Milan and Beijing may decide stopping enrolment of TIA patients if their proportion is becoming greater than expected.
* A haemorrhagic stroke (1 to 6 months previously) is also a qualifying event, but only for the BP-lowering component of the trial (see Exclusion criteria).
* Age: 65 years and above. No fixed upper age limit is introduced, but frail patients aged above 80 years should not be enrolled.
* Gender: either gender.
* BP: Only hypertensive patients: untreated patients with SBP ≥140 mmHg; patients on antihypertensive treatment with any BP (but see exclusion criteria)
* LDL-C: Patients without statin treatment with LDL-C \> 2.8 mmol/l; patients on statin treatment with any LDL-C value (but see exclusion criteria)
* Antiplatelet therapy: All patients should be under antiplatelet therapy (agents and doses chosen by the investigator according to accepted guidelines), unless contraindicated. Anticoagulant (instead of antiplatelet) therapy whenever indicated (e.g. atrial fibrillation).

Exclusion Criteria:

* Qualifying event:

  1. Patients in unstable clinical conditions
  2. Clinical disturbances caused by non-stroke pathology
  3. patients with haemodynamically significant carotid stenosis or requiring carotid revascularization
  4. haemorrhagic stroke is an exclusion criterion for the lipid lowering component of the trial; however, these patients should be randomized to the BP component, but considered in addition to the number of patients requested to each enrolling unit, in order not to decrease the power of the lipid-lowering component.
* BP: - known secondary hypertension;
* SBP \>140 mmHg under three antihypertensive drugs at full doses (these patients are unlikely to achieve SBP \< 125 mmHg, if so randomized);
* orthostatic hypotension (SBP fall \> 25 mmHg on standing);
* LDL-C: - LDL-C \>2.8 mmol/l under full dose of a statin (these patients are unlikely to achieve LDL-C targets).
* LDL-C \> 4.5 mmol/l under low dose of a statin or untreated (these patients are unlikely to achieve the lower LDL-C target).
* Others: - Patients with a myocardial infarction (preceding or subsequent to the qualifying stroke or TIA) if their baseline LDL-C is \< 1.8 mmol/l
* Dementia
* Severe disability (modified Rankin scale \> 4)
* Severe chronic renal failure defined as serum creatinine \> 250 micromol/l
* Hepatic disease as determined by either AST or ALT values \> 2 times the upper limit of normal
* History of hepatic encephalopathy, esophageal varices or portocaval shunt
* History of gastrointestinal surgery or disorders which could interfere with drug absorption
* Known allergy or contraindications to one of the drugs to be administered in the study
* History of malignancy including leukaemia and lymphoma (but not basal cell skin cancer) within the last 5 years
* History of clinically significant autoimmune disorders such as systemic lupus erythematosus
* History of drug or alcohol abuse within the last 5 years
* History of non-compliance to medical regimens and/or patients who are considered potentially unreliable
* Inability or unwillingness to give free informed consent

Answer: B