Please select the eligibility criteria that correspond to the clinical trial below.
Title: Systolic Blood Pressure Intervention Trial
Brief Summary: Elevated blood pressure (BP) is an important public health concern. It is highly prevalent, the prevalence may be increasing, and it is a risk factor for several adverse health outcomes, especially coronary heart disease, stroke, heart failure, chronic kidney disease, and decline in cognitive function. The Systolic Blood Pressure Intervention Trial (SPRINT) is a 2-arm, multicenter, randomized clinical trial designed to test whether a treatment program aimed at reducing systolic blood pressure (SBP) to a lower goal than currently recommended will reduce cardiovascular disease (CVD) risk.


Options:
A: 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
B: Inclusion Criteria:

* 75 years of age or older
* Seated clinic systolic BP \>150 mmHg in the untreated state (see criterion D)
* At risk for cerebrovascular disease (history of smoking, dyslipidemia, type 2 diabetes, longstanding hypertension, family history). Patients must have visible (0.5% WMH or more)white-matter hypertensity lesions on screening magnetic resonance imaging
* To achieve success in maintaining a 24-hour systolic BP of \<140-145 mmHg in the standard treatment group or a systolic BP \<125-130 mmHg in the intensive treatment group, patients will be eligible for inclusion if (1) their clinic systolic BP is 150-170 mmHg, and they are taking 0 to 2 antihypertensives, (2) their systolic BP is \>170 mmHg and they are taking 0 to 1 antihypertensives

Exclusion Criteria:

* Uncontrolled diabetes mellitus (HBA1c \>10%)
* History of stroke, dementia or clinically impaired gait (Mini-mental status exam score (MMSE) \<24, Short Physical Performance Battery for gait (SPPB) \< 9,)
* Body Mass Index \> 45 kg/m2 and/or arm circumference \> 44 cm)
* Poor kidney function (defined as estimated GFR \<30 ml/minute)
* Active liver disease or serum transaminases \>3 times the upper limit of normal
* Major cardiovascular event (e.g. myocardial infarction) or procedure (e.g. cardiac bypass surgery) in past 3 months; stroke with residual gait abnormality
* Uncompensated congestive heart failure (NYHA class III or IV or documented ejection fraction \<30%)
* Chronic atrial fibrillation that disallows ambulatory BP monitoring to be successfully performed
* Medical conditions that limit survival to \< 3 years
* Non-dermatologic cancer diagnosed within 2 years
* Organ transplantation requiring anti-rejection drug therapy
* Severe and unexplained weight loss (\>15%) in past 6 months
* Medical need to undergo recurrent phlebotomy or blood transfusions
* Current participation in another investigational trial
* Unable to obtain informed consent
* Factors limiting adherence to the interventions
* MRI contraindications (including MRI-incompatible implants, severe claustrophobia).
C: Inclusion Criteria:

* At least 50 years old

Systolic blood pressure of

* 130 - 180 mm Hg on 0 or 1 medication
* 130 - 170 mm Hg on up to 2 medications
* 130 - 160 mm Hg on up to 3 medications
* 130 - 150 mm Hg on up to 4 medications

Risk (one or more of the following)

1. Presence of clinical or subclinical cardiovascular disease other than stroke
2. CKD, defined as eGFR 20 - 59 ml/min/1.73m2
3. A Framingham Risk Score for 10-year CVD risk ≥ 15%
4. Age greater than 75 years

Exclusion Criteria:

* An indication for a specific BP lowering medication that the person is not taking and the person has not been documented to be intolerant of the medication class.
* Known secondary cause of hypertension that causes concern regarding safety of the protocol.
* One minute standing SBP \< 110 mm Hg.
* Proteinuria in the following ranges (based on a measurement within the past 6 months)

  * 24 hour urinary protein excretion ≥1 g/day, or
  * 24 hour urinary albumin excretion ≥ 600 mg/day, or
  * spot urine protein/creatinine ratio ≥ 1 g/g creatinine, or
  * spot urine albumin/creatinine ratio ≥ 600 mg/g creatinine, or
  * urine dipstick ≥ 2+ protein
* Arm circumference too large or small to allow accurate blood pressure measurement with available devices
* Diabetes mellitus,
* History of stroke (not CE or stenting)
* Diagnosis of polycystic kidney disease
* Glomerulonephritis treated with or likely to be treated with immunosuppressive therapy
* eGFR \< 20 ml/min /1.73m2 or end-stage renal disease (ESRD)
* Cardiovascular event or procedure (as defined above as clinical CVD for study entry) or hospitalization for unstable angina within last 3 months
* Symptomatic heart failure within the past 6 months or left ventricular ejection fraction (by any method) \< 35%
* A medical condition likely to limit survival to less than 3 years or a malignancy other than non-melanoma skin cancer within the last 2 years
* Any factors judged by the clinic team to be likely to limit adherence to interventions.
* Failure to obtain informed consent from participant
* Currently participating in another clinical trial (intervention study). Note: Patient must wait until the completion of his/her activities or the completion of the other trial before being screened for SPRINT.
* Living in the same household as an already randomized SPRINT participant
* Any organ transplant
* Unintentional weight loss \> 10% in last 6 months
* Pregnancy, currently trying to become pregnant, or of child-bearing potential and not using birth control.
D: 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.

Answer: C