Please select the eligibility criteria that correspond to the clinical trial below.
Title: European Society of Hypertension and Chinese Hypertension League Stroke in Hypertension Optimal Treatment Trial
Brief Summary: Stroke is one of the major causes not only of mortality, but of disease burden worldwide, because of residual disability and cognitive decline. Although blood pressure lowering has been clearly shown to be the most effective means for primary and secondary prevention of stroke, the systolic blood pressure (SBP) levels to achieve by treatment in order to optimize prevention results are unknown, and whether SBP levels lower than those usually recommended are accompanied by further or reduced benefits is undecided yet. Likewise, while low-density lipoprotein cholesterol (LDL-C) lowering by statins has been shown to be associated with primary and secondary stroke prevention, whether more intense lowering is or is not of further benefit is unknown. The Stroke in Hypertension Optimal Treatment Trial (ESH-CHL-SHOT) is a factorial 3 x 2 arm, multicenter, randomized clinical trial designed to test the hypothesis that in elderly patients at high risk of recurrent stroke (previous recent stroke or TIA) antihypertensive treatment programs aimed at reducing SBP to the usually recommended values (\< 145 to 135 mmHg), to a lower goal (\< 135 to 125 mmHg) or to even lower values (\< 125 mmHg) will result in progressively greater reductions in recurrent stroke, incidence of cardiovascular outcomes and cognitive decline. Parallely, the preventive efficacy of more and less intense LDL-C reductions will be tested on the same outcomes.


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:

* 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.
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:

* Male or female
* Age 50 to no upper limit
* Hypertension documented according to the 6th report of the Joint National Committee on Detection and Evaluation of the treatment of high BP (JNC VI) and the need for drug therapy (previously documented hypertension in patients currently taking antihypertensive agents is acceptable)
* Documented CAD (e.g., classic angina pectoris (stable angina pectoris; Heberden angina pectoris), myocardial infarction three or more months ago, abnormal coronary angiography, or concordant abnormalities on two different types of stress tests)
* Willingness to sign informed consent

Exclusion Criteria:

* Unstable angina, angioplasty, coronary artery bypass graft surgery (CABG) or stroke within one month. Patients taking beta blockers after myocardial infarction are excluded if study enrollment is planned within 12 months of myocardial infarction. No time limitation if not taking beta-blocker.
* Use of a ß-blocker within past two weeks
* Patients without a pacemaker and any of the following:

  * Sinus bradycardia (\< 50 beats/min.)
  * Sick sinus syndrome
  * Atrioventricular (AV)-block of more than 1st degree
* Documented contraindication to verapamil; documented contraindication to both atenolol and hydrochlorothiazide
* Atrial fibrillation/flutter with Wolff-Parkinson-White (WPW)-Syndrome
* Severe heart failure (New York Heart Association \[NYHA\] IV).
* Concomitant illnesses (e.g., severe renal failure \[Serum creatinine ≥4.0 mg/dl\], severe hepatic failure or known cirrhosis, etc.) which may affect outcome variables or where life expectancy is two years or less or which are likely to require frequent hospitalizations and/or treatment adjustments.
* Patients with psychiatric, cognitive, or social (e.g., alcoholism, etc.) conditions that would interfere with giving consent or cooperating or remaining available for follow-up for two years.

Answer: A