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:

* written informed consent to the study
* age \>= 55 years at randomization. There is no upper age limit
* systolic blood pressure \>= 150 mmHg in 2 visits at distance of 7-14 days, irrespective of diastolic pressure. Duration of treatment before visit 1 must be at least 12 weeks
* at least one additional risk factor including the following:
* current cigarette smoking
* total cholesterol \>= 20 mmg/dl, or High Density Lipoproteins (HDL) \< 40 mg/dl, or Low Density Lipoproteins (LDL) cholesterol \>= 130 mg/dl
* family history of cardiovascular disease in male first degree relative \< 55 years or female first degree relative \< 65 years
* previous TIA or stroke
* previous coronary artery disease
* history of peripheral occlusive arterial disease (claudication intermittens associated with angiographic or echographic evidence of \> 60% stenosis)

Exclusion Criteria:

* diabetes (fasting glucose \> 125 mg/dl in two samples or ongoing diabetic treatment)
* renal failure, defined by a serum creatinine \> 2.0 mg/dl
* chronic atrial fibrillation or flutter
* clinically significant hepatic or hematological disorders, alcoholism, drug addiction
* causes precluding ECG interpretation for LVH: complete right or left bundle block, Wolff-Parkinson-White syndrome, previous Q-wave myocardial infarction
* any disease causing reduced life expectancy
* unwilling to participate
* significant (more than traces of) valvular heart disease
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:

* 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
D: 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.

Answer: D