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:

1. Male or female aged ≥ 19 years and \< 80 years
2. Diagnosis of mild-moderate AS or mild-moderate AR
3. Applicable to 2.0\~3.9 m/s of aortic jet velocity for mild-moderate AS or to 0.2\~0.6 cm of Vena contracta for mild-moderate AR
4. Diagnosis of hypertension (SBP \> 130 mmHg if being treated or SBP \> 140 mmHg if being untreated)
5. For females of childbearing potential; negative pregnancy test results during the screening period and prior to administration of the investigational product, and agreement on use of medically allowable contraceptive measures (condom, oral contraceptive pills, injectable or implantable contraceptives, intrauterine devices, birth control patches, etc.) during the study period
6. Voluntary written consent to taking part in the clinical study and willingness to comply with requirements of the study

Exclusion Criteria:

1. History of a cardiac valve replacement surgery (replacement surgery of mitral valve, aortic valve or tricuspid valve)
2. Accompanied by severe mitral regurgitation
3. Admitted to needing a surgery by the current treatment guidelines
4. Accompanied by symptoms such as angina pectoris, exertional dyspnea, syncope, etc.
5. \< 50% of left ventricular ejection fraction
6. History of hypersensitivity reaction to active ingredients of the investigational product (Amlodipine, Losartan and Chlorthalidone), dihydropyridine derivatives, thiazide drugs and other sulfonamide derivatives or their compositions
7. Pregnant or breastfeeding
8. Symptomatic orthostatic hypotension
9. Severe liver failure or renal failure (\< 30 mL/min of creatinine clearance)
10. Hereditary angioedema or history of angioedema at treatment with ACE inhibitors or angiotensin II receptor blockers
11. Primary hyperaldosteronism
12. Genetic problems such as galactose intolerance, Lapp Lapp lactase deficiency or glucose-galactose malabsorption
13. Anuria
14. Refractory hypokalemia
15. Hyponatremia or hypercalcemia
16. Symptomatic hyperuricemia (history of gout or uric acid lithiasis)
17. Untreated Addison's disease
18. Appropriately uncontrolled diabetes
19. Congenital or incurable hypertension
20. Diagnosis of severe cerebrovascular disorders (stroke, cerebral infarction, cerebral hemorrhage, etc.) within six months prior to the date of ICF obtainment
21. Wasting disease, autoimmune disease or connective tissue disease
22. Diagnosis of malignant tumor within five years prior to the date of ICF obtainment
23. Administration of another investigational product within four weeks prior to the date of ICF obtainment
24. For a patient who is taking anticoagulants and thrombolytic agents; considered difficult to keep a stable dosage/regimen by the investigator.
25. Considered unsuitable to be a subject by the investigator
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:

* 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).
D: Inclusion Criteria:

* Systolic Blood Pressure (SBP) between 130 and 180 mm Hg:

  * 130 to 150 mm Hg (if on 0-4 medications)
  * 130 to 160 mm Hg (if on 0-3 medications)
  * 130 to 170 mm Hg (if on 0-2 medications)
  * 130 to 180 mm Hg (if on 0-1 medications)
* Type 2 diabetes
* To be considered as having a high cardiovascular risk, including AT LEAST ONE of the following factors:

  1. Established cardiovascular disease (CVD), including:

     * Coronary artery disease: previous myocardial infarction, previous acute coronary syndrome, previous percutaneous coronary intervention, previous coronary artery bypass graft surgery, or at least 50% stenosis in a main coronary artery associated with typical angina pectoris; or
     * Cerebrovascular disease: previous stroke (except those events caused by intracranial aneurysm or arteriovenous malformation) or previous transient ischemic attack (TIA), stable for at least 2 weeks preceding inclusion in the study; or
     * Carotid artery disease: previous carotid endarterectomy, previous percutaneous intervention with carotid stent implantation, or stenosis of at least 50% in a carotid shown by the Doppler ultrasonography, CT angiography or MR angiography; or
     * Peripheral artery disease: prior surgical or percutaneous revascularization of a peripheral artery, limb amputation due to vascular cause, abdominal aortic aneurysm ≥ 5 cm (with or without prior surgical or percutaneous repair), or stenosis of at least 50% in a peripheral artery associated to intermittent claudication.
  2. Subclinical CVD, including:

     * Coronary calcium score ≥ 300 Agatston units; or
     * Ankle-brachial index ≤ 0.90 in the last two years; or
     * Left ventricular hypertrophy on the electrocardiogram, echocardiogram or other cardiac imaging exam in the last two years.
  3. Chronic kidney disease (CKD):

     ▪ Definition of CKD: glomerular filtration rate (GFR) between 20 and 59 ml/min/1.73m2 calculated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI).
  4. Additional cardiovascular risk factors, including:

     * Active smoking: Defined as regular use of cigarettes or other tobacco products, such as cigars and pipe, in the last six months;
     * Dyslipidemia: Defined as LDL cholesterol \> 70 mg/dL or non-HDL cholesterol \> 100 mg/dL in patients with previous CVD; or LDL cholesterol \> 100 mg/dL or non-HDL cholesterol \> 130 mg/dL in patients without previous CVD; or Triglycerides \> 200 mg/dL or HDL \< 40 mg/dL regardless of treatment; or use of statins or other lipid lowering medication; or
     * Age ≥ 75 years

Exclusion Criteria:

* Refusal to provide written informed consent
* Body mass index \> 45 kg/m2
* Known secondary cause of hypertension
* Severe renal dysfunction with GFR \< 20 mL/min/1.73m2 calculated by the CKD-EPI equation
* Angina at rest Class IV Canadian Cardiovascular Society (CCS)
* Acute coronary syndrome in the last six months
* Symptomatic heart failure Class IV New York Heart Association (NYHA) or ejection fraction \< 35% on Doppler echocardiography in the last six months
* Factors that at the research team´s judgment may limit adherence to the intervention and study protocol, including, but not limited to, the following examples:

  * Recent history of alcohol and illicit drug abuse
  * Psychiatric comorbidities (severe depression, schizophrenia, psychosis, etc.)
  * History of poor medication adherence and attendance to consultations
  * Any plans to move the city of residence in the next four years
  * Any plans to leave the city of residence for more than three months in the next few years
  * Living in the same residence of another patient previously included in this study
* Patients currently enrolled in another study for CVD prevention, including those evaluating pharmacological and non-pharmacological interventions
* Pregnancy or breastfeeding

Answer: B