Please select the eligibility criteria that correspond to the clinical trial below.
Title: Stop Atherosclerosis in Native Diabetics Study
Brief Summary: Compared to standard treatment goals achieving lower targets for LDL cholesterol (bad cholesterol) and blood pressure in people with diabetes will slow the progression of atherosclerosis as measured by carotid artery thickness, and reduce clinical cardiovascular events such as heart attacks and strokes. This study is a randomized 3-year trial. The primary endpoint will be a combination of various measures of the carotid artery, (which is an easy, non-invasive way to detect cardiovascular disease) and events such as heart attacks and strokes. The study will also look at secondary endpoints such as how well the heart pumps, fat,protein and inflammatory markers in the blood,and kidney function. The study enrolled 549 American Indian men and women with diabetes, \> 40 years of age and is being conducted in four field centers involving Indian Health Service/Tribal primary care facilities in Phoenix/Sacaton, Arizona; Chinle, Arizona; Rapid City/Pine Ridge, South Dakota; and Lawton, Oklahoma, with input from American Indian physicians and community members.


Options:
A: Inclusion Criteria:

1. American Indian men and women 40 years of age or older
2. Type 2 DM (according to 1997 ADA criteria and/or previously diagnosed by former ADA or WHO criteria): fasting plasma glucose \>= 7.0 mmol/L (126 mg/dL) or 2-hour glucose \>= 11.0 mmol/L (\>200 mg/dL) after a 75-gram oral glucose tolerance test.
3. LDL cholesterol \>= 100 mg/dL. within the previous 12 months.
4. Systolic BP \>= 130 mm Hg. within the previous 12 months.

Exclusion Criteria:

1. New York Heart Association Stage III- IV congestive heart failure.
2. SBP \>180 mmHg (2% of population) or patients with known causes of hypertension.
3. History of angioedema.
4. Any medical condition that study physicians believe would interfere with study participation or evaluation of results.
5. Mental incapacity and/or cognitive impairment on the part of the patient that would preclude adequate understanding of, or cooperation with, the study protocol.
6. Serum hepatic transaminase levels 2X the upper limit of normal.
7. Participation in any clinical trial of any investigational medication within 3 months prior to this trial.
8. Renal insufficiency as indicated by serum creatinine \>2.0 for women and \>2.4 for men.
9. Diagnosis of primary hyperlipidemia in medical record.
10. Secondary hypercholesterolemia due to hypothyroidism or nephrotic syndrome. Patients on stable doses of thyroid replacement therapy will be eligible.
11. Presence of malignancy or history of any cancer except skin cancer within the past 5 years.
12. Pregnancy or lactation. Premenopausal women will be requested to use birth control methods throughout the study and provided educational materials about the risks of using the study medications during pregnancy.
13. Unable to obtain quantifiable carotid measure during screening examination.
14. Concomitant long term use of cyclosporins (Sandimmune), macrolide antibiotics (erythromycin -many generic and brand name forms, clarithromycin, Biaxin, and Zithromax), azole antifungals (itraconazole-Sporanox, ritonavir, Norvir, and nelfinavir (Viracept).
15. Orthostatic hypotension as defined by the following:

    1. The individual has a measured fall of \>20 mmHg in systolic BP upon standing associated with symptoms lasting more than one minute (or severe symptoms that would not allow further lowering of BP)
    2. The standing systolic blood pressure is less than 90 mm.
16. Triglyceride level \>350 mg/dl.
17. Severe aortic stenosis with valve area \<=1.0 square cm.
B: 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
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:

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

Answer: A