Please select the eligibility criteria that correspond to the clinical trial below.
Title: Large-Scale Randomized Clinical Trial Assessing Intensive Blood Pressure Control for Reduction of Major Cardiovascular Events in Patients With Diabetes Mellitus (OPTIMAL-DIABETES)
Brief Summary: High blood pressure (BP) is a major public health concern, especially in low and middle income countries. High BP is a highly prevalent condition, and it is usually associated with diabetes mellitus. Both high BP and diabetes are risk factors for major cardiovascular events including cardiovascular death, acute myocardial infarction, stroke, unstable angina and heart failure. In addition, high BP is also related to cognitive decline. The OPTIMAL-DIABETES trial consists of a two-arm, multicenter, randomized clinical trial designed to test whether a lower systolic blood pressure (SBP) target will reduce the occurrence of major cardiovascular events in diabetic patients compared to the standard SBP target.


Options:
A: Inclusion Criteria:

* History of ischemic stroke or transient ischemic attack (TIA), considered clinically stable in the 48 hours prior to inclusion in the study. (they will be classified into a recent stroke \<120 days or chronic when\> 120 days), AND
* Systolic Blood Pressure (SBP) between 130 and 180 mmHg:

  * 130 -180 and use of up to one antihypertensive drug;
  * 130-170 and use of up to two drugs;
  * 130-160 and use of up to three drugs;
  * 130-150 and use of up to four drugs. AND

Exclusion Criteria:

* Severe disability after the event that qualified the patient for the study, defined as a modified Rankin (mRankin) scale equal to or greater than 4.
* Being part of another clinical trial involving interventions for cardiovascular prevention.
* Body mass index \> 45 kg/m2.
* Pregnancy or Breastfeeding.
* Secondary hypertension.
* Class IV Canadian Cardiovascular Society (CCS) Resting Angina.
* Acute coronary syndrome in the last six months
* Severe renal dysfunction with GFR \< 20 mL/min/1.73m2 calculated by the CKD-EPI equation
* Refusal to consent.
* Symptomatic heart failure - Class IV New York Heart Association (NYHA) or ejection fraction \<35% on Doppler echocardiography.
* Conditions that, at the investigators' discretion, limit the patient's participation in the study, including but not limited to the following:

  * Recent history of alcohol and illicit drug abuse.
  * Psychiatric comorbidities (severe depression, schizophrenia, psychosis, etc.).
  * History of poor drug adherence and no attendance at consultations.
  * Planning to change of address in the next four years.
  * Planning to be absent from home city for more than three months in the next year.
  * Residing in the same residence of another patient previously included in this study.
B: 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
C: Inclusion Criteria:

* Men and women aged ≥40 years
* A history of symptomatic, MRI/CT-confirmed ischemic stroke (3-12 months since last acute onset)
* Systolic BP ≥140 mmHg on 0 medication; 135-180 mmHg on 1 medication; 135-170 mmHg on up to 2 medications; 135-160 mmHg on up to 3 medications; or 135-150 mmHg on up to 4 medications

Exclusion Criteria:

* Documented symptomatic intracranial and/or extracranial stenosis (≥50%), or asymptomatic intracranial and/or extracranial stenosis (≥70%)
* Disabling stroke (modified Rankin score of ≥4)
* Previous intracranial hemorrhage from a non-traumatic cause
* Any symptoms of orthostatic hypotension during the standing BP measurement, or standing systolic BP \<110 mmHg
* Severe heart failure (NY Heart Association class III and IV) within the past six months or left ventricular ejection fraction (by any method) \<35%
* Any history of atrial fibrillation, ventricular aneurysm, or suspicion of cardioembolic pathology for stroke
* Other specific cause of stroke identified by routine clinical care (e.g., arteritis, dissection, migraine/vasospasm, drug abuse)
* Dialysis, eGFR \<20 ml/min/1.73 m2, urine protein-to-creatinine ratio ≥1 g/g, or albumin-to-creatinine ratio ≥ 600 mg/g
* Planned or probable revascularization (any angioplasty or vascular surgery) within three months after screening
* A medical condition likely to limit survival to less than three years
* A cancer diagnosed and treated within the past two years that, in the judgment of clinical study staff, would compromise a participant's ability to comply with the protocol and complete the trial (except non-melanoma skin cancer, early-stage prostate cancer, or localized breast cancer)
* Any factors judged by the clinic team to be likely to limit adherence to the intervention
* Failure to obtain informed consent from a participant
* Currently participating in another intervention study
* Pregnant, currently trying to become pregnant, or of child-bearing potential and not using birth control
D: 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

Answer: B