Please select the eligibility criteria that correspond to the clinical trial below.
Title: Italian Study on the Cardiovascular Effects of Systolic Blood Pressure Control - CARDIOSIS Study
Brief Summary: Multicenter, prospective, randomised, open study comparing the effect of the following two strategies in hypertensive subjects \> 55 years and poorly controlled (systolic blood pressure \>= 150 mmHg) by antihypertensive treatment:

* usual strategy: reduction of systolic blood pressure to below 140 mmHg, independently of diastolic blood pressure levels;
* intensive strategy: reduction of systolic blood pressure to below 130 mmHg, independently of diastolic blood pressure levels.

During the initial run in period two qualifying visits at distance of 7-14 days will be carried out to establish whether blood pressure remains uncontrolled (systolic blood pressure \>=150 mmHg)by current drug treatment. At the end of the second visit eligible patients will be admitted to the study and the following examinations will be carried out: clinical visit, routine laboratory tests, 12-lead ECG. At this point eligible patients will be randomised to one of the two blood pressure goals outlined above.

Subsequent clinical visits will be carried out at 4 month-intervals up to the end of the study (4, 8, 12, 16, 20, 24 months).


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:

* acute symptomatic ischemic stroke having relevant lesion on DWI(Diffusion weighted image) MRI 7 days after and 42 days within onset.
* relevant stenosis(more than 50%) or occlusion from MCA(middle cerebral artery)(M1) to distal of ICA(internal carotid artery ) on MR(Magnetic resonance) angiogram or CT angiogram.
* mean systolic blood pressure\>=140mmHg or taking antihypertensive drug on screening.

Exclusion Criteria:

* taking more than 3 antihypertensive drugs and mean systolic blood pressure\>=150mmHg on screening.
* history of recent thrombolysis but stenosis or occlusion remained after thrombolysis.
* evidence of orthostatic hypotension
* suspicious embolic cerebrovascular stenosis
* planned state of cerebrovascular surgery or angioplasty or stent 7 months within screening.
* severe stroke-NIHSS\>=16
* mean systolic blood pressure\>=200mmHg which is not able to control on screening.
* abnormal blood test finding (abnormal LFT(liver function test), anemia, renal insufficiency)
* pregnant or breast-feeding
* severe stroke sequela or medical problem
* suspicious secondary hypertension
* disease causing edema or significant ankle edema on screening.
* severe heart failure which correspond to NYHA (New York Heart Association )heart failure classification class III or IV.
* inappropriate condition determined by investigator
* Patient who do not have FLAIR image on or two months prior to screening.
C: 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
D: 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

Answer: A