The Association of Hypertensive Disorders of Pregnancy with Infant Mortality, Preterm Delivery, and Small for Gestational Age.

Gestational hypertension, preeclampsia, eclampsia, and chronic hypertension (CHTN) are associated with adverse infant outcomes and disproportionately affect minoritized race/ethnicity groups. We evaluated the relationships between hypertensive disorders of pregnancy (HDP) and/or CHTN with infant mortality, preterm delivery (PTD), and small for gestational age (SGA) in a statewide cohort with a diverse racial/ethnic population. All live, singleton deliveries in South Carolina (2004-2016) to mothers aged 12-49 were evaluated for adverse outcomes: infant mortality, PTD (20 to less than <37 weeks) and SGA (<10th birthweight-for-gestational-age percentile). Logistic regression models adjusted for sociodemographic, behavioral, and clinical characteristics. In 666,905 deliveries, mothers had superimposed preeclampsia (HDP + CHTN; 1.0%), HDP alone (8.0%), CHTN alone (1.8%), or no hypertension (89.1%). Infant mortality risk was significantly higher in deliveries to women with superimposed preeclampsia, HDP, and CHTN compared with no hypertension (relative risk [RR] = 1.79, 1.39, and 1.48, respectively). After accounting for differing risk by race/ethnicity, deliveries to women with HDP and/or CHTN were more likely to result in PTD (RRs ranged from 3.14 to 5.25) or SGA (RRs ranged from 1.67 to 3.64). As CHTN, HDP and superimposed preeclampsia confer higher risk of adverse outcomes, prevention efforts should involve encouraging and supporting mothers in mitigating modifiable cardiovascular risk factors.

Pathology-based brain arterial disease phenotypes and their radiographic correlates.

INTRODUCTION: Brain arterial diseases, including atherosclerosis, vasculitis, and dissections, are major contributors to cerebrovascular morbidity and mortality worldwide. These diseases not only increase the risk of stroke but also play a significant role in neurodegeneration and dementia. Clear and unambiguous terminology and classification of brain arterial disease phenotypes is crucial for research and clinical practice. MATERIAL AND METHODS: This review aims to summarize and harmonize the terminology used for brain large and small arterial phenotypes based on pathology studies and relate them to imaging phenotypes used in medical research and clinical practice. CONCLUSIONS AND RESULTS: Arteriosclerosis refers to hardening of the arteries but does not specify the underlying etiology. Specific terms such as atherosclerosis, calcification, or non-atherosclerotic fibroplasia are preferred. Atherosclerosis is defined pathologically by an atheroma. Other brain arterial pathologies occur and should be distinguished from atherosclerosis given therapeutic implications. On brain imaging, intracranial arterial luminal stenosis is usually attributed to atherosclerosis in the presence of atherosclerotic risk factors but advanced high-resolution arterial wall imaging has the potential to more accurately identify the underlying pathology. Regarding small vessel disease, arteriosclerosis is ambiguous and arteriolosclerosis is often used to denote the involvement of arterioles rather than arteries. Lipohyalinosis is sometimes used synonymously with arteriolosclerosis, but less accurately describes this common small vessel thickening which uncommonly shows lipid. Specific measures of small vessel wall thickness, the relationship to the lumen as well as changes in the layer composition might convey objective, measurable data regarding the status of brain small vessels.

Optimal Medical Management of Atherosclerotic Intracranial Stenosis.

Reducing the high risk of recurrent stroke in patients with symptomatic intracranial atherosclerotic stenosis (sICAS) has proven to be challenging, but aggressive medical management, with intensive risk factor control and antithrombotic therapy, has been shown to be beneficial. High-intensity statins are recommended for patients with atherosclerotic stroke, including sICAS. Ezetimibe and PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitors are beneficial for those who fail to reach low-density lipoprotein targets or those with statin intolerance. The treatment target for sICAS is low-density lipoprotein <70 mg/dL. In neurologically stable patients, blood pressure should be treated to goal <140/90 mm Hg with the use of thiazide diuretics, angiotensin-converting enzyme inhibitors, or angiotensin II receptor blockers preferentially. For those with diabetes, treat to goal hemoglobin A1C ≤7% for most patients through combination of diet, insulin, and hypoglycemic drugs. Some degree of physical activity (eg, walking, stationary biking with arms or legs, etc) should be encouraged in all patients with sICAS who are not severely disabled. A minimum of 10 minutes of moderate-intensity aerobic activity 4 times a week is recommended for patients who are capable of exercise. For all patients with severe sICAS (70%-99% stenosis), dual antiplatelet therapy for up to 90 days followed by single antiplatelet agent is recommended.

Hypertensive Disorders of Pregnancy and Pre-Pregnancy Hypertension with Subsequent Incident Venous Thromboembolic Events.

Hypertensive disorders of pregnancy (HDP) and pre-pregnancy hypertension contribute to maternal morbidity and mortality. We examined the association of HDP and pre-pregnancy hypertension with subsequent venous thromboembolic (VTE) events. The retrospective cohort study included 444,859 women with ≥1 live, singleton birth in South Carolina (2004-2016). Hospital and emergency department visit and death certificate data defined incident VTE, HDP, and pre-pregnancy hypertension. Birth certificate data also defined the exposures. Adjusted Cox proportional hazards methods modeled VTE events risk. Of the cohort, 2.6% of women had pre-pregnancy hypertension, 5.8% had HDP, 2.8% had both pre-pregnancy hypertension and HDP (both conditions), and 88.8% had neither condition. The risk of incident VTE events within one year of delivery was higher in women with HDP (hazard ratio [HR] = 1.62, 95% confidence interval [CI]: 1.15-2.29) and both conditions (HR = 2.32, 95% CI: 1.60-3.35) compared to those with neither condition as was the risk within five years for women with HDP (HR = 1.35, 95% CI: 1.13-1.60) and for women with both conditions (HR = 1.82, 95% CI: 1.50-2.20). One- and five-year risks did not differ in women with pre-pregnancy hypertension compared to women with neither condition. Compared to non-Hispanic White (NHW) women with neither condition, the incident VTE event risk was elevated within five years of delivery for NHW (HR = 1.29, 95% CI: 1.02-1.63; HR = 1.59, 95% CI: 1.16-2.17) and non-Hispanic Black (NHB; HR = 1.51, 95% CI: 1.16-2.96; HR = 2.08, 95% CI: 1.62-2.66) women with HDP and with both conditions, respectively, and for NHB women with pre-pregnancy hypertension (HR = 1.50, 95% CI: 1.09-2.07). VTE event risk was highest in women with HDP, and the event rates were higher in NHB women than in NHW women in the same exposure group.

Preparing clinicians to be site investigators in multicenter clinical trials: A training program at an academic medical center.

Clinical trials are essential in the translation of biomedical discoveries to new clinical interventions and therapeutics. Successful multisite clinical trials require qualified site investigators with an understanding of the full spectrum of processes and requirements from trial identification through closeout. New site investigators may be deterred by competing demands on their time, the complexity of administrative and regulatory processes for trial initiation and conduct, and limited access to experienced mentor networks. We established a Clinical Trialist Training Program (CTTP) and complimentary Clinical Trials Bootcamp at our institution to address these barriers and increase the number of local site investigators enabled to lead successful clinical trials. An initial cohort of four CTTP scholars received salary support with protected time, didactic training, assistance with study identification and start-up navigation, and quarterly progress meetings. By the end of the 12-month program, this initial cohort identified 33 new trials, utilized feasibility assessments, and reported being on target to sustain their protected time from new clinical trials. Bootcamp attendees demonstrated increased knowledge of resources, offices, and processes associated with clinical trial conduct. Our results support providing compensated protected time, training, and access to experienced clinical research professionals to enable clinicians to become successful site investigators.

Ameliorating Racial Disparities in Vascular Risk Factor Management With Aggressive Medical Management in the SAMMPRIS Trial.

BACKGROUND: The WASID trial (Warfarin-Aspirin Symptomatic Intracranial Disease) and the SAMMPRIS trial (Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis) evaluated optimal management of symptomatic intracranial atherosclerotic stenosis. The aim of this retrospective, observational study was to determine whether aggressive medical management used in the SAMMPRIS trial ameliorated disparities in risk factor control between Black and non-Black patients. METHODS: The SAMMPRIS trial was a randomized controlled trial that enrolled patients with symptomatic intracranial atherosclerotic stenosis between November 2008 and April 2011. The frequency of risk factors at study entry (baseline) and mean levels of systolic blood pressure, diastolic blood pressure, LDL (low-density lipoprotein), hemoglobin A1c, and exercise level (quantified by physician-based assessment and counseling for exercise score) at baseline and at 1 year of follow-up were compared between Black (n=104) versus non-Black patients (n=347). RESULTS: Significant differences at baseline in Black patients (listed first) versus non-Black patients were age (57.5 versus 61.0 years; P=0.004), hypertension (95.2% versus 87.5%; P=0.027), diabetes (52.9% versus 39.7%; P=0.017), mean diastolic blood pressure (82.4 versus 79.5 mm Hg; P=0.035), and mean physician-based assessment and counseling for exercise score (2.7 versus 3.3; P=0.002). The mean diastolic blood pressure and mean physician-based assessment and counseling for exercise scores at 1 year in Black versus non-Black patients were 74.7 versus 75.5 mm Hg (P=0.575) and 4.2 versus 4.1 (P=0.593), respectively. No disparities in other modifiable risk factors emerged at 1 year. CONCLUSIONS: Significant differences in important risk factors (physical activity and diastolic blood pressure) at baseline between Black and non-Black patients resolved at 1 year, suggesting that aggressive medical management may have an important role in ameliorating disparities in risk factor control between Black and non-Black patients.

Change in Smoking Behavior and Outcome After Ischemic Stroke: Post-Hoc Analysis of the SPS3 Trial.

BACKGROUND: Cigarette smoking is a known risk factor for cardiovascular disease, including ischemic stroke. The literature regarding the rate of persistent smoking after acute ischemic stroke and its effect on subsequent cardiovascular events is scarce. With this study, we aimed to report the rate of persistent smoking after ischemic stroke and the association between smoking status and major cardiovascular outcomes. METHODS: This is a post-hoc analysis of the SPS3 trial (Secondary Prevention of Small Subcortical Strokes). Patients were divided into 4 groups based on smoking status at trial enrollment: (1) never smokers, (2) former smokers, (3) smokers who quit at 3 months, and (4) persistent smokers. The primary outcome is a major adverse cardiovascular events composite of stroke (ischemic and hemorrhagic), myocardial infarction, and mortality. Outcomes were adjudicated after month 3 of enrollment until an outcome event or the end of study follow-up. RESULTS: A total of 2874 patients were included in the study. Of the total cohort, 570 patients (20%) were smokers at enrollment, of whom 408 (71.5%) patients continued to smoke and 162 (28.4%) quit smoking by 3 months. The major adverse cardiovascular events outcome occurred in 18.4%, 12.4%, 16.2%, and 14.4%, respectively, in persistent smokers, smokers who quit, prior smokers, and never smokers. In a model adjusted for age, sex, race, ethnicity, education, employment status, history of hypertension, diabetes, hyperlipidemia, myocardial infarction, and intensive blood pressure randomization arm, the risk of major adverse cardiovascular events, and death were higher in the persistent smokers compared with never smokers (HR for major adverse cardiovascular events: 1.56 [95% CI, 1.16-2.09]; HR for death: 2.0 [95% CI, 2.18-3.12]). The risk of stroke, and MI did not differ according to smoking status Conclusions: Compared with never smoking, persistent smoking after acute ischemic stroke was associated with an increased risk of cardiovascular events and death. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT00059306.

Adapting to Evolving Technologies and Treatment Guidelines in a Procedural Trial: A Qualitative Review of the CREST-2 Experience.

Multiple challenges confront procedural trials, including slow enrollment, lack of equipoise among patients and physicians, and failure to achieve adequate masking. Nonetheless, randomized clinical trials provide the best evidence of efficacy. The evolution of technology, techniques, and standards of care during the conduct of procedural trials challenges external validity. In this study, we review how a multicenter trial of revascularization of asymptomatic carotid arteries for stroke prevention has managed changes in treating carotid stenosis and medical management of atherothrombotic disease. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov number: NCT02089217.

The CASSISS Randomized Clinical Trial.

The CASSISS trial (China Angioplasty & Stenting for Symptomatic Intracranial Severe Stenosis), recently published in JAMA, is the most recent of several randomized controlled trials that have failed to show a benefit of percutaneous angioplasty and stenting over medical therapy for the prevention of stroke due to intracranial atherosclerotic stenosis. Current practice guidelines recommended that percutaneous angioplasty and stenting should not be performed routinely as a treatment for stroke prevention in patients with intracranial atherosclerotic stenosis. The CASSISS trial reinforces those recommendations and will not change practice, but it may provide some important lessons for future trial design.

White matter hyperintensity progression is associated with incident probable dementia or mild cognitive impairment.

BACKGROUND: White matter hyperintensity (WMH) on brain MRI is associated with developing dementia or mild cognitive impairment (MCI), but WMH progression over time has not been fully investigated as an independent risk factor. METHODS: We performed a post hoc analysis of the Systolic Blood Pressure Intervention Trial - Memory and Cognition in Decreased Hypertension (SPRINT MIND) trial. The primary outcome was incident probable dementia or MCI (dementia/MCI) before the follow-up MRI at 48 months from enrolment. The primary predictor was WMH progression, defined as the Z score difference between the follow-up and baseline WMH volumes. The secondary predictor was a binary WMH progression threshold (≥1.4 mL vs <1.4 mL). RESULTS: Among the 433 included patients, 33 (7.6%) developed dementia/MCI. There were 156 (36.0%) patients who met the WMH progression threshold of ≥1.4 mL, in whom the rate of dementia/MCI was 12.8% (20/156) vs 4.7% (13/277) of patients with <1.4 mL WMH progression (p=0.002). In multivariable logistic regression, the Z score of WMH progression was associated with dementia/MCI (OR 1.51, 95% CI 1.12 to 2.04, p=0.007) as was the WMH progression threshold of ≥1.4 mL (OR 2.89, 95% CI 1.23 to 6.81, p=0.015). CONCLUSIONS: In this post hoc analysis of SPRINT MIND, WMH progression over 48 months was associated with the development of probable dementia or MCI.

Stroke Prevention in Symptomatic Large Artery Intracranial Atherosclerosis Practice Advisory: Report of the AAN Guideline Subcommittee.

BACKGROUND AND OBJECTIVES: To review treatments for reducing the risk of recurrent stroke or death in patients with symptomatic intracranial atherosclerotic arterial stenosis (sICAS). METHODS: The development of this practice advisory followed the process outlined in the American Academy of Neurology Clinical Practice Guideline Process Manual, 2011 Edition, as amended. The systematic review included studies through November 2020. Recommendations were based on evidence, related evidence, principles of care, and inferences. MAJOR RECOMMENDATIONS: Clinicians should recommend aspirin 325 mg/d for long-term prevention of stroke and death and should recommend adding clopidogrel 75 mg/d to aspirin for up to 90 days to further reduce stroke risk in patients with severe (70%-99%) sICAS who have low risk of hemorrhagic transformation. Clinicians should recommend high-intensity statin therapy to achieve a goal low-density lipoprotein cholesterol level <70 mg/dL, a long-term blood pressure target of <140/90 mm Hg, at least moderate physical activity, and treatment of other modifiable vascular risk factors for patients with sICAS. Clinicians should not recommend percutaneous transluminal angioplasty and stenting for stroke prevention in patients with moderate (50%-69%) sICAS or as the initial treatment for stroke prevention in patients with severe sICAS. Clinicians should not routinely recommend angioplasty alone or indirect bypass for stroke prevention in patients with sICAS outside clinical trials. Clinicians should not recommend direct bypass for stroke prevention in patients with sICAS. Clinicians should counsel patients about the risks of percutaneous transluminal angioplasty and stenting and alternative treatments if one of these procedures is being contemplated.

Long-Term Secondary Prevention: Management of Blood Pressure After a Transient Ischemic Attack or Stroke.

Reducing blood pressure (BP) is a highly effective strategy for long-term stroke prevention. Despite overwhelmingly clear evidence from randomized trials that antihypertensive therapy substantially reduces the risk of stroke in primary prevention, uncertainty still surrounds the issue of BP lowering after cerebrovascular events, and the risk of recurrent stroke, coronary events, and vascular death remains significant. Important questions in a secondary prevention setting include should everyone be treated regardless of their poststroke BP, how soon after a stroke should BP-lowering treatment be commenced, how intensively should BP be lowered, what drugs are best, and how should long-term BP control be optimized and monitored. We review the evidence on BP control after a transient ischemic attack or stroke to address these unanswered questions and draw attention to some recent developments that hold promise to improve management of BP in current practice.

Hypertensive Disorders of Pregnancy With and Without Prepregnancy Hypertension Are Associated With Incident Maternal Kidney Disease Subsequent to Delivery.

BACKGROUND: Maternal morbidity and mortality are related to prepregnancy hypertensive disease and hypertensive disorders of pregnancy (HDP) including preeclampsia (41.1% of HDP), eclampsia (1.3% of HDP), and gestational hypertension (39.9% of HDP). Less information is available on the risk of maternal kidney disease and potential racial/ethnic differences following a hypertensive condition during pregnancy. Our objective was to examine the relationships between HDP and prepregnancy hypertension with maternal incident kidney disease subsequent to delivery (up to 3, 5, and 14 years) with consideration of racial/ethnic differences. METHODS: In a retrospective cohort study, 391 838 women 12 to 49 years of age had a live birth in South Carolina between 2004 and 2016; 35.1% non-Hispanic Black (NHB) and 64.9% non-Hispanic White (NHW). Hospitalization, emergency department, and birth certificate data defined prepregnancy hypertension and HDP. Hospitalization and death certificate data identified incident kidney disease. RESULTS: 317 006 (80.8%) women experienced neither condition, 1473 (0.4%) had prepregnancy hypertension, 64 050 (16.3%) had HDP, and 9662 (2.5%) had both conditions (prepregnancy hypertension with superimposed HDP, ie, preeclampsia). Five years after delivery, incident kidney disease risk was increased for NHB and NHW women with HDP (NHB: hazard ratio, 2.30 [95% CI, 1.94-2.73]; NHW: hazard ratio, 1.97 [95% CI, 1.64-2.37]) and with both conditions (NHB: hazard ratio, 3.88 [95% CI, 3.05-4.93]; NHW: hazard ratio, 1.86 [95% CI, 1.20-2.87]) compared with counterparts with neither condition after adjustment (P value for race/ethnicity interaction=0.003). CONCLUSIONS: Increased kidney disease risk 5 years after delivery was observed for women with HDP and with both compared with neither condition, with associated risk higher in NHB than NHW women.

Intracranial atherosclerotic stenosis: risk factors, diagnosis, and treatment.

Intracranial atherosclerotic stenosis (ICAS) is one of the most frequent causes of stroke worldwide and confers one of the greatest risks of recurrent stroke compared with other causes of stroke. Asymptomatic ICAS is increasingly recognised as a risk factor for silent brain infarctions and dementia, magnifying the global burden of ICAS. Although ICAS is a lumen-based diagnosis, newer diagnostic imaging techniques, such as high-resolution MRI, might help to identify high-risk population subgroups to test interventions that might reduce the risk of stroke recurrence. Secondary stroke prevention in patients with ICAS currently consists of intensive management of modifiable risk factors and dual antiplatelet therapy, which is subsequently reduced to aspirin alone. Despite these therapies, the risk of recurrent stroke in patients presenting with stroke related to 70-99% ICAS exceeds 20% at 1 year; as such, better therapies are urgently needed. The optimal duration and combination of dual antiplatelet therapy in patients with ICAS is uncertain and is being investigated in addition to low-dose anticoagulation and aspirin. Other ongoing or planned studies will provide high-quality observational data on the role of transluminal angioplasty and stenting, submaximal balloon angioplasty alone, direct or indirect arterial bypass, and ischaemic conditioning for prevention of stroke in patients with ICAS.

Cilostazol for Secondary Stroke Prevention: History, Evidence, Limitations, and Possibilities.

Cilostazol is a PDE3 (phosphodiesterase III) inhibitor with a long track record of safety that is Food and Drug Administration and European Medicines Agency approved for the treatment of claudication in patients with peripheral arterial disease. In addition, cilostazol has been approved for secondary stroke prevention in several Asian countries based on trials that have demonstrated a reduction in stroke recurrence among patients with noncardioembolic stroke. The onset of benefit appears after 60 to 90 days of treatment, which is consistent with cilostazol's pleiotropic effects on platelet aggregation, vascular remodeling, blood flow, and plasma lipids. Cilostazol appears safe and does not increase the risk of major bleeding when given alone or in combination with aspirin or clopidogrel. Adverse effects such as headache, gastrointestinal symptoms, and palpitations, however, contributed to a 6% increase in drug discontinuation among patients randomized to cilostazol in a large secondary stroke prevention trial (CSPS.com [Cilostazol Stroke Prevention Study for Antiplatelet Combination]). Due to limitations of prior trials, such as open-label design, premature trial termination, large loss to follow-up, lack of functional or cognitive outcome data, and exclusive enrollment in Asia, the existing trials have not led to a change in clinical practice or guidelines in Western countries. These limitations could be addressed by a double-blind placebo-controlled randomized trial conducted in a broader population. If positive, it would increase the evidence in support of long-term treatment with cilostazol for secondary prevention in the millions of patients worldwide who have experienced a noncardioembolic ischemic stroke.

Incident Heart Failure Within the First and Fifth Year after Delivery Among Women With Hypertensive Disorders of Pregnancy and Prepregnancy Hypertension in a Diverse Population.

Background Hypertensive disorders of pregnancy (HDP) and pre-pregnancy hypertension are associated with increased morbidity and mortality for the mother. Our aim was to investigate the relationships between HDP and pre-pregnancy hypertension with maternal heart failure (HF) within 1 and 5 years of delivery and to examine racial/ethnic differences. Methods and Results We conducted a retrospective cohort study in South Carolina (2004-2016) involving 425 649 women aged 12 to 49 years (58.9% non-Hispanic White [NHW], 31.5% non-Hispanic Black [NHB], 9.6% Hispanic) with a live, singleton birth. Incident HF was defined by hospital/emergency department visit and death certificate data. Pre-pregnancy hypertension and HDP (preeclampsia, eclampsia, or gestational hypertension) were based on hospitalization/emergency department visit and birth certificate data (i.e., gestational hypertension for HDP). The 425 649 women had pre-pregnancy hypertension without superimposed HDP (pre-pregnancy hypertension alone; 0.4%), HDP alone (15.7%), pre-pregnancy hypertension with superimposed HDP (both conditions; 2.2%), or neither condition in any pregnancy (81.7%). Incident HF event rates per 1000 person-years were higher in NHB than NHW women with HDP (HDP: 2.28 versus 0.96; both conditions: 4.30 versus 1.22, respectively). After adjustment, compared with women with neither condition, incident HF risk within 5 years of delivery was increased for women with pre-pregnancy hypertension (HR,2.55, 95% CI: 1.31-4.95), HDP (HR,4.20, 95% CI: 3.66-4.81), and both conditions (HR,5.25, 95% CI: 4.24-6.50). Conclusions Women with HDP and pre-pregnancy hypertension were at higher HF risk (highest for superimposed preeclampsia) within 5 years of delivery. NHB women with HDP had higher HF risk than NHW women, regardless of pre-pregnancy hypertension.

Non-Adherence to Antihypertensive Guidelines in Patients with Asymptomatic Carotid Stenosis.

IMPORTANCE: Hypertension and carotid stenosis are both risk factors for stroke, but the presence of carotid stenosis might dampen enthusiasm for tight control of hypertension because of concerns for hypoperfusion. OBJECTIVE: To determine the extent to which there are opportunities to potentially improve pharmacotherapy for hypertension in patients known to have asymptomatic high-grade carotid stenosis. DESIGN: We examined anti-hypertensive medication prescription and adherence to evidence-based hypertension treatment guidelines in a cross-sectional analysis of baseline data of patients enrolled in a clinical trial. SETTING: The Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Trial (CREST-2) is a multicenter prospective randomized open blinded end-point clinical trial of intensive medical management with or without revascularization by endarterectomy or stenting for asymptomatic high-grade carotid stenosis. PARTICIPANTS: 1479 participants (38.6% female; mean age 69.8 years) from 132 clinical centers enrolled in the CREST-2 trial as of April 6, 2020 who were taking ≥1 antihypertensive drug at baseline. EXPOSURES: Pharmacotherapy for hypertension. MAIN OUTCOME: Adherence to evidence-based guidelines for treating hypertension. RESULTS: Of 1458 participants with complete data, 26% were on one, 31% on 2, and 43% on ≥3 antihypertensive medications at trial entry. Thirty-two percent of participants were prescribed thiazide; 74%, angiotensin converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB); 38%, calcium channel blocker (CCB); 56%, a beta blocker; 11%, loop diuretic; and 27%, other. Of those prescribed a single antihypertensive medication, the proportion prescribed thiazide was 5%; ACEI or ARB, 55%, and CCB, 11%. The prevalence of guideline-adherent regimens was 34% (95% CI, 31-36%). CONCLUSIONS AND RELEVANCE: In a diverse cohort with severe carotid disease and hypertension, non-adherence to hypertension guidelines was common. All preferred classes of antihypertensive drug were under-prescribed. Using staged iterative guideline-based care for hypertension, CREST-2 will characterize drug tolerance and stroke rates under these conditions. TRIAL REGISTRATION: ClinicalTrials.gov Number NCT02089217.