Date of Award

January 2018

Document Type

Open Access Thesis

Degree Name

Medical Doctor (MD)

Department

Medicine

First Advisor

Erica S. Spatz

Abstract

Where one lives affects one’s blood pressure. Observational studies demonstrate

that living in communities of low socioeconomic status is associated with higher blood

pressure and worse cardiovascular outcomes. In understanding the reasons for these

disparities, a key question is whether evidence-based antihypertensive medication therapy

is less effective in lowering blood pressure and improving cardiovascular outcomes in

lower socioeconomic communities. If so, then anti-hypertensive therapies derived from

randomized clinical trials (RCTs) may be suboptimal in achieving expected outcomes.

Despite standardized protocols and balancing of demographic and clinical characteristics

between study arms of RCTs, the socioeconomic environment in which people live is

rarely examined, potentially exerting an unmeasured effect on study outcomes.

To determine the impact of socioeconomic context on response to

antihypertensive medication in clinical trials, we analyzed data from the Antihypertensive

and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), the largest

existing RCT of hypertension treatment. This trial, conducted from 1994 to 2002,

randomized 42,418 people, 55 years or older, with hypertension and at least one other

cardiovascular risk factor, to chlorthalidone, lisinopril, amlodipine or doxazosin (mean

follow-up of 4.9 years). After excluding non-continental U.S. sites and the doxazosin arm

(terminated early in ALLHAT) our study included 27,862 participants. We defined

socioeconomic context by mapping study site ZIP codes to counties and stratifying these

counties into income quintiles based on the national distribution of county median

household income, adjusted for cost-of-living, from the 2000 U.S. census.

We compared baseline and clinical characteristics, visit and medication

adherence, blood pressure control, and cardiovascular outcomes between ALLHAT

participants in the lowest and highest income sites using multivariable regression models.

Participants receiving care in Quintile 1 (Q1, lowest income sites) (n = 2169, 7.8%) were

more likely to be female, black, Hispanic, have fewer total years of education, live in the

South, and have fewer cardiovascular risk factors than participants in Quintile 5 (Q5,

highest income sites) (n = 10458, 37.6%). Compared with Q5, participants in Q1 were

less likely to achieve blood pressure control (<140/90 mmHg) (OR, 0.48; 95% CI, 0.37-

0.63), and experienced higher all-cause mortality (HR, 1.25; 95% CI, 1.10-1.41), heart

failure hospitalizations or mortality (HR, 1.26; 95% CI, 1.03-1.55) and end-stage renal

disease (ESRD) (HR, 1.86; 95% CI, 1.26-2.73), though lower angina hospitalizations

(HR, 0.70; 95% CI, 0.59-0.83) and coronary revascularization (HR, 0.71; 95% CI, 0.57-

0.89). There were no differences in stroke, myocardial infarction, or peripheral arterial

disease.

Despite having access to standardized treatment protocols, participants in the

lowest income sites experienced poorer blood pressure control, higher mortality, ESRD

and heart failure morbidity, and decreased coronary revascularization compared to those

in the highest income sites. These findings suggest a need to better measure and bolster

the socioeconomic context beyond the medical environment to eliminate disparities in

outcomes for RCTs of antihypertensive medications. Understanding these relationships

may guide the generalizability of RCT findings, promote the assessment of participants’

socioeconomic context in clinical trials and hypertension treatment guidelines, and

inform broader strategies for combating hypertension in populations living in low

socioeconomic environments.

Comments

This is an Open Access Thesis.

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