Abstract
BACKGROUND
Hypertension control in Hispanics/Latinos lag behind general US trends by 10–15%. Intensive systolic blood pressure (SBP) management <120 mm Hg may significantly reduce morbidity/mortality risk in adults with hypertension; less is known about cognition. We investigated cross-sectional associations of cognition with observed hypertension control at currently recommended (SBP < 140 mm Hg) and more intensive (SBP < 120 mm Hg) levels using baseline data from the Hispanic Community Health Study/Study of Latinos.
METHODS
From this multicenter cohort study, we focused on 1,735 Hispanic/Latino men and women ages 45–74 years with hypertension and verified antihypertensive use. Verbal fluency, information processing speed, learning, and memory were tested in Spanish or English.
RESULTS
Separate linear regressions revealed that being on 1 vs. >1 antihypertensive medication was not associated with cognition; however, individuals with SBP controlled to currently recommended levels outperformed individuals with uncontrolled SBP on verbal fluency [Beta = 1.44 (0.52), P < 0.01] and information processing speed [Beta = 3.01 (0.89), P < 0.001] in age-adjusted regression analyses; only information processing speed remained significant (P < 0.05) after additional adjustments including acculturation, health insurance, and other cardiovascular disease risk factors. When regrouping individuals based on more intensive SBP control, individuals with levels <120 mm Hg outperformed individuals with higher SBP on verbal fluency regardless of adjustments (P < 0.01). More intensive rather than currently recommended levels of control associated with higher verbal fluency performance regardless of adjustments (P < 0.05).
CONCLUSIONS
Individual cognitive test scores related to distinct SBP management with more intensive management appearing more robust against confounders. While cognitive associations with hypertension in Hispanics/Latinos may be multifactorial, different levels of SBP control should be considered in future prospective intervention studies.
Keywords: antihypertensive treatment, blood pressure, blood pressure control, cognition, hypertension, HCHS/SOL, Hispanics/Latinos.
Hispanics/Latinos have some of the highest prevalence rates of cardiovascular disease (CVD) including uncontrolled hypertension in the United States.1 Large-scale epidemiological studies in non-Hispanic populations suggest that the presence of hypertension2 and even prehypertension3 may lower the threshold for developing cognitive impairment and dementia.4 Thus, uncontrolled hypertension may predispose Hispanics/Latinos to an increased risk for dementia.5 In contrast, the use of antihypertensive medications may slow the pathological processes6,7 linking hypertension with dementia.8 Recent evidence from the Systolic Blood Pressure Intervention Trial suggests that more intensive management of systolic blood pressure (SBP) below commonly used targets, i.e., <120 mm Hg as opposed to <140 mm Hg, lowers prevalence of cardiovascular events and death by 33% and 25%, respectively.9 To our knowledge, an examination of the cognitive associates of more intensive SBP management has not been reported in response to these findings.
The Hispanic Community Health Study/Study of Latinos (HCHS/SOL) is a large-scale epidemiological cohort study of cardiovascular risk in over 16,000 Hispanic/Latino adults. Its scope allowed us to examine the cross-sectional cognitive associates of observed hypertension treatment-related control at currently recommended (<140/90 mm Hg)10 vs. more intensive levels.9 We hypothesized that among individuals prescribed medication for high BP, those displaying uncontrolled BP by currently recommended levels would have poorer cognitive performance (i.e., memory and executive functioning) than those with controlled hypertension after adjustment for age and other confounds. We further hypothesized that when individuals were regrouped based on more intensive SBP management, those with more intensively controlled BP would demonstrate better cognition compared to those with uncontrolled BP as well as when compared to those with SBP controlled to currently recommended levels.
METHODS
The HCHS/SOL is a prospective, population-based, cohort study of 16,415 Hispanic/Latino adults aged 18–74 years from 4 US cities (Chicago, IL; Miami, FL; Bronx, NY; San Diego, CA).11 The baseline clinical examination (2008–2011)12 included comprehensive cardiovascular, behavioral, and sociodemographic assessments. The cohort includes participants who self-identified as from Central American, Cuban, Dominican, Mexican, Puerto Rican, or South American background. The study oversampled persons ages 45–74 to facilitate examination of target outcomes. The Institutional Review Boards at each site approved this study and all subjects gave written consent.
Assessment of Hypertension
BP was measured on the right arm using an OMRON HEM-907 XL (Omron Healthcare, Lake Forest, IL) automatic sphygmomanometer with the participant in a seated position and the arm resting.12,13 The upper arm circumference was used to determine cuff size (4 cuff sizes were available). Three BP readings were obtained at 1-minute intervals following a 5-minute rest period; the average of the 3 readings was used for hypertension determination. We averaged all available measures for the 3 participants (0.1% of the 2,889 participants deemed hypertensive) that had <3 time points. Hypertension was defined as SBP ≥140 mm Hg or diastolic BP ≥90 mm Hg or antihypertensive medication use (self-reported and/or verified at the study visit).
Determination of treatment and control
Currently recommended BP levels for controlled hypertension were SBP <140 mm Hg and diastolic BP <90 mm Hg.10 Uncontrolled hypertension was defined as SBP ≥140 mm Hg or diastolic BP ≥90 mm Hg. More intensive control of SBP was defined as treated SBP <120 mm Hg combined with treated diastolic BP< 90 mm Hg.9 Participants were not randomized into groups, as this was an observational cohort study, not a clinical trial.
Cognitive assessment
Tests were administered in the participants’ preferred language by study staff trained and supervised by licensed clinical neuropsychologists.
Verbal fluency required participants to generate as many words as possible within 60 seconds that began with a specific letter (“F” and “A”).14,15 The total number of correctly generated words summed across trials (range = 0–50) represents word retrieval and the executive ability of establishing and maintaining mental set over time.16
Information processing speed was assessed with the Digit Symbol Substitution Test (DSST) of the Wechsler Adult Intelligence Scale-Revised.17 This task requires the rapid copying and encoding of symbols to numbers within 90 seconds. The variable of interest is the total number of correctly transcribed symbols during the allotted time (range = 0–80).
Learning and memory was assessed using the Brief Spanish English Verbal Learning Test (B-SEVLT).18 Participants are asked to recall items from a 15-item list presented for 3 consecutive “learning” trials. This is followed by a 15-item distractor list and a delayed free recall trial immediately following the distractor trial.16,19 B-SEVLT variables included total learning across all 3 trials (range = 0–45) and total recalled during the delayed free recall (memory) trial (range = 0–15).
Potential confounders
Other CVD risk factors were measured including self-reported smoking status (current vs. never/former); diabetes (presence/absence) defined based on the American Diabetes Association definition,20 and hypercholesterolemia (presence/absence) defined based on the National Cholesterol Education Program Expert Panel.21 Information was obtained on self-reported health insurance status (yes/no).
The Center for Epidemiologic Studies of Depression (CESD, 10-item) scale22 measured subjective depressive symptomatology. A six-item screener (SIS)23 measured global cognitive functioning much like the Mini-Mental State Examination.24 Information was obtained on US residence status and immigrant generational status (i.e., 1st generation, 2nd, etc.). The Short Acculturation Scale for Hispanics provided a subscale of language-based acculturation.25
Participants
Men and women 44 years and older for whom data were available on BP, antihypertension medication use and cognition—and who met the criteria for hypertension—were included in this study. Exclusion criteria consisted of a reported history of stroke (n = 189) and/or psychotropic medication use (n = 1,378).
Since the purpose of this study was to understand pharmacological control of hypertension as related to cognition, analyses focused on participants whose antihypertensive medication use could be verified at the study visit (n = 1,735). Hypertensive individuals with (and without) self-reported medication use as well as those that did not bring their medications to their study visit, e.g., for whom self-reported antihypertensive use could not be verified, were excluded from the main study analyses. Given this conservative approach to understanding the control of hypertension, we included hypertensive individuals with and without self-reported medication use in supplemental analyses to see if and how results changed when including untreated individuals and individuals without verified self-reported antihypertensive medication use (n = 1,154).
Statistical analyses
All reported values were weighted to account for selection probability and nonresponse.11 The adjusted weights were also trimmed to limit precision losses due to the variability of the adjusted weights, and calibrated to the age, sex, and Hispanic/Latino background distributions from 2010 Census characteristics for each field site’s population. All analyses also account for cluster sampling and the use of stratification in sample selection. For continuous responses, all means and prevalence estimates for the target population of Hispanic/Latinos were calculated using survey linear regression. All analyses were performed using SAS 9.3 software (SAS Institute, Cary, NC).
Descriptive statistics were compared for individuals with BP controlled to currently recommended levels versus those with uncontrolled hypertension. Formal comparisons were carried out via overall Wald test. Multivariable linear regression was used to adjust for potential confounders with statistical significance assessed via P values <0.05 and 95% confidence intervals.
For each cognitive outcome (i.e., fluency, DSST, B-SEVLT learning and memory), we fit 2 survey linear regression models for each recommendation criteria (current and more intensive levels). Model 1 included treatment-related control status as the predictor variable adjusting for age. In addition to age, model 2 adjusted for sex, background, education, SIS, CESD, other CVD risk factors including current smoking status, presence of diabetes and/or hypercholesterolemia, health insurance status, income, immigrant generational status, and language-based acculturation. Given that more intensive BP management required multiple antihypertensive medications,9,26 we fit 2 survey linear regression models (models 1 and 2) for each cognitive outcome using the number of antihypertensive medications used (0, 1, or ≥2) as the predictor variable.
RESULTS
Of the 1,735 hypertensives, 63% (n = 1,128) were observed to be adequately controlled on their medications based on current recommendations; the remaining 37% (n = 607) showed elevated BP despite antihypertensive medication verification. When regrouped using more intensive SBP criteria, 23% (n = 457) were adequately controlled on their medications while 77% or 1,278 had SBP above 120 mm Hg.
Compared to individuals with uncontrolled hypertension, individuals who met current recommendations for BP control (<140/90 mm Hg) were significantly younger [difference in years (95% confidence interval) = −2.2 (−3.6, −0.8)], had disproportionately fewer individuals with less than a high school education [difference in percent (95% confidence interval) = −9.5 (−17.6, −1.5)], and had lower prevalence of diabetes [difference in percent (95% confidence interval) = 6.8 (0.3, 13.4)]. The presence of other CVD risk factors did not differ significantly between the groups (Table 1). Groups also differed in terms of income, background, and language-based acculturation (P values ≤ 0.02; Table 1). Sex distribution, SIS, CESD scores, marital status, US residence status, generational status, language preference for testing, and health insurance status did not differ between groups.
Table 1.
Participant characteristics for all and by current recommendations for blood pressure control
| N = 1,735 | All | Current level of control group (n = 1,128) | Uncontrolled group (n = 607) | Difference in 95% CI | P value |
|---|---|---|---|---|---|
| Age (mean, year) | 60.0 (59.5–60.6) | 59.2 (58.4–60.0) | 61.4 (60.4–62.4) | −2.2 (−3.6 to −0.8) | 0.0020 |
| Female (%) | 55.4 (51.5–59.4) | 53.9 (49.4–58.4) | 58.1 (51.9–64.3) | −4.2 (−11.2 to 2.9) | 0.2494 |
| Six-item screener | 5.27 (5.18 to 5.35) | 5.30 (5.20–5.40) | 5.21 (5.10–5.33) | 0.08 (−0.04 to 0.20) | 0.1681 |
| 10-item CESD | 7.2 (6.8–7.7) | 7.4 (6.8–8.0) | 7.0 (6.5–7.6) | 0.3 (−0.5 to 1.2) | 0.4359 |
| Background (F-statistic P value = 0.02) | |||||
| Mexican | 27.9 (23.4–32.3) | 31.2 (25.7–36.7) | 22.3 (16.3–28.2) | 8.9 (1.6 to 16.3) | 0.0169 |
| Cuban | 28.5 (23.7–33.3) | 27.0 (21.7–32.4) | 31.0 (24.0–38.0) | −4.0 (−11.5 to 3.5) | 0.2946 |
| Puerto Rican | 20.7 (17.2–24.2) | 21.8 (16.9–26.7) | 18.8 (14.4–23.2) | 3.1 (−3.5 to 9.6) | 0.3591 |
| Dominican | 9.8 (8.0–11.6) | 7.6 (5.7–9.5) | 13.4 (9.8–17.1) | −5.8 (−10.0 to −1.7) | 0.0063 |
| Central American | 5.6 (4.5–6.7) | 4.3 (3.1–5.6) | 7.7 (5.6–9.8) | −3.3 (−5.7 to −0.9) | 0.0063 |
| South American | 4.4 (3.3–5.6) | 4.8 (3.3–6.4) | 3.8 (2.2–5.3) | 1.1 (−1.1 to 3.3) | 0.3326 |
| Other | 3.1 (0.7–5.6) | 3.2 (0.0–7.0) | 3.1 (1.3–4.8) | 0.1 (−4.2 to 4.4) | 0.9584 |
| Education (F-statistic P value = 0.048) | |||||
| <High school | 42.7 (38.9 to 46.4) | 39.1 (34.2 to 44.0) | 48.6 (42.6 to 54.6) | −9.5 (−17.6 to −1.5) | 0.0204 |
| High school graduate | 22.2 (19.0–25.3) | 23.8 (19.2–28.3) | 19.5 (15.3–23.6) | 4.3 (−2.2 to 10.8) | 0.1923 |
| Greater than high school | 35.2 (31.3–39.1) | 37.1 (32.0–42.3) | 31.9 (26.8–37.0) | 5.2 (−1.8 to 12.2) | 0.1419 |
| (Annual family) income (F-statistic P value = 0.02) | |||||
| <$20,000 | 43.7 (40.0–47.3) | 40.9 (36.3–45.5) | 48.3 (42.2–54.5) | −7.5 (−15.3 to 0.4) | 0.0616 |
| $20,000–50,000 | 36.7 (33.2–40.1) | 39.0 (34.0–43.9) | 32.8 (27.1–38.5) | 6.1 (−2.0 to 14.3) | 0.1385 |
| >50,000 | 10.7 (8.3–13.0) | 12.3 (9.3–15.3) | 7.9 (5.1–10.6) | 4.5 (0.7 to 8.2) | 0.0189 |
| Not reported | 9.0 (7.1–10.9) | 7.8 (5.5–10.2) | 11.0 (8.0–13.9) | −3.1 (−6.8 to 0.5) | 0.0916 |
| Marital status (F-statistic P value = 0.13) | |||||
| Single | 14.1 (11.7–16.5) | 12.3 (9.8–14.8) | 17.1 (12.4–21.8) | −4.7 (−10.0 to 0.5) | 0.0787 |
| Married or living with a partner | 54.2 (50.0–58.3) | 56.6 (51.3–61.9) | 50.0 (44.1–55.8) | 6.6 (−1.0 to 14.3) | 0.0879 |
| Separated, divorced or widowed | 31.7 (28.2–35.3) | 31.0 (25.9–36.2) | 32.9 (27.3–38.6) | −1.9 (−10.1 to 6.3) | 0.6471 |
| US residence > 10 year (%) | 77.2 (73.6–80.8) | 77.6 (73.4–81.7) | 76.5 (71.1–81.9) | 1.1 (−5.0 to 7.2) | 0.7301 |
| Immigrant generational status (F-statistic: P value = 0.36) | |||||
| First (%) | 91.1 (89.3–93.0) | 90.5 (88.2–92.9) | 92.1 (89.5–94.8) | −1.6 (−5.0 to 1.7) | 0.3467 |
| Second or higher (%) | 8.9 (7.0–10.7) | 9.5 (7.1–11.8) | 7.9 (5.2–10.5) | 1.6 (−1.7 to 5.0) | 0.3467 |
| Language preference and acculturation | |||||
| Spanish preference (%) | 87.1 (83.8–90.4) | 85.6 (80.8–90.4) | 89.7 (86.7–92.6) | −4.1 (−9.5 to 1.3) | 0.1381 |
| English preference (%) | 12.9 (9.6–16.2) | 14.4 (9.6–19.2) | 10.3 (7.4–13.3) | 4.1 (−1.3 to 9.5) | 0.1381 |
| Language-based acculturation | 1.71 (1.63–1.79) | 1.78 (1.68–1.89) | 1.58 (1.49–1.67) | 0.20 (0.07 to 0.33) | 0.0022 |
| Health insurance | 69.4 (65.8–73.0) | 70.7 (66.4–75.0) | 67.2 (61.8–72.5) | 3.5 (−2.8 to 9.8) | 0.2770 |
| Diabetes (%) | 48.0 (44.1–51.9) | 50.5 (45.7–55.4) | 43.7 (38.3–49.1) | 6.8 (0.3 to 13.4) | 0.0419 |
| High total cholesterol (%) | 68.3 (64.9–71.8) | 67.1 (62.8–71.4) | 70.5 (65.1–75.8) | −3.4 (−10.1 to 3.4) | 0.3256 |
| Current smoker (%) | 13.2 (11.0–15.5) | 13.2 (10.4–15.9) | 13.4 (9.1–17.7) | −0.2 (−5.6 to 5.1) | 0.9353 |
| Number of antihypertensive medications | |||||
| =1 | 91.5 (89.5–93.5) | 92.7 (90.2–95.2) | 89.5 (85.9–93.1) | 3.2 (−1.3 to 7.7) | 0.1666 |
| >1 | 8.5 (6.49–10.5) | 7.3 (4.7–9.8) | 10.5 (6.9–14.0) | −3.2 (−7.7 to 1.3) | 0.1666 |
Current level of control group, i.e., current recommendations for treatment-related control: <140/90 mm Hg. All values are weighted means and CIs unless otherwise noted. Abbreviations: CESD, Center for Epidemiologic Studies of Depression; CI, confidence interval.
Current recommendation treatment-related control and individual cognitive outcomes
Hypertensive individuals with BP controlled to <140/90 mm Hg, showed significantly better DSST performance than hypertensive individuals without adequately controlled BP regardless of adjustments (Table 2), producing 1.5 (model 2 P < 0.05) to 3 (model 1 P < 0.001) more items. Those with controlled BP also showed better verbal fluency compared to their counterparts with uncontrolled BP after age-adjustment only (Table 2). Findings for learning and memory were not significant.
Table 2.
Associations of current recommendations for treatment-related control (<140/90 mm Hg) and individual cognitive outcomes
| Total n = 1,735 | Individual cognitive outcomes | ||||
|---|---|---|---|---|---|
| Model | Variable | Fluency beta (SE) | DSST beta (SE) | B-SEVLT learning beta (SE) | B-SEVLT memory beta (SE) |
| 1 | Current level of control group (n = 1,128) vs. uncontrolled group (n = 607) | 1.44 (0.52)** | 3.01 (0.89)*** | 0.50 (0.34) | 0.24 (0.18) |
| 2 | Current level of control group (n = 1,128) vs. uncontrolled group (n = 607) | 0.90 (0.48) | 1.43 (0.59)* | 0.20 (0.31) | 0.09 (0.17) |
Current level of control group, i.e., current recommendations for treatment-related control: <140/90 mm Hg. Beta (SE) = raw regression coefficients and SE. Model 1: analyses are adjusted for age. Model 2: analyses are adjusted for age, sex, background, education, six-item screener and CESD scores, individual cardiovascular disease risk factors including current smoking status, diabetes, and total cholesterol, as well as health insurance status, income, immigrant generational status, and language-based acculturation. Abbreviations: B-SEVLT, Brief Spanish English Verbal Learning Test; DSST, Digit Symbol Substitution Test.
*P < 0.05, **P < 0.01, ***P < 0.001.
In supplemental analyses of all 2,889 individuals with hypertension, i.e., including the 1,154 individuals who were either nonmedicated or whose self-reported medication use could not be verified at study visit, findings were no longer significant for fluency, were attenuated for DSST performance (model 1 P < 0.05; model 2 P = 0.053) and remained nonsignificant for learning and memory (Supplementary Table 1a).
More intensive treatment-related control and individual cognitive outcomes
When participants were regrouped based on more intensive treatment-related control, hypertensive individuals with SBP <120 mm Hg and diastolic BP <90 mm Hg showed significantly better performance on verbal fluency regardless of adjustments (Table 3) compared to individuals with SBP ≥120 mm Hg and diastolic BP ≥90 mm Hg. These individuals produced ~1.5 (model 2 P < 0.01) to 2 (model 1 P < 0.01) more words during this task compared to those with uncontrolled hypertension. Associations of intensively controlled BP with DSST trended toward significance for model 1 only (P = 0.08); learning and memory results were not significant regardless of adjustments. Inclusion of nonmedicated individuals and individuals whose self-reported medication use could not be verified at study visit did not alter this pattern of results (Supplementary Table 1b).
Table 3.
Associations of more intensive recommendations for treatment-related control (<120/90 mm Hg) and individual cognitive outcomes
| Total n = 1,735 | Individual cognitive outcomes | ||||
|---|---|---|---|---|---|
| Model | Variable | Fluency beta (SE) | DSST beta (SE) | B-SEVLT learning beta (SE) | B-SEVLT memory beta (SE) |
| 1 | More intensive control group (n = 457) vs uncontrolled group (n = 1,278) | 1.97 (0.61)** | 1.92 (1.10) | 0.59 (0.44) | 0.27 (0.21) |
| 2 | More intensive control group (n = 457) vs. uncontrolled group (n = 1,278) | 1.64 (0.54)** | 1.06 (0.69) | 0.46 (0.36) | 0.13 (0.20) |
More intensive recommendations for treatment-related control: <120/90 mm Hg. Beta (SE) = raw regression coefficients and SE. Model 1: analyses are adjusted for age. Model 2: analyses are adjusted for age, sex, background, education, six-item screener and CESD scores, individual cardiovascular disease risk factors including current smoking status, diabetes, and total cholesterol, as well as health insurance status, income, immigrant generational status, and language-based acculturation. Abbreviations: B-SEVLT, Brief Spanish English Verbal Learning Test; DSST, Digit Symbol Substitution Test.
*P < 0.05, **P < 0.01, ***P < 0.001.
More intensive vs. current recommendations for SBP control and individual cognitive outcomes
To compare more intensive BP control to currently recommended levels for control, individuals with treated SBP from 120 to 140 mm Hg were classified as meeting current recommendations for BP control and those with SBP <120 mm Hg were classified as having more intensively controlled BP. Criteria for controlled diastolic BP was <90 mm Hg for both groups. Participant characteristics of these 2 groups may be found in Supplementary Table 2; it should be noted that groups did not differ in terms of number of self-reported antihypertensive medications used (P values = 0.43).
Individuals with more intensively controlled BP performed significantly better on verbal fluency compared to those with BP controlled to currently recommended level, producing 1.5 more words regardless of adjustments (P values < 0.05; Table 4). Results for DSST, learning, and memory were not significant. Separate linear regression models stratified by sex revealed no differences for men. In contrast, women with SBP <120 mm Hg produced 2 more words during verbal fluency than women with SBP between 120 and 140 mm Hg regardless of adjustments: model 1 beta = 2.24 (0.98), model 2 beta = 2.13 (0.88); P values <0.05.
Table 4.
Comparison of different recommendations for treatment-related control and individual cognitive outcomes in hypertensive individuals
| Total n = 1,128 | Individual cognitive outcomes | ||||
|---|---|---|---|---|---|
| Model | Variable | Fluency beta (SE) | DSST beta (SE) | B-SEVLT learning beta (SE) | B-SEVLT memory beta (SE) |
| 1 | More intensive controlled (n = 457) vs. current controlled (n = 671) | 1.67 (0.66)* | 0.82 (1.21) | 0.50 (0.50) | 0.21 (0.25) |
| 2 | More intensive controlled (n = 457) vs. current controlled (n = 671) | 1.41 (0.58)* | 0.38 (0.77) | 0.44 (0.41) | 0.11 (0.23) |
More intensive recommendations for treatment-related control: SBP <120 mm Hg; current recommendations for treatment-related control:120 = SBP <140 mm Hg. DBP for both recommendation levels set to <90 mm Hg. Beta (SE) = raw regression coefficients and SE. Model 1: analyses are adjusted for age. Model 2: analyses are adjusted for age, sex, background, education, six-item screener and CESD scores, individual cardiovascular disease risk factors including current smoking status, diabetes, and total cholesterol, as well as health insurance status, income, immigrant generational status, and language-based acculturation. Abbreviations: B-SEVLT, Brief Spanish English Verbal Learning Test; DSST, Digit Symbol Substitution Test.
*P < 0.05, **P < 0.01, ***P < 0.001.
Number of antihypertensive medications used and individual cognitive outcomes
Regardless of model adjustments, the number of antihypertensive medications used, verified at the study visit, (i.e., 1 vs. >1) was not associated with any cognitive outcome.
DISCUSSION
Current findings suggest a relationship between more intensive management of hypertension and higher word retrieval and mental set (i.e., verbal fluency) regardless of adjustments. This association remained when including untreated individuals as well as individuals whose self-reported medication could not be verified at the study visit; and it remained when compared to SBP management at current recommendations. In contrast, a similarly robust verbal fluency relationship was not seen for SBP controlled at currently recommended levels after adjusting for factors other than age. Instead, a significant association was noted, regardless of adjustments, with better DSST performance; a relationship that did not withstand the addition of the larger sample suggesting a more circumscribed result.
Information processing speed and aspects of executive functioning may be related to distinct levels of SBP management and that associations appeared more robust against confounders when considering intensive control of SBP. Including untreated individuals and individuals whose self-reported medication could not be verified resulted in weaker and/or nonsignificant results when considering current recommendation levels for SBP control. This suggests that studies relying solely on hypertension status and/or self-reported medication use may underestimate cognitive associates when BP control is set at the traditional SBP ≥140 mm Hg or diastolic BP ≥90 mm Hg. These methodological distinctions should be considered in future studies.
The statistically significant associations between hypertension treatment-related control and individual cognitive outcomes does not reflect immediate clinical significance at the individual level; however, it may represent harbingers of cognitive decline in later life given the relatively young age of our cohort. More specifically, the point differences between groups may not meet SD cut-points for at-risk states for dementia now27,28; however, it may place younger adults with uncontrolled hypertension at increased risk for dementia sooner by moving his/her score closer to these cut-points compared to individuals with controlled hypertension. At the population level, results suggest we may be able to effect change—even by small increments—in cognition through the manipulation of BP. Longitudinal follow-up in the HCHS/SOL will be invaluable to evaluate these assertions.
Our study did not find any differences in B-SEVLT learning or memory indices based on treatment and control of hypertension using either current or more intensive SBP criteria. Our lack of results could be due to several factors. While elevations in BP can disrupt nutrient delivery8,29 and propagate neuronal damage within the temporal lobe30 responsible for learning and memory,31 these alterations take time. The HCHS/SOL data used in this manuscript was cross-sectional and thus lacked detailed information on duration of hypertension and/or duration of controlled BP; patient-related characteristics that may have helped to explain our null findings. Furthermore, while groups did not differ on other CVD risk factors, unaccounted details related to duration and/or treatment of these risk factors may have also contributed to our null findings. Alternatively, differences in learning and memory as it relates to hypertension (and other measures of cardiac functioning)32 may only be revealed when affected individuals are compared to a normotensive group or when multiple indices of each cognitive domain are used. Work is underway investigating these issues in HCHS/SOL.
The cross-sectional associations of cognitive outcomes with being prescribed more than 1 antihypertensive medication were not significant. It may be that the type of antihypertensive medication as opposed to the number matters most for cognition. For example, calcium channel blockers are thought to exhibit a neuroprotective effect in older adults independent of their cardiovascular effect.7 It may also be that our comparison between 1 and >1 medication was too limited, particularly given that an average of 2.8 medications was required to maintain more intensively managed SBP.9,26 Future studies are needed to address these and other patient-related distinctions especially since our controlled BP group may have merely responded better to treatment, had less severe hypertension than our uncontrolled BP group or had differential levels of compliance and/or other participant-based characteristics that may point toward a phenotypic difference not addressed in this cross-sectional study.
Reports from HCHS/SOL have documented differences in cognition18 and CVD risk factors including hypertension33 by sex and background. Sample size limitations did not permit an analysis of background. Preliminary results for sex-related differences suggested that women with more intensively controlled SBP performed significantly better on verbal fluency than women with SBP controlled at currently recommended levels. No cognitive distinctions were noted for men. This is despite the fact that the percentage of men and women within each group were roughly equivalent. This is consistent with reports of more significant associations between CVD risk factors including elevated BP and cognition in women than men.32,34 Together results may suggest that women experience greater cognitive benefits from more intensively controlled SBP; however, given the cross- sectional nature of our study these results may also suggest that women with better cognition are more likely to have better BP control. Replication and extension of this study into a longitudinal cohort or a prospective randomized clinical trial is needed before treatment-related causality and/or sex-specific treatment recommendations may be inferred.
While longitudinal HCHS/SOL data are currently being collected which may help to determine the direction and causal nature of our findings, the current study aim was to determine the cognitive associates of SBP control in Hispanic/Latino adults. Results of this observational study found significant associations of more intensive management of hypertension (i.e., to lower target SBP levels than currently recommended) with cognitive outcomes in Hispanic/Latino adults that withstand multiple adjustments. Given that this is a population whose treatment and control of hypertension lags behind US trends by 10–15%,13,35 we felt it useful to conduct an observational study of possible target thresholds for treatment-related BP control that may guide future randomized control intervention trials to address not only heart health but also brain, i.e., cognitive, health in this vulnerable population.
In conclusion, studies in non-Hispanic Whites suggest that having untreated or uncontrolled hypertension may contribute to an earlier diagnosis of dementia.36 Our study provides cross-sectional evidence of positive cognitive, i.e., information processing and verbal fluency, associates of hypertension treatment-related control, particularly at distinct SBP management, in Hispanics/Latinos who often present with higher levels of CVD risk and lower levels of disease management.13 These cognitive results may help inform future longitudinal studies of CVD risk and cognitive decline to determine the direction and causal mechanisms of these correlations. Furthermore, when compared to more intensive recommendations for BP control, current recommendations for adequate BP control may not be as strongly associated with individual cognitive measures once other CVD risk factors and aspects of acculturation are taken into consideration. Thus, participant characteristics may be contributing to our findings including differences in adherence, disease severity as well as more basic demographic and acculturation-related variables. While the problems of pathological and/or accelerated aging in Hispanics/Latinos may be multifactorial, and more work is needed to determine the safety and efficacy of more intensive hypertension control in younger cohorts than those originally tested,9 our findings pointing toward factors positively associated with cognition may contribute to the larger framework for development of prospective randomized control intervention studies on how to protect against cognitive decline in this vulnerable population.
SUPPLEMENTARY MATERIAL
Supplementary data are available at American Journal of Hypertension online.
DISCLOSURE
The authors declared no conflict of interest.
Supplementary Material
ACKNOWLEDGMENTS
The authors thank the staff and participants of HCHS/SOL for their important contributions. A complete list of staff and investigators has been provided by Sorlie P, et al. in Ann Epidemiol. 2010 Aug; 20: 642–649 and is also available on the study website http://www.cscc.unc.edu/hchs/. The Hispanic Community Health Study/Study of Latinos was carried out as a collaborative study supported by contracts from the National Heart, Lung, and Blood Institute (NHLBI) to the University of North Carolina (N01-HC65233), University of Miami (N01-HC65234), Albert Einstein College of Medicine (N01-HC65235), Northwestern University (N01-HC65236), and San Diego State University (N01-HC65237). The following Institutes/Centers/Offices contribute to the HCHS/SOL through a transfer of funds to the NHLBI: National Center on Minority Health and Health Disparities, the National Institute of Deafness and Other Communications Disorders, the National Institute of Dental and Craniofacial Research, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute of Neurological Disorders and Stroke, and the Office of Dietary Supplements. Drs González, Tarraf, and Daviglus receive additional support from AG48642. Funding for M.L. was provided by NIA K01-AG040192. This work was presented in poster form at the 2016 Cognitive Aging Conference in Atlanta, GA.
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