American Journal of Hypertension Advance Access published July 1, 2015
Original Article
Hypertension, Dietary Sodium, and Cognitive Decline: Results From the Women’s Health Initiative Memory Study Bernhard Haring,1 Chunyuan Wu,2 Laura H. Coker,3 Arjun Seth,4 Linda Snetselaar,5 JoAnn E. Manson,6 Jacques E. Rossouw,7 and Sylvia Wassertheil-Smoller4 BACKGROUND To investigate the relationships of hypertension, antihypertensive treatment, and sodium intake on cognitive decline in older women.
RESULTS Hypertension was associated with an increased risk for cognitive decline (HR 1.20; 95% confidence interval (CI) 1.04, 1.39; P = 0.02). Among women
CONCLUSIONS Women with antihypertensive treatment and uncontrolled BP showed highest risk estimates for developing cognitive decline compared to non-hypertensive women. Sodium intake did not modify the risk for cognitive decline in women with hypertension or receiving antihypertensive medication. clinical trial registration http://www.clinicaltrials.gov. Unique identifier: NCT00685009 and NCT00745056 Keywords: antihypertensive treatment; blood pressure; cognitive decline; dietary sodium; hypertension. doi:10.1093/ajh/hpv081
The number of individuals affected by cognitive decline is expected to rise over the next few decades.1 Investigating the effects of risk factors and life-style modification on the preservation of cognitive functioning is of major public health interest.2 Blood pressure (BP) control has emerged to be a key target for long-term interventions to reduce cognitive deterioration but age-dependent results exist.2,3 Hypertension in mid-life is associated with cognitive decline while antihypertensive treatment is shown to be protective.4,5 Nonetheless, in elderly individuals data on the effect of BP control on cognitive decline are still inconsistent.3,6 Differences may be explained by the duration of exposure before incident disease.6 Late-life onset hypertension simply may not last long
enough to result in cognitive dysfunction. Large populationbased long-term studies are needed for further clarification. Dietary sodium intake is related to the incidence and severity of hypertension.7–9 In 2010, mean sodium intake in the United States and Canada was approximately 3,800 mg/ day,10 even though the physiologically necessary daily intake of sodium is estimated to be only approximately 180 to 230 mg/day.11 But, while scientific evidence for the benefits of dietary sodium reduction on BP control is strong,7,12,13 to this point surprisingly little is known about the effect of sodium intake on hypertension and cognitive decline.14 The objective of this study was first to evaluate the effect of hypertension and antihypertensive treatment on cognitive
Correspondence: Bernhard Haring ([email protected]).
1Department of Internal Medicine I, Comprehensive Heart Failure Center, University of Würzburg, Würzburg, Bavaria, Germany; 2Women’s Health Initiative, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA; 3Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA; 4Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York, USA; 5Department of Epidemiology, University of Iowa College of Public Health, Iowa City, Iowa, USA; 6Division of Preventive Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA; 7National Heart, Lung, and Blood Institute, Bethesda, Maryland, USA.
Initially submitted January 13, 2015; date of first revision May 7, 2015; accepted for publication May 8, 2015.
© American Journal of Hypertension, Ltd 2015. All rights reserved. For Permissions, please email: [email protected]
American Journal of Hypertension 1
Downloaded from http://ajh.oxfordjournals.org/ at University of Georgia on July 18, 2015
METHODS Prospective follow-up of 6,426 cognitively intact women aged 65–79 years enrolled in the Women’s Health Initiative Memory Study (WHIMS) with a median follow-up of 9.1 years. Dietary sodium intake was determined by food frequency questionnaires. Hypertension was defined as self-report of current drug therapy for hypertension. Blood pressure (BP) control was assessed by treatment for hypertension and clinic measurement of systolic BP ≥ 140 mm Hg or diastolic BP ≥ 90 mm Hg at baseline. Cognitive functioning was assessed annually by global cognitive screening, neurocognitive, and neuropsychiatric evaluations. Cognitive decline was identified by the incidence of mild cognitive impairment (MCI) or probable dementia (PD). Cox proportional hazards analyses were used to calculate hazard ratios (HRs).
with antihypertensive medication, those with BP ≥140/90 mm Hg (uncontrolled BP) were at highest risk for developing cognitive decline (HR 1.30; 95% CI 1.05, 1.60) compared to women without treatment and BP 1,500 mg/day did not alter the risk for cognitive decline in hypertensive women or women with antihypertensive treatment (Pfor interaction = 0.96 or 0.97).
Haring et al.
decline in elderly postmenopausal women. Second, we aimed to investigate the effect of dietary sodium on the incidence of cognitive decline in women with hypertension or antihypertensive medication. METHODS Study population
Sodium intake was derived from self-report Women’s Health Initiative food frequency questionnaires (WHIFFQs) that were administered to all WHI participants at baseline.19,24,25 The WHI-FFQ was based on the Block FFQ and has demonstrated good validity.19,25,26 Nonetheless, as several limitations of dietary sodium assessment by FFQs have been reported previously,27 we additionally conducted separate analyses based on 24-hour urine excretions in a subsample of women to correct dietary self-report data of sodium intake for potential measurement errors (Supplementary Tables 1 and 2).28 BP was measured by certified staff using standardized procedures in a WHI clinic.19 The average of two baseline readings taken at the same clinic visit was used for the analyses. Hypertension was defined as self-report of current drug therapy for hypertension. BP control was assessed by treatment for hypertension and clinic measurement of systolic BP ≥ 140 mm Hg or diastolic BP ≥ 90 mm Hg at baseline. Antihypertensive medication data were collected during inperson clinic visits at baseline.29 Outcome assessment
The primary outcome measure for this study was cognitive decline (MCI/PD) which we identified by the incidence of “MCI or PD.” Cognitive functioning was evaluated in all women enrolled in WHIMS annually using the Modified Mini-Mental State Examination (3MS) as an initial screening test. It summed from 0 to 100 with higher scores reflecting better cognitive functioning.30 If a participant scored below preestablished cut-points depending on previous education, further neurocognitive and neuropsychiatric examinations were conducted to establish the presence of MCI or PD. The diagnosis MCI or PD was based on the criteria established by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition.31 A detailed description of the WHIMS protocol has been published previously.17,18 MCI was diagnosed if the participant showed poor performance (10th or lower percentile) in at least 1 area of cognitive function on modified neuropsychological tests established by the Consortium to Establish a Registry for Alzheimer’s Disease32 or if the participant was reported to
Total Number of women (WHIMS Trial) (n =7,479)
Not included in this study (n=1,053): Missing baseline (n=67) MCI at baseline (n=8) Missing Follow-up (n=240) Incomplete Dietary Informaon or extreme calorie intake (n=206) Missing covariates (n=532) Final study populaon (n=6,426)
Figure 1. Study inclusion.
2 American Journal of Hypertension
Downloaded from http://ajh.oxfordjournals.org/ at University of Georgia on July 18, 2015
The total study population included 7,479 postmenopausal women enrolled in the Women’s Health Initiative Memory Study (WHIMS). WHIMS consisted of two parallel randomized clinical trials designed to investigate the effect of estrogen alone (E alone) or in combination with progestin (E + P) on the incidence of probable dementia (PD) and mild cognitive impairment (MCI).15–18 WHIMS participants were recruited between May 1996 and December 1999 at 39 US clinical centers from women enrolled in the Women’s Health Initiative (WHI) hormone therapy trials who were aged 65–79 years and were free of dementia at enrollment. Details of the study population and of the initial screening process for the WHI and WHIMS have been reported previously.18,19 WHIMS participants returned to in-clinic visits annually for cognitive assessment and were contacted by semiannual questionnaires to ascertain selected exposures and medical outcomes.18,19 The WHIMS E + P trial ended earlier than planned in July 200216,17 due to adverse risk to benefit ratio in the WHI parent study20; and in February 2004, the E Alone Study ended with early termination of WHI trial.15,21,22 WHIMS participants continued annual post-trial cognitive assessment through the WHIMS Extension Study until 2007/2008 and then through the “Women’s Health Initiative (WHI) Memory Study-Epidemiology of Cognitive Health Outcomes” (WHIMS-ECHO) study to present. For this analysis, we excluded WHIMS participants with missing baseline or follow-up information (n = 307). Eight women with MCI at baseline and 532 women with missing covariate data were not considered; 206 participants with incomplete dietary information or with extreme calorie intake (i.e., 3,500 kcal per day) were excluded from further analysis.23 Our final study population was 6,426 postmenopausal women (Figure 1). Individuals were followed up through 31 December 2012 with a median followup of 9.11 years.
Exposure assessment
Hypertension, Dietary Sodium, and Cognitive Decline
Covariates
Information on all covariates was derived from self-report or by physical measure at WHI baseline.19 Cardiovascular disease was defined as history of myocardial infarction, angina pectoris, atrial fibrillation, heart failure, peripheral vascular disease, coronary bypass surgery, angioplasty, carotid endarterectomy, or stroke. Women were coded positive for diabetes on the basis of self-report of diabetes or diabetes treatment. Body mass index was defined as weight in kg/height in m2. Physical activity was measured with metabolic equivalent tasks (METs) in hours per week.33 Statistical analysis
The characteristics of included women are presented by hypertension status at baseline (Table 1). To analyze the effect of hypertension or antihypertensive treatment on cognitive decline incidence rates of MCI or PD were determined (Tables 2–7). Corresponding rate ratios were calculated by dividing the rate among women with hypertension or antihypertensive treatment by the rate without hypertension or antihypertensive medication. Three Cox proportional hazards models were used to estimate the risk for developing cognitive decline. To control for confounding, we first adjusted our analyses for menopausal hormone therapy (WHI HT arm—active vs. placebo), age (10-year age group), race, education level, and baseline 3MSE level (Model 1). Additionally, we adjusted for alcohol, smoking status, physical activity, diabetes status, categorical body mass index, depression, and total energy intake (Model 2). Last, we added history of cardiovascular disease to our model (Model 3). To assess the effect of sodium intake on the relationship between hypertension, antihypertensive medication use, and cognitive decline, Cox proportional hazards regression models were performed separately according to various amounts of sodium intake. Data on sodium intake were derived from FFQs (Table 8 and 9) and corrected using
calibration equations based on 24-hour urine excretions (Supplementary Tables 1 and 2). All P values were 2-tailed. All the analyses were conducted using SAS statistical software (version 9.3; SAS Institute, Cary, NC). RESULTS
The characteristics of women by hypertension status are shown in Table 1. Hypertensive women were older, had higher body mass index, lower education, were less physically active and more likely to be treated for diabetes compared to normotensive women. Women with hypertension also had slightly lower 3MS scores and consumed on average more sodium per day. During a median follow-up of 9.1 years 498 women were diagnosed with “MCI,” 389 with “PD” and 753 women with “MCI or PD” (MCI/PD). Three hundred and sixty-four women developed MCI only, 134 women with MCI further developed PD and 255 women were diagnosed with PD without having had a previous diagnosis of MCI. The multivariate-adjusted hazard ratios (HRs) for incident MCI, PD, or MCI/PD related to BP control are presented in Tables 2–7. After fully adjusting for confounding variables (Model 3), women with self-report of hypertension were at greater risk for developing cognitive decline (MCI/PD) compared to normotensive individuals (HR 1.20; 95% confidence interval (CI) 1.04, 1.39; P value = 0.02) (Table 4). In detailed analyses of BP control, among women with antihypertensive medication (treated), those with BP ≥140/90 mm Hg (uncontrolled BP) showed highest risk estimates for developing cognitive decline (HR 1.30; 95% CI 1.05, 1.60) compared to women without treatment (untreated) and BP 1,500 mg/day tended to increase the risk for MCI/PD in women with hypertension (HR 1.24; 95% CI 1.02, 1.52) and antihypertensive medication (HR 1.19; 95% CI 0.97, 1.46), whereas sodium intake ≤ 1,500 mg/day did not significantly alter this risk (HR 1.23; 95% CI 0.85, 1.78 and HR 1.18; 95% CI 0.81, 1.71). Formal tests for interaction were not significant. As determining sodium intake by FFQ has methodological limitations,27 we additionally examined potential interactions using corrected dietary self-report data of sodium intake (Supplementary Tables 1 and 2). After applying calibration equations based on 24-hour urine excretions method, the exposure distribution of our study sample changed reflecting higher actual sodium consumption than as assessed by American Journal of Hypertension 3
Downloaded from http://ajh.oxfordjournals.org/ at University of Georgia on July 18, 2015
suffer from some functional impairment excluding a basic activity of daily living by a reliable informant. Prior to the diagnosis, other medical or psychiatric conditions, including depression were excluded as potential reasons for the participant’s cognitive functioning. Participants showing additional impairments in social and occupational functioning secondary to cognitive impairment and not otherwise explained by other medical causes were classified as having PD. All clinical and test data including MCI and PD cases were transmitted to the WHIMS Clinical Coordinating Center for review and central adjudication.15,17 In 2008, cognitive assessment in WHIMS transitioned from in-clinic post-trial annual follow-up to participation in the WHIMS-Epidemiology of Cognitive Health Outcomes’ (WHIMS-ECHO) study. Instead of in-clinic visits and faceto-face evaluation, participants in WHIMS-ECHO underwent an annual centralized, validated cognitive telephone interview for tracking changes in cognitive status as previously described.
Haring et al. Table 1. Baseline characteristics by hypertension status Normotensive
Age group (year)
Race: Caucasian Education
N
%
N
%
65–69
1,662
50.79
1,340
42.49
70–74
1,126
34.41
1,167
37.00
75–79
484
14.79
647
20.51
No
295
9.02
472
14.97
Yes
2,977
90.98
2,682
85.06
.
200
6.11
234
7.42
0.0121
Original Article
Hypertension, Dietary Sodium, and Cognitive Decline: Results From the Women’s Health Initiative Memory Study Bernhard Haring,1 Chunyuan Wu,2 Laura H. Coker,3 Arjun Seth,4 Linda Snetselaar,5 JoAnn E. Manson,6 Jacques E. Rossouw,7 and Sylvia Wassertheil-Smoller4 BACKGROUND To investigate the relationships of hypertension, antihypertensive treatment, and sodium intake on cognitive decline in older women.
RESULTS Hypertension was associated with an increased risk for cognitive decline (HR 1.20; 95% confidence interval (CI) 1.04, 1.39; P = 0.02). Among women
CONCLUSIONS Women with antihypertensive treatment and uncontrolled BP showed highest risk estimates for developing cognitive decline compared to non-hypertensive women. Sodium intake did not modify the risk for cognitive decline in women with hypertension or receiving antihypertensive medication. clinical trial registration http://www.clinicaltrials.gov. Unique identifier: NCT00685009 and NCT00745056 Keywords: antihypertensive treatment; blood pressure; cognitive decline; dietary sodium; hypertension. doi:10.1093/ajh/hpv081
The number of individuals affected by cognitive decline is expected to rise over the next few decades.1 Investigating the effects of risk factors and life-style modification on the preservation of cognitive functioning is of major public health interest.2 Blood pressure (BP) control has emerged to be a key target for long-term interventions to reduce cognitive deterioration but age-dependent results exist.2,3 Hypertension in mid-life is associated with cognitive decline while antihypertensive treatment is shown to be protective.4,5 Nonetheless, in elderly individuals data on the effect of BP control on cognitive decline are still inconsistent.3,6 Differences may be explained by the duration of exposure before incident disease.6 Late-life onset hypertension simply may not last long
enough to result in cognitive dysfunction. Large populationbased long-term studies are needed for further clarification. Dietary sodium intake is related to the incidence and severity of hypertension.7–9 In 2010, mean sodium intake in the United States and Canada was approximately 3,800 mg/ day,10 even though the physiologically necessary daily intake of sodium is estimated to be only approximately 180 to 230 mg/day.11 But, while scientific evidence for the benefits of dietary sodium reduction on BP control is strong,7,12,13 to this point surprisingly little is known about the effect of sodium intake on hypertension and cognitive decline.14 The objective of this study was first to evaluate the effect of hypertension and antihypertensive treatment on cognitive
Correspondence: Bernhard Haring ([email protected]).
1Department of Internal Medicine I, Comprehensive Heart Failure Center, University of Würzburg, Würzburg, Bavaria, Germany; 2Women’s Health Initiative, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA; 3Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA; 4Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York, USA; 5Department of Epidemiology, University of Iowa College of Public Health, Iowa City, Iowa, USA; 6Division of Preventive Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA; 7National Heart, Lung, and Blood Institute, Bethesda, Maryland, USA.
Initially submitted January 13, 2015; date of first revision May 7, 2015; accepted for publication May 8, 2015.
© American Journal of Hypertension, Ltd 2015. All rights reserved. For Permissions, please email: [email protected]
American Journal of Hypertension 1
Downloaded from http://ajh.oxfordjournals.org/ at University of Georgia on July 18, 2015
METHODS Prospective follow-up of 6,426 cognitively intact women aged 65–79 years enrolled in the Women’s Health Initiative Memory Study (WHIMS) with a median follow-up of 9.1 years. Dietary sodium intake was determined by food frequency questionnaires. Hypertension was defined as self-report of current drug therapy for hypertension. Blood pressure (BP) control was assessed by treatment for hypertension and clinic measurement of systolic BP ≥ 140 mm Hg or diastolic BP ≥ 90 mm Hg at baseline. Cognitive functioning was assessed annually by global cognitive screening, neurocognitive, and neuropsychiatric evaluations. Cognitive decline was identified by the incidence of mild cognitive impairment (MCI) or probable dementia (PD). Cox proportional hazards analyses were used to calculate hazard ratios (HRs).
with antihypertensive medication, those with BP ≥140/90 mm Hg (uncontrolled BP) were at highest risk for developing cognitive decline (HR 1.30; 95% CI 1.05, 1.60) compared to women without treatment and BP 1,500 mg/day did not alter the risk for cognitive decline in hypertensive women or women with antihypertensive treatment (Pfor interaction = 0.96 or 0.97).
Haring et al.
decline in elderly postmenopausal women. Second, we aimed to investigate the effect of dietary sodium on the incidence of cognitive decline in women with hypertension or antihypertensive medication. METHODS Study population
Sodium intake was derived from self-report Women’s Health Initiative food frequency questionnaires (WHIFFQs) that were administered to all WHI participants at baseline.19,24,25 The WHI-FFQ was based on the Block FFQ and has demonstrated good validity.19,25,26 Nonetheless, as several limitations of dietary sodium assessment by FFQs have been reported previously,27 we additionally conducted separate analyses based on 24-hour urine excretions in a subsample of women to correct dietary self-report data of sodium intake for potential measurement errors (Supplementary Tables 1 and 2).28 BP was measured by certified staff using standardized procedures in a WHI clinic.19 The average of two baseline readings taken at the same clinic visit was used for the analyses. Hypertension was defined as self-report of current drug therapy for hypertension. BP control was assessed by treatment for hypertension and clinic measurement of systolic BP ≥ 140 mm Hg or diastolic BP ≥ 90 mm Hg at baseline. Antihypertensive medication data were collected during inperson clinic visits at baseline.29 Outcome assessment
The primary outcome measure for this study was cognitive decline (MCI/PD) which we identified by the incidence of “MCI or PD.” Cognitive functioning was evaluated in all women enrolled in WHIMS annually using the Modified Mini-Mental State Examination (3MS) as an initial screening test. It summed from 0 to 100 with higher scores reflecting better cognitive functioning.30 If a participant scored below preestablished cut-points depending on previous education, further neurocognitive and neuropsychiatric examinations were conducted to establish the presence of MCI or PD. The diagnosis MCI or PD was based on the criteria established by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition.31 A detailed description of the WHIMS protocol has been published previously.17,18 MCI was diagnosed if the participant showed poor performance (10th or lower percentile) in at least 1 area of cognitive function on modified neuropsychological tests established by the Consortium to Establish a Registry for Alzheimer’s Disease32 or if the participant was reported to
Total Number of women (WHIMS Trial) (n =7,479)
Not included in this study (n=1,053): Missing baseline (n=67) MCI at baseline (n=8) Missing Follow-up (n=240) Incomplete Dietary Informaon or extreme calorie intake (n=206) Missing covariates (n=532) Final study populaon (n=6,426)
Figure 1. Study inclusion.
2 American Journal of Hypertension
Downloaded from http://ajh.oxfordjournals.org/ at University of Georgia on July 18, 2015
The total study population included 7,479 postmenopausal women enrolled in the Women’s Health Initiative Memory Study (WHIMS). WHIMS consisted of two parallel randomized clinical trials designed to investigate the effect of estrogen alone (E alone) or in combination with progestin (E + P) on the incidence of probable dementia (PD) and mild cognitive impairment (MCI).15–18 WHIMS participants were recruited between May 1996 and December 1999 at 39 US clinical centers from women enrolled in the Women’s Health Initiative (WHI) hormone therapy trials who were aged 65–79 years and were free of dementia at enrollment. Details of the study population and of the initial screening process for the WHI and WHIMS have been reported previously.18,19 WHIMS participants returned to in-clinic visits annually for cognitive assessment and were contacted by semiannual questionnaires to ascertain selected exposures and medical outcomes.18,19 The WHIMS E + P trial ended earlier than planned in July 200216,17 due to adverse risk to benefit ratio in the WHI parent study20; and in February 2004, the E Alone Study ended with early termination of WHI trial.15,21,22 WHIMS participants continued annual post-trial cognitive assessment through the WHIMS Extension Study until 2007/2008 and then through the “Women’s Health Initiative (WHI) Memory Study-Epidemiology of Cognitive Health Outcomes” (WHIMS-ECHO) study to present. For this analysis, we excluded WHIMS participants with missing baseline or follow-up information (n = 307). Eight women with MCI at baseline and 532 women with missing covariate data were not considered; 206 participants with incomplete dietary information or with extreme calorie intake (i.e., 3,500 kcal per day) were excluded from further analysis.23 Our final study population was 6,426 postmenopausal women (Figure 1). Individuals were followed up through 31 December 2012 with a median followup of 9.11 years.
Exposure assessment
Hypertension, Dietary Sodium, and Cognitive Decline
Covariates
Information on all covariates was derived from self-report or by physical measure at WHI baseline.19 Cardiovascular disease was defined as history of myocardial infarction, angina pectoris, atrial fibrillation, heart failure, peripheral vascular disease, coronary bypass surgery, angioplasty, carotid endarterectomy, or stroke. Women were coded positive for diabetes on the basis of self-report of diabetes or diabetes treatment. Body mass index was defined as weight in kg/height in m2. Physical activity was measured with metabolic equivalent tasks (METs) in hours per week.33 Statistical analysis
The characteristics of included women are presented by hypertension status at baseline (Table 1). To analyze the effect of hypertension or antihypertensive treatment on cognitive decline incidence rates of MCI or PD were determined (Tables 2–7). Corresponding rate ratios were calculated by dividing the rate among women with hypertension or antihypertensive treatment by the rate without hypertension or antihypertensive medication. Three Cox proportional hazards models were used to estimate the risk for developing cognitive decline. To control for confounding, we first adjusted our analyses for menopausal hormone therapy (WHI HT arm—active vs. placebo), age (10-year age group), race, education level, and baseline 3MSE level (Model 1). Additionally, we adjusted for alcohol, smoking status, physical activity, diabetes status, categorical body mass index, depression, and total energy intake (Model 2). Last, we added history of cardiovascular disease to our model (Model 3). To assess the effect of sodium intake on the relationship between hypertension, antihypertensive medication use, and cognitive decline, Cox proportional hazards regression models were performed separately according to various amounts of sodium intake. Data on sodium intake were derived from FFQs (Table 8 and 9) and corrected using
calibration equations based on 24-hour urine excretions (Supplementary Tables 1 and 2). All P values were 2-tailed. All the analyses were conducted using SAS statistical software (version 9.3; SAS Institute, Cary, NC). RESULTS
The characteristics of women by hypertension status are shown in Table 1. Hypertensive women were older, had higher body mass index, lower education, were less physically active and more likely to be treated for diabetes compared to normotensive women. Women with hypertension also had slightly lower 3MS scores and consumed on average more sodium per day. During a median follow-up of 9.1 years 498 women were diagnosed with “MCI,” 389 with “PD” and 753 women with “MCI or PD” (MCI/PD). Three hundred and sixty-four women developed MCI only, 134 women with MCI further developed PD and 255 women were diagnosed with PD without having had a previous diagnosis of MCI. The multivariate-adjusted hazard ratios (HRs) for incident MCI, PD, or MCI/PD related to BP control are presented in Tables 2–7. After fully adjusting for confounding variables (Model 3), women with self-report of hypertension were at greater risk for developing cognitive decline (MCI/PD) compared to normotensive individuals (HR 1.20; 95% confidence interval (CI) 1.04, 1.39; P value = 0.02) (Table 4). In detailed analyses of BP control, among women with antihypertensive medication (treated), those with BP ≥140/90 mm Hg (uncontrolled BP) showed highest risk estimates for developing cognitive decline (HR 1.30; 95% CI 1.05, 1.60) compared to women without treatment (untreated) and BP 1,500 mg/day tended to increase the risk for MCI/PD in women with hypertension (HR 1.24; 95% CI 1.02, 1.52) and antihypertensive medication (HR 1.19; 95% CI 0.97, 1.46), whereas sodium intake ≤ 1,500 mg/day did not significantly alter this risk (HR 1.23; 95% CI 0.85, 1.78 and HR 1.18; 95% CI 0.81, 1.71). Formal tests for interaction were not significant. As determining sodium intake by FFQ has methodological limitations,27 we additionally examined potential interactions using corrected dietary self-report data of sodium intake (Supplementary Tables 1 and 2). After applying calibration equations based on 24-hour urine excretions method, the exposure distribution of our study sample changed reflecting higher actual sodium consumption than as assessed by American Journal of Hypertension 3
Downloaded from http://ajh.oxfordjournals.org/ at University of Georgia on July 18, 2015
suffer from some functional impairment excluding a basic activity of daily living by a reliable informant. Prior to the diagnosis, other medical or psychiatric conditions, including depression were excluded as potential reasons for the participant’s cognitive functioning. Participants showing additional impairments in social and occupational functioning secondary to cognitive impairment and not otherwise explained by other medical causes were classified as having PD. All clinical and test data including MCI and PD cases were transmitted to the WHIMS Clinical Coordinating Center for review and central adjudication.15,17 In 2008, cognitive assessment in WHIMS transitioned from in-clinic post-trial annual follow-up to participation in the WHIMS-Epidemiology of Cognitive Health Outcomes’ (WHIMS-ECHO) study. Instead of in-clinic visits and faceto-face evaluation, participants in WHIMS-ECHO underwent an annual centralized, validated cognitive telephone interview for tracking changes in cognitive status as previously described.
Haring et al. Table 1. Baseline characteristics by hypertension status Normotensive
Age group (year)
Race: Caucasian Education
N
%
N
%
65–69
1,662
50.79
1,340
42.49
70–74
1,126
34.41
1,167
37.00
75–79
484
14.79
647
20.51
No
295
9.02
472
14.97
Yes
2,977
90.98
2,682
85.06
.
200
6.11
234
7.42
0.0121
