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Published in final edited form as: Hypertension. 2011 Sep 26;58(5):895–901. doi: 10.1161/HYPERTENSIONAHA.111.178178

Isolated diastolic hypotension and incident heart failure in older adults

Jason L Guichard a, Ravi V Desai b, Mustafa I Ahmed a, Marjan Mujib a, Gregg C Fonarow c, Margaret A Feller a, O James Ekundayo c,d, Vera Bittner a, Inmaculada B Aban a, Michel White e, Wilbert S Aronow f, Thomas E Love g, George L Bakris h, Susan J Zieman i, Ali Ahmed a,j,*
PMCID: PMC3390027  NIHMSID: NIHMS328373  PMID: 21947466

Abstract

Aging is often associated with increased systolic blood pressure and decreased diastolic blood pressure. Isolated systolic hypertension or an elevated systolic blood pressure without an elevated diastolic blood pressure is a known risk factor for incident heart failure in older adults. In the current study, we examined whether isolated diastolic hypotension, defined as a diastolic blood pressure <60 mm Hg and a systolic blood pressure ≥100 mm Hg, is associated with incident heart failure. Of the 5795 Medicare-eligible community-dwelling adults age ≥65 years in the Cardiovascular Health Study, 5521 were free of prevalent heart failure at baseline. After excluding 145 individuals with baseline systolic blood pressure <100 mm Hg, the final sample included 5376 participants, of whom 751 (14%) had isolated diastolic hypotension. Propensity scores for isolated diastolic hypotension were calculated for each of the 5376 participants and used to match 545 and 2348 participants with and without isolated diastolic hypotension, respectively who were balanced on 58 baseline characteristics. During over 12 years of median follow-up, centrally-adjudicated incident heart failure developed in 25% and 20% of matched participants with and without isolated diastolic hypotension respectively (hazard ratio associated with isolated diastolic hypotension, 1.33; 95% confidence interval, 1.10–1.61; p=0.004). Among the 5376 pre-match individuals, multivariable-adjusted hazard ratio for incident heart failure associated with isolated diastolic hypotension was 1.29 (95% confidence interval, 1.09–1.53; p=0.003). As in isolated systolic hypertension, among community-dwelling older adults without prevalent heart failure, isolated diastolic hypotension is also a significant independent risk factor for incident heart failure.

Keywords: aging, blood pressure, diastolic, heart failure, pulse pressure

Arterial stiffening is common in older adults and may contribute to the elevation of systolic blood pressure (SBP) and the depression of diastolic blood pressure (DBP), and a resultant widening of the pulse pressure (PP), all commonly observed in this population.1 Although isolated systolic hypertension (ISH), defined as isolated elevation of SBP without a concomitant elevation of DBP, is a known risk factor for incident heart failure (HF) in older adults,2, 3 little is known about the effect of an isolated diastolic hypotension (IDH), where DBP is decreased without a concomitant decrease in SBP. The purpose of this study was to examine the association between IDH and incident HF in community-dwelling older adults.

Methods

Study Design and Participants

The Cardiovascular Health Study (CHS) is a National Heart, Lung, and Blood Institute (NHLBI)-funded population-based prospective study of cardiovascular disease in older adults, the details of which have been reported previously.4–6 Briefly, 5888 Medicare-eligible community-dwelling older adults (≥65 years of age) were recruited in two phases: an original cohort of 5201 participants recruited during 1989–1990 was later supplemented with a second cohort of 687 African-American participants recruited during 1992–1993. For the purpose of the current study, we used a de-identified public-use copy of the CHS data obtained from the NHLBI. These data, prepared by the CHS Central Coordinating Center at the University of Washington, Seattle, are identical to the original CHS data except that it contains data on 5795 participants (93 did not consent to be included in the public-use copy of the data).

Of the 5795 participants, 274 had centrally-adjudicated prevalent HF at baseline and hence were excluded from the current analysis. Of the remaining 5521 participants, data on baseline SBP and DBP were available on 5504 participants. Because our definition of IDH excludes patients with SBP <100 mm Hg, we excluded 128 participants with SBP <100 mm Hg. Thus, the final sample size comprised of 5376 participants without baseline HF and with SBP ≥100 mm Hg. We included participants with and without treated hypertension to determine if the effect of IDH on incident HF varied by antihypertensive therapy.

Baseline IDH and Other Measurements

Seated SBP and DBP were measured at baseline in the right arm after a five minute rest with a Hawksley random-zero sphygmomanometer and the average of two measurements corrected for zero values was used.2 IDH was defined as DBP <60 mm Hg (and SBP ≥100 mm Hg), and of the 5376 participants, 751 (14%) had IDH. Because blood pressure is a continuous variable and our definition of IDH is categorical, to understand the clinical characteristics of those with IDH better, we also categorized those with IDH into the following SBP categories: 100–109, 110–119, 120–129, and 130–139 and ≥140 mm Hg. Data on demographics, past medical history, clinical findings, and laboratory variables were collected at baseline and have been described in detail previously.2, 4, 5 Missing values for continuous variables were imputed based on values predicted by age, sex and race.

Assembly of the Balanced Cohort

Considering significant imbalances in baseline characteristics between participants with and without IDH (Table 1 and Figure 1), we used propensity score matching to assemble a population in which those with and without IDH would be well-balanced in all measured baseline characteristics.7, 8 Propensity scores for IDH were estimated for each of the 5376 participants using a non-parsimonious multivariable logistic regression model, in which IDH was the dependent variable and 58 baseline characteristics (Figure 1) were used as covariates.3, 9–13 Using a greedy matching protocol we matched each IDH participant with up to five no-IDH participants who had similar propensity scores, thus matching 545 IDH participants to 2348 no-IDH participants.3, 9–13 Absolute standardized differences for all 58 covariates were estimated and presented as Love plots.

Table 1.

Baseline characteristics of older adults without prevalent heart failure by isolated diastolic hypotension (IDH)* before and after propensity score matching

n (%) or mean (±SD) Before matching P value After matching P value
No IDH
(n=4625)		 IDH
(n=751)		 No IDH
n=2348)		 IDH
(n=545)
Demographics
     Age ≥75 years 1458 (32%) 337 (45%) <0.001 890 (38%) 221 (41%) 0.253
     Female 2609 (56%) 486 (65%) <0.001 1452 (62%) 338 (62%) 0.938
     Non-white 798 (17%) 60 (8%) <0.001 237 (10%) 48 (9%) 0.364
     Education college or higher 1992 (43%) 320 (43%) 0.813 1026 (44%) 238 (434%) 0.991
Past Medical History
     Coronary artery disease 757 (16%) 181 (24%) <0.001 441 (19%) 113 (21%) 0.297
     Hypertension 2870 (62%) 321 (43%) <0.001 1169 (50%) 252 (46%) 0.135
     Diabetes mellitus 717 (16%) 134 (18%) 0.103 374 (16%) 92 (17%) 0.586
     Stroke 180 (4%) 31 (4%) 0.757 91 (4%) 24 (4%) 0.570
     Peripheral artery disease 568 (12%) 116 (15%) 0.016 459 (18%) 86 (24%) 0.007
     Loss of balance 1041 (23%) 200 (27%) 0.013 574 (24%) 145 (27%) 0.293
     Dizzy or light headed on standing up 939 (20%) 153 (20%) 0.965 480 (20%) 110 (20%) 0.892
     Frequent falls 147 (3%) 28 (4%) 0.431 79 (3%) 20 (4%) 0.724
     Self-reported fair to poor general health 1089 (24%) 178 (24%) 0.926 509 (22%) 126 (23%) 0.464
     Current smoker 537 (12%) 110 (15%) 0.018 313 (13%) 70 (13%) 0.763
     Alcohol, units per week 2.7 (±6.7) 1.6 (±4.2) <0.001 1.8 (±4.5) 1.9 (±4.6) 0.633
Physical Examination
     Body mass index, kg/m2 26.7 (±4.1) 25.9 (±3.9) <0.001 26.3 (±4.0) 26.2 (±3.8) 0.582
     Heart rate, bpm 68 (±11) 66 (±11) <0.001 67 (±10) 67 (±11) 0.672
     Systolic blood pressure, mm Hg 139 (±21) 126 (±18) <0.001 131 (±17) 130 (±18) 0.028
     Diastolic blood pressure, mm Hg† 74 (±9) 53 (±5) <0.001 71 (±8) 54 (±5) <0.001
     Pulse pressure, mm Hg† 66 (±11) 73 (±11) <0.001 60 (±16) 76 (±20) <0.001
     Mini-mental state examination 27.6 (±2.7) 27.3 (±2.9) 0.008 27.6 (±2.8) 27.4 (±2.6) 0.423
     Depression score 4.6 (±4.5) 4.9 (±4.8) 0.036 4.6 (±4.6) 4.7 (±4.7) 0.624
Cardiopulmonary Testing
     Atrial fibrillation by electrocardiogram 99 (2%) 11 (2%) 0.225 39 (2%) 11 (32%) 0.564
     Left ventricular hypertrophy by electrocardiogram 200 (4%) 35 (5%) 0.676 100 (4%) 24 (54%) 0.881
     Borderline or abnormal left ventricular systolic function 336 (7%) 66 (9%) 0.141 184 (8%) 44 (8%) 0.853
Medications
     Angiotensin-converting enzyme inhibitors 319 (7%) 28 (4%) 0.001 131 (6%) 21 (4%) 0.104
     Beta-blockers 593 (13%) 96 (13%) 0.977 324 (14%) 63 (12%) 0.166
     Calcium channel blockers 568 (12%) 106 (14%) 0.159 291 (12%) 62 (11%) 0.513
     Diuretics 1263 (27%) 208 (28%) 0.825 637 (27%) 150 (28%) 0.852
     Any antihypertensive drug 2133 (46%) 331 (44%) 0.297 1055 (45%) 235 (43%) 0.443
Laboratory Values
     Serum creatinine, mg/dL 0.96 (±0.38) 0.94 (±0.33) 0.106 0.94 (±0.36) 0.94 (±0.34) 0.922
     Serum uric acid, mg/dL 5.67 (±1.51) 5.57 (±1.49) 0.090 5.61 (±1.50) 5.60 (±1.50) 0.850
     Serum glucose, mg/dL 111 (±36) 112 (±38) 0.658 110 (±37) 111 (±35) 0.766
     Serum insulin, mcU/mL 17 (±24) 16 (±24) 0.606 16 (±23) 17 (±27) 0.593
     Serum potassium, mEq/L 4.16 (±0.38) 4.19 (±0.38) 0.020 4.17 (±0.37) 4.17 (±0.38) 0.994
     Total cholesterol, mg/dL 212 (±39) 209 (±40) 0.057 212 (±38) 211 (±40) 0.424
     Serum albumin, g/dL 4.00 (±0.28) 3.98 (±0.31) 0.059 3.99 (±0.28) 3.98 (±0.32) 0.200
     Serum C-reactive protein, mg/dL 4.6 (±7.7) 5.0 (±9.7) 0.217 4.6 (±7.4) 4.5 (±8.6) 0.767
     Hemoglobin, g/dL 14.1 (±1.3) 13.7 (±1.3) <0.001 13.9 (±1.3) 13.8 (±1.3) 0.357
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*

Defined as an average diastolic blood pressure <60 mm Hg and systolic blood pressure ≥100 mm Hg

†

Diastolic blood pressure and pulse pressure are related to the exposure variable, IDH, and are expected to be imbalanced and are presented as baseline descriptive purposes only

Figure 1.

Figure 1

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Love plot displaying absolute standardized differences in baseline characteristics between older adults with and without isolated diastolic hypotension (IDH), before and after propensity score matching

Incident Heart Failure and Other Outcomes

The primary outcome for this study was centrally-adjudicated incident HF during a median follow-up of over 12 years, which has been described previously.5, 14–19 Briefly, self-reports of physician-diagnosed HF ascertained during semi-annual visits were adjudicated by CHS Events Committee through the examination of participant’s medical records for clinical symptoms, physical signs, and other supporting evidence including medications commonly used for HF and follow-up surveillances. Secondary outcomes were all-cause mortality and other incident cardiovascular events.

Statistical Analysis

For descriptive analyses the Pearson’s chi-square test, student t-test, analysis of variance, Wilcoxon rank-sum test, and paired sample t-test were used as appropriate for between group comparisons. We used Kaplan Meier and Cox proportional hazard analyses to estimate the associations between IDH and outcomes. Subgroup analyses were performed to determine the homogeneity of this association. Sensitivity analyses were performed (1) to quantify the degree of a hidden bias that would need to be present to invalidate our conclusions based on the propensity-matched cohort;20 (2) to estimate the multivariable-adjusted association of IDH with incident HF in the 5376 pre-match participants using the 58 covariates used in the propensity model; and (3) to estimate the effect of IDH in 3141 pre-match participants without hypertension (after excluding 157 and 2078 participants with and without IDH who had SBP ≥140 mm Hg). All statistical tests were two-tailed with 95% confidence levels and a p-value <0.05 was considered significant. SPSS for Windows Version 15 (Chicago, IL) was used for all data analysis.

Results

Baseline Characteristics

Compared with participants without IDH, those with IDH were more likely to be older, female, Caucasian, current smokers, have coronary artery disease, but less likely to have hypertension, and have similar orthostatic symptoms, all of which were balanced after matching (Table 1 and Figure 1). Overall, 267 (5%) had DBP ≥90 mm Hg, and among the remaining 5109 participants, 1995 (39%) had ISH and 3114 (61%) had normal SBP. Among the 751 older adults with IDH, 41% had normal SBP, 38% had pre-hypertension, and 21% had ISH of whom respectively 37%, 48% and 53% received anti-hypertensive therapy (Table 2). Mean DBP was similar across SBP categories regardless of the use of anti-hypertensive drugs (Table 2).

Table 2.

Baseline characteristics of the 751 pre-match participants with isolated diastolic hypotension (IDH), by baseline systolic blood pressure (SBP)

Variable IDH
(Total)		 SBP (mm Hg) P value
100–109 110–119 120–129 130–139 >=140
Number (%), mean 751 (100) 126 (17) 184 (25) 158 (21) 126 (17) 157 (21)
Mean age 75 73 74 74 75 77 <0.001
Female 486 (65%) 81 (64%) 105 (57%) 105 (67%) 82 (65%) 113 (72%) 0.073
Hypertension 321 (43%) 24 (19%) 44 (24%) 52 (33%) 44 (35%) 157 (100%) <0.001
Coronary artery disease 181 (24%) 33 (26%) 42 (23%) 43 (27%) 26 (21%) 37 (24%) 0.707
Diabetes 134 (18%) 18 (14%) 27 (15%) 28 (18%) 21 (17%) 40 (26%) 0.069
Mean blood pressure in mm Hg in persons not receiving any antihypertensive drug
     SBP 125 105 115 124 134 155 <0.001
     DBP 54 55 54 54 54 53 0.197
     PP 71 50 61 70 80 102 <0.001
Any antihypertensive drugs 331 (44%) 45 (36%) 68 (37%) 74 (47%) 61 (48%) 83 (53%) 0.008
Mean blood pressure in mm Hg in persons receiving any antihypertensive drug
     SBP 129 106 115 124 134 152 <0.001
     DBP 54 54 53 54 54 54 0.200
     PP 75 52 62 70 80 99 <0.001
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DBP, diastolic blood pressure; PP, pulse pressure

Association of IDH with Incident HF

During over 12 years of median follow-up, incident HF developed in 25% and 20% of matched participants with and without IDH, respectively (hazard ratio {HR} when IDH was compared with no-IDH, 1.33; 95% confidence interval {CI}, 1.10–1.61; p=0.004; Table 3 and Figure 2). A hidden binary covariate that is a near-perfect predictor of incident HF would need to increase the odds of IDH by 17% to explain away this association. This association was homogenous across a wide spectrum of matched participants (Figure 3). Pre-match associations of IDH with incident HF are displayed in Table 3. The multivariable-adjusted HR for IDH-associated incident HF in pre-match participants with SBP <140 mm Hg was 1.43 (95% CI, 1.16–1.77; p=0.001).

Table 3.

Association of isolated diastolic hypotension (IDH)* with incident heart failure and all-cause mortality.

Outcomes Number of events (%) Absolute risk
difference† 		Hazard ratio
(95% confidence
interval)		 P value
No IDH IDH
Incident heart failure
Before matching (n=5376) n=4625 n=751
     Unadjusted 929 (20%) 189 (25%) + 5% 1.28 (1.10–1.50) 0.002
     Multivariable-adjusted --- --- --- 1.29 (1.09–1.53) 0.003
After matching (n=2893) n=2348 n=545
     Propensity-matched 459 (20%) 137 (25%) + 5% 1.33 (1.10–1.61) 0.004
All-cause mortality
Before matching (n=5376) n=4625 n=751
     Unadjusted 1997 (43%) 381 (51%) + 8% 1.19 (1.07–1.33) 0.002
     Multivariable-adjusted --- --- --- 1.14 (1.01–1.29) 0.031
After matching (n=2893) n=2348 n=545
     Propensity-matched 1039 (44%) 266 (49%) + 5% 1.12 (0.98–1.28) 0.096
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*

Defined as an average diastolic blood pressure <60 mm Hg and systolic blood pressure ≥100 mm Hg

†

Absolute risk differences were calculated by subtracting the percent of events in the isolated diastolic hypotension group from the percent of events in the no isolated diastolic hypotension group (before values were rounded)

Figure 2.

Figure 2

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Kaplan-Meier plot for incident heart failure by isolated diastolic hypotension (IDH). (CI=confidence interval; HR=hazard ratio)

Figure 3.

Figure 3

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Association of baseline isolated diastolic hypotension (IDH) with incident heart failure in subgroups of propensity score-matched older adults (IDH=isolated diastolic hypotension; CI=confidence interval)

Association of IDH with Other Outcomes

All-cause mortality occurred in 49% and 44% of matched participants with and without IDH respectively (HR associated with IDH, 1.12; 95% CI, 0.98–1.28; p=0.096; Table 3). IDH had no significant association with acute myocardial infarction (HR, 0.94; 95% CI, 0.69–1.27; p=0.664), angina pectoris (HR, 1.04; 95% CI, 0.83–1.32; p=0.724), stroke (HR, 0.95; 95% CI, 0.74–1.24; p=0.720), transient ischemic attack (HR, 1.21; 95% CI, 0.72–2.04; p=0.475), and peripheral arterial disease (HR, 0.81; 95% CI, 0.48–1.36; p=0.420).

Discussion

The results of the current analysis demonstrate that IDH was an independent risk factor for incident HF among community-dwelling older adults, which was similar in magnitude to the effect of ISH on incident HF in this cohort.3 We also demonstrate that the effect of IDH on incident HF was homogeneous across a wide spectrum of older adults, including those with SBP <140 mm Hg. Although diastolic hypotension has been shown to be associated with adverse cardiovascular outcomes,21 to the best of our knowledge, this is the first report of a propensity-matched study identifying IDH as a significant independent risk factor for centrally-adjudicated incident HF in community-dwelling older adults.

As in ISH and wide PP, IDH is also primarily a manifestation of impaired aortic compliance associated with aging which results in an rise in SBP and a fall in DBP thus widening the PP. 22–26,27 The resultant increased afterload and myocardial oxygen demand may result in myocardial ischemia and subsequent systolic and diastolic dysfunction.28, 29 Poor outcomes associated with a DBP ≤60 mm Hg in frail older adults has been reported to be independent of aortic compliance and LVEF.30 Hypertension or uncontrolled SBP is unlikely to explain the association between IDH and incident HF as the association persisted after excluding those with SBP ≥140 mm Hg. In addition, the use of anti-hypertensive drugs is unlikely to explain this association, as the mean SBP and DBP were similar regardless of the use of antihypertensive drugs. Although both ISH and IDH are associated with wide PP, the role of SBP and DBP in these two conditions may differ. For example, despite a similar PP (70 mm Hg), DBP may not play a role in the development of incident HF in ISH (150/80 mm Hg) while SBP may not play a role in the development of incident HF in IDH (120/50 mm Hg).31 Further studies are needed to elucidate the detailed mechanisms by which IDH is associated with incident HF.

In patients with hypertension and coronary artery disease, a low DBP has been shown to be associated with poor outcomes and it has been suggested that excessive reduction in DBP should be avoided in these patients.30, 32 Despite the fact that in our study the mean SBP and DBP were similar regardless of antihypertensive therapy, data from ISH suggest that antihypertensive therapy is often associated with concomitant lowering of DBP.33 Because intensive lowering of SBP may not reduce major cardiovascular events,34 taken together with the findings of the current study, it may be reasonable to keep DBP at or above 60 mm Hg in older adults with ISH. Future hypertension guidelines need to focus on optimal DBP parameters for older adults receiving antihypertensive therapy.

Several limitations of our study need to be acknowledged. We had no data on dosages of antihypertensive drugs used to determine if those with IDH were receiving higher doses. It is possible that participants without IDH at baseline may have developed IDH during follow-up and this regression dilution may have underestimated the associations observed in our study.35 The association of IDH with outcomes may vary across various subsets of SBP, which needs to be examined in the future. Despite the displayed balance in all measured baseline covariates, bias due to residual imbalance or imbalance in an unmeasured covariate is possible. However, findings from our sensitivity analysis suggest that the association of IDH with incident HF was rather insensitive to an unmeasured covariate.

Perspectives

Isolated diastolic hypotension (IDH), defined as a diastolic blood pressure <60 mm Hg with a systolic blood pressure ≥100 mm Hg, is an independent risk factor for incident heart failure in community-dwelling older adults, the magnitude of which is similar to the effect of isolated systolic hypertension on incident heart failure.

Acknowledgements

The Cardiovascular Health Study (CHS) was conducted and supported by the National Heart, Lung, and Blood Institute (NHLBI) in collaboration with the CHS investigators. This manuscript was prepared using a limited access dataset obtained from the NHLBI and does not necessarily reflect the opinions or views of the CHS or the NHLBI.

Sources of Funding

Dr. Ahmed is supported by the National Institutes of Health through grants (R01-HL085561, R01-HL085561-S and R01-HL097047) from the National Heart, Lung, and Blood Institute and a generous gift from Ms. Jean B. Morris of Birmingham, Alabama.

Footnotes

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Disclosures

None.

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