Abstract

BACKGROUND

Prehypertension (blood pressure (BP) of 120–139mm Hg systolic and/or 80–89mm Hg diastolic) is highly prevalent and is associated with increased cardiovascular risk. Our goal was to investigate the extent to which prehypertension is associated with end-organ alterations in cardiac structure and function in a large biracial cohort of older men and women.

METHODS

We studied 4,871 participants of the Atherosclerosis Risk in Communities (ARIC) study who attended visit 5 (2011–2013) and underwent two-dimensional echocardiography while free of prevalent coronary heart disease or heart failure. We categorized participants into 3 groups: optimal BP (BP <120mm Hg and <80mm Hg) ( n = 402), prehypertension ( n = 537), and hypertension ( n = 3,932).

RESULTS

Individuals with prehypertension (75±5 years) had higher left ventricular (LV) mass index and wall thickness, and higher prevalence of abnormal LV geometry than those with optimal BP (74±5 years), but lower than those with frank hypertension (76±5 years). In addition, participants with prehypertension had impairment of diastolic parameters (E/A, E′ and E/E′), and had higher prevalence of mild and moderate-severe diastolic dysfunction compared to those with optimal BP, but no differences in systolic parameters. These differences in cardiac structure and function remained significant after adjusting for important clinical covariates.

CONCLUSION

In the ARIC cohort at visit 5, prehypertension was associated with increased LV remodeling and impaired diastolic function, but not systolic function, suggesting that even mildly elevated BP within the normal range is associated with cardiac end-organ damage.

Prehypertension is defined as blood pressure (BP) ranging from 120 to 139mm Hg systolic and/or from 80 to 89mm Hg diastolic in adults not taking any BP lowering medication. 1 Prehypertension affects approximately 36% of US adults, 2 increases in prevalence with age, and occurs more often in men than women and in blacks than whites. 3 , 4 This category of BP, previously thought to constitute normal levels of BP, has increasingly been recognized as contributing to cardiovascular risk. 5–7 In the Atherosclerosis Risk in Communities (ARIC) study, the relative risk of cardiovascular disease in persons with prehypertension was 2.3-fold higher than for those with optimal BP (<120 and 80mm Hg), and this risk was even higher in African-Americans and in individuals with diabetes, low-density lipoprotein 100–129mg/dl, or body mass index >30kg/m 2 . 8 Recent meta-analyses have shown that prehypertension augments the risk of coronary heart disease and stroke independent of other cardiovascular risk factors and even in the setting of a BP ranging from 120 to 129mm Hg systolic and/or from 80 to 84mm Hg diastolic. 9–11 Despite these data, current guidelines have not recommended aggressively treating prehypertension even among individuals with concomitant cardiovascular risk factors. 12 , 13

To investigate the extent to which prehypertension may be associated with preclinical target organ damage, particularly among subgroups of individuals at higher risk for cardiovascular events, we comprehensively investigated the association of prehypertension with parameters of left ventricular (LV) structure and function in a large, biracial community-based cohort of elderly men and women.

METHODS

Study sample

The ARIC study is a prospective epidemiologic study designed to investigate atherosclerotic disease in 15,792 men and women recruited from 4 US communities (Forsyth County, NC; Jackson, MS; suburbs of Minneapolis, MN; and, Washington County, MD). 14 Participants, aged 45 to 64 years at the baseline examination (1987–1989), were subsequently evaluated during 3 follow-up clinical visits (visits 2, 3, and 4) at approximately 3-year intervals, and again at a fifth visit (2011–2013). Annual telephone contact and surveillance for incident cardiovascular events have been conducted since the baseline visit. The present investigation was a cross-sectional study of the ARIC cohort during visit 5 (2011–2013), including participants who attended visit 5 and had an echocardiographic exam with acceptable image quality. We excluded participants previously classified as non-hypertensive if they were missing data for BP components or data on antihypertensive medication use at visit 5. Additional exclusion criteria included prevalent coronary heart disease, heart failure or prior myocardial infarction, or missing data about these conditions, and race other than black or white. The final sample for this analysis was composed of 4,871 participants ( Figure 1 ). All study protocols were approved by the Institutional Review Boards of each ARIC Field Center and the ARIC Echocardiography Reading Center at the Brigham and Women’s Hospital, and all participants provided written informed consent.

Figure 1.

Study sampling strategy.

Figure 1.

Study sampling strategy.

Study variables

BPs were measured utilizing a standardized protocol 15 during each ARIC study visit. Three hierarchical categories of participants were created according to their BP levels and use of antihypertensive drugs at visit 5 1 and history of hypertension in previous visits (1 to 4) or annual telephone contacts:

  • - Optimal BP: systolic BP < 120mm Hg and diastolic BP < 80mm Hg, no history of antihypertensive drugs use, and no prior history of hypertension.

  • - Prehypertension: 120mm Hg ≤ systolic BP < 140mm Hg and/or 80mm Hg ≤ diastolic BP < 90mm Hg, no history of antihypertensive drugs use, and no prior history of hypertension.

  • - Hypertension: systolic BP ≥ 140mm Hg or diastolic BP ≥ 90mm Hg, or antihypertensive drugs use, or prior history of hypertension.

Transthoracic echocardiograms were obtained at the fifth ARIC visit. Images were acquired on identically configured echo machines (IE33; Philips, Andover, MA) according to standard protocols, 16 and were transferred in digital format to the Cardiovascular Imaging Core Lab at Brigham and Women’s Hospital, Boston, MA. Standard echocardiographic and Doppler parameters were analyzed using an offline analysis workstation. All measurements were made in triplicate in accordance with the recommendations of the American Society of Echocardiography 17 and included LV diameters and volumes, LV wall thickness, LV mass indexed by the body surface area and by height 2.7 , LV ejection fraction, mitral inflow propagation, and mitral annular relaxation velocities. LV ejection fraction was calculated as (LV end-diastolic volume − LV end-systolic volume)/LV end-diastolic volume. LV wall thickness was the average between interventricular septal wall and posterior wall thickness, and relative wall thickness (RWT) was calculated as 2 × (posterior wall thickness)/LV end-diastolic diameter. LV hypertrophy (LVH) was defined as LV mass indexed to body surface area >95g/m 2 in women and >115g/m 2 in men. Normal geometry was classified as RWT ≤ 0.42 and no LVH; and abnormal geometry was defined as concentric remodeling (RWT > 0.42 and no LVH); concentric hypertrophy (RWT > 0.42 and LVH); and eccentric hypertrophy (RWT ≤ 0.42 and LVH).

Diastolic function was assessed by an approach similar to a previous community study, 18 integrating Doppler measurements of the mitral inflow and tissue Doppler of the mitral annulus using the lateral annulus velocity. Our population was classified as: normal diastolic function (deceleration time of E wave (DT) >140ms, 0.75 < E/A < 2 and E/E′ < 10); mild diastolic dysfunction (DT > 140ms, E/A < 0.75, and E/E′ < 10); and moderate to severe diastolic dysfunction (0.75 < E/A < 2 and E/E′ ≥ 10; or DT < 140ms, E/A > 2 and E/E′ ≥ 10). Participants not falling into 1 of these 3 categories were labeled unclassified diastolic function.

To evaluate parameters of subclinical systolic dysfunction, LV myocardial deformation function was measured using B-mode speckle-tracking vendor-independent software (TomTec Imaging Systems, Unterschleissheim, Germany). 19 , 20 Global longitudinal strain was calculated as the average LV longitudinal strain values across the apical 4- and 2-chamber views and global circumferential strain was derived as the average of LV circumferential strain values measured in the parasternal short-axis view at the mid-ventricular level. 21

Reproducibility of the echocardiographic measures was performed in approximately 160 cases, and the intra-observer variability (coefficient of variation and intra-class correlation) for key echocardiographic measures was previously published. 16

Statistical analyses

Continuous normally distributed data were displayed as mean and SD, and categorical data were shown as a total sample and proportion. Variables were compared using analysis of variance with Bonferroni corrected P value and χ2 followed by pairwise χ2 if global P value <0.05. Tests of equal variance for the analysis of variance models were performed. We made multivariable linear and logistic regressions (multinomial logistic regression for diastolic function analysis using normal function as the referent outcome) to investigate the association between echocardiographic parameters and categories of hypertension. Models were adjusted a priori for age, sex, race, heart rate, body mass index, diabetes, and estimated glomerular filtration rate in 2 different models. Additionally, we investigated the differences in cardiovascular structure and function between women and men in prehypertension. All statistical analyses were performed with the STATA software package (version 12; Stata, College Station, TX). All tests were 2-sided and P values of <0.05 were considered statistically significant.

RESULTS

Sample characteristics

Participants with prehypertension ( n = 537; 75.4±4.8 years) were slightly older than those with optimal BP ( n = 402; 74.4±4.8 years) and were of similar age than those with hypertension ( n = 3,932; 75.9±5.1 years). Women and Caucasians accounted for the majority of participants, although the proportion of African-Americans was greatest in the hypertension group. There were no differences in heart rate, body mass index, history of diabetes, renal function, and high sensitivity troponin T between the prehypertension and optimal BP groups, although differences in these parameters were observed between hypertension and the other 2 categories. The proportions of prehypertension and optimal BP participants with high-sensitivity C-reactive protein >3mg/l or NT-proBNP >300 pg/ml were similar ( Table 1 ), though substantially lower than in hypertension.

Table 1.

Sample characteristics

Characteristic  Optimal BP
( n = 402)  
Prehypertension
( n = 537)  
Hypertension
( n = 3,932)  
Age (years) 74.4±4.8 75.4±4.8* 75.9±5.1* 
Female, n (%)  255 (63) 306 (57)*  2,447 (62)  
African-American, n (%)  27 (7) 45 (8)  1,024 (26)* ,† 
Heart rate (bpm) 61±10 62±9  63±11* ,† 
Systolic blood pressure (mm Hg) 110±8 129±6*  133±18* ,† 
Diastolic blood pressure (mm Hg) 60±7 68±8* 68±11* 
Body mass index (kg/m 2 )  26.0±4.7 26.7±4.3  29.1±5.7* ,† 
Current smoker, n (%)  27 (7) 34 (7) 210 (6) 
Diabetes, n (%)  71 (18) 83 (15)  1,534 (39)* ,† 
Glycated hemoglobin (%) 5.6±0.5 5.7±0.6  6.0±0.8* ,† 
Total cholesterol (mg/dl) 196±38 196±42  183±40* ,† 
HDL cholesterol(mg/dl) 57±14 55±14  52±14* ,† 
Creatinine (ml/dl) 0.87±0.19 0.89±0.20  0.98±0.36* ,† 
eGFR (ml/min/1.73 m2) 75.3±13.1 74.2±13.5  69.9±17.2* ,† 
HS-TnT (ng/dl) 0.9±0.7 1.0±0.7  1.3±1.6* ,† 
HS-CRP (>3mg/l) 93 (23%) 149 (28%)  1,483 (38%)* ,† 
NT-proBNP (>300 pg/ml) 38 (10%) 51 (10%)  722 (19%)* ,† 
Characteristic  Optimal BP
( n = 402)  
Prehypertension
( n = 537)  
Hypertension
( n = 3,932)  
Age (years) 74.4±4.8 75.4±4.8* 75.9±5.1* 
Female, n (%)  255 (63) 306 (57)*  2,447 (62)  
African-American, n (%)  27 (7) 45 (8)  1,024 (26)* ,† 
Heart rate (bpm) 61±10 62±9  63±11* ,† 
Systolic blood pressure (mm Hg) 110±8 129±6*  133±18* ,† 
Diastolic blood pressure (mm Hg) 60±7 68±8* 68±11* 
Body mass index (kg/m 2 )  26.0±4.7 26.7±4.3  29.1±5.7* ,† 
Current smoker, n (%)  27 (7) 34 (7) 210 (6) 
Diabetes, n (%)  71 (18) 83 (15)  1,534 (39)* ,† 
Glycated hemoglobin (%) 5.6±0.5 5.7±0.6  6.0±0.8* ,† 
Total cholesterol (mg/dl) 196±38 196±42  183±40* ,† 
HDL cholesterol(mg/dl) 57±14 55±14  52±14* ,† 
Creatinine (ml/dl) 0.87±0.19 0.89±0.20  0.98±0.36* ,† 
eGFR (ml/min/1.73 m2) 75.3±13.1 74.2±13.5  69.9±17.2* ,† 
HS-TnT (ng/dl) 0.9±0.7 1.0±0.7  1.3±1.6* ,† 
HS-CRP (>3mg/l) 93 (23%) 149 (28%)  1,483 (38%)* ,† 
NT-proBNP (>300 pg/ml) 38 (10%) 51 (10%)  722 (19%)* ,† 

Data are shown as mean ± SD or n (percentage). P value was calculated by analysis of variance (ANOVA) ( post hoc analysis using Bonferroni test) or χ2 ( post hoc analysis using χ2 test if P global <0.05).

Abbreviations: HDL, high-density lipoprotein; eGFR, estimated glomerular filtration rate; HS-TnT, high sensitivity troponin T; HS-CRP, high-sensitivity C-reactive protein.

* P < 0.05 vs. optimal BP, P < 0.05 vs. prehypertension.

Cardiac structure and function

Participants with prehypertension had greater LV mass index (73.6±14.8g/m 2 in prehypertension vs. 69.9±16.4g/m 2 in optimal BP), and LV wall thickness (0.94±0.11cm in prehypertension vs. 0.91±0.12cm in optimal BP) than those with optimal BP, but lower than those with hypertension ( Table 2 ). Although SDs of cardiovascular structure and function were slightly larger in the hypertension group, violating the standard assumption of equal variance across groups, sensitivity analyses using a robust variance estimator found similar or more significant results than those reported above. These differences remained statistically significant after multivariable analysis adjusted in the first model by age, sex, and race and in the second model by those parameters as well as heart rate, body mass index, diabetes, and estimated glomerular filtration rate ( Table 3 ). Nevertheless, the LV remodeling in prehypertension was not associated with an increase in LV dimensions, as was observed in hypertension. Compared to participants with optimal BP, those with prehypertension had a nominally higher prevalence of abnormal LV geometry (concentric hypertrophy, eccentric hypertrophy, or concentric remodeling; adjusted P value = 0.053; Figure 2 ).

Table 2.

Cardiovascular structure and function

Characteristic  Optimal BP
( n = 402)  
Prehypertension
( n = 537)  
Hypertension
( n = 3,932)  
LV ejection fraction (%) 66±5 66±5 66±6 
LV end-diastolic volume (ml) 75.9±21.3 79.0±21.9 81.0±23.8* 
LV end-diastolic volume index(ml/m 2 )  41.9±9.2 43.2±9.2 43.3±10.5* 
LV end-systolic volume (ml) 26.2±9.4 27.1±9.8 28.3±12.0* 
LV end-systolic volume index(ml/m 2 )  14.4±4.3 14.8±4.5 15.1±5.7 
LV mass index (g/m 2 )  69.9±16.4 73.6±14.8*  79.3±19.5* ,† 
LV mass/height 2.7 (g/m 2.7 )  30.8±7.5 32.9±7.1*  36.7±9.7* ,† 
Interventricular septal wall thickness (cm) 0.95±0.14 0.99±0.13*  1.05±0.16* ,† 
Posterior wall thickness (cm) 0.87±0.13 0.89±0.11*  0.93±0.14* ,† 
LV wall thickness (cm) 0.91±0.12 0.94±0.11*  0.99±0.13* ,† 
Relative wall thickness 0.41±0.07 0.42±0.06  0.43±0.07* ,† 
LA volume index (ml/m 2 )  23.2±7.4 24.0±7.4  25.9±8.8* ,† 
E/A ratio 0.95±0.30 0.87±0.26* 0.84±0.29* 
DT (ms) 202±43 204±42 203±47 
E′ lateral (cm/s) 7.8±2.1 7.2±2.1*  6.9±2.0* ,† 
E/E′ lateral 8.8±3.4 9.6±3.1*  10.3±3.8* ,† 
Longitudinal strain (%) −18.6±2.2 −18.5±2.3  −17.9±2.5* ,† 
Circumferential strain (%) −27.6±3.7 −28.0±3.6 −27.9±3.9 
Characteristic  Optimal BP
( n = 402)  
Prehypertension
( n = 537)  
Hypertension
( n = 3,932)  
LV ejection fraction (%) 66±5 66±5 66±6 
LV end-diastolic volume (ml) 75.9±21.3 79.0±21.9 81.0±23.8* 
LV end-diastolic volume index(ml/m 2 )  41.9±9.2 43.2±9.2 43.3±10.5* 
LV end-systolic volume (ml) 26.2±9.4 27.1±9.8 28.3±12.0* 
LV end-systolic volume index(ml/m 2 )  14.4±4.3 14.8±4.5 15.1±5.7 
LV mass index (g/m 2 )  69.9±16.4 73.6±14.8*  79.3±19.5* ,† 
LV mass/height 2.7 (g/m 2.7 )  30.8±7.5 32.9±7.1*  36.7±9.7* ,† 
Interventricular septal wall thickness (cm) 0.95±0.14 0.99±0.13*  1.05±0.16* ,† 
Posterior wall thickness (cm) 0.87±0.13 0.89±0.11*  0.93±0.14* ,† 
LV wall thickness (cm) 0.91±0.12 0.94±0.11*  0.99±0.13* ,† 
Relative wall thickness 0.41±0.07 0.42±0.06  0.43±0.07* ,† 
LA volume index (ml/m 2 )  23.2±7.4 24.0±7.4  25.9±8.8* ,† 
E/A ratio 0.95±0.30 0.87±0.26* 0.84±0.29* 
DT (ms) 202±43 204±42 203±47 
E′ lateral (cm/s) 7.8±2.1 7.2±2.1*  6.9±2.0* ,† 
E/E′ lateral 8.8±3.4 9.6±3.1*  10.3±3.8* ,† 
Longitudinal strain (%) −18.6±2.2 −18.5±2.3  −17.9±2.5* ,† 
Circumferential strain (%) −27.6±3.7 −28.0±3.6 −27.9±3.9 

Data are shown as mean ± SD. P value calculated by analysis of variance (ANOVA; post hoc analysis using Bonferroni test). Abbreviations: LV, left ventricular; IVS, interventricular septal wall; DT, deceleration time of E wave.

* P < 0.05 vs. optimal BP, P < 0.05 vs. prehypertension.

Table 3.

Associations of echocardiographic parameters with hypertension status

Dependent variable  Model 1
Optimal BP vs. prehypertension  
Model 2
Optimal BP vs. prehypertension  
Model 1
Optimal BP vs. hypertension  
Model 2
Optimal BP vs. hypertension  
Model 1
Prehypertension vs. hypertension  
Model 2
Prehypertension vs. hypertension  
B coefficient (SE) 
LV ejection Fraction (%) 0.27 (0.39) 0.44 (0.39) 0.07 (0.31) 0.27 (0.32) −0.19 (0.27) −0.16 (0.28) 
LV end-diastolic volume (ml) 1.66 (1.27) 1.18 (1.21) 4.84** (1.02) 2.87** (0.99) 3.18** (0.89) 1.69 (0.87) 
LV end-systolic volume (ml) 0.29 (0.67) 0.00 (0.67) 1.71** (0.54) 0.88 (0.55) 1.42** (0.47) 0.88 (0.48) 
LV mass index (g/m 2 )  3.0* (1.22) 2.7* (1.21) 9.2**(0.98) 7.6** (0.99) 6.20** (0.86) 4.97** (0.87) 
LV wall thickness (cm) 0.03** (0.01) 0.02* (0.01) 0.07**(0.01) 0.05**(0.01) 0.05** (0.01) 0.03** (0.01) 
Relative wall thickness 0.05 (0.05) 0.04 (0.05) 0.14** (0.04) 0.09* (0.04) 0.09* (0.03) 0.05 (0.03) 
LA volume index (ml/m 2 )  0.49 (0.56) 0.54 (0.56) 2.32** (0.45) 2.3** (0.46) 1.83** (0.39) 1.75** (0.40) 
E/A ratio −0.07** (0.02) −0.07** (0.02) −0.09** (0.02) −0.07** (0.02) −0.02 (0.01) −0.00 (0.01) 
E′ lateral (cm/s) −0.55** (0.13) −0.54** (0.13) −0.80** (0.11) −0.75** (0.11) −0.25** (0.09) −0.21* (0.10) 
E/E′ lateral 0.75** (0.24) 0.73** (0.24) 1.41** (0.19) 1.18** (0.19) 0.66** (0.17) 0.45** (0.17) 
Longitudinal strain (%) 0.07 (0.16) 0.02 (0.16) 0.50** (0.13) 0.33** (0.13) 0.44** (0.11) 0.31** (0.11) 
Circumferential strain (%) −0.45 (0.27) −0.62* (0.27) −0.47* (0.22) −0.77**(0.22) −0.02 (0.19) −0.16 (0.19) 
Dependent variable  Model 1
Optimal BP vs. prehypertension  
Model 2
Optimal BP vs. prehypertension  
Model 1
Optimal BP vs. hypertension  
Model 2
Optimal BP vs. hypertension  
Model 1
Prehypertension vs. hypertension  
Model 2
Prehypertension vs. hypertension  
B coefficient (SE) 
LV ejection Fraction (%) 0.27 (0.39) 0.44 (0.39) 0.07 (0.31) 0.27 (0.32) −0.19 (0.27) −0.16 (0.28) 
LV end-diastolic volume (ml) 1.66 (1.27) 1.18 (1.21) 4.84** (1.02) 2.87** (0.99) 3.18** (0.89) 1.69 (0.87) 
LV end-systolic volume (ml) 0.29 (0.67) 0.00 (0.67) 1.71** (0.54) 0.88 (0.55) 1.42** (0.47) 0.88 (0.48) 
LV mass index (g/m 2 )  3.0* (1.22) 2.7* (1.21) 9.2**(0.98) 7.6** (0.99) 6.20** (0.86) 4.97** (0.87) 
LV wall thickness (cm) 0.03** (0.01) 0.02* (0.01) 0.07**(0.01) 0.05**(0.01) 0.05** (0.01) 0.03** (0.01) 
Relative wall thickness 0.05 (0.05) 0.04 (0.05) 0.14** (0.04) 0.09* (0.04) 0.09* (0.03) 0.05 (0.03) 
LA volume index (ml/m 2 )  0.49 (0.56) 0.54 (0.56) 2.32** (0.45) 2.3** (0.46) 1.83** (0.39) 1.75** (0.40) 
E/A ratio −0.07** (0.02) −0.07** (0.02) −0.09** (0.02) −0.07** (0.02) −0.02 (0.01) −0.00 (0.01) 
E′ lateral (cm/s) −0.55** (0.13) −0.54** (0.13) −0.80** (0.11) −0.75** (0.11) −0.25** (0.09) −0.21* (0.10) 
E/E′ lateral 0.75** (0.24) 0.73** (0.24) 1.41** (0.19) 1.18** (0.19) 0.66** (0.17) 0.45** (0.17) 
Longitudinal strain (%) 0.07 (0.16) 0.02 (0.16) 0.50** (0.13) 0.33** (0.13) 0.44** (0.11) 0.31** (0.11) 
Circumferential strain (%) −0.45 (0.27) −0.62* (0.27) −0.47* (0.22) −0.77**(0.22) −0.02 (0.19) −0.16 (0.19) 

Model 1: Adjusted by age, sex, race; Model 2: Adjusted by age, sex, race, heart rate, body mass index, diabetes, and estimated glomerular filtration rate (eGFR).

Abbreviations: BP, blood pressure; LV, left ventricular.

* P < 0.05, ** P < 0.01.

Figure 2.

Abnormal LV geometry by categories of hypertension status. Abnormal geometry was defined as presence of concentric remodeling, concentric hypertrophy or eccentric hypertrophy. Optimal BP as a reference group: * P values <0.05.

Figure 2.

Abnormal LV geometry by categories of hypertension status. Abnormal geometry was defined as presence of concentric remodeling, concentric hypertrophy or eccentric hypertrophy. Optimal BP as a reference group: * P values <0.05.

Neither LV ejection fraction nor circumferential strain significantly differed across the 3 groups, but longitudinal strain was lower in hypertension group compared with the 2 other groups. Parameters of diastolic function (E/A, E′, and E/E′) were progressively worse in prehypertension and hypertension in comparison with optimal BP ( Table 2 ). In addition, the prevalence of mild and moderate to severe diastolic dysfunction was higher in prehypertension (59%) as compared with optimal BP (44%) and lower than in hypertension (67%) even after adjustments ( Figure 3 ). LA volume was similar between participants with prehypertension and optimal BP and highest in those with hypertension. BP levels were correlated with most of parameters of LV remodeling and diastolic function ( Supplementary Figure 1 ).

Figure 3.

Diastolic dysfunction by categories of hypertension status. Abbreviations: DD, diastolic dysfunction; DF, diastolic function. All unadjusted and adjusted P values for the comparisons of optimal BP vs. prehypertension (preHTN) and optimal BP vs. hypertension (HTN) were <0.01. P values adjusted for age, sex, race, HR, body mass index (BMI), estimated glomerular filtration rate (eGFR), history of diabetes; *%’s may not add to 100 due to rounding.

Figure 3.

Diastolic dysfunction by categories of hypertension status. Abbreviations: DD, diastolic dysfunction; DF, diastolic function. All unadjusted and adjusted P values for the comparisons of optimal BP vs. prehypertension (preHTN) and optimal BP vs. hypertension (HTN) were <0.01. P values adjusted for age, sex, race, HR, body mass index (BMI), estimated glomerular filtration rate (eGFR), history of diabetes; *%’s may not add to 100 due to rounding.

In prehypertension, men had higher LV dimensions and LV wall thickness, while LV mass indexed for heigh 2.7 was similar to women. The LV filling pressure (E/E′) was higher in women ( Table 4 ).

Table 4.

Cardiovascular structure and function by sex in prehypertension

Characteristic Prehypertension 
Female ( n = 306)   Male ( n = 231)  
LV ejection fraction (%) 66±5 66±5 
LV end-diastolic volume (ml) 66.5±13.5 95.2±20.1* 
LV end-diastolic volume index (ml/m 2 )  39.5±7.3 48.0±9.1* 
LV end-systolic volume (ml) 22.6±6.7 33.0±10.1* 
LV end-systolic volume index (ml/m 2 )  13.4±3.7 16.7±4.8* 
LV mass index (g/m 2 )  70.8±12.9 77.4±16.3* 
LV mass/height 2.7 (g/m 2.7 )  33.9±6.7 32.9±7.7 
Interventricular septal wall thickness (cm) 0.96±0.12 1.04±0.14* 
Posterior wall thickness (cm) 0.86±0.10 0.93±0.11* 
LV wall thickness (cm) 0.91±0.09 0.98±0.11* 
Relative wall thickness 0.42±0.06 0.41±0.06 
LA volume index (ml/m 2 )  23.1±6.6 25.1±8.1 
E/A ratio 0.87±0.26 0.87±0.26 
DT (ms) 196±40 213±42* 
E′ lateral (cm/s) 7.1±2.1 7.4±2.1 
E/E′ lateral 10.2±3.1 8.8±2.9* 
Longitudinal strain (%) −18.6±2.3 −18.2±2.2 
Circumferential strain (%) −28.4±3.5 −27.3±3.5* 
Characteristic Prehypertension 
Female ( n = 306)   Male ( n = 231)  
LV ejection fraction (%) 66±5 66±5 
LV end-diastolic volume (ml) 66.5±13.5 95.2±20.1* 
LV end-diastolic volume index (ml/m 2 )  39.5±7.3 48.0±9.1* 
LV end-systolic volume (ml) 22.6±6.7 33.0±10.1* 
LV end-systolic volume index (ml/m 2 )  13.4±3.7 16.7±4.8* 
LV mass index (g/m 2 )  70.8±12.9 77.4±16.3* 
LV mass/height 2.7 (g/m 2.7 )  33.9±6.7 32.9±7.7 
Interventricular septal wall thickness (cm) 0.96±0.12 1.04±0.14* 
Posterior wall thickness (cm) 0.86±0.10 0.93±0.11* 
LV wall thickness (cm) 0.91±0.09 0.98±0.11* 
Relative wall thickness 0.42±0.06 0.41±0.06 
LA volume index (ml/m 2 )  23.1±6.6 25.1±8.1 
E/A ratio 0.87±0.26 0.87±0.26 
DT (ms) 196±40 213±42* 
E′ lateral (cm/s) 7.1±2.1 7.4±2.1 
E/E′ lateral 10.2±3.1 8.8±2.9* 
Longitudinal strain (%) −18.6±2.3 −18.2±2.2 
Circumferential strain (%) −28.4±3.5 −27.3±3.5* 

Data are shown as mean ± SD.

Abbreviations: LV, left ventricular; IVS, interventricular septal wall; DT, deceleration time of E wave.

* P < 0.05.

DISCUSSION

In the ARIC cohort at visit 5, participants with prehypertension had higher LV mass and wall thickness than those with optimal BP, although this LV remodeling was less severe than what was seen in participants with overt hypertension. Moreover, those with prehypertension had impaired diastolic function with a higher prevalence of mild and moderate to severe diastolic dysfunction compared to optimal BP, even after adjustment for important clinical covariates. These findings demonstrate for the first time in an elderly cohort the previously described association between prehypertension and target organ damage.

LV remodeling is a well-known marker of cardiovascular risk 22 and BP is one of the major determinants of increased LV mass and changes in LV geometry. In a young 23 to middle-aged 24–27 population, prehypertension had been related to increased LV mass and wall thickness, compared with a normotensive population. Our study extends these findings to an elderly prehypertension sample from a large biracial population and identifies differences in LV remodeling between hypertension and prehypertension in this population. In prehypertension, LV remodeling was based only on increasing LV wall thickness, with no difference in LV dimensions between prehypertension and optimal BP. The observed decline in LV dimensions with increasing age 28 may have attenuated the effect of the BP on the LV size in those patients. In prehypertension, the sex differences in cardiac structure were consistent with the constitutional differences between sexes 17 and the higher filling pressure in women was similar to the findings in general population that may contribute to increased prevalence of Heart Failure with Preserved Ejection Fraction in women. 29 , 30

Additionally, we observed lower LV relaxation and higher filing pressure in prehypertension and hypertension participants compared to those with optimal BP, and more frequent mild and moderate to severe diastolic dysfunction in the former 2 groups. Although there was a tendency toward increasing LA size with higher BP, there was no statistically significant difference in LA size between prehypertension participants and those with optimal BP, similar to our findings regarding LV size. Considering diastolic dysfunction to be a pathophysiological intermediate between hypertension and heart failure, 31 the impact of prehypertension on diastolic LV function may contribute to the increased cardiovascular risk shown in this population. We did not find differences in LV systolic function in prehypertension compared to optimal BP as previously shown in a small population. 32 It seems that even systolic abnormalities restricted to the subendocardial fibers might be present only in a more advanced hypertension status.

It is generally accepted that prehypertension is associated with increased risk of progression to hypertension, 33 and the linear and continuous relationship between BP levels and cardiovascular events, starting at BP values of 115 and 75mm Hg, has been well established. 34 A better understanding of the subclinical organ damage associated with prehypertension can aid in delineating future strategies for prevention of and treatment for this condition, since lifestyle modification management is the only strategy recommended currently. 1

Some limitations of this analysis should be noted. The cross-sectional analysis precludes drawing conclusions about causality. As our sample included predominantly elderly Caucasian and African-American individuals from 4 prespecified sites from United States, the generalizability of these findings across age groups, racial/ethnic groups, and regions may be limited.

In summary, in a large contemporary cohort of community-dwelling older adults, we observed that prehypertension was associated with increased LV remodeling and impaired diastolic function, but not systolic function. Understanding the adverse myocardial effects associated with prehypertension may help to better define treatment strategies for this condition.

SUPPLEMENTARY MATERIAL

Supplementary materials are available at American Journal of Hypertension ( http://ajh.oxfordjournals.org ).

DISCLOSURE

The authors declared no conflict of interest.

ACKNOWLEDGMENTS

The authors thank the staff and participants of the ARIC study for their important contributions to this research. A.B.S.S. acknowledges a grant support (0281-12-3) from CAPES (Brazil).

The Atherosclerosis Risk in Communities study is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute contracts (HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN2682 01100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, and HHSN268201100012C). This work was also supported by National Heart, Lung, and Blood Institute cooperative agreement NHLBI-HC-11-08 (Brigham and Women’s Hospital).

S.C. is supported in part by R00-HL-107642 and a grant from the Ellison Foundation. A.M.S. is supported in part by K08-HL-116792 and a grant from the American Heart Association (14CRP20380422). N.A.B. is supported by NIH/NHLBI T32 HL007374-34. D.K.G. is supported by award number K12HL109019 from the National Heart, Lung, and Blood Institute.

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