Interventricular Septum Thickness Predicts Future Systolic Hypertension in Young Healthy Pilots
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15 Hypertens Res Vol.31 (2008) No.1 p.15-20 Original Article Interventricular Septum Thickness Predicts Future Systolic Hypertension in Young Healthy Pilots Chagai GROSSMAN1), Alon GROSSMAN2), Nira KOREN-MORAG3), Bella AZARIA2), Liav GOLDSTEIN2), and Ehud GROSSMAN1) Left ventricular hypertrophy (LVH) has been associated with hypertension, although debate exists as to whether LVH is caused by elevated blood pressure (BP) or is a risk factor for its development. The present study evaluates the association between left ventricular structure and the development of hypertension in a young healthy population. We followed young healthy Israeli Air Force aviators from initial echocardio- graphy at the start of their military service to a mean of 7.5±3.0 years. Data collection included annual BP measurements, height, weight, smoking habits, and lipid profile. We monitored 500 Air Force men with a mean age of 20.5±3.3 (range, 17–40) years and baseline BP of 125±13/74±8 mmHg. Systolic BP during fol- low-up was associated with baseline systolic BP, interventricular septum (IVS) thickness, and ejection frac- tion, whereas diastolic BP was associated only with baseline diastolic BP and body mass index. The probability that the systolic BP during follow-up would be higher than the median was twice that in those with an IVS thickness greater than the median. In conclusion, IVS thickening was associated with long-term elevation of systolic BP. Therefore, it seems that IVS thickening is not merely a result of long-term BP ele- vation, but may predict the development of systolic hypertension. (Hypertens Res 2008; 31: 15–20) Key Words: echocardiography, normotensives, blood pressure of debate whether BP is a risk factor for the development of Introduction LVH or merely a result of it. Several studies, mainly in chil- dren, have shown that increased LVM may precede hyperten- Elevated blood pressure (BP) and obesity are risk factors that sion (10–14). de Simone et al. followed a group of 132 affect the structure and function of the left ventricle (1–3). subjects without hypertension for 4.7 years, during which 15 Left ventricular hypertrophy (LVH) is an independent risk (11%) developed hypertension. Those who developed hyper- factor for cardiovascular disease (4, 5). tension were found to have a greater LVM at baseline com- The association between hypertension and left ventricular pared with their normotensive counterparts (11). These mass (LVM) has been clearly demonstrated in several studies results were the basis for the hypothesis that LVH may in fact (1, 6–9). Lauer et al. demonstrated that systolic BP, and to a be a risk factor for the development of hypertension (10–14). lesser degree diastolic BP, are independent markers associ- Yet, data regarding the significance of LVH in the future ated with increased LVM (9). Harpaz et al. evaluated a group development of hypertension in young, healthy subjects are of healthy subjects and showed that isolated interventricular scarce. The aim of this study was to evaluate the significance septum (IVS) hypertrophy, even in the presence of a normal of LVM on the future development of hypertension in healthy LVM, is associated with hypertension (8). Yet, it is a matter normotensive subjects. From the 1)Department of Internal Medicine D and Hypertension Unit, The Chaim Sheba Medical Center, Tel Hashomer affiliated to the Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel; 2)Israel Air Force Aeromedical Center, Tel Hashomer, Israel; 3)Division of Epidemiology, Sackler Medical Faculty, Tel Aviv University, Tel Aviv, Israel. Address for Reprints: Ehud Grossman, M.D., Internal Medicine D and Hypertension Unit, The Chaim Sheba Medical Center, Tel Hashomer 52621, Israel. E-mail: [email protected] Received May 4, 2007; Accepted in revised form July 25, 2007. 16 Hypertens Res Vol. 31, No. 1 (2008) Table 1. Baseline Subjects’ Characteristics and Echocardiographic Values Variable Mean±SD Median Range Age (years) 20.5±3.3 19 17–40 Baseline SBP (mmHg) 125±13 120 90–180 Baseline DBP (mmHg) 74±8 75 50–120 Baseline HR (beats/min) 68±13 66 34–160 Height (cm) 178±6 178 157–193 Baseline weight (kg) 67±8 67 48–97 Baseline BMI (kg/m2) 21.3±2.1 21.1 16.6–30.6 Total cholesterol (mg/dL) 165±32 160 95–279 Triglycerides (mg/dL) 81±42 71 19–337 LDL cholesterol (mg/dL) 103±33 100 22–226 HDL cholesterol (mg/dL) 52±12 50 25–116 End-diastolic dimension (cm) 5.1±0.4 5.1 4.0–6.5 End-systolic dimension (cm) 3.1±0.4 3.1 2.3–4.4 Interventricular septum thickness (cm) 0.9±0.1 0.9 0.6–1.2 Posterior wall thickness (cm) 0.9±0.1 0.9 0.6–1.2 Left atrium (cm) 3.4±0.4 3.4 2.0–4.5 Ejection fraction (%) 77±6 78 59–84 Left ventricular mass index (g/m2) 103.2±19.7 101.6 54.3–182.9 Relative wall thickness 0.35±0.05 0.35 0.27–0.53 SBP, systolic blood pressure; DBP, diastolic blood pressure; HR, heart rate; BMI, body mass index; LDL, low-density lipoprotein; HDL, high-density lipoprotein. technique. Two-dimensional M-mode guided measurements Methods were performed according to the recommendations of the American Society of Echocardiography (15). Data collected included diastolic and systolic left ventricular (LV) diameter, Subjects posterior wall (PW) and interventricular septum (IVS) thick- The study population consisted of 500 consecutively exam- ness, and left atrial (LA) diameter. The intra- and inter- ined Israeli Air Force aviators. These healthy subjects under- observer variations in these measurements were less than went baseline evaluation and routine echocardiography prior 10%. LA diameter was taken from the leading edge of the to their enlistment and were then evaluated annually. The posterior aortic wall to the leading edge of the posterior left evaluation included BP, height, weight, and lipid profile. Sub- atrial wall as described by the American Society of Echocar- jects whose echocardiographs were inconclusive for technical diography (15). LVM was determined by the cube formula, reasons were excluded from the study, as were those with sig- using the Penn convention, as suggested by Devereux and nificant cardiac defects. Subjects who did not have at least 1 Reichek (16). Left ventricular mass index (LVMI) was calcu- year of BP follow-up were also excluded. lated by dividing the LVM by the body surface area (BSA). LVH was defined if either the PW or IVS thickness was greater than 11 mm as measured by M-mode echocardio- BP Measurements graphy, or if the LVMI was at least 134 g/m2. Relative wall BP was measured at every visit twice in the sitting position thickness (RWT) was calculated by dividing the sum of the following 2 min of rest using a sphygmomanometer, and the IVS and PW thicknesses by the diastolic dimension. The LV mean of the measurements was recorded. The BP was mea- ejection fraction was calculated from end diastolic and end- sured in the same arm every visit by skilled physicians who systolic LV volumes derived by the method of Teichholz et were unaware of the echocardiographic findings. al. (17). In all subjects, weight, height, and body mass index (BMI) were determined. Additional information obtained from the Echocardiographic Evaluation patients’ medical records included smoking habits, a family Echocardiography was performed by an HP SONOS 2500 history of premature atherosclerosis, and lipid profile (total device (Hewlett-Packard, Palo Alto, USA) using a 2.5 MHz cholesterol, low-density lipoprotein [LDL]-cholesterol, high- transducer. All examinations were performed using a similar density lipoprotein [HDL]-cholesterol, and triglycerides). Grossman et al: Interventricular Septum and Hypertension 17 Table 2. Change in Parameters during Follow-Up Variable Baseline Follow-up p value Systolic blood pressure (mmHg) 125±13 120±8 <0.001 Diastolic blood pressure (mmHg) 74±873±4 <0.001 Heart rate (beats/min) 68±13 62±7 <0.001 Body mass index (kg/m2) 21.3±2.1 22.5±1.8 <0.001 Table 3. Comparison between Those Who Were Pre-Hypertensives and Those Who Were Normotensives during Follow-Up Normotensives Pre-hypertensives p value Number 305 195* Age (years) 21±120±3 <0.05 Systolic BP (mmHg) 115±4 127±7 <0.001 Diastolic BP (mmHg) 71±475±4 <0.001 Heart rate (beats/min) 61±764±8 <0.001 BMI (kg/m2) 22.3±1.7 22.8±2.0 <0.005 Positive family history (%) 5.9 7.2 n.s. Smokers (%) 12.1 6.7 <0.05 Serum total cholesterol (mg/dL) 165±34 164±31 n.s. Serum triglycerides (mg/dL) 79±39 85±48 n.s. Interventricular septum thickness(cm) 0.89±0.12 0.93±0.11 <0.01 Posterior wall thickness (cm) 0.86±0.11 0.88±0.12 <0.01 End-diastolic dimension (cm) 5.1±0.4 5.1±0.4 n.s. End-systolic dimension (cm) 3.1±0.3 3.1±0.4 n.s. Left atrium (cm) 3.3±0.4 3.4±0.4 <0.01 Left ventricular mass (g) 184±39 197±42 <0.001 Left ventricular mass index (g/m2) 101±19 105±19 <0.05 Relative wall thickness 0.35±0.05 0.35±0.05 n.s. Concentric pattern (%) 2.3 2.6 n.s. *Including 12 patients with mild hypertension. BP, blood pressure; BMI, body mass index. To test the hypothesis that IVS thickness at baseline is a Statistical Analysis predictor of hypertension, receiver-operating characteristic Data are expressed as mean±SD and by median and range.