**2. Methods**

### **2.1 Study group**

Participants of African ancestry were recruited from Soweto, a township in the southwest of Johannesburg. The lower age limit for the participants was 18 years and there was no upper age limit. Based on their conventional and ambulatory BP measurements were divided into the following six groups:


### **2.2 Blood pressure measurement**

Participants were invited to visit the Human Nutrition Clinic at the School of Physiology, Wits Medical School where conventional BP was measured using an automated pressure monitor (Omron, Kyoto, Japan) after they were allowed to rest for 10 minutes. Twenty four-hour ambulatory BP was measured using a 24-hour BP monitor (Spacelab, model 91207). Monitors were set to measure BP every 15 minutes from 06:00–22:00 and every 30 minutes thereafter until 06:00 the next morning. On average, participant bedtime was 19:00 and wake up time was 05:00. Based on this, the 09:00–19:00 and 23:00–05:00 intervals were used to define daytime and night time respectively.

#### **2.3 Anthropometric measurements**

Anthropometric measurements were taken while the participants were barefoot and wearing lightweight indoor robes. Weight was measured using a floor scale

(Health o meter® Professional, USA) and was recorded to the nearest 0.1 kg. For this measurement, the participant was asked to stand upright on the middle of the scale with their weight distributed evenly between both feet. Height was measured to the nearest 0.1 m using a wall-mounted stadiometer (Seca®, Germany), with the participant standing upright and the headpiece of the stadiometer was placed horizontally on the vertex (highest point) of the participant's head and the corresponding reading was recorded. Body Mass Index (BMI) was calculated as weight in kilogrammes divided by the square of the height in metres. Participants with a BMI ≥ 25 kg/m2 were considered overweight, and those with a BMI ≥ 30 kg/m<sup>2</sup> were considered obese. Waist circumference was measured in at the end of normal expiration using an inextensible measuring tape aligned parallel to the floor at the narrowest point between the costal margin and the upper iliac crest.

#### **2.4 Pulse wave velocity measurement**

A high fidelity tonometer interfaced with a SphygmoCor computer software (AtCor Medical Pty. Ltd., West Ryde, New South Wales, Australia - version 9.0) was used to perform pulse wave assessments of pulse wave velocity (PWV), an index of arterial stiffness. Participants were allowed to rest in the supine position for 15 minutes prior to assessment. Using an inextensible measuring tape, distances (in mm) between the relative sampling sites (femoral and carotid) and the suprasternal notch were measured. The difference between the two distances was considered as the pulse wave distance. Applanation tonometry was then used to record sequential wave forms at the participant's dominant carotid and femoral regions. A three lead chest ECG was performed concurrently with the waveform sampling in order to assess the time differences in the generation of the waveforms. The pulse transit time was defined as the average of 10 consecutive beats. The PWV was automatically calculated as the difference between the aforementioned distances (i.e. the pulse wave distance) divided by the pulse transit time.

#### **2.5 Echocardiography**

Echocardiography was used to determine the left ventricular mass index for the participants. All echocardiographic measurements were carried out by an experienced technician using an echocardiogram - the Acuson SC2000 Diagnostic Ultrasound System (Siemens Medical Solutions USA, Inc.) linked to a 10-MHz linear array transducer and electrocardiogram. Participants were asked to lie in the left lateral decubitus position. M-mode images were taken at a frame rate of >110 frames per second. M-mode echocardiography of the short axis of the heart was obtained as close to the tip of the mitral valve as possible using the parasternal long axis view (2D). The resulting images were used to measure left ventricular dimensions only when the endocardial surfaces of the septal and posterior walls, as well as both the left and right septal surfaces, could be clearly seen. Wall dimensions, namely the Left Ventricular Internal Diameter at end Diastole (LVIDD), the Posterior Wall Thickness in Diastole (PWTD) and the Interventricular Septal Thickness in Diastole (IVSTD) were obtained from M-mode images. Left ventricular mass values were indexed for body.

### **3. Statistical analysis**

Database management and statistical analyses were performed with SAS software, version 9.4 (The SAS Institute Inc., Cary, North Carolina, USA). Data

**83**

*Ambulatory Isolated Systolic Hypertension and Cardiovascular Target Organ Damage in People…*

from individual subjects were averaged and expressed as mean ± SD for continuous variables and categorical variables were expressed as percentages. The differences between the means was calculated using the General Linear Model (GLM) and adjustments were made for the following covariates; age, gender, BMI, alcohol intake and cigarette smoking. A p value <0.05 was considered significant. The Receiver Operator Characteristics (ROC) curve analysis was used to determine how well the different subgroups of ISH would predict an increased PWV and LVMI. The ROC curve analysis is used in clinical prediction to assess how well a test can discriminate between absence or presence of a condition. The analysis yields a curve of sensitivity versus 1-specificity, where the Area Under the Curve (AUC) is a measure of predictive power of the test to a maximum of 1 [50]. The closer the AUC is to 1, the greater the ability of the test in question to discriminate whether the presence of a condition is associated with a change in a

**Table 1** shows the demographic, general and clinical characteristics of the population under study. Of the 549 participants, 41 (7.5%) had ISH as measured by conventional means (ISHC). This figure is similar to those obtained for the ambulatory sub-types of ISH, namely 24-hour, Night-time and Daytime ISH which had 39 (7.1%), 42 (7.7%) and 41 (7.5%) participants respectively. Systolic-diastolic hypertension was observed in 161 (29%) of the participants. The mean age of the population was 45.3 ± 18.5 years and the ISHC group was significantly older (65.3 ± 13.5 years) than both normotensives (39.7 ± 17.6 years) and hypertensives (52.1 ± 15.5 years). There were slight reductions in average age within the other ISH subtypes, with ISH24 at 57.8 ± 20.1 years, ISHN at 55.4 ± 24.6 years and ISHD at 53.7 ± 20.9 years. We observed that all the ISH subgroups had greater proportions of female participants than the normotensive or hypertensive groups [51]. Anthropometry revealed significantly higher waist circumference in the ISHC group than in the normotensives, this was also true for all the other ISH subgroups albeit of no known significance. In addition to this, the overall population was

. Both ISHC and hypertensives were obese

respectively), the former group hav-

).

*DOI: http://dx.doi.org/10.5772/intechopen.96521*

overweight with a BMI of 29.1 ± 7.8 kg/m2

and 30.9 ± 7.5 kg/m<sup>2</sup>

cantly so for those participants with ISHC (PP = 69.7 ± 12.3 mm Hg).

ing a significantly higher BMI than the normotensives (BMI = 28.0 ± 7.7 kg/m<sup>2</sup>

The average SBPC of the ISHC group (153.1 ± 11.7 mm Hg) was higher than that of the hypertensive group (149.6 ± 20.3 mm Hg), and significantly higher than that of the normotensives (129.7 ± 21.4 mm Hg). Overall, the SBPC values for all ISH sub-types were high. Conventional ISH had an average DBPC of 83.5 ± 4.8 mm Hg, significantly higher than that of normotensives (77.6 ± 7.2 mm Hg) and significantly lower than that of hypertensives (98.6 ± 8.4 mm Hg). Similarly, 24-hour, night-time and daytime ISH all had conventional diastolic blood pressures below those of hypertensives but above those of normotensives. All sub-types of ISH had higher pulse pressure values than both normotensives and hypertensive groups, signifi-

**Tables 2** and **3** show the ROC curve analysis of the relationships between the sub-types of ISH and cardiovascular target organ changes. All subtypes of ISH were significantly associated with increased PWV and LVMI. Conventional ISH strongly predicts arterial stiffness and left ventricular hypertrophy, with area under the curve (AUC) values of 0.88 ± 0.03 (CI: 0.83 to 0.93) and 0.86 ± 0.03 (CI: 0.88 to 0.92), respectively. Daytime ISH was shown to be a strong predictor of both (PWV and LVMI) with all the values exceeding 0.8. all three organ changes under study

(BMI of 31.4 ± 7.5 kg/m2

given parameter [50].

**4. Results**

*Ambulatory Isolated Systolic Hypertension and Cardiovascular Target Organ Damage in People… DOI: http://dx.doi.org/10.5772/intechopen.96521*

from individual subjects were averaged and expressed as mean ± SD for continuous variables and categorical variables were expressed as percentages. The differences between the means was calculated using the General Linear Model (GLM) and adjustments were made for the following covariates; age, gender, BMI, alcohol intake and cigarette smoking. A p value <0.05 was considered significant. The Receiver Operator Characteristics (ROC) curve analysis was used to determine how well the different subgroups of ISH would predict an increased PWV and LVMI. The ROC curve analysis is used in clinical prediction to assess how well a test can discriminate between absence or presence of a condition. The analysis yields a curve of sensitivity versus 1-specificity, where the Area Under the Curve (AUC) is a measure of predictive power of the test to a maximum of 1 [50]. The closer the AUC is to 1, the greater the ability of the test in question to discriminate whether the presence of a condition is associated with a change in a given parameter [50].
