Olebogeng H.I. Majane

Obesity promotes left ventricular concentric rather than eccentric geometric remodeling and hypertrophy independent of blood pressure.

BACKGROUND As it is uncertain whether excess adiposity promotes primarily concentric or eccentric left ventricular hypertrophy (LVH), we aimed to determine at a population level, the independent relationship between waist circumference (WC) and LV geometric changes and the potential hemodynamic mechanisms thereof. METHODS We assessed the relations between WC and LV end-diastolic diameter (EDD), LV mean wall thickness (MWT = posterior + septal wall thickness/2), LV relative wall thickness (RWT = MWT/EDD), LV mass index (LVMI), concentric LVH (LVMI > 51 g/m2.7 and RWT > 0.45), eccentric LVH (LVMI > 51 g/m2.7 and RWT < 0.45), or concentric LV remodeling (normal LVMI and RWT > 0.45), in 309 never treated for hypertension, randomly recruited adult participants with a high prevalence of excess adiposity ( approximately 25% overweight; 38% obese). Pulse-wave analysis was performed to determine central artery blood pressures (BPs). Two hundred and thirty-one participants had high-quality ambulatory BP monitoring. RESULTS Approximately 7% of participants had concentric LVH, approximately 16% concentric LV remodeling, and approximately 15% eccentric LVH. After adjustments for potential confounders including conventional systolic BP (SBP), WC was related to MWT (partial r = 0.23, P = 0.0001), RWT (partial r = 0.13, P = 0.03), concentric LVH (P < 0.04), concentric LV remodeling (P = 0.02), but not with EDD or eccentric LVH (P = 0.91). Similar outcomes were noted after adjustments for central or 24-h SBP, and for conventional, central, or 24-h pulse pressure. Separate analysis in normotensive subjects revealed similar outcomes. CONCLUSIONS In a population sample with a high prevalence of obesity, excess adiposity promotes concentric, rather than eccentric LV geometric changes, effects which are independent of conventional, central artery or 24-h BP measured on a single occasion.

Relationship Between Urinary Salt Excretion and Pulse Pressure and Central Aortic Hemodynamics Independent of Steady State Pressure in the General Population

Although central pulse pressure (PPc) is strongly related to central mean arterial pressure (MAPc), PPc predicts cardiovascular outcomes beyond MAPc. Whether modifiable risk factors for hypertension contribute to PPc and its determinants, independent of MAPc, is uncertain. In 635 randomly recruited participants, we assessed the independent relationship between 24-hour urinary sodium (Na+) or potassium (K+) excretion and brachial artery PP (in office or 24-hour; n=487), PPc, the forward (P1) and augmented (Paug) pressure wave components of PPc, central augmentation index, and determinants of central pressure waves, including aortic pulse wave velocity, effective reflecting distance, and reflective wave transit time. Central dynamics were determined using applanation tonometry of the carotid, femoral, and radial arteries. With adjustments for potential confounders, urinary Na+/K+ was independently associated with in-office, central, and 24-hour PP, as well as Paug, P1, and central augmentation index (P<0.05 to P<0.005). With further adjustments for MAPc (or diastolic BP), urinary Na+/K+ was independently associated with PPc, 24-hour PP, Paug, P1, and central augmentation index (P<0.05 to P=0.005) but not with in-office PP, pulse wave velocity, effective reflecting distance, or reflective wave transit time. In conclusion, in a population of African ancestry, urinary salt excretion is independently related to central and 24-hour PP independent of MAPc or diastolic BP, effects that are attributed to increases in both P1 and Paug but not to pulse wave velocity. Hence, modifying salt intake could influence cardiovascular risk through effects on 24-hour and central PPs, as well as P1 and Paug, independent of steady-state pressure (MAP or diastolic BP) or pulse wave velocity.

Nurse-recorded auscultatory blood pressure at a single visit predicts target organ changes as well as ambulatory blood pressure

Aim To determine whether high-quality nurse-recorded auscultatory blood pressure (BP) values obtained at a single visit predict cardiovascular target organ changes as closely as ambulatory BP measurements. Methods In a randomly selected population sample (n = 458, 21% receiving antihypertensive treatment; approximately 40% hypertensive), we compared high-quality single visit nurse-recorded auscultatory BP values to same-day 24-h ambulatory BP in their ability to predict multiple target organ changes [left ventricular mass index (LVMI), left ventricle (LV) mean wall thickness (MWT), early-to-late transmitral velocity ratios (E/A), (echocardiography); log of urinary albumin-to-creatinine ratios (log ACR) (24-h urine samples); large artery dysfunction [carotid-femoral pulse wave velocity (PWV) and central augmentation index (Alc) (applanation tonometry)]. Results Nurse-recorded systolic BP (SBP) measurements obtained at a single visit were as closely associated with LVMI (r = 0.44), LV MWT (r = 0.44), E/A (r = −0.55), log ACR (r = 0.20), PWV (r = 0.62) and AIc (r = 0.41) (P < 0.0001 for all relations) as was 24-h SBP (LVMI; r = 0.33, LV MWT; r = 0.37, E/A; r = −0.35, log ACR; r = 0.24, PWV; r = 0.41, and AIc; r = 0.18, P < 0.001 for all relations) and either day or night SBP. On multivariate regression analysis with both nurse-recorded SBP and 24-h SBP in the same model, nurse-recorded SBP was independently associated with LVMI (P = 0.006), LV MWT (P = 0.03), E/A (P < 0.02), PWV (P < 0.0001) and AIc (P = 0.0002), and 24-h SBP was independently and positively associated with log ACR (P < 0.005), and PWV (P = 0.01). Conclusion One or more, high-quality single visit nurse-recorded auscultatory BP measurements may be equally as effective as ambulatory BP in predicting target organ damage in a population sample of African ancestry.

Is prehypertension an independent predictor of target organ changes in young-to-middle-aged persons of African descent?

Aim We sought to determine whether prehypertension (BP = 120–139/80–89 mmHg) is associated with target organ changes independent of confounders. Methods In 771 participants from a population sample of African ancestry, approximately 46% of whom had hypertension, and approximately 30% prehypertension, organ damage was assessed from echocardiography (left ventricular mass indexed to height2.7, the mean of posterior and septal wall thickness and early-to-late transmitral velocity), 24-h urine samples (urinary albumin-to-creatinine ratio), serum creatinine concentrations, and carotid–femoral pulse wave velocity. Ambulatory blood pressure values that met with prespecified quality control criteria were available in 539 participants. Results A greater proportion of hypertensives (P < 0.0001) but not prehypertensives had elevated 24-h blood pressure values as compared with participants with optimal blood pressure values. Before adjustment for confounders, hypertension was associated with all target organ changes (P < 0.0001), and after adjustment, an independent association was noted between hypertension and all target organ changes (P < 0.05–0.005) except albumin-to-creatinine ratio or serum creatinine concentrations. Before adjustment, prehypertension was associated with left ventricular mass indexed to height2.7, mean wall thickness, pulse wave velocity, and early-to-late transmitral velocity (P < 0.05–0.001), but not with other target organ changes. After adjustment, however, prehypertension was not independently associated with target organ changes. Other factors independently associated with target organ changes were age (all target organs), waist circumference (left ventricular mass indexed to height2.7 and early-to-late transmitral velocity) and diabetes mellitus (albumin-to-creatinine ratio and pulse wave velocity). Interactions between prehypertension and any of the alternative risk factors were not independent predictors of target organ changes. Conclusion Although associated with it, prehypertension is not an independent predictor of organ damage in young-to-middle-aged persons of African ancestry.

Brachial blood pressure-independent relations between radial late systolic shoulder-derived aortic pressures and target organ changes.

Central aortic blood pressure (BP; BPc) predicts outcomes beyond brachial BP. In this regard, the application of a generalized transfer function (GTF) to radial pulse waves for the derivation of BPc is an easy and reproducible measurement technique. However, the use of the GTF may not be appropriate in all circumstances. Although the peak of the second shoulder of the radial waveform (P2) is closely associated with BPc, and, hence, BPc may be assessed without the need for a GTF, whether P2-derived BPc is associated with adverse cardiovascular changes independent of brachial BP is uncertain. Thus, P2- and GTF-derived aortic BPs were assessed using applanation tonometry and SphygmoCor software. Left ventricular mass was indexed for height1.7 (n=678) and carotid intima-media thickness (IMT; n=462) was determined using echocardiography and vascular ultrasound. With adjustments for nurse-derived brachial pulse pressure (PP), P2-derived central PP was independently associated with left ventricular mass indexed for height1.7 (partial r=0.18; P<0.0001) and IMT (partial r=0.40; P<0.0001). These relations were similar to nurse-derived brachial PP-independent relations between GTF-derived central PP and target organ changes (left ventricular mass indexed for height1.7: partial r=0.17, P<0.0001; IMT: partial r=0.37, P<0.0001). In contrast, with adjustments for central PP, nurse-derived brachial PP-target organ relations were eliminated (partial r=−0.21 to 0.05). Twenty-four–hour, day, and night PP-target organ relations did not survive adjustments for nurse-derived brachial BP. In conclusion, central PP derived from P2, which does not require a GTF, is associated with cardiovascular target organ changes independent of brachial BP. Thus, when assessing adverse cardiovascular effects of aortic BP independent of brachial BP, P2-derived measures may complement GTF-derived measures of aortic BP.

Contribution of Central and General Adiposity to Abnormal Left Ventricular Diastolic Function in a Community Sample With a High Prevalence of Obesity

The relative independent contribution of excess adiposity, as indexed by measures of central, general, or peripheral adiposity, toward abnormal cardiac diastolic chamber function at a community level is unclear. In 377 randomly selected participants >16 years old from a community sample with a high prevalence of excess adiposity ( approximately 25% overweight and approximately 43% obese), we assessed the independent contribution of the indexes of adiposity to the variation in early-to-late (atrial) transmitral velocity (E/A). After adjustments for a number of confounders, including age, gender, pulse rate, conventional diastolic (or systolic) blood pressure, antihypertensive treatment, left ventricular mass index, and the presence of diabetes mellitus or a hemoglobin A1c level >6.1%; waist circumference was an independent predictor of a reduced E/A (p = 0.0038). Body mass index (p = 0.07), waist-to-hip ratio (p = 0.23), and skinfold thickness (p = 0.37) were not independently associated with E/A, whereas waist circumference was independently associated with E/A, even after adjustments for other adiposity indexes, including body mass index (p <0.05 to 0.005). In contrast to the effects on diastolic function, the waist circumference did not correlate with the left ventricular ejection fraction (p = 0.23). The independent relation between the waist circumference and E/A (standardized beta coefficient -0.14 +/- 0.05, p = 0.0038) was second only to age (standardized beta coefficient -0.57 +/- 0.05, p <0.0001) and similar to blood pressure (standardized beta coefficient -0.11 +/- 0.04, p = 0.0075) in the magnitude of the independent effect on E/A. The inclusion of the relative wall thickness rather than the left ventricular mass index in the regression equation produced similar outcomes. The exclusion of the left ventricular mass index and relative wall thickness from the regression equations or the inclusion of carotid-femoral pulse wave velocity or 24-hour blood pressure as confounders failed to modify the relation between waist circumference and E/A. In conclusion, the waist circumference was second only to age in the impact on an independent association with E/A in a population sample with a high prevalence of excess adiposity. This effect was not accounted for by left ventricular hypertrophy or remodeling, the 24-hour blood pressure, or arterial stiffness.

The relationship between blood pressure and left ventricular mass index depends on an excess adiposity

Aim To determine whether blood pressure (BP)–LVM relationships depend in-part on the influence of an excess adiposity and whether this translates into a greater effect of hypertension on LVM in obese as compared with lean people. Methods In 399 randomly recruited participants from a general population with a high prevalence of excess adiposity (∼68%), we assessed whether the relationships between conventional blood pressure (BP) and LVM indexed for height2.7 (LVMI) (determined from echocardiography) are influenced by adiposity. We confirmed these outcomes using 24-h ambulatory measurements in 297 participants; and carotid-femoral pulse wave velocity (PWV) (applanation tonometry) in 328 participants and from plasma leptin concentrations, we assessed whether leptin could mediate this effect. Results After adjustments for appropriate confounders, including the individual terms for adiposity and BP, interactions between adiposity indices (either waist circumference or the mean of subscapular and triceps skin-fold thickness) and either conventional systolic BP (SBP), 24-h SBP, PWV, conventional pulse pressure (PP), or 24-h PP were independently associated with LVMI (P < 0.001 for interactions). The adiposity index-haemodynamic interaction translated into a steeper slope of the BP–LVMI and PWV–LVMI relations in obese as compared with lean participants. Every one SD increase in conventional SBP (∼22 mmHg) was associated with a 1.61 g/m2.7 increase in LVMI in participants with a normal waist circumference, in comparison to a 5.24 g/m2.7 increase in LVMI in those with an increased waist circumference (P < 0.0001). Furthermore, the adiposity index–haemodynamic interaction resulted in an increased LVMI in never-treated hypertensives with central obesity (LVMI, normotensives = 45.6 g/m2.7, hypertensives = 51.0 g/m2.7, P < 0.02), but not in participants with a normal waist circumference (LVMI, normotensives = 43.4 g/m2.7, hypertensives = 45.0 g/m2.7). Significant plasma leptin concentration–haemodynamic interactions were also associated with LVMI independent of confounders and adiposity indices, an effect that translated into a steeper slope of the haemodynamic factor-LVMI relations in participants with a plasma leptin concentration above as compared with those below the median for the group. Conclusion Adiposity-induced increases in LVM reflect an enhanced effect of BP on LV growth, an effect that may be mediated by leptin. This translates into an impact of never-treated hypertension on LVMI in centrally obese, but not in lean people in groups of African descent in South Africa.

Contribution of Circulating Angiotensinogen Concentrations to Variations in Aldosterone and Blood Pressure in a Group of African Ancestry Depends on Salt Intake

In high-Na+, low-K+ diets, which suppress renin release in salt-sensitive groups, the mechanisms maintaining increases in renin-angiotensin-aldosterone system activation downstream from renin and renin-angiotensin-aldosterone system–induced effects on blood pressure (BP) are uncertain. Whether circulating angiotensinogen concentrations (AGT) or its determinants may contribute to maintaining serum aldosterone concentrations (aldosterone) and increases in BP on high-Na+, low-K+ diets was evaluated in 579 participants of a community sample of African ancestry. Plasma renin concentrations were inversely related to BP (P<0.0001) and an index of salt intake (24-hour urinary Na+/K+, P<0.0001). An interaction between AGT and urinary Na+/K+ was independently associated with aldosterone (P<0.001) and systolic BP (SBP; P<0.05). Independent of confounders, in participants with urinary Na+/K+ at or more than the median for the sample, AGT was positively associated with aldosterone (P<0.0001) and SBP (P<0.005). No independent AGT-aldosterone or AGT-SBP relationships were noted in participants with urinary Na+/K+ less than the median for the sample. Standardized &bgr;-coefficients (slopes) of AGT-aldosterone and AGT-SBP relationships were greater in participants with urinary Na+/K+ at or more than the median (AGT-aldosterone=0.30±0.06, AGT-SBP=0.16±0.05) compared with those with urinary Na+/K+ less than the median (AGT-aldosterone=−0.04±0.06; AGT-SBP=−0.03±0.05; P<0.01–0.0001 for comparison of slopes). The AGT-SBP relationship in participants with urinary Na+/K+ at or more than the median for the sample was equivalent to the relationship between body mass index and BP. In conclusion, in participants of African ancestry, in the presence of high-Na+, low-K+ diets, which suppress renin release, renin-angiotensin-aldosterone system activation and its impact on BP are maintained in part by AGT.

The association of waist circumference with ambulatory blood pressure is independent of alternative adiposity indices.

Aim The relationship between waist circumference (WC) and conventional blood pressure (BP) is independent of other clinical indices of adiposity. As ambulatory BP may offer more prognostic information than conventional BP, we aimed to identify whether indices of central adiposity are associated with ambulatory BP independent of other indices of adiposity. Methods The relationship between indices of adiposity [WC, waist-to-hip ratio, body mass index (BMI) or skin-fold thickness] and ambulatory or conventional BP was determined in 300 randomly selected individuals of African descent living in an urban developing community in South Africa. Relationships were determined with multiple indices of adiposity in the same regression model and after adjusting for age, gender, alcohol and tobacco intake, the presence or absence of diabetes mellitus or inappropriate blood glucose control [haemoglobin A1c (HbA1c)], antihypertensive therapy and menopausal status. Results Sixty-five per cent of participants were overweight or obese. With respect to the relationships between indices of adiposity, BMI and WC showed the strongest correlation (r = 0.84, P < 0.0001). After including all indices of adiposity and confounders in the model, WC was the only clinical index of adiposity which independently predicted 24-h (partial r = 0.15, P < 0.005) and conventional (partial r = 0.14, P < 0.005) systolic BP and 24-h (partial r = 0.13, P < 0.02) and conventional (partial r = 0.40, P < 0.0001) diastolic BP. After adjusting for other adiposity indices and confounders, every 1 SD (15 cm) increase in WC resulted in a 4.04 mmHg increase in 24-h systolic BP and a 4.33 mmHg increase in 24-h diastolic BP. Similar results were obtained in the subgroup of 237 participants not receiving antihypertensive therapy. Conclusion WC is the only clinical index of adiposity that is associated with 24-h and conventional BP independent of other adiposity indices in a community with a high prevalence of obesity.

Dietary-Induced Obesity Hastens the Progression From Concentric Cardiac Hypertrophy to Pump Dysfunction in Spontaneously Hypertensive Rats

We explored whether dietary-induced obesity hastens the transition from concentric left ventricular (LV) hypertrophy to pump dysfunction in spontaneously hypertensive rats (SHRs) and the mechanisms thereof. After feeding rats a diet for 4 to 5 months, obesity was induced in SHRs and Wistar-Kyoto (WKY) control rats. Obesity was not associated with abnormal blood glucose control (glycosylated hemoglobin) or with increases in systolic blood pressure. However, in SHRs, but not in WKY rats, obesity was associated with a reduced LV chamber systolic function, as determined by echocardiography, and in isolated perfused heart studies. A marked increase in LV end diastolic diameter and a right shift in the LV diastolic pressure-volume relation were noted in obese SHRs but not in obese WKY rats. Moreover, LV intrinsic myocardial systolic function, as determined from the slope of the linearized LV systolic stress-strain relationship (LV myocardial end systolic elastance), was markedly reduced in obese as compared with lean SHRs, whereas LV myocardial end systolic elastance was maintained in obese WKY rats. Obesity increased LV weight, cardiomyocyte width, cardiomyocyte apoptosis (TUNEL), the activity of myocardial matrix metalloproteinases (zymography), and serum leptin concentrations in SHRs but not in WKY rats. In conclusion, SHRs are susceptible to the adverse effects of dietary-induced obesity on the heart, an effect that hastens the progression from concentric LV hypertrophy to pump dysfunction independent of blood pressure changes or alterations in glycosylated hemoglobin. This effect may be mediated through a proclivity of SHRs to developing both obesity-induced effects on cardiomyocyte apoptosis and activation of myocardial collagenases through leptin resistance and obesity-induced hypertrophy.