Role of atrial natriuretic peptide in the dissociation between flow relations with ventricular mass and function in a community with volume-dependent hypertension.

Background: Whether differential effects of volume load on left ventricular mass (LVM) and function occur in sustained volume-dependent primary hypertension, and the impact of atrial natriuretic peptide (ANP) on these effects, is unknown.

Methods: From aortic pressure, velocity and diameter measurements and echocardiography, we determined in an African community ( = 772), the impact of systemic flow-induced increases in central pulse pressure (PPc) and circulating ANP (ELISA) on LVM and indexes of function.

Results: Stroke volume (SV), but not aortic flow (Q), was associated with LVM and mean wall thickness (MWT) beyond stroke work and confounders ( < 0.

Proximal aortic stiffness modifies the relationship between heart rate and backward wave and hence central arterial pulse pressure.

Aims: A lower heart rate (HR) increases central blood pressure through enhanced backward wave pressures (Pb). We aimed to determine whether these relationships are modified by increases in aortic stiffness.

Methods: Using non-invasive central pressure, aortic velocity and diameter measurements in the outflow tract (echocardiography), we assessed the impact of aortic stiffness on relationships between HR and arterial wave morphology in 603 community participants < 60 years of age, 221 ≥ 60 years, and in 287 participants with arterial events [stroke and critical limb ischemia (CLI)].

Attenuated Relationships Between Indexes of Volume Overload and Atrial Natriuretic Peptide in Uncontrolled, Sustained Volume-Dependent Primary Hypertension.

Background: Whether systolic blood pressure (SBP) control in sustained volume-dependent primary hypertension is associated with blunted ANP (atrial natriuretic peptide) relationships with indexes of volume load is unknown.

Methods: Systemic hemodynamics (central pressure, echocardiographic aortic velocity and diameter measurements in the outflow tract), circulating ANP concentrations (ELISA assays) and glomerular and tubular function (24-hour urine collections [n=519]) were determined in a community of African ancestry (n=772).

Results: As compared with those with a controlled SBP, those with an uncontrolled SBP (n=198) showed lower ANP concentrations (<0.

Contribution of Increases in Late Systolic Ejection Volume to the Impact of Heart Rate on Central Arterial Pulse Pressure in a Community Sample.

Background: A lower heart rate (HR) increases left ventricular (LV) ejection volume. Whether this contributes to the adverse effects of HR on central pulse pressure (PPc) through reservoir volume effects is uncertain.

Methods: Using noninvasive central pressure, aortic velocity, and diameter measurements in the outflow tract (echocardiography), we assessed the role of LV ejection volume as a determinant of HR relations with PPc in 824 community participants.

Marked intrafamilial aggregation and heritability of aortic flow in a community with prevalent volume-dependent hypertension in Africa.

Aims: Although peak aortic flow (Q) is now recognized as a major determinant of hypertension in Africa, current therapy has no proven ability to target this change. The mechanisms of this effect, therefore, require elucidation. We compared the intrafamilial aggregation and heritability of Q to that of the vascular determinants of pulse pressure (PP) and SBP in Africa.

Increased Backward Wave Pressures Rather than Flow Explain Age-Dependent Heart Rate Effects on Central, But not Peripheral Arterial Pressure.

Through both backward (Pb) and forward (Pf) wave effects, a lower heart rate (HR) associates with increased central (PPc), beyond brachial pulse pressure (PP). However, the relative contribution to Pf of aortic flow (Q) versus re-reflection of Pb, has not been determined. Using central pressure, aortic velocity and diameter measurements in the outflow tract (echocardiography), we constructed central pressure waveforms that account for the relative contribution of Q versus re-reflection to Pf.

Independent relationships between renal mechanisms and systemic flow, but not resistance to flow in primary hypertension in Africa.

Aims: Whether renal mechanisms of hypertension primarily translate into increases in systemic vascular resistance (SVR) in all populations is uncertain. We determined whether renal mechanisms associate with either increases in SVR (and impedance to flow) or systemic flow in a community of African ancestry.

Method: In a South African community sampled across the full adult age range (n = 546), we assessed stroke volume (SV), peak aortic flow (Q), SVR, characteristic impedance (Zc) and total arterial compliance (TAC) from velocity and diameter measurements in the outflow tract (echocardiography) and central arterial pressures.

Hemodynamic and Functional Correlates of Concentric vs. Eccentric LVH in a Community-Based Sample With Prevalent Volume-Dependent Hypertension.

Background: Whether in volume-dependent primary hypertension, concentric left ventricular (LV) remodeling beyond hypertrophy (LVH) represents the impact of a pressure rather than a volume overload, is unclear.

Methods: Using central arterial pressure, and aortic velocity and diameter measurements in the outflow tract (echocardiography), we determined the factors that associate with concentric LVH or remodeling in a community of African ancestry (n = 709) with prevalent volume-dependent primary hypertension.

Results: Both left ventricular mass index (LVMI) and relative wall thickness (RWT) were positively and independently associated with end diastolic volume (EDV), stroke volume (SV), and peak aortic flow (Q) (P < 0.

Impact of stroke work on the ability of left ventricular mass to account for pressure effects on function in a community with prevalent systemic flow-dependent hypertension.

Aims: To determine whether the confounding influence of stroke work on left ventricular mass (LVM) limits the ability of LVM to detect hypertensive LV dysfunction in systemic flow-dependent hypertension.

Methods: In a community with prevalent systemic flow-dependent hypertension (n = 709), arterial haemodynamics, LVM and LV function were determined using central arterial pressure, aortic velocity and diameter measurements in the outflow tract, and echocardiography with tissue Doppler imaging.

Results: In multivariate models, stroke work showed markedly stronger relations with LVM index (LVMI) than blood pressure load [central arterial SBP (SBPc), backward wave pressure (Pb), 24-h SBP] (P < 0.

Contribution of systemic blood flow to untreated or inadequately controlled systolic--diastolic or isolated systolic hypertension in a community sample of African ancestry.

Aims: Age-related increases in systemic blood flow [stroke volume (SV), cardiac output (CO), and aortic flow (Q)] contribute substantially to untreated or inadequately controlled (uncontrolled) blood pressure (BP) in Africa. We aimed to identify the haemodynamic determinants of uncontrolled systolic--diastolic (Syst--diast HT) versus uncontrolled isolated systolic (ISH) or diastolic (IDH) hypertension.

Methods: Using central arterial pressure and aortic outflow tract velocity and diameter measurements (echocardiography), the haemodynamic correlates of BP were determined in 725 community participants of African ancestry (19.

Distinct Contribution of Systemic Blood Flow to Hypertension in an African Population Across the Adult Lifespan.

Although hypertension in groups of African ancestry is volume-dependent, the relative impact of systemic flow (stroke volume, peak aortic flow [Q]) versus vascular mechanisms (systemic vascular resistance, aortic characteristic impedance [Zc], total arterial compliance) components of arterial load has not been evaluated across the adult age range. In participants of African ancestry (n=824, age=16-99 years, 68.3% female), using central arterial pressure and aortic velocity and diameter measurements in the outflow tract, we determined the hemodynamic correlates of age-related increases in blood pressure.

Marked Arterial Functional Changes in Patients With Arterial Vascular Events Across the Early Adult Lifespan.

Objective: The age at which arteriosclerosis begins to contribute to events is uncertain. We determined, across the adult lifespan, the extent to which arteriosclerosis-related changes in arterial function occur in those with precipitous arterial events (stroke and critical limb ischemia). Approaches and Results: In 1082 black South Africans (356 with either critical limb ischemia [n=238] or stroke [n=118; 35.

Hemodynamic Determinants of Age Versus Left Ventricular Diastolic Function Relations Across the Full Adult Age Range.

The relative contribution of loading conditions at different ages across the full adult lifespan to decreases in left ventricular (LV) diastolic function is unclear. Using central arterial pressure and aortic velocity and diameter measurements in the outflow tract, we determined the contribution of systemic vascular resistance, compression wave pressures (characteristic impedance [Zc]×aortic flow [Q], [P]) and backward wave pressures (Pb) to LV diastolic function (echocardiography) in a community sample across the full adult lifespan (n=605). Starting from early adulthood, stepwise age-related increases in LV filling pressures (E/e') and decreases in myocardial relaxation (e') were noted (<0.

Increased Aortic Characteristic Impedance Explains Relations Between Urinary Na/K and Pulse or Systolic Blood Pressure.

Alterations in sodium (Na) relative to potassium (K) intake increase systolic blood pressure, effects in-part attributed to enhanced pulsatile loads (pulse pressure) beyond steady-state pressures (mean arterial pressure). Whether this effect is through reversible changes (increases in blood volume and hence aortic flow [Q] or wave reflection [Pb]), or potentially irreversible structural changes in the proximal aorta, is unknown. In 581 black South Africans, we determined 24-hour urinary Na and K excretion and aortic function from central aortic pressure (radial pulse wave analysis [SphygmoCor software]), velocity, and diameter measurements.

Impact of metabolic and inflammatory changes on glomerular function beyond conventional risk factors in an urban South Africa community with prevalent obesity.

Objectives: To determine the extent to which metabolic and inflammatory changes are associated with renal damage beyond conventional risk factors in a community sample with a high prevalence of obesity in urban South Africa.

Methods: This was a cross-sectional, community-based study in 1 010 ( = 872 without diabetes mellitus, DM) randomly selected participants over 16 years of age in an urban, developing community (Soweto, Johannesburg) with a high prevalence of obesity (41.8%).

Associations between circulating resistin concentrations and left ventricular mass are not accounted for by effects on aortic stiffness or renal dysfunction.

Background: Although, in-part through an impact on left ventricular mass (LVM), resistin (an adipokine) may contribute to heart failure, whether this is explained by the adverse effects of resistin on aortic stiffness and renal function is unknown.

Methods: Relationships between circulating resistin concentrations and LVM index (LVMI), and LVM beyond that predicted by stroke work (inappropriate LVM [LVM]) (echocardiography) were determined in 647 randomly selected community participants, and in regression analysis, the extent to which these relations could be explained by aortic pulse wave velocity (PWV) or estimated glomerular filtration rate (eGFR) was evaluated.

Results: Independent of confounders, resistin concentrations were independently associated with LVMI, LVM, LV hypertrophy (LVH), PWV and eGFR.

Limited contribution of insulin resistance and metabolic parameters to obesity-associated increases in ambulatory blood pressure in a black African community.

Although accounting for a striking proportion of obesity effects on blood pressure (BP) in other populations, the extent to which obesity-associated increases in BP are explained by insulin resistance and metabolic changes in populations of African ancestry is uncertain. We determined the contribution of insulin resistance and associated metabolic abnormalities to variations in office or ambulatory BP in a black African community with prevalent obesity and hypertension. In 1225 randomly selected participants of black South African ancestry (age>16years, 43.

Limited contribution of left ventricular mass and remodelling to the impact of blood pressure on diastolic function in a community sample.

Aims: Although the development of left ventricular (LV) dysfunction in hypertension has traditionally been viewed as a transition process from a phase of structural LV remodelling to dysfunction, the extent to which LV mass (LVM) and remodelling account for blood pressure (BP)-associated alterations in LV diastolic function is uncertain. In product of coefficient mediation analysis, we aimed to determine the extent to which LVM index (LVMI) or relative wall thickness (RWT) account for relations between BP and LV diastolic function.

Methods: In 709 randomly selected participants from a community sample with a high prevalence of hypertension (49.

Insulin resistance influences the impact of hypertension on left ventricular diastolic dysfunction in a community sample.

Background: Although obesity-associated metabolic abnormalities (insulin resistance-IR) may not play as marked a role in determining left ventricular (LV) diastolic dysfunction (DD) as hypertension, the impact of combinations of these risk factors on DD is unknown.

Hypothesis: We hypothesized that IR influences the impact of hypertension on DD.

Methods: In 704 randomly selected participants from a community sample with a high prevalence of hypertension (50.

Organ-Specific, Age-Dependent Associations of Steady-State Pressures and Pulsatile Pressure Wave Components With End-Organ Measures.

Background: The contribution of steady-state pressures and the forward (Pf) and backward (reflected) (Pb) wave pressure components of pulse pressure to risk prediction have produced contrasting results. We hypothesized that the independent contribution of steady-state pressures (mean arterial pressure [MAP]), Pf and Pb, to cardiovascular damage is organ specific and age dependent.

Methods: In 1,384 black South Africans from a community sample, we identified independent relations between MAP, Pf, or Pb (applanation tonometry and SphygmoCor software) and left ventricular mass index (LVMI) (n = 997) (echocardiography), carotid intima-media thickness (IMT) (n = 804) (B-mode ultrasound), or aortic pulse wave velocity (PWV) (n = 1,217).

Independent of left ventricular mass, circulating inflammatory markers rather than pressure load are associated with concentric left ventricular remodelling.

Background: A reason for concentric left ventricular (LV) remodelling predicting cardiovascular outcomes independent of conventional risk factors and LV mass (LVM) has not been provided. We hypothesized that independent of LVM, concentric LV remodelling is associated with inflammatory changes rather than a pressure load on the LV.

Methods: In 764 randomly selected community participants, we assessed relations between several inflammatory markers (ELISA) and LV relative wall thickness (RWT) (echocardiography), LV mass index (LVMI), and indexes of diastolic function.

Impact of Blunted Nocturnal Blood Pressure Dipping on Cardiac Systolic Function in Community Participants Not Receiving Antihypertensive Therapy.

Background: Blunted nocturnal blood pressure (BP) dipping (nondipping) predicts cardiovascular morbidity and mortality, and is associated with heart failure (HF) independent of office BP. Whether nondipping is independently associated with cardiac systolic function prior to the development of HF is uncertain.

Methods: We assessed whether nocturnal BP dipping pattern and nocturnal BP were associated with indexes of cardiac systolic function [endocardial fractional shortening (endFS), midwall FS (mFS), ejection fraction (EF)] independent of left ventricular mass index (LVMI) and relative wall thickness (RWT) in 491 randomly selected community participants not receiving antihypertensive therapy.

Aortic Pulse Pressure Does Not Adequately Index Cardiovascular Risk Factor-Related Changes in Aortic Stiffness and Forward Wave Pressure.

Background: Through the impact of conventional risk factors on arteries, several changes in aortic function contribute to cardiovascular events. It is nevertheless uncertain whether these effects are accurately reflected by changes in central aortic pulse pressure (PPc). We, therefore, aimed to determine the extent to which relations between modifiable risk factors and aortic function translate into increases in PPc.

Contribution of backward and forward wave pressures to age-related increases in aortic pressure in a community sample not receiving antihypertensive therapy.

Reports on the contribution of aortic forward (Pf) and backward (Pb) wave pressures to age-related increases in central aortic pulse pressure (PPc) have been confounded by the use of participants receiving antihypertensive therapy. We assessed the relative contribution of Pf and Pb to age-related increases in PPc (radial applanation tonometry and SphygmoCor software using an assumed triangular wave for wave separation analysis) in 892 community participants not receiving antihypertensive therapy. We validated our results using aortic flow waves (echocardiography) for wave separation analysis in 254 of these participants.