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Systemic Angiotensinogen Concentrations Are Independently Associated With Left Ventricular Diastolic Function in a
Aletta M E Millen1, Angela J Woodiwiss1, Monica Gomes1
1Cardiovascular Pathophysiology and Genomics Research Unit, School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
Insights
Systemic angiotensinogen (AGT) concentrations are linked to left ventricular (LV) diastolic dysfunction in Black Africans. This suggests the renin-angiotensin-aldosterone system (RAAS) may influence heart function in this population.
Area of Science:
- Cardiology
- Renal Physiology
- Population Health
Background:
- Left ventricular (LV) diastolic dysfunction is a key feature of heart failure with preserved ejection fraction.
- The renin-angiotensin-aldosterone system (RAAS) is known to impair LV diastolic function.
- The specific role of systemic angiotensinogen (AGT) in this process remains unclear.
Purpose of the Study:
- To investigate the association between systemic AGT concentrations and LV diastolic function.
- To explore the potential contribution of systemic AGT to diastolic dysfunction in an African population.
Main Methods:
- LV diastolic function assessed using myocardial tissue Doppler imaging (average e') and mitral inflow velocity (E/e') in 445 Black African participants.
- Multivariate regression models adjusted for multiple demographic, clinical, and lifestyle factors.
Main Results:
- Serum AGT concentrations were independently associated with E/e' (P=0.04), a marker of diastolic dysfunction.
- No significant association was found between AGT and average e', nor between plasma renin and diastolic function markers.
- The association between AGT and E/e' persisted after adjusting for blood pressure and other confounders.
Conclusions:
- Circulating AGT levels are associated with LV diastolic function in a Black African population, independent of blood pressure.
- Systemic AGT, via the RAAS, may play a significant role in the development of LV diastolic dysfunction in this demographic.
- Further research is warranted to elucidate the precise mechanisms.
Background:
Left ventricular (LV) diastolic dysfunction characterizes heart failure with a preserved ejection fraction. Although it is recognized that the renin-angiotensin-aldosterone system (RAAS) decreases LV diastolic function, whether systemic angiotensinogen (AGT) contributes to these effects is uncertain. Hence, the aim was to determine the relationship between systemic AGT concentrations and LV diastolic function.
Methods:
LV diastolic function was determined from the mean of the lateral and septal wall myocardial tissue lengthening at the mitral annulus (average e') and from the ratio of early transmitral blood flow velocity (E) to average e' (E/e') in 445 Black African participants from a community sample.
Results:
In multivariate regression models with adjustments for age, sex, waist circumference diabetes mellitus, alcohol and tobacco use, hypertension treatment, systolic blood pressure (BP), and relative wall thickness, the square root of serum AGT concentrations was independently associated with E/e' (partial r (95% confidence interval [CI]) = 0.11 (0.02-0.21), P = 0.04), but not with average e' (partial r (95% CI) = -0.06 (-0.15 to 0.04), P = 0.25). There was no association between plasma renin concentrations and markers of diastolic function (all P > 0.05).
Conclusion:
Circulating AGT concentrations are associated with LV diastolic function beyond BP and other confounders in an African population. Hence, through circulating AGT, the systemic RAAS may play an important role in contributing to LV diastolic function in Black Africans.
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