Heritability of Central Systolic Pressure Augmentation

Abstract

Abstract-Less than 50% of the variance in left ventricular mass is explained by conventional factors such as age, blood pressure, and body size. Genetic influences may account for part of the unexplained variance. The central (aortic) pressure augmentation index has been suggested as a noninvasive measure of pulsatile load, which is a likely determinant of left ventricular mass. We quantified the genetic influence on augmentation index and determined the extent to which this influence is dependent on the effects of age, height, heart rate, and blood pressure. We performed a classical twin study composed of 225 monozygotic and 594 dizygotic female white twin pairs aged 18 to 73 years. Augmentation index and mean arterial pressure were based on the central pressure wave derived from the radial waveform as measured by applanation tonometry. Quantitative genetic modeling techniques were used to analyze the data. The heritability of augmentation index was 37%, whereas heritabilities for blood pressure traits varied between 13% and 25%. Most of the variance in augmentation index could be explained by genetic and environmental factors specifically influencing augmentation index. Only a relatively small part of the total variance in augmentation index could be attributed to genes in common with height (3.1%), heart rate (4.6%), and mean arterial pressure (5.6%). Age explained 19% of the total variation in augmentation index. In conclusion, augmentation index has a significant heritable component, which is largely independent of the influence of blood pressure, heart rate, height, and age. Finding genes for the augmentation index could help to unravel pathophysiological mechanisms causing left ventricular hypertrophy and lead to improvements in prevention, diagnosis, and treatment of at-risk populations. 4 It has been suggested that inheritance may account for part of the unexplained variance. [5][6][7] One hemodynamic factor that has been suggested to influence left ventricular mass is pulsatile vascular load, 8 -10 although this has been difficult to measure in large populations. Murgo et al 11 showed that patterns of augmentation index (AI) relate to invasively measured pulsatile vascular load. Recent studies indicate that the AI can be measured accurately noninvasively, providing a reliable method of studying arterial properties in a large population. 12 AI is defined as the ratio of augmented systolic pressure (due to the late systolic peak in the central pressure waveform) to pulse pressure 8 and represents a measure of a combination of factors related to large arterial function. It is increased in association with arterial stiffness, caused by the degeneration of the arterial wall as a result of repetitive cyclic stress, which is a major determinant of increasing systolic pressure with age and in patients with hypertension. 13 Stiffening of the main central arteries also leads to increased velocity of the pulse wave as it travels down the arteries, which causes wave reflections from peripheral sites to return ea...

Relative roles of heredity and physical activity in adolescence and adulthood on blood pressure

“…Several studies have demonstrated that BP is partly determined genetically (9,25). Our present results are concordant with those of earlier studies, where the proportion of variance in BP accounted for by interindividual genetic differences ranges from 15 to 73% (8,9,14,15,16,20,24,37,39,42).…”

The T-allele of the C825T polymorphism is associated with higher arterial stiffness in young healthy males

“…These findings support the hypothesis that arterial stiffening may pathogenetically contribute to the development of hypertension in carriers of the T-allele. This study also supports the idea that stiffening of large arteries may be influenced by genetic factors, 24 and is not just a mere consequence of aging or the presence of cardiovascular disease. Similar to other genes of the cardiovascular system including endothelin gene variants, 25 an influence of the C825T polymorphism may first be detected in arterial parameters.…”

Structural and Genetic Bases of Arterial Stiffness

“…In a recent study, AIx was found to be higher in the offspring of families with hypertension than in control subjects after correction for known cardiovascular risk factors. 14 Because aortic PWV was similar in the 2 groups, this study 15 indicated the existence of a functional and/or structural decrease in the caliber of small arteries. The Strong Heart Study, 8 performed in 950 adult men and women from 13 American Indian communities, assessed the heritability of carotid stiffness, estimated as the proportion of residual phenotypic variance caused by the additive effects of genes after accounting for the effects of covariates (sex, age, diabetes, etc).…”

“…AIx inheritance has also been studied in twins, using a co-twin case-control analysis in monozygotic and dizygotic female twins. 15 A quantitative genetic modeling technique was used, based on comparison of the variancecovariance matrices for monozygotic and dizygotic twins. Up to 37% of the variance of AIx was found to be determined by genetic factors, and only a small proportion of the total variance was caused by genes also affecting height, heart rate, and mean BP.…”