Pulse pressure and aortic calcification: Did we learn something?

Atherosclerosis is systemic vascular disease which affects the whole vascular bed, with some variations and predilection places. Calcification is a key component of atherosclerotic process. Coronary calcification could be easily quantified using computed tomography (CT) and estimated by coronary calcium score that represents an important predictor of cardiovascular morbidity and mortality. ¹ Calcification of abdominal aorta has not been established as independent cardiovascular risk factor yet. However, studies showed that abdominal aortic calcification was related to cardiovascular events including myocardial infarction, stroke, heart failure, and cardiovascular mortality. ² , ³ Abdominal CT represents the best imaging modality for quantification of abdominal aortic calcification (AAC). However, dual‐energy X‐ray absorptiometry (DXA) could also provide semiquantitative measurement of AAC. ⁴

Pulse pressure (PP) represents an important predictor of cardiovascular mortality, stroke, and cognitive decline. ⁵ The clinical significance of PP is still controversial because recent study showed that the young patients with highest PP had the lowest risk of incident hypertension. ⁶ In the current issue of the Journal, Heffernan et al ⁷ presented data from the National Health and Nutrition Examination Survey 2013‐2014 and reported that PP was a predictor of the presence of AAC in fully adjusted models in adult US population. In the partial statistical model which did not include age and BP medications showed that systolic BP, diastolic BP, and PP were associated with AAC in patients in both age groups (>60 and <60 years old). However, after adjustment for age and antihypertensive therapy only PP remained associated with AAC in the whole population. Results regarding AAC score were different. The investigators revealed that only PP, but not SBP and DBP, was associated with AAC score in partial statistical model, but even is significance vanished after adjustment for age and antihypertensive medications. ⁷ There are several important points of this investigation that deserve further discussion.

Abdominal aortic calcification is an active pathophysiological process, which is associated with advancing age, smoking, chronic inflammatory disorders, metabolic disorders, and chronic renal disease. ⁸ There are two types of AAC: (a) atherosclerotic or intimal calcifications and (b) non‐atherosclerotic medial calcific sclerosis. Arterial intimal calcification is associated with lipid accumulations and increased macrophages activity within advanced atheromatous lesions. Medial calcifications are the result of degeneration of the vascular smooth muscle cells and calcification of the elastin fibrils. ⁸ The later is frequently seen in patients with advanced age, type II diabetes, and chronic renal disease. However, it is unclear if the presence of both forms of calcification within the abdominal aorta is consequence of common risk factors or other local and systemic factors. Even though DXA represents widely available imaging methods, there are no sufficient data that DXA could differentiate atherosclerotic and non‐atherosclerotic calcifications.

There are several semiquantitative methods for AAC assessment: (a) 24‐point or simplified 8‐point semiquantitative scoring method developed in the Framingham study; (b) Rotterdam scale; and (c) Mayo scale. ⁴ However, only the first scale has been validated. These methods are based on the results obtained by lateral spine radiographs or CT. Densitometric lateral spine images may not be able to detect small AAC volume that can be detected on lateral spine radiographs due to lower resolution of densitometric lateral spine images. However, both techniques may fail to detect smaller calcifications seen on CT.

Heffernan et al ⁷ used 24‐point semiquantitative score on DXA. For this analysis, the anterior and posterior aortic walls were separated into four segments, corresponding to the areas of the lumbar vertebrae (L1‐L4). Within each of these eight segments, aortic calcification was visually estimated with a score ranging from 0 to 24. ⁷ This illustrates the potential limitation in assessment of AAC and unrecognizing small calcifications that could be prevalent in general population that has been described in the present study. However, despite this limitation, authors showed significant difference in AAC between patients younger and older than 60 years. There was no difference in prevalence of hypertension, diabetes, high cholesterol, and family history of myocardial infarction in patients <60 years old. Smoking status and PP were the only two parameters that differed between patients with AAC and those without AAC in the population below 60 years. ⁷ More parameters were responsible for AAC in the participants older than 60 years. SBP and PP were higher, while DBP was lower in patients with AAC than in individuals without AAC. The prevalence of hypertension was also significantly more prevalent in older patients with AAC. ⁷ However, there was no difference in prevalence of diabetes, high cholesterol, and family history of ischemic heart disease. This underlines the importance of arterial hypertension over other common cardiovascular risk factors (diabetes, dyslipidemia, and family history of coronary artery disease) in development of AAC. This could have even broader perspective if AAC would be considered as surrogated for atherosclerosis because these findings would mean that arterial hypertension has more important role in development of atherosclerosis than other mentioned cardiovascular risk factors. However, one should be careful in drawing this conclusion because AAC could be the result of both atherosclerotic and non‐atherosclerotic changes and DXA is not able to differentiate between these two types.

In the current study, PP was independently associated with AAC presence in both age groups, whereas it did not show that strong association with amount of AAC. ⁷ This discrepancy could be explained by semiquantitative AAC assessment by DXA, which was used in this study. However, it can also be related to other parameters such as age, BMI, smoking, and diabetes that were included in the model and showed significant and independent association with amount of AAC. ⁷ It is also possible that antihypertensive, antihyperlipidemic, and antidiabetic medications had significant roles as confounding factors and interfered the relation between PP and AAC volume.

The increment of PP in this study was the result of concurrent increase in SBP and decrease in DBP, which is expected in older population with more extensive atherosclerosis and vascular calcification, which altogether increase arterial stiffness and help in later development of isolated systolic hypertension. In the current study, there is no evidence that isolated systolic hypertension plays an important role, but there is a trend of wider PP and increased volume of AAC among older patients, which indirectly implicates the importance of isolated systolic hypertension in this population.

There are two most important clinical implications related to the current study. First, DXA represents relative uncomplicated, inexpensive and broadly available method for evaluation of aortic calcification, which is also not associated with high radiation dosage and is already used in large number of indications and primarily for assessment of bone density in patients with suspected osteopenia, osteoporosis, or fracture. The limitation of this clinical implication is the prevalent usage in female, but not in male population. Second, PP has an important impact on arterial remodeling independent of SBP and DBP. However, it seems that age and antihypertensive medications could be the major confounding factors that limit association between PP and AAC. Additionally, this is cross‐sectional study and causal relationship between PP and AAC could not be determined, but it can serve as a good hypothesis for future longitudinal studies or at least retrospective follow‐up investigation that could provide more robust and comprehensive information on this topic.

The further research should be directed toward assessment predictive value of PP on occurrence of aortic calcification in normotensive and hypertensive individuals, separately. The other significant task is to establish quantitative AAC scoring, which should be validated using accurate imaging methods such as CT and potentially replace current semiquantitative methods.

CONFLICT OF INTEREST

None.

AUTHOR CONTRIBUTIONS

Marijana Tadic involved in writing the article; Cesare Cuspidi involved in detailed review with constructive remarks that substantially changed the article.

Tadic M, Cuspidi C. Pulse pressure and aortic calcification: Did we learn something?. J Clin Hypertens. 2020;22:886–887. 10.1111/jch.13845