This secondary analysis of the SPRINT data revealed the association of higher AIP with a significantly higher risk of composite cardiovascular outcomes in hypertensive older adults. The benefits of intensive BP control on composite cardiovascular outcomes were consistent across different AIP quartiles. No evidence was found for the interaction between intensive BP control and AIP on the risk of the primary outcome.
A previous study found that the predominance of sdLDL in plasma was significantly associated with an increased risk of coronary heart disease . Compared with larger and looser LDL particles, sdLDL particles are more likely to penetrate the artery wall and deposit in the vascular endothelium . In addition, sdLDL are more susceptible to oxidation, which further increases atherogenicity . Therefore, the relative proportion of sdLDL may be an important predictive factor of cardiovascular outcomes. However, LDL subclass patterns are usually determined by non-denaturing polyacrylamide GGE, which is ideally not performed when patients are admitted to a hospital . Dobiasova et al. proposed AIP as an indicator of atherogenic lipoprotein phenotype and demonstrated its negative correlation with LDL particle size, making AIP a surrogate for sdLDL in predicting the atherogenicity of plasma lipoproteins .
Previous studies have reported a positive association between AIP and the risk of MACEs in different populations. A 15-year cohort study on healthy adults revealed the value of AIP in the prediction of developing cardiovascular events and its related mortality . The results of a study on the Iranian population indicated that AIP was positively associated with the risk of cardiovascular diseases . A cohort study on postmenopausal Chinese women (aged over 50 years) concluded that AIP was an independent predictor of cardiovascular risk. A study on the Health Risk Assessment Study and Korea Health Insurance Review and Assessment Service cohort found a positive correlation between the AIP quartile and the incidence of ischemic heart disease . Older adults with a higher baseline BP had a higher Framingham score (a sex-specific algorithm for predicting the 10-year cardiovascular disease risk of an individual ), which represented a higher cardiovascular risk. Although a large body of evidence has proven the positive association between AIP and the risk of MACEs, this association has not been fully elucidated and needs to be studied in older adults with hypertension. Consistent with previous studies, this study found that elevated AIP was positively associated with a higher risk of MACEs in non-diabetic hypertensive older adults, and that AIP (Area Under Curve: 0.703 vs. 0.669, P < 0.001) was an efficient biomarker than LDL in predicting the incidence of MACEs (Fig. S1).
TG level was suggested to be positively associated with a higher prevalence of cardiovascular outcomes . Within the high TG level group, patients with low HDL-C levels showed a higher risk of cardiovascular disease than those with high HDL-C levels . Both increased TG levels and decreased HDL-C levels are strong indicators of cardiovascular risk. This mechanism may explain why elevated AIP, as a parameter of blood lipid levels, is strongly associated with an increased risk of MACEs. In addition, a previous study found that AIP levels were correlated with abnormal glucose metabolism, inferred from the degree of insulin resistance . Insulin resistance, and related hyperinsulinemia, hyperglycemia, and adipocytokines may also cause vascular endothelial dysfunction, dyslipidemia, hypertension, and vascular inflammation, all of which contribute to the development of cardiovascular diseases.
According to a 9-year longitudinal study in Taiwan, AIP was proven to be significantly and positively correlated with the prevalence of hypertension . A longitudinal study following a cohort of Hanzhong hypertensive adolescents for 12 years found that a high AIP level was a strong risk factor for hypertension-associated renal damage . With a growing body of evidence showing a linear relationship between BP and the risk of cardiovascular diseases, the benefits of intensive BP control in decreasing MACEs risks have already been proven in older patients with hypertension [26, 27]. Therefore, this study evaluated the relationship between AIP and the effect of intensive BP management on the risk of cardiovascular diseases and found that the benefit of intensive BP control is consistent in different AIP quartiles. Additionally, no interaction between intensive BP control and AIP for the risk of primary outcome was found.
Comparisons with other studies and what does the current work add to the existing knowledge
Previous studies on the association of AIP with major adverse cardiovascular events did not focus on in the older adults with non-diabetic hypertension, a group which was common in clinical practice but may be underemphasized. This study further demonstrated the prognostic value of AIP in this population. Moreover, SPRINT database was used in this study to further study the relationship between AIP and cardiovascular prognosis under different antihypertensive strategies.
Study strengths and limitations
This study has the following strengths. First, this study had a sufficient sample size and reliable data source. Second, the population of the study was older adults with non-diabetic hypertension, which was of great need of attention in clinical practice. Finally, the population was grouped according to different antihypertensive strategies to test the consistent of the relationship between AIP and major adverse cardiovascular events.
This study had some limitations. First, the SPRINT trial did not define AIP subgroups, which limited the expansion of the results. Second, some AIP-related data, such as waist circumference and diet, may have altered the study results; this data could not be acquired. Furthermore, an optimal AIP cut-off value for predicting MACEs risks that could aid in finding better risk stratification in clinical settings is yet to be determined.