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Objective Pregnancy-associated plasma protein-A2 (PAPP-A2) is the homolog of PAPP-A in the vertebrate genome and its role in protecting against salt-induced hypertension in salt-sensitive rats has been confirmed. We sought to examine the associations of plasma PAPP-A2 levels and its genetic variants with salt sensitivity, blood pressure (BP) changes and hypertension incidence in humans. Methods Eighty participants (18-65 years old) sequentially consuming a usual diet, a 7-day low-salt diet (3.0 g/day) and a 7-day high-salt diet (18 g/day). In addition, we studied participants of the original Baoji Salt-Sensitive Study, recruited from 124 families in Northern China in 2004 who received the same salt intake intervention, and evaluated them for the development of hypertension over 14 years. Results The plasma PAPPA2 levels significantly decreased with the change from baseline to a low-salt diet and decreased further when converting from the low-salt to high-salt diet. SNP rs12042763 in the PAPP-A2 gene was significantly associated with systolic BP responses to both low-salt and high-salt diet while SNP rs2861813 showed a significant association with the changes in SBP and pulse pressure at 14-year follow-up. Additionally, SNPs rs2294654 and rs718067 demonstrated a significant association with the incidence of hypertension over the 14-year follow-up. Finally, the gene-based analysis found that Pappa2 was significantly associated with longitudinal SBP changes and the incidence of hypertension over the 14-year follow-up. Conclusions This study shows that dietary salt intake affects plasma PAPP-A2 levels and that PAPP-A2 may play a role in salt sensitivity, BP progression and development of hypertension in the Chinese populations.

Objective Cyclooxygenase (COX)-2, an inducible isoform of the major rate-limiting enzymes that regulate the production of prostaglandins is associated with injury, inflammation and proliferation. We sought to examine whether plasma COX-2 levels and its genetic variants is associated with salt sensitivity, BP changes and/or hypertension in humans. Methods Eighty participants (aged 18-65 years) were maintained sequentially either on a usual diet for 3 days, a low-salt diet (3.0 g) for 7 days, and a high-salt diet (18.0 g) for an additional 7 days. In addition, we studied participants of the original Baoji Salt-Sensitive Study, recruited from 124 families from seven Chinese villages in 2004 who received the same salt intake intervention, and evaluated them for the development of hypertension. Results Plasma COX-2 levels were significantly decreased with reduction of salt intake from the usual to a low-salt diet and decreased further when converting from the low-salt to the high-salt diet. SNPs rs12042763 in the COX-2 gene was significantly associated with SBP responses to both low-salt and high-salt diet. SNPs rs689466 and rs12042763 were significantly associated with longitudinal changes in BPs. In addition, several COX-2 SNPs were significantly associated with incident hypertension over an 8-year follow-up. Gene-based analyses also supported the overall association of COX-2 with longitudinal changes in SBP and hypertension incidence. Conclusion This study shows that dietary salt intake affects plasma COX-2 levels and that COX-2 may play a role in salt sensitivity, BP progression and development of hypertension in the Chinese populations studied.

Objective Atherosclerotic diseases are the leading cause of death worldwide. This study aimed to investigate the predictors of brachial-ankle pulse wave velocity (baPWV) and carotid intima-media thickness (CIMT) progression in a Chinese cohort over a 12-year follow-up period and to determine whether these predictors differ by follow-up time. Methods A total of 202 participants were recruited from a previously established cohort in Shaanxi Province, China. Both baPWV and CIMT were measured in 2013 and 2017. Multivariable regression was used to determine the predictors of CIMT and baPWV progression. Results Men had higher CIMT and baPWV and a higher rate of CIMT progression during two follow-ups than women. A 4-year change in SBP was associated with baPWV progression, whereas a 12-year change in DBP was associated with baPWV progression. The increased progression of baPWV presented a linear trend when subgrouping all the participants according to SBP and DBP changes over 4 and 12 years, respectively. In addition, heart rate (HR) change over 4 and 12 years was consistently associated with CIMT progression, and a linear trend was also seen when subgrouping the population. Conclusion Our study demonstrated that SBP and DBP contributed differently in different stages to the progression of arterial stiffness in this Chinese cohort. Moreover, HR was consistently involved in the increased progression of CIMT in all periods. These findings underline the importance of early detection and control of blood pressure and resting HR for the prevention of arterial stiffness progression.