Cyclic guanosine monophosphate and 10-year change in left ventricular mass: the Multi-Ethnic Study of Atherosclerosis (MESA)

Abstract

Purpose: Cyclic guanosine monophosphate (cGMP) is a second messenger for natriuretic peptide (NP) and nitric oxide pathways; its enhancement a target for heart failure and cardiovascular disease (CVD). We evaluated whether plasma cGMP was associated with change in left ventricular mass (LVM) among individuals free of CVD and if this differed by sex.

Methods and Results: In 611 men and 612 women aged 45–84 years with plasma cGMP measured at baseline and cardiac MRI performed at baseline and 10 years later, we tested associations of cGMP [log-transformed, per 1 SD increment] with LVM, adjusting for CVD risk factors and N-terminal pro-B-type-NP (NT-proBNP). Participants had mean (SD) age of 63.1(8.5) years and cGMP 4.8(2.6) pmol/mL. Cross-sectionally, higher cGMP was associated with lesser LVM, non-lin- early. In contrast, longitudinally, higher cGMP was associated with increase in LVM [1.70g (0.61, 2.78)] over 10 years. Higher cGMP was associated with greater LVM change in men [2.68g (1.57, 3.79)] but not women [0.24g ((−0.92, 1.39); p-interaction < 0.001].

Conclusion: In conclusion, in a community-based cohort, higher cGMP levels were associated with increase in LVM over 10 years independent of CVD risk factors and NT-proBNP in men, perhaps reflecting compensatory changes. Further studies are needed to understand mechanistic roles of cGMP in LV remodelling and associated sex differences.

Keywords:

• cGMP
• left ventricular hypertrophy
• cardiac MRI
• remodelling
• sex differences

Acknowledgements

The authors thank the other investigators, the staff, and the MESA participants for their valuable contributions. A full list of participating MESA investigators and institutions can be found at http://www.mesa-nhlbi.org.

Disclosure statement

Dr. Shah has received research grants from Actelion, AstraZeneca, Corvia, and Novartis; and has received consulting fees from Actelion, Amgen, AstraZeneca, Bayer, Boehringer-Ingelheim, Cardiora, Eisai, Ionis, Ironwood, Merck, Novartis, Pfizer, Sanofi, and United Therapeutics. All other authors do not report any relevant conflicts of interest.

Additional information

Funding

This project was funded by the American Heart Association Go Red for Women Strategically Focussed Research Network grant 16SFRN27870000 and 16SFRN28620000. The MESA study was supported by contracts HHSN268201500003I, N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168 and N01-HC-95169 from the National Heart, Lung, and Blood Institute (NHLBI), and by grants UL1-TR-000040, UL1-TR-001079, and UL1-TR-001420 from NCATS. This research was also supported by R01 HL127659 from the NHLBI to Dr. Heckbert. Dr. Shah is supported by grants R01 HL107577, R01 HL127028, R01 HL140731, and R01 HL149423 from the NHLBI. Drs. Michos and Zhao are additionally funded by the Blumenthal Scholars Award in Preventive Cardiology at Johns Hopkins University.