Open AccessAsymmetric Dimethylarginine and Cardiovascular Risk: Systematic Review and Meta‐Analysis of 22 Prospective Studies
Author(s) -
Willeit Peter,
Freitag Daniel F.,
Laukkanen Jari A.,
Chowdhury Susmita,
Gobin Reeta,
Mayr Manuel,
Di Angelantonio Emanuele,
Chowdhury Rajiv
Publication year - 2015
Publication title -
journal of the american heart association
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.494
H-Index - 85
ISSN - 2047-9980
DOI - 10.1161/jaha.115.001833
Subject(s) - medicine , asymmetric dimethylarginine , prospective cohort study , meta analysis , confidence interval , cardiology , disease , arginine , biochemistry , amino acid , chemistry
Background Asymmetric dimethylarginine ( ADMA ) inhibits the production of nitric oxide, a key regulator of the vascular tone, and may be important in the development of cardiovascular disease ( CVD ). Our aim was to reliably quantify the association of ADMA and its isomer symmetric dimethylarginine ( SDMA ) with the risk of CVD outcomes in long‐term cohort studies. Methods and Results Data were collated from 22 prospective studies involving a total of 19 842 participants, which have recorded 2339 CVD , 997 coronary heart disease, and 467 stroke outcomes during a mean follow‐up of 7.1 years. In a comparison of individuals in the top with those in the bottom third of baseline ADMA values, the combined risk ratios were 1.42 (95% confidence interval: 1.29 to 1.56) for CVD , 1.39 for coronary heart disease (1.19 to 1.62), and 1.60 for stroke (1.33 to 1.91). Broadly similar results were observed according to participants' baseline disease status (risk ratios for CVD : 1.35 [1.18 to 1.54] in general populations; 1.47 [1.16 to 1.87] in individuals with pre‐existing CVD ; and 1.52 [1.26 to 1.84] in individuals with pre‐existing kidney disease) and by different study characteristics, including geographical location, sample type, assay method, number of incident outcomes, and level of statistical adjustment (all P values>0.05). In contrast, in 8 prospective studies involving 9070 participants and 848 outcomes, the corresponding estimate for SDMA concentration was 1.32 (0.92 to 1.90) for CVD . Conclusions Available prospective studies suggest associations between circulating ADMA concentration and CVD outcomes under a broad range of circumstances. Further research is needed to better clarify these associations, particularly in large general population studies.