Blood glucose and subsequent cardiovascular disease: update of a meta-analysis

Abstract

Background/purpose:

A 1999 meta-analysis described the relationship between blood glucose and subsequent cardiovascular events (MI, stroke, cardiovascular mortality). More studies have been published; therefore, we updated and refined estimates of this relationship in people without diabetes.

Acceptability criteria:

We accepted prospective studies that reported screening results for blood glucose levels (either fasting, 2-hour postprandial, 1-hour postprandial, or casual) divided into ≥3 quantiles. Required data within each quantile were numbers exposed plus study duration or person-years at risk, and numbers of cardiovascular outcomes (myocardial infarction, stroke, death). No restrictions were placed on language or publication date.

Data sources:

Two reviewers searched Medline, Embase, Scopus, and Cochrane databases from inception until December 2009. Consensus settled discrepancies.

Data synthesis:

Poisson regression quantified the relationship between glucose quantile and outcomes. Beta values were combined with inverse variance weightings using a random effects meta-analytic model.

Results:

We found 36 articles with 141 datasets examining the relationship between blood glucose (32 fasting, 52 2-hour postprandial, 37 1-hour postprandial, 20 casual) in 191,249 patients without diabetes (73% male) for 3 million person-years. There were 12,537 (6.6%) cardiovascular deaths, 14,445 (7.6%) cardiovascular events, 6862 (3.6%) cardiac and 3412 (1.7%) stroke deaths. Relative risks/unit increase in blood glucose were all significant for total cardiovascular events (RRs ranged from 1.09–1.51, all p-values < 0.005) and cardiovascular deaths (RR = 1.05–1.24, p < 0.007), and all for cardiac deaths (p < 0.05) except casual glucose; stroke mortality was less clear. The two strongest relationships were found between fasting levels and all events (RR = 1.51, CI: 1.20–1.89) and with cardiovascular mortality (RR = 1.40, CI: 1.18–1.60). With 2-hour postprandial levels, the respective RRs were 1.22 (1.17–1.28) and 1.24 (1.19–1.30). A limitation is the assumption of a continuous relationship between variables.

Conclusions:

We have provided refined estimates confirming the association between elevated blood glucose and subsequent cardiovascular events.

Keywords::

• Blood glucose
• Cardiac death
• Cardiovascular death
• Cardiovascular events
• Cerebrovascular mortality
• Death
• Meta-analysis
• Mortality
• Myocardial infarction
• Prospective studies
• Stroke

Transparency

Declaration of funding

This study was sponsored by Novo Nordisk A/S, Bagsværd Denmark.

Declaration of financial/other relationships

T.R.E. has disclosed that he has received sponsorship and research grants from Novo Nordisk and Janssen Cilag, and is on the Speakers’ Bureau of Janssen. M.M. has no relevant financial relationships to disclose. M.E.H.H. has disclosed that he is an employee of Janssen Cilag, but was an employee of Novo Nordisk at the time of preparation of this manuscript.

CMRO peer reviewers may have received honoraria for their review work. The peer reviewers on this manuscript have disclosed that they have no relevant financial relationships.