Archive for June, 2012

Journal Club 27 June 2012


Associations of dietary calcium intake and calcium supplementation with myocardial infarction and stroke risk and overall cardiovascular mortality in the Heidelberg cohort of the European Prospective Investigation into Cancer and Nutrition study



Summary (abstract from paper):


It has been suggested that a higher calcium
intake might favourably modify cardiovascular risk
factors. However, findings of an ultimately decreased risk
of cardiovascular disease (CVD) are limited. Instead,
recent evidence warns that taking calcium supplements
might increase myocardial infarction (MI) risk.

To prospectively evaluate the associations of
dietary calcium intake and calcium supplementation with
MI and stroke risk and overall CVD mortality.

Data from 23 980 Heidelberg cohort
participants of the European Prospective Investigation
into Cancer and Nutrition study, aged 35e64 years and
free of major CVD events at recruitment, were analysed.
Multivariate Cox regression models were used to
estimate HRs and 95% CIs.

After an average follow-up time of 11 years,
354 MI and 260 stroke cases and 267 CVD deaths were
documented. Compared with the lowest quartile, the
third quartile of total dietary and dairy calcium intake had
a significantly reduced MI risk, with a HR of 0.69 (95%
CI 0.50 to 0.94) and 0.68 (95% CI 0.50 to 0.93),
respectively. Associations for stroke risk and CVD
mortality were overall null. In comparison with non-users
of any supplements, users of calcium supplements had
a statistically significantly increased MI risk (HR¼1.86;
95% CI 1.17 to 2.96), which was more pronounced for
calcium supplement only users (HR¼2.39; 95% CI 1.12
to 5.12).

Increasing calcium intake from diet might
not confer significant cardiovascular benefits, while
calcium supplements, which might raise MI risk, should
be taken with caution.


  • DBC provided background information from meta-analyses suggesting hazard for myocardial infarction from supplemental calcium and vitamin D. The contribution of the calcium versus vitamin D is uncertain
  • The paper presented suggested dietary calcium may confer reduction in cardiovascular events and supplemental calcium a small hazard.  The latter observation is based on 7 events in 256 patients. The population attributable risk is small, therefore. The relative effect is similar magnitude to clinically meaningful therapeutic benefits.
  • The need for efficacy data in terms of supplemental calcium and vitamin D in terms of clinical bone or other outcomes are required to determine net position of such treatment
  • There was a3 to4% use of supplemental calcium and this spanned all quartiles of dietary calcium ingestion
  • The authors used 4 models to assess the robustness of their findings

Journal Club 20 June 2012

SC presented GRAVITAS and TRIGGER-PCI papers.

GRAVITAS examined the value of the double dose maintenance clopidogrel (150 mg per day) versus standard dose on patient’s with reactive platelets despite clopidogrel as assessed by VerifyNow assay.  TRIGGER-PCI examined  prasugrel versus clopidogrel in stable patients with elevated platelet reactivity (using VerifyNow)  undergoing PCI.

Some  comments:

  • both trials were negative, i.e. the active regimen was not significantly different to standard care
  • the prevalence of high platelet reactivity on clopidogrel is from 20 to 40% depending on definition and assay
  • high platelet reactivity is associated with higher frequency of adverse clinical events
  • double does clopidogrel did not significantly alter platelet function or clinical events
  • prasugrel did significantly reduce platelet reactivity compared with clopidogrel, however, this did not translate into a significantly lower rate of clinical events
  • the TRIGGER-PCI trial was low risk patients, had lower event rates than the power calculations modelled for. It is noted that the outcomes in the trial are directionally consistent with the hypothesis of improved outcome and increased bleeding
  • the role of platelet function testing in intervention remains uncertain, particularly if there is substitution for clopidogrel by ticagrelor/prasugrel  (there being no superior alternative to these). If there is a role, it would relate to a ‘rationing’ or cost effectiveness argument with large price differential in favour of clopidogrel