Clinical Pathology Selected Abstracts, 8/13

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Dietary and supplemental calcium intake and cardiovascular disease death

Among older adults, calcium intake through supplements is promoted for bone health, but concerns have emerged about the possible adverse effects of high calcium intake on cardiovascular health. Several randomized control trials found an increased risk of various cardiovascular disease events with calcium supplements. The authors conducted a study in which they examined the relationship between calcium intake and cardiovascular mortality in a large cohort of U.S. men and women. They analyzed 388,229 men and women aged 50 to 71 years from the National Institutes of Health–AARP Diet and Health Study. The authors assessed supplemental and dietary intake of calcium at baseline in 1995. After a mean of 12 years of followup, results showed 7,904 and 3,874 cardiovascular disease (CVD) deaths in men and women, respectively. In men, supplemental calcium intake was associated with an elevated risk of CVD death (relative risk, 1.20), more specifically, with death from heart disease. In women, supplemental calcium intake was not associated with death. Of interest, dietary calcium intake was unrelated to CVD death in men and women. The investigators concluded that a higher intake of supplemental calcium was associated with an excess risk of CVD death in men. They proposed that this may be the case because calcium causes vascular calcification, which places men at risk for increased atherosclerotic plaque burden. This association between calcium supplements and CVD death was not observed in women, and additional studies are needed to determine if there is a gender difference in the cardiovascular effects of calcium supplements.

Xiao Q, Murphy RA, Houston DK. Dietary and supplemental calcium intake and cardiovascular disease mortality. JAMA Intern Med. 2013;173:639–646.

Correspondence: Qian Xiao at qian.xiao@nih.gov

Investigational vaccine for preventing S.aureus infections after cardiothoracic surgery

Infections with Staphylococcus aureus after median sternotomy are associated with substantial morbidity and mortality. A safe and effective vaccine against S. aureus strains was investigated in a clinical trial to reduce this significant complication of cardiothoracic surgery. The vaccine, V710, contains the highly conserved S. aureus 0657nI iron surface determinant B (IsdB). It showed protectivity in animal models and immunogenicity in healthy volunteers within 14 days of a single dose of an adjuvanted or nonadjuvanted formulation. The authors conducted a double-blind, randomized, event-driven trial to evaluate the efficacy and safety of preoperative vaccination in preventing serious postoperative S. aureus infection in patients undergoing cardiothoracic surgery. The trial was conducted between December 2007 and August 2011 and involved 8,031 patients ages 18 years or older. The patients were scheduled for full median sternotomy within 14 to 60 days of vaccination at 165 sites in 26 countries. They were randomized to receive a single 0.5-mL intramuscular injection of either V710 vaccine, 60 µg (n=4,015), or a placebo (n=4,016). The primary endpoint of the study was prevention of S. aureus bacteremia or deep sternal wound infections through postoperative day 90, or both. Secondary endpoints included all S. aureus surgical site and invasive infections through postoperative day 90. Based on the second interim analysis, the study was terminated because results showed that the V710 vaccine was not significantly more efficacious than the placebo in preventing either the primary or secondary endpoints. Interestingly, the results occurred despite a robust antibody response in patients. Furthermore, the mortality rate in patients with staphylococcal infections was significantly higher among those receiving the V710 vaccine than among placebo control patients. The authors concluded that patients undergoing cardiothoracic surgery with median sternotomy did not benefit from a vaccine against S. aureus compared with placebo controls. To that end, this study does not support the routine use of the V710 vaccine for patients undergoing median sternotomy.

Fowler VG, Allen KB, Moreira ED, et al. Effect of an investigational vaccine for preventing Staphylococcus aureus infections after cardiothoracic surgery: a randomized trial. JAMA. 2013;309:1368–1378.

Correspondence: Vance G. Fowler at fowle003@mc.duke.edun