Copenhagen University Hospital

Increased mortality linked to genetically low vitamin D

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Børge G. Nordestgaard, MD, DMSc, professor at Copenhagen University Hospital in Denmark, and colleagues evaluated 95,766 white participants from three cohorts in Copenhagen to determine whether genetically low 25-(OH)D concentrations are linked to increased mortality. Plasma 25-(OH)D measurements were available for 35,334 participants.

Borge Nordestgaard

Børge G. Nordestgaard

Participants were evaluated for genetic variants in DHCR7 and CYP2R1. From the study entry until its end in 2013, 10,349 participants died.

All-cause and cause-specific mortality were associated with a 20 nmol/L lower plasma 25-(OH)D concentration; specifically, the adjusted HRs were 1.19 (95% CI, 1.14-1.25) for all-cause mortality, 1.18 (95% CI, 1.09-1.28) for CV mortality, 1.12 (95% CI, 1.03-1.22) for cancer mortality and 1.27 (95% CI, 1.15-1.4) for other mortality.

There was a 1.9-nmol/L decrease in plasma 25-(OH)D concentration associated with each increase inDHCR7/CYP2R1 allele score. For each one DHCR7/CYP2R1 allele score increase, the HRs were 1.02 (95% CI, 1-1.03) for all-cause mortality, 0.98 (95% CI, 0.96-1.01) for CV mortality, and 1.03 (95% CI, 1-1.06) for cancer mortality and other mortality.

For all-cause mortality, the OR was 1.3 (95% CI, 1.05-1.61) for a genetically determined 20 nmol/L lower plasma 25-(OH)D concentration.

“Our data suggest that low vitamin D is a direct cause of increased mortality,” Nordestgarrd told Endocrine Today. “The best advice to patients is to get enough sunshine (up to half an hour on arms, face and neck a couple of times a week) and to get fatty fish. Whether vitamin D supplements are advisable for healthy people await publication of large randomized trials in 2017.”

In an accompanying editorial, Paul Welsh, PhD, and Naveed Sattar, MD, PhD, of the University of Glasgow, wrote that the study findings provide optimism for upcoming results of new trials, “more so if they are rapidly confirmed by additional Mendelian randomization studies with greater power.”

“Mendelian randomization is an important emerging research tool, is here to stay, and is beginning to be recognized by guideline committees,” Welsh and Sattar wrote. “Of course, in research where randomized trials are possible (or indeed ongoing), mendelian randomization studies should not displace them as the gold standard evidence in clinical guidelines or in the minds of health care professionals. In the meantime, there may well be yet more ‘groundhog days’ for vitamin D.” – by Amber Cox

The Long-Term Effects of Childhood Bacterial Meningitis.

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Adult survivors of childhood bacterial meningitis have lower educational achievement and a lower likelihood of economic self-sufficiency than matched healthy controls.

 

The short-term sequelae of childhood bacterial meningitis can include hearing loss, motor deficits, seizures, and cognitive impairment. But what about functioning in adult life? In a recent cohort study, investigators used national patient registries in Denmark to compare the educational achievement and economic self-sufficiency of individuals with meningococcal, pneumococcal, or Haemophilus influenzae meningitis diagnosed between 1977 and 2007, before age 12 years, with those of age- and sex-matched controls who had not had meningitis. To assess for family-related cofactors, the researchers also evaluated the siblings and parents of these two cohorts.

Survivors of pneumococcal or H. influenzae meningitis were less likely than matched controls to complete high school or to obtain higher education by age 35. They also were less likely to attain these goals than their siblings, who performed similarly to the siblings of controls. In contrast, although meningococcal meningitis survivors were less likely than controls to complete high school or to obtain higher education by age 35, these survivors had educational achievement comparable to that of their siblings, who had lower achievement than the siblings of controls. Educational achievement was lower among parents of meningococcal meningitis survivors than among parents of controls; achievement among pneumococcal and H. influenzae meningitis survivor parents was comparable to that among controls. By 2010, fewer survivors than controls were economically self-sufficient (–3.8%, –10.6%, and –4.3%, respectively, for meningococcal, pneumococcal, and H. influenzae meningitis).

Comment: This large, well-designed study confirms sustained intellectual and economic sequelae of childhood bacterial meningitis but also suggests different routes to these long-term effects. Intellectual and economic impairments are likely direct consequences of the severity of pneumococcal and H. influenzae meningitis. However, family factors appear to predominate in the poorer intellectual and economic achievements of meningococcal meningitis survivors.

 

Source: Journal Watch Infectious Diseases