Here are a few of the papers which make the mistake of adjusting for a variable which is strongly associated with Vitamin D.
After adjusting, there is no longer any vitamin D association.
This should not be a surprise.
It is like trying to adjust out the variation of
- Dark skin among African-Americans
- Metabolic syndrome for those who are obese
- BMI for those who are obese
- PTH for those who are low on vitamin D (oops - this is one of the papers below)
Adjust for PTH
Vitamin d deficiency and cardiovascular events in patients with coronary heart disease: data from the heart and soul study.
Am J Epidemiol. 2014 Jun 1;179(11):1279-87. doi: 10.1093/aje/kwu059. Epub 2014 Apr 3.
Welles CC, Whooley MA, Karumanchi SA, Hod T, Thadhani R, Berg AH, Ix JH, Mukamal KJ.
A growing body of evidence supports an association between vitamin D and cardiovascular disease. However, the mechanisms underlying this association are unknown. From 2000 to 2002, we identified 946 participants with stable cardiovascular disease in San Francisco, California, and followed them prospectively for cardiovascular events (heart failure, myocardial infarction, stroke, or cardiovascular death). We then examined the extent to which the association was attenuated by adjustment for poor health behaviors, comorbid health conditions, and potential biological mediators. During a median follow-up period of 8.0 years (through August 24, 2012), 323 subjects (34.1%) experienced a cardiovascular event. Following adjustment for sociodemographic factors, season of blood measurement, health behaviors, and comorbid conditions, 25-hydroxyvitamin D levels under 20 ng/mL remained independently associated with cardiovascular events (hazard ratio = 1.30, 95% confidence interval: 1.01, 1.67). However, after further adjustment for potential biological mediators, the independent association was no longer present (hazard ratio = 1.11, 95% confidence interval: 0.85, 1.44). Parathyroid hormone, a potentially modifiable biological factor downstream from 25-hydroxyvitamin D, was responsible for the majority of this attenuation. These findings highlight the need for randomized controlled trials to determine whether vitamin D supplementation in persons with deficiency could be beneficial for the primary or secondary prevention of cardiovascular events.
Adjust for cardiovascular risk factors
Vitamin D deficiency and myocardial structure and function in older men and women: the Hoorn study.
J Endocrinol Invest. 2010 Oct;33(9):612-7. doi: 10.3275/6883. Epub 2010 Mar 5.
Pilz S1, Henry RM, Snijder MB, van Dam RM, Nijpels G, Stehouwer CD, Kamp O, Tomaschitz A, Pieber TR, Dekker JM.
BACKGROUND: Vitamin D deficiency is frequently observed in heart failure patients and it has been shown that vitamin D exerts various effects on the heart that may be relevant for the pathogenesis of myocardial diseases.
AIMS: We aimed to elucidate the largely unknown association of 25-hydroxyvitamin D [25(OH)D] serum levels with echocardiographic measures of left ventricular (LV) structure and function.
MATERIAL/SUBJECTS AND METHODS: We measured 25(OH)D serum levels and performed standardized LV echocardiograms in 614 persons from a population-based cohort of older men and women. Echocardiographic data were used to calculate LV mass and geometry and for classification of systolic and diastolic dysfunction. To consider the seasonal variations of 25(OH)D levels we categorized our study participants according to season-specific 25(OH)D quartiles.
RESULTS: LV systolic function, mass and geometry were not significantly associated with 25(OH)D serum levels. In binary logistic regression analyses, the prevalence of LV diastolic dysfunction was significantly higher in the first season-specific 25(OH)D quartile when compared to the fourth quartile [odds ratio 2.32 (95% CI: 1.42-3.80); p=0.001] but significance was lost after adjustments for age [odds ratio 1.51 (0.89-2.57); p=0.123] and established risk factors for heart failure [odds ratio 1.47 (0.84-2.59); p=0.178].
CONCLUSIONS: Serum levels of 25(OH)D are not significantly associated with LV structure and function but a non-significant trend towards increased risk of diastolic dysfunction in persons with vitamin D deficiency warrants further studies.