High cortisol and low DHEA both predict increased cardiovascular mortality

Posted on September 30, 2010 by Dr. Jonathan

More evidence for the link between adrenal dysregulation and death from cardiovascular disease is reported in a study recently published in the Journal of Clinical Endocrinology & Metabolism. The authors observe:

“The stress hormone cortisol has been linked with unfavorable cardiovascular risk factors, but longitudinal studies examining whether high levels of cortisol predict cardiovascular mortality are largely absent…The aim of this study was to examine whether urinary cortisol levels predict all-cause and cardiovascular mortality over 6 yr of follow-up in a general population of older persons.”

They studied 861 subjects by assessing 24 hour urinary cortisol levels at the beginning, then followed them for 6 years during which they documented death from all causes and death from ischemic and cerebrovascular disease in particular. What did the data show?

“After adjustment for sociodemographics, health indicators, and baseline cardiovascular disease, urinary cortisol did not increase the risk of noncardiovascular mortality, but it did increase cardiovascular mortality risk. Persons in the highest tertile of urinary cortisol had a five times increased risk of dying of cardiovascular disease. This effect was found to be consistent across persons with and without cardiovascular disease at baseline.”

Their concluding comments express the robustness of their findings and suggest that circulatory damage may be an important mechanism by which high cortisol is so harmful for the brain:

“High cortisol levels strongly predict cardiovascular death among persons both with and without preexisting cardiovascular disease. The specific link with cardiovascular mortality, and not other causes of mortality, suggests that high cortisol levels might be particularly damaging to the cardiovascular system.”

Interestingly, we find another paper just published in the same journal that ‘fleshes out’ the connection between adrenal dysregulation and death from cardiovascular disease. The authors state:

“The age-related decline in dehydroepiandrosterone (DHEA) levels is thought to be of importance for general and vascular aging…We tested the hypothesis that low serum DHEA and DHEA sulfate (DHEA-S) levels predict all-cause and cardiovascular disease (CVD) death in elderly men.”

Both cortisol and DHEA, an important androgen for vitality, body composition, mood and immune regulation, are produced in the adrenal glands. Excessive production of cortisol typically depletes the resources to produce DHEA, a phenomenon call the ‘pregnenolone steal’. The authors analyzed baseline levels of DHEA in 2644 Swedish men, then correlated this with mortality data:

“Low levels of DHEA-S predicted death from all causes; but not cancer. Analyses with DHEA gave similar results.”

It was particularly interesting to note that…

“The association between low DHEA-S and CVD death remained after adjustment for C-reactive protein and circulating estradiol and testosterone levels. When stratified by the median age of 75.4 yr, the mortality prediction by low DHEA-S was more pronounced among younger than older men.”

The discerning clinician will recognize that for cardiovascular risk assessment to be complete, cortisol and DHEA levels should be evaluated—ideally by salivary hormone collections that delineate the important diurnal cortisol rhythm.

Two new studies confirm statins do not help in primary prevention of cardiovascular disease

Posted on June 30, 2010 by Dr. Jonathan

Archives of Internal Medicine Although there is evidence that pharmacological lowering of lipids with statins may reduce mortality when coronary heart disease has already been established, there is a massive accumulation of data that confirm they do not reduce mortality when used for prevention. The authors of a study just published in Archives of Internal Medicine observe:

“…it remains uncertain whether statins have similar mortality benefit in a high-risk primary prevention setting. Notably, all systematic reviews to date included trials that in part incorporated participants with prior cardiovascular disease (CVD) at baseline. Our objective was to reliably determine if statin therapy reduces all-cause mortality among intermediate to high-risk individuals without a history of CVD.”

The authors synthesized data from 11 studies including 65,229 participants encompassing 244,000 person-years. What did the data show?

“The use of statins in this high-risk primary prevention setting was not associated with a statistically significant reduction in the risk of all-cause mortality.”

To fully appreciate the significance of their findings, consider the editorial statement in the same issue:

“Ray and colleagues present what is to date the cleanest and most complete meta-analysis of pharmacological lipid lowering for primary prevention. Limiting the analysis to patients without existing coronary disease is critical because studies that include both groups of patients may appear to show benefit for all patients, when all the benefit accrues to those with existing disease. The patients in their analysis reduced their average levels of low-density lipoprotein cholesterol from 139 to 98 mg/dL and are therefore representative of those being treated in primary care today.”

This puts the authors’ conclusion in perspective:

“This literature-based meta-analysis did not find evidence for the benefit of statin therapy on all-cause mortality in a high-risk primary prevention set-up.”

And this same issue of Archives includes a critical reappraisal of the evidence for the use of statins for prevention from the much-touted JUPITER ((Justification for the Use of Statins in Primary Prevention) study. Their forthright conclusion is consonant with the rest of the evidence:

“The results of the trial do not support the use of statin treatment for primary prevention of cardiovascular diseases and raise troubling questions concerning the role of commercial sponsors.”

IMHO: I consider elevated lipoprotein phospholipase A2 (Lp-PLA2) as evidence of already existing vascular disease even when the person has not suffered a heart attack or stroke. I then seriously consider recommending a natural statin with the appropriate co-factors and customized supports until we confirm that the condition has been brought under control.

RDW is an inexpensive but powerful indicator often overlooked on your routine blood test

Posted on March 7, 2010 by Dr. Jonathan

Archives of Internal Medicine 0210 RDW stands for Red (Blood Cell) Distribution Width, an index for the degree of variability in the size and shape of your red blood cells. Recent studies are showing it to be a powerful indicator of overall health and the risk of death from multiple causes. RDW is always included in the standard Complete Blood Count (CBC), one of the most routine lab tests in modern medicine, but there’s evidence that the usual lab reference range is too broad and it’s value is not widely appreciated. It has been established for some time that RDW predicts mortality form cardiovascular disease, but this study recently published in the Archives of Internal Medicine is particularly interesting because it shows that RDW predicts mortality in the general population independent of cardiovascular disease. The authors state:

“Higher RDW values were strongly associated with an increased risk of death…Even when analyses were restricted to nonanemic participants or to those in the reference range of RDW (11%-15%) without iron, folate, or vitamin B12 deficiency, RDW remained strongly associated with mortality. The prognostic effect of RDW was observed in both middle-aged and older adults for multiple causes of death.”

Two weeks later the another paper was published in the same journal on the same topic that begins with this observation:

“Red blood cell distribution width (RDW), an automated measure of red blood cell size heterogeneity (eg, anisocytosis) that is largely overlooked, is a newly recognized risk marker in patients with established cardiovascular disease (CVD).”

They set out to investigate

“the association of RDW with all-cause mortality and with CVD, cancer, and chronic lower respiratory tract disease mortality in 15,852 adult participants.”

Their conclusion:

“Higher RDW is associated with increased mortality risk in this large, community-based sample, an association not specific to CVD.”

Another paper just published in The Journals of Gerontology confirms these findings with an analysis of seven community-based studies of older adults. Their conclusion:

“RDW is a routinely reported test that is a powerful predictor of mortality in community-dwelling older adults with and without age-associated diseases.”

Diabetes Care 0210.2 This paper just published in the journal Diabetes Care reports on the link between RDW, metabolic syndrome and cardiovascular disease: “A possible explanation for the observed association between RDW and MetS is that high RDW reflects an underlying inflammatory state that leads to impaired erythrocyte (red blood cell) maturation and anisocytosis (size variation), as suggested previously (1–3). In fact, MetS exacerbates oxidative and inflammatory stress in obese adults, which is a potential mechanism for the increased cardiovascular risk in this condition.”

And as you would expect, the European Journal of Heart Failure recently published a study on heart failure that compares RDW with N-terminal brain natriuretic peptide (NT-proBNP) in which the authors conclude:

“Red cell distribution width is a readily available test in the HF-population with similar independent prognostic power to NT-proBNP across the first to third quartiles. Prognostic models in HF (heart failure) should include RDW.”

And the ‘plot thickens’. In this paper published in the journal Digestive Diseases and Sciences the investigators observe:

“Impaired iron absorption or increased loss of iron was found to correlate with disease activity and markers of inflammation in inflammatory bowel disease (IBD). Red cell distribution width (RDW) could be a reliable index of anisocytosis with the highest sensitivity to iron deficiency.”

Their compelling conclusion:

“Among the laboratory tests investigated, including fibrinogen, CRP, ESR, and platelet counts…analysis indicated RDW to be the most significant indicator of active UC [ulcerative colitis]. For CD [Crohn's disease], CRP was an important marker of active disease.”

Lastly, you’ll appreciate the broadest statement yet about the value of this inexpensive and readily available marker. In a recent paper published in the Archives of Pathology & Laboratory Medicine. The authors begin by chiming in with the neighborhood chorus:

“A strong independent association has been recently observed between elevated red blood cell distribution width (RDW) and increased incidence of cardiovascular events;”

but they aim to

“assess whether RDW is associated with plasma markers of inflammation.”

Their conclusion:

“To our knowledge, our study demonstrates for the first time a strong, graded association of RDW with hsCRP and ESR independent of numerous confounding factors.”

In other words, RDW is inexpensive, easily obtained, and a powerful marker for inflammation in general, the common denominator of most chronic disease.

Here’s the ‘take home’ message (if you’ve gotten this far): If you have almost any blood work done at all it’s likely to include RDW automatically. Make good use of it, keeping in mind that laboratory reference ranges do not reflect the latest research and your doctor may not be aware of this. Functional medicine doctors want RDW to be no more than 13%.

A possible explanation for the observed association between RDW and MetS is that high RDW reflects an underlying inflammatory state that leads to impaired erythrocyte maturation and anisocytosis, as suggested previously (1–3). In fact, MetS exacerbates oxidative and inflammatory stress in obese adults, which is a potential mechanism for the increased cardiovascular risk in this condition

Lower Vitamin D again linked to earlier death

Posted on November 10, 2009 by Dr. Jonathan

In yet another study, this one just published in the journal Clinical Endocrinology, lower levels of vitamin D were associated with (30.6 nm/L) associated with a 124 increased risk of all-cause mortality [death from all diseases] and a 378 per cent increased risk from cardiovascular mortality. The researchers additionally state: “Apart from the maintenance of muscular and skeletal health, vitamin D may also protect against cancer, infections, autoimmune and vascular diseases, suggesting that vitamin D deficiency might contribute to a reduced life expectancy.”

Vitamin D Reduces Death From Everything

Posted on October 22, 2009 by Dr. Jonathan

Yet another study on the connection between serum levels of 25-Hydroxy Vitamin D, (the form we measure in our screening blood test) and death from ‘all-cause mortality’ (everything) as well as cardiovascular disease.