Magnesium plays a critical role in heart disease

Posted on September 29, 2011 by Dr. Jonathan

The symposium proceedings on Oxidative Stress and Cardiovascular Injury of the Southern Society for Clinical Investigation presented during this year’s scientific session of the Southern Society for Clinical Investigation included an important paper on critical role of magnesium (Mg2+) deficiency in oxidative stress-induced cardiomyopathy.

“As emphasized by Weglicki and coworkers, Mg2+ deficiency is all too common and carries with it an increased risk of associated adverse cardiovascular events, including oxidative stress. Hypomagnesemia appears when dietary Mg2+ intake is restricted. It may also be the result of drug-induced Mg2+ wasting, such as occurs with loop diuretics and chemotherapeutics, or the neurohormonal activation that accompanies acute and chronic stressor states (ie, CHF, diabetes and the metabolic syndrome).”

The authors demonstrated that magnesium deficiency results in a rise in neurotransmitter substance P (SP) which in turn triggers a systemic inflammatory effect that includes cardiac and intestinal tissues. Elevations in substance P are sustained when the enzyme neutral endopeptidase (NEP) that is supposed to degrade it is impaired by reactive oxygen and nitrogen species. Importantly…

“An associated increase in intestinal permeability with evidence of mucosal invasion by inflammatory cells and accompanying fall in mucosal barrier function with endotoxemia are seen with Mg2+ deficiency. Endotoxin can stimulate the secretion of tumor necrosis factor-α from diverse cellular sources, including macrophages and cardiomyocytes, and can be attenuated by SP receptor blockade. Thus, this neurogenic signal-transduction pathway involving SP, endotoxemia and elevated tumor necrosis factor-α can contribute to the progressive nature of heart failure, including a decline in myocardial contractility.”

In other words, magnesium deficiency is a potent promoter of inflammatory damage to the heart (and the intestinal lining). This further explains why antagonizing magnesium with calcium supplementation can contribute to cardiovascular disease. Clinicians should bear in mind the concluding statement:

“The importance of careful monitoring of serum Mg2+ in the prevention and prompt correction of hypomagnesemia cannot be overemphasized.”

Readers may wish to read the previous posts on antacids and magnesium deficiency and increase in heart attack risk with calcium supplements.

A paper published only a couple months earlier in the journal Magnesium Research adds further emphasis. The authors state:

“Hypomagnesemia continues to cause difficult clinical problems, such as significant cardiac arrhythmias where intravenous magnesium therapy can be lifesaving. Nutritional deficiency of magnesium may present with some subtle symptoms such as leg cramps and occasional palpitation…We found that neuronal sources of the neuropeptide, substance P (SP), contributed to very early prooxidant/proinflammatory changes during Mg deficiency. This neurogenic inflammation is systemic in nature, affecting blood cells, cardiovascular, intestinal, and other tissues, leading to impaired cardiac contractility similar to that seen in patients with heart failure…Our findings emphasize the essential role of this cation in preventing cardiomyopathic changes and intestinal inflammation in a well-studied animal model, and also implicate the need for more appreciation of the potential clinical relevance of optimal magnesium nutrition and therapy.”

Clinical Pearl: serum and even erythrocyte membrane levels of magnesium reflect tissue levels poorly. Results of the intracellular x-ray fluorescence test (performed on cells scraped from the floor of the mouth) reliably correlate with heart, muscle and deep organ tissue mineral content.

Borderline anemia increases risk of death in coronary disease

Posted on June 12, 2011 by Dr. Jonathan

Earlier posts have offered evidence for the need to take even slightly low levels of hemoglobin very seriously. Now a research article just published in PLoS Medicine (Public Library of Science) reports that borderline anemia makes coronary artery disease significantly more lethal. The authors note:

“Coronary artery disease is the main cause of death in high-income countries and the second most common cause of death in middle- and low-income countries…Recent studies have suggested that low hemoglobin may be associated with mortality in patients with coronary artery disease. Therefore, using blood hemoglobin level as a prognostic biomarker for patients with stable coronary artery disease may be of potential benefit especially as measurement of hemoglobin is almost universal in such patients and there are available interventions that effectively increase hemoglobin concentration.”

They examined the data for 20,131 with stable angina and another 14,171 who had survived a first heart attack for an average of 3.2 years, correlating outcomes with hemoglobin values. Their findings are very important for clinicians and patients, who should inquire about their hemoglobin values, to bear in mind:

“For men with MI, the threshold value was 13.5 g/dl; the 29.5% of patients with haemoglobin below this threshold had an associated hazard ratio for mortality of 2.00 compared to those with haemoglobin values in the lowest risk range. Women tended to have lower threshold haemoglobin values (e.g, for MI 12.8 g/dl) but the shape and strength of association did not differ between the genders, nor between patients with angina and MI.”

In other words, hemoglobin below 13.5 g/dl in men and slightly lower in women doubled the risk of death. The authors conclude:

“There is an association between low haemoglobin concentration and increased mortality. A large proportion of patients with coronary disease have haemoglobin concentrations below the thresholds of risk defined here.“

Low cholesterol associated with higher mortality

Posted on January 21, 2011 by Dr. Jonathan

Most readers here are aware that cholesterol is the substrate for all steroid hormones and a component of all cell membranes, so that when too low it is a contributing factor to a range of disorders. A study just published in the Journal of Epidemiology provides more evidence for the association between low cholesterol and death from all causes. The authors state:

“We investigated the relationship between low cholesterol and mortality and examined whether that relationship differs with respect to cause of death.”

They conducted their study using 12,334 healthy adults from 12 rural areas in Japan. They correlated serum total cholesterol with total mortality, noting sex and cause of death. The average follow-up period was 11.9 years. What did their data show?

“As compared with a moderate cholesterol level (4.14-5.17 mmol/L)[161.5-201.5 mg/dL], the age-adjusted hazard ratio (HR) [risk] of low cholesterol (<4.14 mmol/L)[161.5 mg/dL] for mortality was 1.49 [50% increase in mortality]… High cholesterol (≥6.21 mmol/L)[≥242 mg/dL] was not a risk factor. This association was unchanged in analyses that excluded deaths due to liver disease… The multivariate-adjusted HRs [hazard ratios = risks]…of the lowest cholesterol group for hemorrhagic stroke, heart failure (excluding myocardial infarction), and cancer mortality [were] significantly higher than those of the moderate cholesterol group, for each cause of death.”

Numerous lines of reasoning, documented in a broad accumulation of scientific evidence (of which a small ‘taste’ is reported in this venue) converge on the assertion that inflammation, rather than cholesterol per se, is the primary villain in cardiovascular disease. Clinicians and patients alike should bear in mind the authors’ conclusion:

“Low cholesterol was related to high mortality even after excluding deaths due to liver disease from the analysis. High cholesterol was not a risk factor for mortality.“

Low testosterone increases heart disease mortality in men

Posted on October 29, 2010 by Dr. Jonathan

More evidence of the importance of testosterone in preventing heart disease for men is offered in a study just published in the journal Heart in which the authors set out to…

“…examine the effect of serum testosterone levels on survival in a consecutive series of men with confirmed coronary disease and calculate the prevalence of testosterone deficiency.”

They followed 930 men with coronary disease for an average of seven years and correlating all-cause mortality and vascular mortality with testosterone deficiency. What did the data show?

“The overall prevalence of biochemical testosterone deficiency in the coronary disease cohort using bio-available testosterone (bio-T) was 20.9%, using total testosterone was 16.9% and using either was 24%. Excess mortality was noted in the androgen-deficient group compared with normal (41 (21%) vs 88 (12%). The only parameters found to influence time to all-cause and vascular mortality in multivariate analyses were the presence of left ventricular dysfunction, aspirin therapy, β-blocker therapy and low serum bio-T.”

Notice that the bio-available testosterone (free fraction or unbound testosterone, the small percentage that is actually ‘working’) was more revealing than the total testosterone. This is most conveniently measured in a saliva specimen. Clinicians and patients should bear in mind the authors’ conclusion:

“In patients with coronary disease testosterone deficiency is common and impacts significantly negatively on survival.“

Important: testosterone replacement by gel, cream or patch (transdermal) can easily accumulate to abnormally high (supraphysiologic) levels which ‘back-fires’ by causing testosterone receptor desensitization and pituitary suppression. This may be missed if the correct testosterone test (the bio-active, free fraction portion) is not done.

Normal weight obesity: heart disease from being fat without looking fat

Posted on May 1, 2010 by Dr. Jonathan

This study published not long ago in the European Heart Journal is consonant with my findings for certain patients (using bioelectric impedance analysis for body composition determination) who were slim in appearance but turned out to be metabolically obese. They had a proportionately large amount of fat packed around the internal organs that wasn’t apparent externally. High levels of visceral fat are associated with the chronic inflammation that is a fundamental cause of cardiovascular and other diseases. The authors of this paper suspected this phenomenon:

“We hypothesized that subjects with a normal body mass index (BMI), but high body fat (BF) content [normal weight obesity (NWO)], have a higher prevalence of cardiometabolic dysregulation and are at higher risk for cardiovascular (CV) mortality.”

They thoroughly evaluated 6171 subjects with body composition measurement, blood tests and cardiovascular risk factors. Their data showed that…

“The highest tertile of BF (>23.1% in men and >33.3% in women) was labeled as NWO. When compared with the low BF group, the prevalence of metabolic syndrome in subjects with NWO was four-fold higher. Subjects with NWO also had higher prevalence of dyslipidaemia, hypertension (men), and CV disease (women). After adjustment, women with NWO showed a significant 2.2-fold increased risk for CV mortality in comparison to the low BF group.”

This means that excessive levels of body fat can be present in someone of normal weight and appearance (“metabolic obesity”), contributing to cardiovascular damage in both men and women. In women there is a stronger association with death from cardiovascular disease.

The author’s conclusion:

“Normal weight obesity, defined as the combination of normal BMI and high BF content, is associated with a high prevalence of cardiometabolic dysregulation, metabolic syndrome, and CV risk factors. In women, NWO is independently associated with increased risk for CV mortality.”

Important: There are consumer devices such as scales marketed as bioelectric body composition instruments but these do not give accurate or reliable results. Dependability requires a medical-grade device that utilizes electrodes on both the lower and upper extremities along with validated algorithms.