GGT is an important predictor of diabetes and cardiovascular risk

Posted on September 1, 2011 by Dr. Jonathan

I always include GGT (Serum γ-Glutamyltransferase) in our basic screening blood panel, but find often that this is not included in lab work that patients bring from elsewhere. A study recently published in the journal Obesity shows that, besides being associated with fatty liver, GGT is an important metric for predicting metabolic syndrome, diabetes and hypertension. The authors state:

“Serum γ-glutamyltransferase (GGT) is associated with oxidative stress and hepatic steatosis. The extent to which its value in determining incident cardiometabolic risk (coronary heart disease (CHD), metabolic syndrome (MetS), hypertension and type 2 diabetes) is independent of obesity needs to be further explored in ethnicities.”

They examined a cohort of 1,667 adults from a general population age 52 to 63 with 4 year’s follow-up, measuring GGT activity in association with metabolic syndrome (identified by Adult Treatment Panel-III criteria modified for male abdominal obesity) and multiple markers for cardiovascular disease. Their data bolsters the use of GGT for case management:

“Median GGT activity was 24.9 U/l in men, 17.0 U/l in women…while smoking status was not associated, (male) sex, sex-dependent age, alcohol usage, BMI, fasting triglycerides and C-reactive protein (CRP) were significant independent determinants of circulating GGT. Each 1-s.d. increment in (= 0.53 ln GGT) GGT activity significantly predicted in each sex incident hypertension (hazard ratio (HR) 1.20), and similarly MetS, after adjustment for age, alcohol usage, smoking status, BMI and menopause. Strongest independent association existed with diabetes (HR 1.3) whereas GGT activity tended to marginally predict CHD independent of total bilirubin but not of BMI.”

Interestingly…

“Higher serum total bilirubin levels were protective against CHD risk in women.”

While not any stronger a risk predictor for coronary heart disease (CHD) than body mass index (BMI), GTT is a valuable and underutilized marker to use for the case management of cardiometabolic disorders. The authors conclude:

“We conclude that elevated serum GGT confers, additively to BMI, risk of hypertension, MetS, and type 2 diabetes but only mediates adiposity against CHD risk.”

Single blood pressure measurements both in the clinic and at home are not reliable

Posted on July 6, 2011 by Dr. Jonathan

Research just published in the British Medical Journal reveals that blood pressures measured on single occasions in either the home or clinic results in substantial overdiagnosis and excessive medication. This is obviously a serious concern not just because of the side-effect potential of various antihypertensive medications—suppressing blood pressure lower than necessary results in diminished oxygen delivery to tissues (including the brain). The authors set out to:

“…determine the relative accuracy of clinic measurements and home blood pressure monitoring compared with ambulatory blood pressure monitoring as a reference standard for the diagnosis of hypertension.”

Their screening identified seven studies on blood pressure measurements in the clinic and three studies on home measurement that could be directly compared with ambulatory monitoring. What did the data show?

“Compared with ambulatory monitoring thresholds of 135/85 mm Hg, clinic measurements over 140/90 mm Hg had mean sensitivity and specificity of 74.6% and 74.6%, respectively, whereas home measurements over 135/85 mm Hg had mean sensitivity and specificity of 85.7% and 62.4%.”

That is a lot of error. Interestingly, at home measurements captured hypertensive readings more sensitively than in the clinic but with more false positives. Overall, measurements done in the clinic and at home got it wrong about a quarter of the time. The authors conclude:

“Neither clinic nor home measurement had sufficient sensitivity or specificity to be recommended as a single diagnostic test. If ambulatory monitoring is taken as the reference standard, then treatment decisions based on clinic or home blood pressure alone might result in substantial overdiagnosis. Ambulatory monitoring before the start of lifelong drug treatment might lead to more appropriate targeting of treatment, particularly around the diagnostic threshold.”

The full text of their paper can be read and downloaded here. Coincidentally, another study on the inaccuracy of single blood pressure measurements was just published in the Annals of Internal Medicine. The authors’ objective was to…

“…compare strategies for home or clinic BP measurement and their effect on classifying patients as having BP that was in or out of control.”

They followed 444 hypertensive veterans for 18 months, comparing standardized research blood pressure measurements every six months, measurements taken in the clinic during outpatient visits, and BP measured at home that transmitted the readings electronically. Their data also showed strong variability:

“Systolic BP control rates at baseline (mean SBP <140 mm Hg for clinic or research measurement; <135 mm Hg for home measurement) varied substantially, with 28% classified as in control by clinic measurement, 47% by home measurement, and 68% by research measurement. Short-term variability was large and similar across all 3 methods of measurement, with a mean within-patient coefficient of variation of 10%. Patients could not be classified as having BP that was in or out of control with 80% certainty on the basis of a single clinic SBP measurement from 120 mm Hg to 157 mm Hg. The effect of within-patient variability could be greatly reduced by averaging several measurements, with most benefit accrued at 5 to 6 measurements.”

What to do? To prevent misdiagnosis and especially overtreatment, ambulatory monitoring is the gold standard; but at the least, 5-6 sequential measurements should always be averaged to reduce error. The authors conclude:

“Physicians who want to have 80% or more certainty that they are correctly classifying patients’ BP control should use the average of several measurements. Hypertension quality metrics based on a single clinic measurement potentially misclassify a large proportion of patients.“

Risk for high blood pressure, kidney and cardiovascular disease can persist long after E. coli gastroenteritis

Posted on November 28, 2010 by Dr. Jonathan

Research just published in the British Medical Journal presents another example of acute gastrointestinal infection triggering chronic inflammation that persists long after the infection has subsided. The authors set out to…

“…evaluate the risk for hypertension, renal impairment, and cardiovascular disease within eight years of gastroenteritis from drinking water contaminated with Escherichia coli O157:H7 and Campylobacter.”

They followed 1977 adult participants, 1067 of whom came down with acute gastroenteritis when a municipal water system was contaminated. None of them had a history of the subsequent diseases they were looking for which included hypertension (blood pressure ≥140/90 mm Hg), kidney impairment (microalbuminuria or estimated glomerular filtration rate <60 ml/min/1.73 m2), and cardiovascular disease (heart attack, stroke, or congestive heart failure). What did the data show?

“The adjusted hazard ratios for hypertension and cardiovascular disease after acute gastroenteritis were 1.33 and 2.13 respectively. The adjusted hazard ratio for the presence of either indicator of renal impairment was 1.15 and was 3.41 for the presence of both.”

In other words, having a case of acute gastroenteritis resulted in a later increase of 33% in the risk for high blood pressure, 213% for cardiovascular disease, and a whopping 341% for a combination of the two indicators of kidney impairment (microalbuminuria and lower glomerular filtration rate). Thus the authors conclude:

“Acute gastroenteritis from drinking water contaminated with E coli O157:H7 and Campylobacter was associated with an increased risk for hypertension, renal impairment, and self reported cardiovascular disease…Our findings underline the need for following up individual cases of food or water poisoning by E coli O157:H7 to prevent or reduce silent progressive vascular injury…annual blood pressure monitoring and periodic monitoring of renal function may be warranted for individuals who experience acute gastroenteritis after exposure to food or water contaminated with E coli O157:H7.”

This is another example of how GI infections can trigger the long-term immune system dysregulation that promotes chronic inflammation, the biological basis of cardiovascular disease and renal impairment. Clinicians should be diligent in diagnosing GI infection and astute in examining for immune dysfunction and occult autoimmune disorders.

Sensory ganglionopathy, another way gluten can damage the nervous system

Posted on October 3, 2010 by Dr. Jonathan

Add sensory ganglionopathy, damage to the groupings of sensory neurons at the spinal level and in the cranium causing pain and other symptoms, to the list of depredations done to the nervous system by reactions to gluten according to a paper just published in the journal Neurology. The authors state:

“Gluten sensitivity can engender neurologic dysfunction, one of the two commonest presentations being peripheral neuropathy. The commonest type of neuropathy seen in the context of gluten sensitivity is sensorimotor axonal.”

They examined 409 patients with different kinds of damage to the peripheral nerves. Out of the 13% that had neurophysiologic evidence of sensory ganglionopathy, 32% had antibodies to gluten. (This is especially remarkable since there are factors which can cause the antibodies not the be expressed or detected resulting in a significant number of false negatives.) Another interesting fact was observed:

“The mean age of those with gluten sensitivity was 67 years and the mean age at onset was 58 years. Seven of those with serologic evidence of gluten sensitivity had enteropathy on biopsy…Autopsy tissue from 3 patients demonstrated inflammation in the dorsal root ganglia with degeneration of the posterior columns of the spinal cord.”

In other words, the damage can have started years before the person notices various possible symptoms including pains of various kinds, numbness, weird sensations (parasthesias), problems with walking, balance or coordination; cardiac arrhythmia, orthostatic hypotension (drop in blood pressure on standing with feelings of faintness), sudden hypertension, segmental loss of sweating, tremor, etc. Is there hope for improvement?

“Fifteen patients went on a gluten-free diet, resulting in stabilization of the neuropathy in 11. The remaining 4 had poor adherence to the diet and progressed, as did the 2 patients who did not opt for dietary treatment.“

The authors sum up their findings with this concluding statement:

“Sensory ganglionopathy can be a manifestation of gluten sensitivity and may respond to a strict gluten-free diet.”

Brain health is linked to heart health, implications for blood pressure medication

Posted on August 26, 2010 by Dr. Jonathan

An interesting study just published in the journal Circulation provides evidence of the link between brain health and the capacity of the heart to send blood to the brain. The authors first note the importance of cerebral perfusion (getting blood into the brain):

“Cardiac dysfunction is associated with neuroanatomic and neuropsychological changes in aging adults with prevalent cardiovascular disease, theoretically because systemic hypoperfusion disrupts cerebral perfusion, contributing to subclinical brain injury.“

They set out to test whether the cardiac index (the amount of blood the heart pumps in proportion to body size) as a metric for cardiac function would correlate with loss of brain tissue as shown by brain MRI and neuropsychological markers of ischemia (reduction of oxygen due reduced blood flow) and Alzheimer’s disease. What did the data show?

“…cardiac index was positively related to total brain volume and information processing speed and inversely related to lateral ventricular volume…participants in the bottom cardiac index tertile and middle cardiac index tertile had significantly lower brain volumes than participants in the top cardiac index tertile.”

Even the people with the middle cardiac group (low normal) had showed signs of serious neurodegeneration with brain atrophy (lower brain volume). How important is it to get better than a low normal amount of blood to the brain?

“Although observational data cannot establish causality, our findings are consistent with the hypothesis that decreasing cardiac function, even at normal cardiac index levels, is associated with accelerated brain aging.“

Consider this in light of earlier research that aggressive treatment of blood pressure is harmful. Clinicians must respect the need to balance cardiovascular protection from excessive pressure dynamics with the profound need to ensure adequate cerebral perfusion. Are you concerned that your blood pressure therapy may be stronger than it should? Read the earlier research posts and discuss the matter with your doctor.

Angiotensin-receptor blockers for blood pressure linked to cancer

Posted on August 12, 2010 by Dr. Jonathan

If you are taking an angiotensin-receptor blocker (ARB) such as telmisartan (Micardis) or ramipril (Altace) it would be good to discuss changing to another medication in light of a serious risk factor for cancer brought to light in research published in the The Lancet Oncology. ARBs affect the renin-angiotensin system that regulates tension in the circulatory system; as the authors note:

“Experimental studies implicate the renin-angiotensin system, particularly angiotensin II type-1 and type-2 receptors, in the regulation of cell proliferation, angiogenesis, and tumour progression. We assessed whether ARBs affect cancer occurrence with a meta-analysis of randomised controlled trials of these drugs.”

They analyzed data from a number of trials involving tens of thousands of patients and came to this conclusion:

“This meta-analysis of randomised controlled trials suggests that ARBs are associated with a modestly increased risk of new cancer diagnosis.”

An accompanying editorial in the same issue expresses the gravity of this matter:

“The meta-analysis…is disturbing and provocative, raising crucial drug safety questions for practitioners and the regulatory community.”

Why use this class of medications when there is no evidence that they are more effective than others? A functional approach obviating the need for side-effect producing drugs is often successful if instituted early enough. While research data continues to accumulate about ARBs the author exhorts us to take this finding into serious and cautious consideration when determining the best approach to blood pressure for each person:

“In the interim, we should use ARBs, particularly telmisartan, with greater caution. These drugs are often overprescribed, as a result of aggressive marketing and in the absence of evidence that they are better than angiotensin-converting enzyme (ACE) inhibitors.”

Like spicy food? Chili peppers can lower blood pressure

Posted on August 10, 2010 by Dr. Jonathan

A paper just published in the journal Cell Metabolism reports that capsaicin, the chemical in chili peppers that makes them taste hot, can lower blood pressure by promoting vascular relaxation.

“Here we report that chronic TRPV1 activation by dietary capsaicin increases the phosphorylation of protein kinase A (PKA) and eNOS and thus production of nitric oxide (NO) in endothelial cells…Long-term stimulation of TRPV1…improves vasorelaxation, and lowers blood pressure in genetically hypertensive rats. We conclude that TRPV1 activation by dietary capsaicin improves endothelial function. TRPV1-mediated increase in NO production may represent a promising target for therapeutic intervention of hypertension.”

The endothelium is the inner lining of the blood vessel; good endothelial function is necessary for cardiovascular health. (Viagra and similar medications work by inhibiting the breakdown of nitric oxide, a vasodilator.) An accompanying editorial in the same journal notes that the authors:

“…demonstrate that vascular TRPV1 mediates a beneficial effect of capsaicin in the cardiovascular system, promoting nitric oxide release and lowering blood pressure.”

An editorial in Science Signaling also recognizes this research:

The chemical in chili peppers that makes them taste hot is called capsaicin, and it activates a cation channel of the transient receptor potential family called TRPV1…Now Yang et al. provide evidence that dietary capsaicin may reduce blood pressure if made a constant part of the diet…Additionally, 6-month dietary consumption of capsaicin increased the relaxation response of isolated mouse mesenteric arteries to acetylcholine…How much of capsaicin’s effects on blood pressure are due to a direct effect on the vasculature and how much are mediated through effects on the nervous system remains to be determined, but these results suggest that targeting TRPV1 may be beneficial for the treatment of hypertension.

Don’t over-medicate high blood pressure

Posted on July 21, 2010 by Dr. Jonathan

There are still many practitioners treating patients for hypertension who believe that systolic blood pressure should be suppressed to less than 130 mm Hg with medication. Another study just published in JAMA (The Journal of the American Medical Association) adds more evidence that this is not helpful even for individuals with diabetes and coronary artery disease. The authors set out to:

“…determine the association of systolic BP control achieved and adverse cardiovascular outcomes in a cohort of patients with diabetes and CAD (coronary artery disease).”

They analyzed data for 6400 subjects from 862 sites in 14 countries for more than ten years.

“Patients received first-line treatment of either a calcium antagonist or β-blocker followed by angiotensin-converting enzyme inhibitor, a diuretic, or both to achieve systolic BP of less than 130 and diastolic BP of less than 85 mm Hg. Patients were categorized as having tight control if they could maintain their systolic BP at less than 130 mm Hg; usual control if it ranged from 130 mm Hg to less than 140 mm Hg; and uncontrolled if it was 140 mm Hg or higher.”

The data they accumulated painted this picture:

“…little difference existed between those with usual control and those with tight control…The all-cause mortality rate was 11.0% in the tight-control group vs 10.2% in the usual-control group; however, when extended follow-up was included, risk of all-cause mortality was 22.8% in the tight control vs 21.8% in the usual control group.”

Note that the tight control group had a slightly higher risk of all-cause mortality over the longer time period. Besides the greater likelihood of adverse effects with higher doses of medication, lower blood pressure means diminished delivery of oxygen to tissues (the pressure acts to overcome the increased resistance of less a healthy circulatory system).

Their conclusion clearly states the lack of benefit with suppression to less than 130 mm Hg:

“Tight control of systolic BP among patients with diabetes and CAD was not associated with improved cardiovascular outcomes compared with usual control.”

See another recent study that proves the same point.

Both are good for weight loss, which is better for high blood pressure: higher protein or higher fat?

Posted on April 17, 2010 by Dr. Jonathan

European Journal of Clinical Nutrition 0310 Most of you reading this are aware that a lower glycemic diet can promote weight and fat loss through its beneficial effect on insulin levels. But which is better for blood pressure control, a higher or lower protein to fat ratio? This study recently published in the European Journal of Clinical Nutrition was designed to answer that question.

“There is controversy over dietary protein’s effects on cardiovascular disease risk factors in diabetic subjects. It is unclear whether observed effects are due to increased protein or reduced carbohydrate content of the consumed diets. The aim of this study was to compare the effects of two diets differing in protein to fat ratios on cardiovascular disease risk factors.”

What did their data show? Interestingly,…

“Both diets were equally effective in promoting weight loss and fat loss and in improving fasting glycemic control, total cholesterol and low-density lipoprotein (LDL) cholesterol, but the…HP–LF [high protein-low fat] diet improved significantly both systolic and diastolic blood pressure when compared with the LP–HF [low protein-high fat] diet. No differences were observed in postprandial glucose and insulin responses.”

The authors conclude:

“A protein to fat ratio of 1.5 in diets significantly improves blood pressure and TG [triglyceride] concentrations in obese individuals with DM2 [type 2 diabetes].”

More aggressive blood pressure control for diabetes is not better

Posted on April 2, 2010 by Dr. Jonathan

High blood pressure is common with type 2 diabetes because the excessive levels of insulin that lead up to the breakdown in blood sugar control promote hypertension. This study recently published in The New England Journal of Medicine has practical importance for many people who require treatment for high blood pressure. The authors first note:

“There is no evidence from randomized trials to support a strategy of lowering systolic blood pressure below 135 to 140 mm Hg in persons with type 2 diabetes mellitus. We investigated whether therapy targeting normal systolic pressure (i.e., <120 mm Hg) reduces major cardiovascular events in participants with type 2 diabetes at high risk for cardiovascular events.”

They constructed their study to discriminate outcomes between reducing blood pressure to less than 140 mm Hg and less than 120 mm Hg:

“A total of 4733 participants with type 2 diabetes were randomly assigned to intensive therapy, targeting a systolic pressure of less than 120 mm Hg, or standard therapy, targeting a systolic pressure of less than 140 mm Hg. The primary composite outcome was nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes. The mean follow-up was 4.7 years.”

I have told patients for years that it is not desirable to aggressively medicate blood pressure much below a systolic reading of 135-140 mm Hg because the increased pressure is a compensatory effort by the body to deliver oxygen to the tissues against increased resistance. There has to be a happy medium. What did the data from this investigation show?

“Serious adverse events attributed to antihypertensive treatment occurred in 77 of the 2362 participants in the intensive-therapy group (3.3%) and 30 of the 2371 participants in the standard-therapy group (1.3%).”

This compelled them to conclude that:

“In patients with type 2 diabetes at high risk for cardiovascular events, targeting a systolic blood pressure of less than 120 mm Hg, as compared with less than 140 mm Hg, did not reduce the rate of a composite outcome of fatal and nonfatal major cardiovascular events.