Metabolic syndrome and high blood pressure can be helped by sleep apnea treatment

Posted on January 22, 2012 by Dr. Jonathan

Summary: the stress of oxygen starvation that occurs with sleep disordered breathing (sleep apnea and hypopnea) contributes to metabolic syndrome and high blood pressure. CPAP (continuous positive airway pressure) can help .

I have been finding that people coming to our practice who have been struggling with the depredations of metabolic syndrome including overweight, hypertension, elevated lipids and HgbA1c, etc. have not been evaluated for sleep disordered breathing. A study recently published in The New England Journal of Medicine offers evidence that treatment for sleep apnea can provide significant benefit. The authors state:

“Obstructive sleep apnea is associated with an increased prevalence of the metabolic syndrome and its components…In our double-blind, placebo-controlled trial, we randomly assigned patients with obstructive sleep apnea syndrome to undergo 3 months of therapeutic CPAP followed by 3 months of sham CPAP, or vice versa, with a washout period of 1 month in between.”

They measured anthropometric variables, blood pressure, fasting blood glucose levels, insulin resistance, fasting blood lipids, glycated hemoglobin, carotid intima–media thickness, and visceral fat before and after the real and sham CPAP interventions. Their data showed a worthwhile effect:

“A total of 86 patients completed the study, 75 (87%) of whom had the metabolic syndrome. CPAP treatment (vs. sham CPAP) was associated with significant mean decreases in systolic blood pressure (3.9 mm Hg), serum total cholesterol (13.3 mg per deciliter), non–high-density lipoprotein cholesterol (13.3 mg per deciliter), low-density lipoprotein cholesterol (9.6 mg per deciliter), triglycerides (18.7 mg per deciliter), and glycated hemoglobin (0.2%). The frequency of the metabolic syndrome was reduced after CPAP therapy (reversal found in 11 of 86 patients [13%] undergoing CPAP therapy vs. 1 of 86 [1%] undergoing sham CPAP).”

Clinicians should not fail to consider the possibility of sleep disordered breathing when managing hypertension, overweight and other components of metabolic syndrome. Do you snore or wake in the morning unrefreshed and fall asleep inappropriately during the day? If so, a screening may be appropriate. The authors conclude:

“In patients with moderate-to-severe obstructive sleep apnea syndrome, 3 months of CPAP therapy lowers blood pressure and partially reverses metabolic abnormalities.”

Stroke risk is greater with both higher and lower than normal blood pressure

Posted on December 15, 2011 by Dr. Jonathan

Summary: lower than normal blood pressure results from underlying causes that need investigation and treatment. These underlying factors can increase the risk of stroke comparable to higher than normal blood pressure.

An important study recently published in the JAMA (The Journal of the American Medical Association) offers evidence that lower than normal blood pressure is a risk factor for stroke comparable to blood pressure that is higher than normal. The authors state:

“Recurrent stroke prevention guidelines suggest that larger reductions in systolic blood pressure (SBP) are positively associated with a greater reduction in the risk of recurrent stroke and define an SBP level of less than 120 mm Hg as normal. However, the association of SBP maintained at such levels with risk of vascular events after a recent ischemic stroke is unclear.”

So they set out to…

“…assess the association of maintaining low-normal vs high-normal SBP levels with risk of recurrent stroke.”

They examined two and a half years of data for 20,330 patients from 35 countries who had recently had an ischemic stroke. Patients were categorized based on their average systolic blood pressure as very low–normal (<120 mm Hg), low-normal (120-<130 mm Hg), high-normal (130-<140 mm Hg), high (140-<150 mm Hg), and very high (≥150 mm Hg). Their primary outcome measure was a stroke of any kind, and the secondary outcome was a composite of stroke, heart attack, or death from any other vascular cause. What did the data show?

“The recurrent stroke rates were 8.0% for the very low–normal SBP level group, 7.2% for the low-normal SBP group, 6.8% for the high-normal SBP group, 8.7% for the high SBP group, and 14.1% for the very high SBP group. Compared with patients in the high-normal SBP group, the risk of the primary outcome was higher for patients in the very low–normal SBP group (adjusted hazard ratio [AHR], 1.29), in the high SBP group (AHR, 1.23), and in the very high SBP group (AHR, 2.08). Compared with patients in the high-normal SBP group, the risk of secondary outcome was higher for patients in the very low–normal SBP group (AHR, 1.31), in the low-normal SBP group (AHR, 1.16), in the high SBP group (AHR, 1.24), and in the very high SBP group (AHR, 1.94).”

In other words, while the very high systolic blood pressure was the worst for both primary and secondary outcomes, the very low-normal group was the ‘runner up’ for both recurrent stroke (29%) and the secondary outcomes of heart attack or death from other vascular causes (31%). The authors conclude:

“Among patients with recent non–cardioembolic ischemic stroke, SBP levels during follow-up in the very low–normal (<120 mm Hg), high (140-<150 mm Hg), or very high (≥150 mm Hg) range were associated with increased risk of recurrent stroke.”

It’s important for both clinicians and patients to understand that lower than normal blood pressure is an indicator that things ‘under the surface’ are not working as they should. For example, autoimmune disorders that are Th1 dominant can be associated with lower adrenocortical activity due to the effect on the brain’s paraventricular nucleus—while promoting vascular inflammation.

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.“

Resveratrol helps get blood to the tissues (including brain)

Posted on August 27, 2010 by Dr. Jonathan

The previous post documented that suboptimal blood perfusion results in brain shrinkage. The endothelium (inner lining of blood vessels) regulates local vascular dilation (opening) and constriction. Welcome research just published in the journal Nutrition, Metabolism and Cardiovascular Diseases offers evidence that resveratrol improves endothelial function even in obese subjects. The authors state:

“Flow-mediated dilatation of the brachial artery (FMD) is a biomarker of endothelial function and cardiovascular health. Impaired FMD is associated with several cardiovascular risk factors including hypertension and obesity. Various food ingredients such as polyphenols have been shown to improve FMD. We investigated whether consuming resveratrol, a polyphenol found in red wine, can enhance FMD acutely and whether there is a dose-response relationship for this effect.”

They analyzed plasma resveratrol and FMD after varying doses of resveratrol in overweight and mildly hypertensive study subjects in a double-blind, randomized crossover comparison. What did the data show?

“There was a significant dose effect of resveratrol on plasma resveratrol concentration and on FMD, which increased from 4.1 ± 0.8% (placebo) to 7.7 ± 1.5% after 270 mg resveratrol. FMD was also linearly related to log10 plasma resveratrol concentration.”

This means that resveratrol caused a significant improvement in the ability of the blood vessels to dilate (open) that corresponded closely to the dose. The cardiovascular benefits are obvious, but we can thank the research reported in the previous post for documenting the profound benefits for brain health that result from improving the capacity for the blood to get through to the tissues.

The authors conclude:

“Acute resveratrol consumption increased plasma resveratrol concentrations and FMD in a dose-related manner.”

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.

Watch out for blood pressure surges

Posted on July 27, 2010 by Dr. Jonathan

You might think that blood pressure as a risk factor would be well understood. A paper just published in the prestigious British medical journal The Lancet points out that episodic surges in blood pressure and sharp changes recorded in sequential office visits, often dismissed as a concern, indicate high risk for vascular events. The authors state the background to their investigation:

“The mechanisms by which hypertension causes vascular events are unclear. Guidelines for diagnosis and treatment focus only on underlying mean [average] blood pressure. We aimed to reliably establish the prognostic significance of visit-to-visit variability in blood pressure, maximum blood pressure reached, untreated episodic hypertension, and residual variability in treated patients.”

An editorial in the same issue provides additional perspective:

“Although hypertension is the most prevalent treatable vascular risk factor, how it causes end-organ damage and vascular events is poorly understood. Yet, a widespread belief exists that underlying usual blood pressure can alone account for all blood-pressure-related risk of vascular events and for the benefits of antihypertensive drugs, and this notion has come to underpin all major clinical guidelines on diagnosis and treatment of hypertension. Other potentially informative measures, such as variability in clinic blood pressure or maximum blood pressure reached, have been neglected, and effects of antihypertensive drugs on such measures are largely unknown. Clinical guidelines recommend that episodic hypertension is not treated, and the potential risks of residual variability in blood pressure in treated hypertensive patients have been ignored. This Review discusses shortcomings of the usual blood-pressure hypothesis…“

(By the way, blood pressure variability is not the same as heart rate variability where, generally speaking, the more the better.) The study authors investigated the incidence of transient ischemic attack (TIA, ‘mini-stroke) in relation to changes in BP from visit to visit, maximum blood pressure in patients with previous TIA and in patients with treated high blood pressure. What did their data show?

“…visit-to-visit variability in systolic blood pressure (SBP) was a strong predictor of subsequent stroke, independent of mean SBP… Maximum SBP reached was also a strong predictor of stroke…residual visit-to-visit variability in SBP on treatment was also a strong predictor of stroke and coronary events…all measures of variability were most predictive in younger patients and at lower (<median) values of mean SBP in every cohort.”

In other words, a person’s average systolic blood pressure (‘the first number’) may be OK, but a lot of change from doctor visit to visit, episodic surges, must be recognized as a predictor for stroke. Variability persisting after treatment predicts both strokes and heart attacks. And all measures of variability in BP, at even lower average pressures, are a warning sign for younger people. Clinicians and patients managing their blood pressure can remember their concise summary:

“Visit-to-visit variability in SBP and maximum SBP are strong predictors of stroke, independent of mean SBP. Increased residual variability in SBP in patients with treated hypertension is associated with a high risk of vascular events.“

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.

Vitamin D & high blood pressure

Posted on October 30, 2009 by Dr. Jonathan

This a recent review of the evidence for and mechanisms of the role of Vitamin D in arterial hypertension in Nature Reviews Cardiology. Not surprisingly, the investigators found the antihypertensive effect of Vitamin D to be especially prominent when both deficiency and elevated blood pressure are present. “Thus, in view of the relatively safe and inexpensive way in which vitamin D can be supplemented, we believe that vitamin D supplementation should be prescribed to patients with hypertension and 25-hydroxyvitamin D levels below target values.”