Sleep, health risks, and gender
Sleep (or lack thereof) has long-lasting effects on our health. Recent studies show some gender differences in sleeping patterns and health outcomes.
Females who are poor sleepers have increased risks for cardiovascular disease than males exhibiting similar sleeping patterns.
“Self-reported ratings of sleep quality and symptoms of poor sleep have been linked to increased risk of coronary heart disease (CHD), type 2 diabetes and hypertension with recent evidence suggesting stronger associations in women”, according to a recent report [1].
Poor sleep quality, defined as long periods to fall asleep (>30 minutes), was associated with greater psychosocial distress, higher fasting insulin, fibrinogen and higher levels of the inflammatory biomarkers C-reactive protein and interleukin-6 only for women. A survey by the National Sleep Foundation shows that 60% of female respondents suffer from poor sleep and 43% suffer from daytime sleepiness which adversely affects daily activities.
In another study [2], delayed sleep phase syndrome is associated with irregular menstrual cycles and increased premenstrual symptoms in women. Sleep quality is even likely to deteriorate during and after menopause.
Meanwhile, researchers at the University of Minnesota [3] found strong associations between disturbed sleep and mortalities in men older than 67.
References:
1. Suarez EC. Self-reported symptoms of sleep disturbance and inflammation, coagulation, insulin resistance and psychosocial distress: Evidence for gender disparity. Brain Behav Immun. 2008 Mar 5. [Epub ahead of print] Links
2. American Academy of Sleep Medicine. Delayed Sleep Phase Syndrome Linked to Irregular Menstrual Cycles, Premenstrual Symptoms in Women. Press release 10 June 2008.
3. University of Minnesota News. Disturbed Rest, Activity Linked to Mortality in Older Men. 11 June 2008.
Reinventing chocolate: the dark-and-sweet side of clinical trials
More and more evidence are piling up on the health benefits of dark chocolate. Cocoa is rich in flavonoids which have potent antioxidant properties. No wonder that the biggest chocolate manufacturers are scrambling to grab this opportunity to reinvent chocolate from being the number one enemy of weight watchers, diabetics and heart patients to be the next “wonder health food” or dietary supplement that might even surpass soy and omega-3`s in terms of popularity. And no wonder that people are scrambling to volunteer to participate in chocolate clinical trials, free of charge. Given below are overviews of some trials on chocolates, past, present, and future.
Successful trials whose results have been published: [1,2]
This “randomized, controlled, investigator-blinded, parallel-group trial” investigated the effect of chocolate consumption (6.3 g of dark chocolate per day = 30 kcal) on the blood pressure of prehypertensive adults. “From baseline to 18 weeks, dark-chocolate intake reduced mean systolic BP by 2.9 mm Hg (p<0.001) and diastolic BP by 1.9 mm Hg (p<0.001) without changes in body weight, lipids, glucose, or 8-isoprostane. Hypertension prevalence decreased from 86% to 68%.”
In this double-blind randomized study, Swiss researchers at the Zurich University Hospital studied the effect of dark chocolate in 22 heart transplant patients. An intake of 40 g of dark chocolate (70% cocoa) “induces coronary vasodilation, improves coronary vascular function, and decreases platelet adhesion 2 hours after consumption. These immediate beneficial effects were paralleled by a significant reduction of serum oxidative stress and were positively correlated with changes in serum epicatechin concentration.”
The not so-successful: [3]
The Chocolate Happiness Undergoing More Pleasantness (CHUMP) study was designed as a double-blinded clinical trial “to compare the effects of dark chocolate, milk chocolate and normal chocolate consumption on happiness.” However, data analysis somehow went awry because “many participants switched groups mid-study because of their personal chocolate preferences. Although the CHUMP study was pleasurable, it demonstrated the difficulties associated with performing a truly blinded clinical trial.”
This one is ongoing:
The Phase I trial on the “Effects of Dark Chocolate on Insulin Sensitivity in People with High Blood Pressure” (ClinicalTrials.gov Identifier: NCT00099476) examines “whether dark chocolate affects the way patients with hypertension (high blood pressure) respond to insulin, a hormone secreted by the pancreas that regulates blood glucose (sugar) levels. In many people with hypertension, insulin is not as effective in helping the body use glucose. This is called insulin resistance. Insulin also increases blood flow into muscle by opening inactive blood vessels. Laboratory studies suggest that eating dark chocolate may improve blood pressure. This study will determine whether dark chocolate improves insulin resistance or changes how blood vessels react to insulin in hypertensive people.”
This one is still recruiting:
This trial, due to start in June, will investigate whether flavonoids found in chocolate and other foods can reduce the risk of cardiovascular diseases in menopausal women with type 2 diabetes. “The study is funded by … Diabetes UK, and is led by a team at the University of East Anglia (UEA) in Norwich, partnered by the Elsie Bertram Diabetes Centre, Norfolk, Norwich University Hospital (NNUH) and the Institute of Food Research (IFR).”
References:
1. Taubert D, Roesen R, Lehmann C, et al. Effects of low habitual cocoa intake on blood pressure and bioactive nitric oxide. A randomized controlled trial. JAMA 2007; 298:49-60
2. Flammer A, Hermann F, Sudano I, et al. Dark chocolate improves coronary vasomotion and reduces platelet reactivity. Circulation 2007;116:2376-2382.
3. Chan, K. A clinical trial gone awry: the Chocolate Happiness Undergoing More Pleasantness (CHUMP) study. CMAJ 2007; 177 (12).
Move more, live longer: the latest on the benefits of an active lifestyle
Springtime is coming, the days are getting longer and warmer, and we are running out of excuses not to be up and moving again. Here is a short review of recent studies on the benefits of physical exercise.
Exercise and BP in children [1]
A recent UK study, the Avon Longitudinal Study of Parents and Children, shows that physical activity in children lowers childhood blood pressure (BP). Furthermore, it’s not the intensity of the activity that counts but the total amount of physical activity while performing normal daily chores. It could be just as simple as walking to and from school. The important thing is that kids should be mobile and not spend long periods of time in front of the TV or the game boy console. High BP in children can result in adult hypertension.
Aerobics and cholesterol levels [2]
A meta-analysis study by Japanese researchers shows that doing aerobics regularly increases serum concentrations of high-density lipoprotein cholesterol (HDL). This increase in HDL levels lowered the risk of cardiovascular disorders by about 5.1% in men and by 7.6% in women. The rise in HDL depends on duration but not intensity or frequency of the exercise. This beneficial effect of aerobics is most pronounced in people with initially high total cholesterol levels and low body mass index (BMI).
Exercise and telomeres [3]
British researchers found a correlation between physical activity and leukocyte telomere length (LTL) in healthy individuals. LTL is a biological measure of aging in humans.
Researchers at Twin Research Unit at St Thomas’ Hospital in London found that individuals who are inactive, smokers and with high BMI tend to have shorter telomeres than active, non-smoking individuals. The difference in biological age between couch potatoes and physically active people can be as high as 10 years.
Exercise and alcohol [4]
A Danish study followed up 11,914 adults for over 20 years. Their results show that leisure-time physical exercise combined with moderate alcohol intake actually lower risks of fatal ischemic heart disease (IHD). Nondrinking, sedentary individuals have the highest risk of IHD while physically active moderate drinkers have the lowest risk.
The study defined “moderate” drinking as 1 to 14 drinks of alcohol a week. One drink is equivalent to “one bottle of beer, one glass of wine, or one unit of spirit.”
Sources:
Leary SD et al., 2008. Physical activity and blood pressure in childhood: findings from a population-based study. Hypertension 51:92-98.- Kodama S et al., 2007. Effect of aerobic exercise training on serum levels of high-density lipoprotein cholesterol. Arch Intern Med 167:999-1008.
- Cherkas LF et al., 2008, The association between physical activity in leisure time and leukocyte telomere length. Arch Intern Med 168: 154-158.
- Pedersen JØ et al.., 2008. The combined influence of leisure-time physical activity and weekly alcohol intake on fatal ischaemic heart disease and all-cause mortality. European Heart Journal January 2008 29(2):204-212
Fast food and CVD: where`s the connection?
Be it burgers, pizza or fries, what is it with fast food diet that makes it a major CVD risk factor? In the recent issue of the Journal of the American College of Cardiology, researchers published the answers [1].
Consumption of high-calorie, low-nutrient food causes a sudden increase in blood glucose and triglyceride levels and results in a state known as postprandial dysmetabolism. These after-meal spikes in sugar and free fatty acids “overwhelm the body’s ability to handle the surge, resulting in a flooding of the Kreb’s cycle and the production of superoxide anions. The postprandial production of these free radicals acutely triggers atherogenic changes, such as increases in LDL oxidation, sympathetic tone, vasoconstriction, and thrombogenicity [2].”
At the end of the scale, traditional Mediterranean or Okinawan diets (consisting of lean protein, fish oil, whole grains, vegetables and low to moderate amounts of alcohol among others) has been shown to be anti-inflammatory and to lower CVD risks [1].
References:
1. O’Keefe JH, Gheewala NM, O’Keefe JO, 2008. Dietary Strategies for Improving Post-Prandial Glucose, Lipids, Inflammation, and Cardiovascular Health. J Am Coll Cardiol, 2008; 51:249-255, doi:10.1016/j.jacc.2007.10.016
2. O`Riordan M. Big Macs and Whoppers: Spikes in after-meal glucose and lipid levels lead to inflammation and CVD. HeartWire 16 Jan 2008.
ENHANCE trial update: no beneficial effects on CA IMT from ezetimibe
The much-awaited results of the “Ezetimibe and Simvastatin in Hypercholesterolemia Enhances Atherosclerosis Regression” (ENHANCE) trial are finally out – and they are a huge disappointment.
ENHANCE is an international 2-year, randomized, double-blind, controlled trial which compared the combination of ezetimibe and simvastatin to simvastatin monotherapy.
Simvastatin is a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor routinely used in the management of atherosclerosis. The newcomer ezetimibe is a specific cholesterol absorption inhibitor and the 2 drugs supposedly act as complementary agents that can have beneficial effects on the carotid artery intima-media thickness (CA IMT) of atherosclerosis patients. The trial was conducted in 720 patients with heterozygous familial hypercholesterolemia. The primary end point was mean change in the IMT measured at 3 different sites in the carotid arteries [1].
The trial results showed no significant difference in the mean IMT change between patients treated with ezetimibe/simvastatin 10/80 mg vs patients treated with simvastatin 80 mg alone. There was also no significant difference in treatment-related adverse events in both treatment groups. However, ezetimibe was associated with a larger reduction in LDL cholesterol [2].
References:
1. Kastelein et al., 2005. Comparison of ezetimibe plus simvastatin versus simvastatin monotherapy on atherosclerosis progression in familial hypercholesterolemia Design and rationale of the Ezetimibe and Simvastatin in Hypercholesterolemia Enhances Atherosclerosis Regression (ENHANCE) trial. American Heart Journal 149 (2): 234-239.
2. Hughes, S. 2008. ENHANCE results yield disappointment for ezetimibe. Heartwire 14 Jan 2008.
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The newest beta-blocker: will it sell?
It is the 19th of its kind in the market. No wonder cardiovascular experts were not that excited when the US FDA approved the selective beta-blocker Bystolic (nebivolol) this month [1].
However, nebivolol has some characteristics that other beta-blockers don’t have.
Efficacy
Nebivolol offers a new treatment option for hypertension through its “added pharmacological properties of producing vasodilation and reducing total peripheral resistance brought about by modulation of nitric-oxide release.” These properties make the drug more effective than traditional beta-blockers [2].
Safety
Compared to traditional beta-blockers, nebivolol causes relatively lower incidence of side effects normally associated with this class of drugs [1,2]. “Nebivolol is a so-called vasodilating beta blocker. Thus, in contrast to traditional beta blockers, it is more patient friendly in that it maintains systemic flow and blood flow to target organs, lowers vascular resistance, and has very little, if any, metabolic adverse effects”, according to one expert [2].
Both the manufacturer (Mylan Bertek Pharmaceuticals) and the marketing company (Forest Laboratories) hope these properties would be the selling point to make the drug attractive to both doctors and patients.
The main competitors of nebivolol would be the similar but non-selective beta-blocker carvedilol as well as cheap generics.
Sources:
Avandia Remains on Market but with Additional Warning
The US FDA has recommended that Avandia (rosiglitazone) be allowed to remain on market. However, additional warning has been inserted in the existing boxed warning in the product’s labeling. The new warning highlights the potential increased risk for cardiovascular events, especially myocardial infarction [1].
Avandia, manufactured by GlaxoSmithKline (GSK), was approved for marketing in 1999 in the US as oral treatment for type-2 diabetes mellitus. It has the advantage that it can be used as a stand-alone therapy or as co-therapy with other oral anti-diabetes treatments.
An article in NEJM early this year reported a meta-analysis of 42 randomized controlled clinical trials on rosaglitazone. The results show that “rosiglitazone was associated with a significant increase in the risk of myocardial infarction and with an increase in the risk of death from cardiovascular causes that had borderline significance.” [2]
The FDA has requested GSK to conduct a new long-term postmarketing study to evaluate the potential cardiovascular risk of Avandia and the manufacturer agreed to comply [1]. The study is expected to be concluded by 2014.
Sources:
A Promising Vaccine against Hypertension: Results from a Phase II Trial
An investigational vaccine against angiotensin II being tested by Cytos Biotechnology is showing promise. Results from an exploratory Phase IIa trial were presented at the American Heart Association Scientific Sessions 2007 [1] this month. CYT006-AngQb is a virus-like particle-based conjugate vaccine and is indicated for patients with mild to moderate hypertension. Preliminary results show “a significant reduction of daytime ambulatory blood pressure (BP) and a marked reduction in the early morning hours, when most adverse cardiovascular events occur.” [2]
Currently available antihypertensive drugs have a short half-life and must be taken on a daily basis. CYT006-AngQb has the advantage of producing extended antibody response with a half-life of about 4 months [2, 3].
In addition to a good efficacy profile, CYT006-AngQb was reported to be well-tolerated. The most common adverse events reported were pain, erythema, or edema at the injection site, and headache. All events were transient and no drug-related adverse events were reported during the 12-month follow-up period [3].
If approved, the vaccine would be a major breakthrough in the long-term management of hypertension.
Sources:
2 Medscape
Safety issues with prasugrel: the latest from TRITON-TIMI 38
TRITON-TIMI 38 is one of the biggest phase III clinical trials on prasugrel, a new thienopyridine from Lilly/Daiichi Sankyo. The trial was designed as multicenter, randomized, double-blind, and parallel-group. Over 13000 patients from different countries were enrolled based on the main inclusion criterion of having moderate- to high-risk ACS and undergoing PCI. Of these, about 73% had unstable angina/non-ST-segment elevation MI and 37% ST-segment elevation MI [1, 2].
The participants were randomized to either prasugrel or the comparator clopidogrel. Clopidogrel combined with aspirin is the first line antiplatelet therapy for the prevention of thrombotic complications of PCI. Prasugrel is said to be less variable and achieves a higher level of platelet inhibition than the comparator. The primary end point of the trial is the time of the first event of cardiovascular death, MI, or stroke [1, 2].
The latest results from the trial as reported in the latest issue of NEJM [3] show good efficacy profile but fall short in terms of safety. Prasugrel significantly reduced cardiovascular events compared to clopidogrel. However, the incidence of bleeding in prasugrel patients was significantly higher. The risk of bleeding is especially elevated in patients who have had CABG or cerebrovascular problems [3]. Safety concerns in terms of bleeding were actually reported already last year at the World Congress of Cardiology in Barcelona, Spain [4].
Abbreviations:
TRITON_TIMI 38: TRial to assess Improvement in Therapeutic Outcomes by optimizing platelet InhibitioN with prasugrel Thrombolysis In Myocardial Infarction 38.
ACS: acute coronray syndrome
PCI: percutaneous coronary intervention
MI: myocardial infarction
CABG: coronary artery bypass graft
Sources:
- TIMI homepage
- American Heart Journal 152(4):627-635, October 2006
- NEJM 357:2001-2015 November 2007.
- Heartwire 21 September 2006
ENDEAVOR DES System Gets Thumbs Up from FDA
The FDA Advisory Committe recommends approval of a new type of stent system – the Medtronic ENDEAVOR zotarolimus-eluting coronary stent system [1].
Data from the latest clinical trials which included over 4100 patients affirm the efficacy and safety of ENDEAVOR.
ENDEAVOR Efficacy in terms of target vessel failure (TVF) and target lesion vascularization (TLV) is shown to be comparable to that of TAXUS. ENDEAVOR safety profile is shown to be better than that of TAXUS and CYPHER [2].
After the recent safety concerns about DES, ENDEAVOR might just save the day.
