In a comparison of novel cardiovascular risk markers, coronary artery calcium, ankle-brachial index, high-sensitivity C-reactive protein, and family history were independent predictors of coronary heart disease/cardiovascular disease in intermediate-risk individuals beyond traditional risk factors, with coronary artery calcium providing superior discrimination and risk reclassification compared with other risk markers, according to a study.
‘Current trends in primary prevention of cardiovascular disease (CVD) emphasise the need to treat individuals based on their global cardiovascular risk. Accordingly, practice guidelines recommend approaches to classify individuals as high, intermediate, or low risk using the Framingham Risk Score (FRS) or other similar CVD risk prediction models. However, there is increasing recognition of the imprecision of these classifications such that the intermediate-risk group actually represents a composite of higher-risk individuals for whom more aggressive (i.e., drug) therapy might be indicated. The intermediate-risk group also contains lower-risk individuals in whom CVD might be managed with lifestyle measures alone. This recognition has motivated researchers to identify markers that could offer greater discrimination of higher- and lower-risk patients within the intermediate-risk group,’ according to background information in the article.
‘Risk markers including coronary artery calcium (CAC), carotid intima-media thickness (CIMT), ankle-brachial index (ABI), brachial flow-mediated dilation (FMD), high-sensitivity C-reactive protein (CRP), and family history of coronary heart disease (CHD) have been reported to improve on the Framingham Risk Score for prediction of CHD, but there are no direct comparisons of these markers for risk prediction in a single cohort,’ the authors write.
Joseph Yeboah, M.D., M.S., of the Wake Forest University School of Medicine, Winston-Salem, N.C., and colleagues assessed the improvements in CHD/CVD prediction accuracy and reclassification to high- and low-risk categories using CIMT, CAC, FMD, ABI, high-sensitivity CRP, and family history of CHD in asymptomatic adults classified as intermediate risk who participated in the Multi-Ethnic Study of Atherosclerosis (MESA). Of 6,814 MESA participants from 6 U.S. field centres, 1,330 were intermediate risk, without diabetes mellitus, and had complete data on all 6 markers. Recruitment spanned July 2000 to September 2002, with follow-up through May 2011. Analysis was conducted to compare incremental contributions of each marker when added to the FRS, plus race/ethnicity. Incident CHD was defined as heart attack, angina followed by revascularisation, resuscitated cardiac arrest, or CHD death. Incident CVD additionally included stroke or CVD death.
After a median (midpoint) follow-up of 7.6 years, 94 participants (7.1 percent) experienced a CHD event and 123 (9.2 percent) experienced a CVD event. After analyses, the researchers found that each of the novel risk markers was associated with incident CHD; however, after adjusting for confounders, the associations with CIMT and FMD were no longer significant. Among all of the risk markers, CAC had the strongest association. Similarly, for incident CVD, each of the markers was associated with events except high-sensitivity CRP. However, after adjusting for confounders, the associations between CIMT and FMD were no longer significant. CAC also had the strongest association in the multivariable models for CVD.
‘The current study shows that among 6 of the most promising novel risk markers, CAC provides the highest improvement in discrimination over the FRS and Reynolds score (RS) in individuals classified as intermediate risk. The present study provides additional support for the use of CAC as a tool for refining cardiovascular risk prediction in individuals classified as intermediate risk by the FRS or the RS,’ the authors write. ‘Additional research is warranted to explore further both the costs and benefits of CAC screening in intermediate-risk individuals.’
Catalan researchers identify a key component of cell division EurekAlert

Women who begin snoring during pregnancy are at strong risk for high blood pressure and preeclampsia, according to research from the University of Michigan.
The research showed pregnancy-onset snoring was strongly linked to gestational hypertension and preeclampsia, says lead author Louise O’Brien, Ph.D., associate professor in U-M’s Sleep Disorders Center.
‘We found that frequent snoring was playing a role in high blood pressure problems, even after we had accounted for other known risk factors,’ says O’Brien. ‘And we already know that high blood pressure in pregnancy, particularly preeclampsia, is associated with smaller babies, higher risks of pre-term birth or babies ending up in the ICU.’
The study is believed to be the largest of its kind, with more than 1,700 participants. It is the first study to demonstrate that pregnancy-onset snoring confers significant risk to maternal cardiovascular health.
Habitual snoring, the hallmark symptom of sleep-disordered breathing, was defined as snoring three to four nights a week. About 25 percent of women started snoring frequently during pregnancy and this doubled the risk for high blood pressure compared to non-snoring women.
O’Brien writes that these results suggest that up to 19 percent of hypertensive disorders during pregnancy might be mitigated through treatment of any underlying sleep-disordered breathing.
Pregnant women can be treated for sleep-disordered breathing using CPAP (continuous positive airway pressure). It involves a machine, worn during sleep, that uses mild air pressure to keep the airways open. It is possible that use of CPAP may decrease high blood pressure in pregnant women, and O’Brien has such a study currently underway to test this hypothesis.
‘Hypertensive disorders of pregnancy are a leading global cause of maternal and infant deaths and cost billions of dollars annually to treat,’ O’Brien says. University of Michigan Health System

Favourable results have led to crizotinib gaining approval for the treatment of advanced stage ALK-positive non-small cell lung cancer (NSCLC) in Japan, the United States, Canada, and several other countries in Europe and Asia. Now, the identification of an effective therapy for ALK-positive NSCLC places great emphasis on rapid, accurate, and cost-effective way to find patients with this subtype of lung cancer. A recent study concludes immunohistochemistry (IHC) is a reliable screening tool for identification of ALK rearrangement.
Fluorescence in situ hybridisation (FISH) is the current standard method to detect ALK rearrangement. However, FISH is not readily available as a routine method of pathology practice in most laboratories because it is time consuming and requires advanced technical and professional expertise. In contrast, IHC is relatively inexpensive, faster, and is perfectly adapted for routine practice by academics and most community hospitals.
Researchers screened 377 stage I or II NSCLC cases, diagnosed between 1978 and 2002. Tissue microarray results were available on 377 cases by IHC and 273 cases by FISH. Eleven cases were positive or possibly positive by either IHC or FISH, and three cases were positive or possibly positive by both methods.
They found, ‘that all cases exhibiting ALK rearrangement demonstrated adenocarcinoma histology.’ Their results report a sensitivity of 100 percent and high specificity with the IHC with no false-negative results. While researchers acknowledge that further study involving a larger cohort is recommended, IHC is a valid screening test. The International Association for the Study of Lung Cancer

The cellular cause of birth defects like cleft palates, missing teeth and problems with fingers and toes has been a tricky puzzle for scientists.
Now Professor Emily Bates and her biochemistry students at Brigham Young University have placed an important piece of the developmental puzzle. They studied an ion channel that regulates the electrical charge of a cell. In a new study they show that blocking this channel disrupts the work of a protein that is supposed to carry marching orders to the nucleus.
Without those instructions, cells don’t become what they were supposed to become – be that part of a palate, a tooth or a finger. Though there are various disorders that lead to birth defects, this newly discovered mechanism may be what some syndromes have in common.
Bates and her graduate student, Giri Dahal, now want to apply the findings toward the prevention of birth defects – particularly those caused by fetal alcohol syndrome and fetal alcohol spectrum disorder.
‘What we think might be the case is that this is the target for a few similar disorders,’ Bates said. ‘The big thing that we have right now is that this ion channel is required for protein signalling, which means that developmental signalling pathways can sense the charge of a cell. And that’s exciting for a lot of different reasons.’
For example, the new study might also have implications for the battle against cancer. With cancer, the problem is that cells are receiving a bad set of instructions that tells them to multiply and spread. If they can devise a way to block the ion channel, it may stop those cancerous instructions from getting through.
‘This protein signalling pathway is the same one that tells cancer cells to metastasise,’ Bates said. ‘We’re planning to test a therapy to specifically block this channel in just the cells that we want to stop.’ Brigham Young University

Chronic kidney disease changes the composition of intestinal bacterial microbes that normally play a crucial role in staving off disease-causing pathogens and maintaining micro-nutrient balance, according to UC Irvine researchers.
This profound alteration of the gut microbial population may contribute to the production of uremic toxins, systemic and local inflammation, and nutritional abnormalities present in patients with advanced renal disease, they said.
Study leader Dr. N.D. Vaziri of the UCI School of Medicine’s Division of Nephrology & Hypertension noted that consumption of high-fibre foods and better control of uremia — a disease common in kidney failure — by diet and dialysis may improve the composition of gut microbes and the well-being of patients.
The researchers studied microbial DNA extracted from the stool samples of a group of renal failure patients and healthy control individuals. They found marked differences in the abundance of some 190 types of bacteria in the gut microbiome of those with kidney disease — and confirmed the results in a concurrent study of rats with and without chronic kidney disease.
Vaziri explained that nitrogen-rich waste products — particularly urea and uric acid, which are usually excreted by the kidneys — accumulate in the body fluids of patients with renal failure. This leads to the massive release of these waste products in the gastrointestinal tract, supporting the growth and dominance of microbial species that can utilise these compounds.
The impact of this flooding of the gut by nitrogenous waste products in patients with advanced kidney disease, Vaziri added, is compounded by dietary restrictions on fruits and vegetables, which contain the indigestible fibres that favourable gut microbes feed on. This is because fruits and vegetables contain large amounts of potassium, a mineral normally excreted by the kidneys. In cases of renal failure, potassium levels are high, increasing the risk of cardiac arrest.
One solution, Vaziri said, is to provide longer, more frequent dialysis treatments. This would let more potassium be removed by dialysis and allow for more potassium in the diet. Alternatively, packaged fibre foods that do not contain potassium could be used as a dietary supplement.
The work adds to a growing body of evidence pointing to the role of gut bacteria in disease and health. Recent research by other groups has identified changes in the composition of intestinal microbial flora in people with diabetes, colorectal cancer, obesity and inflammatory bowel disease, among other conditions. University of California, Irvine