HIGHER HDL CHOLESTEROL MAY REDUCE RISK FOR COLON CANCER

HealthDay (3/8, Reinberg) reported, "High levels of 'good' cholesterol" may reduce the risk of colon cancer, according to a study published online March 7 in Gut. The researchers compared 1,238 people (779 had colon cancer and 459 had rectal cancer) with 1,238 healthy people, and found that "those with the highest levels of HDL cholesterol and another blood fat called apolipoprotein A (apoA) had the least chance of developing colon cancer, but no impact was seen on rectal cancer." Specifically, for each "16.6 milligrams per deciliter (mg/dL) increase in HDL and 32 mg/dL increase in apoA, the risk of colon cancer was cut by 22 percent and 18 percent," respectively. WebMD (3/8, Boyles) and the UK's Press Association (3/8) also covered the study results


Posted by Steven Almany M.D.

REDUCING CHOLESTEROL MAY HELP BODY'S IMMUNE SYSTEM FIGHT VIRAL INFECTIONS

The UK's Press Association (3/9) reports that "cutting cholesterol could help the body's immune system fight viral infections," according to a study published in the journal PLoS Biology. Investigators "found that when the body succumbs to a viral infection a hormone in the immune system sends signals to blood cells, causing cholesterol levels to be lowered." The "researchers said the findings could lead to new ways of treating viral infections, targeting the cholesterol metabolism." The UK's Telegraph (3/9, Adams) and Reuters (3/9, Kelland) also cover the story.

Posted by Steven Almany M.D.

SUGARY DRINKS MAY BE LINKED TO HYPERTENSION

The Los Angeles Times (2/28, Mestel) "Booster Shots" blog reported that a study published online in the journal Hypertension suggests that sugary drinks may be linked to hypertension. Researchers "analyzed data from 2, 696 middle-aged adults in the US and UK."

CNN /Health.com (3/1, Gardner) reports that the investigators found that "each additional soda, lemonade, or fruit drink the study participants consumed on a daily basis was associated with a small but measurable uptick in systolic and diastolic blood pressure of 1.6 and 0.8 points, respectively."

HealthDay (2/28, Mozes) reported that "those drinking more than one sugar-sweetened beverage a day also registered higher average body-mass indexes (BMI) compared with those who drank none, suggesting that those who consumed such drinks also consumed less healthy food." Also covering the story are the UK's Press Association (3/1), HeartWire (2/28, O'Riordan), BBC News (3/1, Roberts), MedPage Today (2/28, Fiore), Reuters (3/1, Kelland), WebMD (2/28, Boyles), and the Time (2/28, Park) "Healthland" blog.



Posted by Steven Almany M.D.

HIGHER DIETARY CONSUMPTION OF POTASSIUM MAY BE ASSOCIATED WITH LOWER RATES OF STROKE

HeartWire (2/28, Nainggolan) reported that "the largest meta-analysis so far conducted examining the impact of potassium intake on cardiovascular outcomes has found that higher dietary consumption of this mineral is associated with lower rates of stroke and could also reduce the risk of coronary heart disease (CHD) and total CVD." These findings "apply to all sectors of society and not just to specific 'at-risk' subgroups, say Dr Lanfranc D'Elia (University of Naples Medical School, Italy) and colleagues in the study, published in the March 8, 2011 issue of the Journal of the American College of Cardiology.

Posted by Steven Almany M.D.

INTERPRETATION AND SIGNIFICANCE OF ELEVATED CARDIAC TROPONIN LEVELS IN PATIENTS WITH RENAL DISEASE WITH AND WITHOUT A POSSIBLE ACUTE CORONARY SYNDROME

Christopher R. DeFilippi, M.D., F.A.C.C.
Ana Paunovic, M.D., M.Sc.

End-stage renal disease (ESRD) affects nearly 500,000 people in the United States. Approximately 50% of those patients will die from cardiovascular disease, although only 20% of cardiac deaths are attributed to myocardial infarction (MI).1 Traditional cardiac risk factors cannot fully account for this high cardiovascular event rate.

Early after the introduction of cardiac troponin T (cTnT), it was recognized that levels were frequently elevated in asymptomatic patients on dialysis.2 This was initially attributed to nonspecific antibody interactions, but even with a second generation revision of the assay that resulted in nearly 100% cardiac specificity, elevated levels were common in this population.3,4 In contrast, cardiac troponin I (cTnI) was infrequently detectable in these same patients.3,4 Subsequently, a substantial amount of literature has been generated over the past 11-12 years to investigate the significance of these findings.

Both troponin assays remain useful diagnostic and prognostic markers for acute coronary syndromes (ACS) in patients with chronic kidney disease, including those on dialysis. However, caveats apply in their interpretation compared to those without impaired renal function.

According to the National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines of 2007, class I evidence supports measurement of cTn in renal failure patients with signs and symptoms of ACS for evaluation of MI.5 In those ESRD patients who have baseline elevation of cTn and present with signs and symptoms of ACS, a dynamic change defined as an increase in troponin value of at least 20% (when the baseline cTn level starts elevated) should be considered diagnostic of an acute MI.5 Utilizing serial change in troponin levels is incorporated in the revised universal definition of MI, recognizing the importance of separating chronic elevations in conditions such as renal disease from ACS.6

In addition to having a diagnostic role in renal failure patients with suspected ACS, cTnT maintains a prognostic role in ACS patients with renal failure. Aviles et al. identified a large cohort of patients with a spectrum of renal disease and suspected ACS, enrolled in the Global Use of Strategies to Open Occluded Arteries IV (GUSTO IV) trial.7 An elevated cTnT at presentation independently predicted short-term (30-day) risk of death and MI across the spectrum of renal function, with the noted limitation of inclusion of only a small number of patients on dialysis.

For patients on dialysis without suspected ACS or other cardiac symptoms, cTn levels, particularly cTnT, remain independently prognostic of all-cause and cardiovascular mortality. A meta-analysis by Khan et al., including 28 studies, best summarizes these findings (Figure 1).8 Evidence for the association of cTnI level and all-cause mortality is more mixed, although overall, the findings from the meta-analysis showed cTnI level to predict all-cause, but not cardiac-specific death in dialysis patients (Figure 2).8




A variety of different assays and diagnostic cut-offs may have accounted for the inconsistent association of cTnI level and mortality in dialysis patients. Several biologic explanations have been offered for the difference in cTnT and cTnI findings, including the presence of immuno-reactive fragments of the cTnI molecule in hemodialysis patients.9 However, the presence of cTnT fragments has been refuted by others.10 Most likely, disparities in assay sensitivity and standardization between cTnT and cTnI are the explanations for the observed differences.

Supporting this hypothesis was the finding in predialysis renal disease patients, without cardiac symptoms, using a newer generation sensitive cTnI assay. This study showed that the prevalence of elevated cTnI levels was similar to cTnT.11 Furthermore, elevation of either cTnT or cTnI with the sensitive assay was associated with a similar poor prognosis compared to those subjects without detectable levels.11 Preliminary data using new highly sensitive cTnT and cTnI assays show a similar proportion of values above the 99th percentile of a normal population in ambulatory renal disease patients not on dialysis. Furthermore, significant associations remain for both assays for the extent of coronary calcium and a history of coronary disease.12

In summary, additional studies will be needed to establish the prognostic value of cTnI in ESRD. Both tests remain critical to the diagnosis of ACS in these patients, and while a single value carries important prognostic information in the presence or absence of symptoms, change in levels by serial measures is required to diagnose MI.5,6

Potential Etiologies of Elevated Cardiac Troponins in Patients With End-Stage Renal Disease
The exact pathophysiologic mechanism for etiology of cTn elevation in asymptomatic patients with renal disease remains unknown. Several associations have been investigated to provide insight into the probable mechanisms of release from the myocardium. These include epicardial coronary artery disease with associated microinfarctions and left ventricular hypertrophy (LVH). In support of an epicardial coronary disease hypothesis is a strong association between increasing cTnT levels and a progressively higher prevalence of multi-vessel coronary disease in 67 asymptomatic ESRD patients volunteering for coronary angiography.13

Additionally, asymptomatic multi-vessel coronary artery stenosis is frequently present at the start of dialysis in patients with detectable cTnT,14 although this association has not been a consistent finding.15 This negative finding may be a result of an overall younger and healthier population selected for pretransplant evaluation versus an all-comers study, but also points to alternative mechanisms for cTn elevation in ESRD.

To follow-up this hypothesis, cardiac magnetic resonance imaging with delayed enhancement gadolinium has been utilized to identify detection of small foci of myocardial necrosis, which can represent epicardial coronary plaque embolization. In this small study of 26 ESRD subjects, one-half of whom had an elevated cTnT level, no significant association was found between cTnT level and presence of delayed enhancement gadolinium.16 The study was limited by the small number of subjects, but with the subsequent recognition of the risk of nephrogenic systemic fibrosis in renal patients exposed to gadolinium contrast, additional studies are unlikely to be performed.

Last, several studies have evaluated the association of LVH and troponin levels. LVH may result in subendocardial ischemia/injury or may be the result of a cardiomyopathic process, both of which could be a source of cardiac injury unrelated to coronary disease. LVH has been associated with elevated troponin in asymptomatic hemodialysis patients.4 Similarly, elevated LV mass index was associated with elevated cTnT levels and was the second strongest predictor of troponin elevation after age.17 However, as with coronary disease, the association of LVH and elevated cTnT is not consistent.13,16

Alternative explanations for elevated cTn levels in the absence of obvious imaging evidence of cardiac pathology may also include uremia-associated cardiac fibrosis. Patients with ESRD and fibrosis ≥30% on cardiac biopsy have a known poor prognosis.18 Fibrosis may represent the link between elevated troponin levels and the poor cardiac prognosis in patients with ESRD that is unrelated to MI. Advanced imaging techniques may eventually be able to test this association.

In conclusion, cardiovascular disease is a major cause of death in patients with ESRD. Elevated levels of cTnT and cTnI are associated with a poor prognosis in both those with and without a diagnosis of ACS. As the sensitivity of both assays improves, there is likely to be little that differentiates them in this patient population.

Currently, the pathology behind cTn elevations in the absence of ACS is incompletely understood. A better understanding of the pathologic process underlying cTn elevations in the absence of symptoms could lead to eventually using these tests to guide therapy prior to the onset of symptomatic cardiovascular disease, or worse, sudden death.

Posted by Steven Almany M.D.

TRAFFIC EXPOSURE, AIR POLLUTION BIGGEST POPULATION-LEVEL TRIGGERS FOR MI

Diepenbeek, Belgium - A comparative risk assessment of various triggers for MI suggests that cocaine is most likely to trigger an event in an individual, but traffic and exposure to air pollution has the greatest effect on triggering an MI at the population level [1].

"Many papers have studied the effects of various triggers of myocardial infarction, but our question was, well, at the population level, which one is the most important one?" lead investigator Dr Tim Nawrot (Hasselt University, Diepenbeek, Belgium) told heartwire. "Cocaine use, in this paper, is definitely the most important risk factor, with a 24-fold increased risk of having an event while using it, but not that many people use cocaine, making it rather weak at the population level. On the other hand, air pollution, in general, has quite a weak individual risk, but because many people are exposed to it at the population level, about 5% to 7% of myocardial infarctions are triggered by this risk factor."

The results of the study are published online February 23, 2011 in the Lancet.

Exposure prevalence ranges from 0.04% to 100%

In the paper, the researchers reviewed 36 epidemiologic studies assessing population-attributable fractions (PAF) of various triggers for MI. The PAFs are calculated using the odds ratios and frequencies of each trigger and provide an estimate of the proportion of MIs that could be avoided if the risk factor were removed. As Nawrot noted, the exposure prevalence in the analysis ranged from 0.04% for cocaine use to 100% for air pollution.

In ranking the triggers based on the odds ratios, cocaine use was associated with 24-fold increase risk of MI, far and away the most significant trigger for an event. The consumption of a heavy meal, smoking marijuana, experiencing negative emotions, physical exertion, experiencing positive emotions, getting angry, sexual activity, traffic exposure, coffee consumption, and air pollution were also associated with a significantly increased risk of MI.

In calculating the PAF, however, traffic exposure was the most important trigger for an acute event at the population level, report investigators. This was followed by physical exertion, alcohol consumption, coffee consumption, and a change of 30 µg/m3 of particulate matter with an aerodynamic diameter of 10 µg or less (PM10). Experiencing negative emotions, anger, eating a heavy meal, experiencing positive emotions, and sexual activity had a PAF ranging 3.9% to 2.2%, respectively, while cocaine and marijuana use had a PAF of 0.9% and 0.8%, respectively.
Prevalence of exposure, pooled odds ratio, and PAF for various triggers of myocardial infarction

Triggers of MI Prevalence of exposure(%) Odds ratio(95% CI) PAF, %(95% CI)
Air pollution, 10 µg/m3 100 1.02(1.01-1.02) 1.57(0.89-2.15)
Air pollution, 30 µg/m3 100 1.05(1.03-1.07) 4.76(2.63-6.28)
Alcohol 3.2 3.1 (1.4-6.9) 5.03(2.91-7.06)
Anger 1.5 3.11(1.8-5.4) 3.07(1.19-6.16)
Cocaine use 0.04 23.7(8.1-66.3) 0.90(0.28-2.55)
Coffee 10.6 1.5(1.2-1.9) 5.03(2.08-2.71)
Physical exertion 2.4 4.25(3.17-5.68) 6.16(4.20-8.64)
Sexual activity 1.1 3.11(1.79-5.43) 2.21(0.84-4.53)
Traffic exposure 4.1 2.92(2.22-3.83) 7.36(4.81-10.49)

Commenting on the results, Nawrot said the traffic exposure could be a combination of pollution, stress, noise, and other factors, although it is assumed that air pollution plays a large role, as drivers are exposed to peak levels while idling in traffic. In studies directly measuring air pollution, decreasing PM10 levels 30 µg/m3 would reduce MIs 5%, while reducing PM10 levels 10 µg/m3 would reduce events by 1.6%.

"Not only in this study, but in the many studies that have been conducted, the acute risk of air pollution on acute myocardial infarction is well established and is recognized as such by the American Heart Association," Nawrot told heartwire. "What this study adds is the perspective from the population level. Improving the air we breathe is a very relevant target to reduce the incidence of this disease in the general population."

In an editorial accompanying the study [2], Dr Andrea Baccarelli (Harvard University, Boston, MA) and Dr Emelia Benjamin (Boston University, MA) call the analysis "an exemplary piece of epidemiological work," saying that the evidence stands as a "warning against overlooking the public-health relevance of risk factors with moderate or weak strength that have high frequency in the community."

They note that reducing PM10 levels 30 µg/m3 would bring several European cities toward the 20 µg/m3 annual mean limit recommended by the World Health Organization, but the decrease is larger than needed, or achievable, in most US cities as well as several European cities. In 2000, most US cities had PM10 levels below 30 µg/m3 and many had levels below 20 µg/m3, but the PAF for reducing air pollution 10 µg/m3 is "far from negligible," at 1.57%, and would go a long way toward reducing the triggering burden in communities exposed to low to moderate levels of air pollution. A 10-µg/m3 and 30-µg/m3 reduction in air pollution is well less than what is needed in most Asian cities, they point out.

Sources
1. Nawrot TS, Perez L, Künzli N, et al. Public health importance of triggers of myocardial infarction: A comparative risk assessment. Lancet 2011; DOI: 10.1016/S0140-6736(10)62296-9. Available at: http://www.thelancet.com.
2. Baccarelli A, Benjamin EJ. Triggers of MI for the individual and the community. Lancet 2011; DOI: 10.1016/S0140-6736(10)62348-3. Available at: http://www.thelancet.com.

February 23, 2011 | Michael O'Riordan
http://www.theheart.org/article/1189071.do

Posted by Steven Almany, M.D.

TIMELY ANGIOPLASTIES BRINGING DOWN CARDIAC MORTALITY RATES IN SOUTHEAST MICHIGAN

Crain's Detroit Business (2/28, Greene) reports, "Mortality rates from heart attacks in Southeast Michigan appear to be falling as hospitals have found ways to shorten the 'door to balloon' time between diagnosis of heart attacks and emergency angioplasties." In fact, "most of Southeast Michigan's cardiovascular hospitals have reduced door-to-balloon time to less than 80 minutes, and they have slashed mortality rates to less than 3 percent from as much as eight percent over the past several years, say hospital officials." The article notes that the "National Cardiovascular Data Registry, operated by the American College of Cardiology...collects door-to-balloon time for all patients, including transfers."

Southeast Michigan Emergency Departments Seeing Increase In Heart Attack Patients. Crain's Detroit Business (2/28, Greene) reports, "Cardiologists and emergency physicians at most heart hospitals in Southeast Michigan say there has been an increase over the past year in the number of people arriving at emergency departments with heart attacks, although there are mixed opinions on whether there also is a corresponding increase in emergency angioplasties." Mark Brautigan, MD, chief of emergency medicine at Detroit Medical Center's Sinai-Grace Hospital in Detroit, "said the number of people arriving at the ER with heart attacks has increased during the past year by several percentage points." He stated, "'Shoveling snow is a big precipitator, but people losing their health insurance and not able to control their medical conditions (hypertension, diabetes and heart failure) is a big reason' for the increase."

Posted by Steven Almany M.D.

HOT FLASHES AT START OF MENOPAUSE ASSOCIATED WITH LOWER RISK FOR HEART ATTACK, DEATH

The AP (2/25, Tanner) reports that, according to a study published online Feb. 24 in the journal Menopause, "Women who had hot flashes at the start of menopause but not later seemed to have a lower risk for heart attack and death than women who never had hot flashes, or those whose symptoms persisted long after menopause began." But, "among the few women who developed hot flashes late -- in some cases many years after menopause began -- there were more heart attacks and deaths when compared with the other groups."

For the study, "researchers analyzed data from 60,000 post-menopausal women who were part of the Women's Health Initiative Observational Study," the Los Angeles Times (2/23, Roan) "Booster Shots" blog reported. They found that "women who had hot flashes or night sweats at the start of menopause were actually at a slightly lower risk for stroke, heart disease and death, compared with women who never had hot flashes or night sweats. The risk reductions were 17% for stroke, 11% for heart disease and 11% death."

As to why hot flashes during the start of menopause lowered the risk for heart attack, according to the Time (2/24, Park) "Healthland" blog, "what may be happening," the study's co-author explained, "is that women who experience flushing during menopause could have blood vessels that are responding appropriately to the change in hormone levels occurring at that time, helping them to ward off the hardening of the arteries and plaque-building associated with heart disease." However, "further studies need to confirm whether that's the case."

The CNN (2/24, Landau) "The Chart" blog reported, "Dr. Rita Redberg, cardiologist at the University of California-San Francisco, and spokeswoman for the American Heart Association, said it's unlikely that hot flashes themselves are protective; her theory is that women are more likely to exercise or go to their doctors more regularly because of hot flashes, and those practices can decrease cardiovascular events." WebMD (2/24, Mann), Reuters (2/25), and the UK's Press Association (2/25) also covered the story.

Posted by Steven Almany M.D.

STUDY RANKS RELATIVE CONTRIBUTIONS OF TRIGGERS TO HEART ATTACKS IN THE GENERAL POPULATION

The Chicago Sun-Times (2/24, Thomas) reports that "air pollution contributes to more heart attacks in the population as a whole than negative emotions, sexual activity and cocaine use, according to a new study" published online in The Lancet.

WebMD (2/23, Goodman) reported that investigators "pooled data from 36 studies of exposures that are thought to play a role in triggering heart attacks." The researchers "then calculated the odds that being exposed to that variable would lead to a heart attack."

HealthDay (2/23, Reinberg) reported that "because so many people are exposed to dirty air, air pollution while stuck in traffic topped the list of potential heart attack triggers, with the researchers pegging 7.4 percent of heart attacks to roadway smog." However, "coffee was also linked to 5 percent of attacks, booze to another 5 percent, and pot smoking to just under 1 percent, the...researchers found." Meanwhile, "among everyday activities, exerting yourself physically was linked to 6.2 percent of heart attacks, indulging in a heavy meal was estimated to trigger 2.7 percent, and sex was linked to 2.2 percent."

Reuters (2/24, Kelland) reports that the researchers wrote, "Of the triggers for heart attack studied, cocaine is the most likely to trigger an event in an individual, but traffic has the greatest population effect as more people are exposed to (it)." The UK's Press Association (2/24), the UK's Daily Mail (2/24, Hope) and HeartWire (2/23, O'Riordan) also covered the story.

Posted by Steven Almany M.D.