Large Genetic Studies May Help Unravel The Triglyceride Problem 1

The precise role of triglycerides in heart disease has been very difficult to determine. To help untangle the knotty problem two research groups studied large populations and identified rare variations in a gene (APOC3) that encodes for apolipoprotein C3, which is known to increase triglyceride levels.

The two studies have received a lot of attention in the media, including, most notably, great stories with lots of details and perspective by Gina Kolata on the front page of the New York Times and Matt Herper in Forbes. Both stories provide lots of background on these studies and present a wide variety of opinions about their significance. In general, though, they suggest that triglycerides and HDL are ready to trade roles: triglycerides are now ready for prime time as HDL fades into the background.

Click here to read the full story on Forbes.

 

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Large Study Uncovers New Details About the Role of Hypertension in CVD Reply

Although high blood pressure has long been recognized and studied as a cardiovascular risk factor, a large new study published in the Lancet provides a more detailed, granular view of the specific role of different forms of hypertension.

Eleni Rapsomaniki and colleagues in the U.K. analyzed data from 1.25 million people without existing cardiovascular disease age 30 and older. An important, and perhaps surprising, new finding is that high blood pressure was not a simple monolithic cardiovascular risk factor. Instead, the researchers found that different types of hypertension at different stages of life had different cardiovascular effects.

Click here to read the full post on Forbes.

 

Glucose Measurements Don’t Improve Cardiovascular Risk Assessment Reply

Although blood glucose and glycated hemoglobin (HbA1c) play a central role in diabetes, the value of these measurements to assess cardiovascular risk has been unclear. Now, in a paper published in JAMA, members of the Emerging Risk Factors Collaboration analyze data from nearly 300,000 people without known diabetes or cardiovascular disease who were enrolled in 73 prospective studies.

Click here to read the full post on Forbes.

 

 

After Long Wait, Updated US Cardiovascular Guidelines Now Emphasize Risk Instead Of Targets 1

Updated cardiovascular health guidelines were released today by  the American Heart Association (AHA) and the American College of Cardiology (ACC). The guidelines are designed to provide primary care physicians with evidence-based expert guidance on cholesterol, obesity, risk assessment, and healthy lifestyle.

The new guidelines reinforce many of the same messages from previous guidelines, but also represent a sharp change in philosophy. That change is most evident in the new lipid guidelines, in which the focus has shifted away from setting numerical targets for cholesterol levels in favor of treatment decisions based on individual risk status.

“This guideline represents a departure from previous guidelines because it doesn’t focus on specific target levels of low-density lipoprotein cholesterol, commonly known as LDL, or ‘bad cholesterol,’ although the definition of optimal LDL cholesterol has not changed,” said Neil J. Stone, chair of the lipid expert panel that wrote the new guideline. “Instead, it focuses on defining groups for whom LDL lowering is proven to be most beneficial.”

The long-awaited and often controversial guidelines are the successors to the extremely influential NHLBI guidelines, including the Adult Treatment Panel (ATP) series of guidelines that brought cholesterol to the consciousness of millions of people. Earlier this year the NHLBI announced that it would no longer issue guidelines but would, instead, provide support for guidelines produced by other organizations. Following the NHLBI announcement, the AHA and the ACC said that they would take over publication of the guidelines.

Statins Indicated for Four Broad Groups

Click here to read the full post on Forbes.

Guideline Maze

Original illustration by Max Husten

 

Hypertension And Smoking Top List Of Global Risk Factors 1

Screen Shot 2012-12-13 at 2.57.27 PMWorldwide, hypertension and tobacco smoking are the single largest causes of death and disability, according to findings from the Global Burden of Disease Study 2010 (GBD 2010), the largest ever assessment and analysis of global health and disease. In an unprecedented move, the Lancet devoted an entire issue to the study, including seven separate articles and eight comments.

GBD 2010 was led by the Institute for Health Metrics and Evaluation (IHME) at the University of Washington. In a press release, IHME director Chris Murray said, “For decision-makers, health-sector leaders, researchers, and informed citizens, the global burden of disease approach provides an opportunity to see the big picture, to compare diseases, injuries, and risk factors, and to understand in a given place, time, and age-sex group, what are the most important contributors to health loss.”

Despite significant reductions in the rate of ischemic heart disease and stroke since 1990, overall these retained their position as the #1 and #2 worldwide causes of death. Among men 15-49 years of age, CV disease was the single largest cause of death, accounting for 12.8% of all deaths. For women of the same age CV disease was the third largest cause of death, following HIV/AIDS and other non-communicable diseases, accounting for 10.7% of all deaths.

Ischemic heart disease in 2010 now ranks as the largest single cause of global years of life lost. In 1990 it had ranked fourth, behind lower respiratory infections, diarrhea, and preterm birth complications. Stroke moved from fifth place to third place.

High blood pressure emerged as the single most important risk factor for death and disability, followed by tobacco smoking. In 1990 the top two risk factors were childhood underweight (#8 in 2010) and household pollution (#4 in 2010).

State Of The Heart: AHA Publishes Year-End Statistical Update Reply

Although deaths from cardiovascular disease have been declining for many years, continued progress is threatened by disturbing trends in US lifestyles. That’s the clear message from the American Heart Association’s year-end report, “Heart Disease and Stroke Statistical Update 2013,” published in Circulation.

“Americans need to move a lot more, eat healthier and less, and manage risk factors as soon as they develop,” said Dr. Alan S. Go, the chairman of the report’s writing committee, in an AHA press release. “If not, we’ll quickly lose the momentum we’ve gained in reducing heart attack and stroke rates and improving survival over the last few decades.”

Here are some of the key statistics contained in the hefty report:

“The Epidemic of Poor Health Behaviors”

  • Among adults, 21.2% of men and 17.5% of women continued to smoke cigarettes. 18.1% of high school students are smokers.
  • Among high school students, 17.7% of girls and 10.0% of boys reported they had less than one hour of moderate-to-vigorous exercise.
  • Thirty-three percent of adults reported engaging in no aerobic leisure-time physical activity.
  • From 1971 to 2004, calorie intake increased from 1542 to 1886 kcal/d (22%) in women and from 2,450 to 2,693 kcal/d (10%) in men. Most of the change is due to an increased consumtpion of starches, refined grains, and sugars.
  • 68.2% of adults are overweight or obese. 34.6% are obese.
  • 31.8% of children 2-19 years of age are overweight or obese. 16.9% are obese.

“Prevalence and Control of Health Factors and Risks Remains an Issue for Many Americans”

  • 13.8% of US adults have serum serum cholesterol levels ≥240 mg/dL.
  • 33.0% of US adults have hypertension. About 82% are aware of their condition, 75% receive antihypertensive therapy, but only a little more than half (53%) have achieved target blood pressure levels.
  • 8.3% of US adults have been diagnosed with diabetes. 38.2% have abnormal fasting glucose levels (prediabetes).

CV Disease and Mortality

  • Although the percentage of deaths attributable to CV disease has been declining for decades, in 2009 CV disease  was responsible for nearly one-third (32.3%) of all deaths in the US.
  • About 635,000 people have a first MI or CHD death each year. About 280,000 have a second MI.
  • About 795,000 people have a new or recurrent stroke each year.
  • The 2009 total direct and indirect estimated cost of CVD and stroke:  $312.6 billion.
  • The 2008 total direct and indirect estimated cost of all cancer and benign neoplasms: $228 billion

Click here to read the AHA press release:

Observational Study Links Common Household Chemical To Cardiovascular Disease Reply

High levels of a manmade chemical widely used in common household products and detectable in more than 98% of people may increase the risk of cardiovascular (CV) disease and peripheral arterial disease (PAD), according to a study published in Archives of Internal Medicine(The study was published online in September and will appear in this week’s print edition of Archives.)

Anoop Shankar and colleagues measured serum levels of perfluorooctanoic acid (PFOA) in 1,216 people participating in the National Health and Nutritional Examination Survey (NHANES) and found a strong correlation between PAD and CV disease and PFOA levels. After adjusting for other risk factors, people in the highest quartile of PFOA levels had about double the risk of CV disease and PAD:

  • Odds ratio for the top quartile of PFOA: CV disease 2.01 (1.12-3.60), PAD 2.78 (1.03-3.08), CVD or PAD 2.28 (1.40-3.71)

The authors cite several studies that support the plausibility of a harmful effect of PFOA. They duly note the risk of “residual confounding and reverse causality” but write that if their findings are replicated “the population-attributable risk of PFOA exposure on CVD risk could potentially be high.”

In an invited commentary, Debabrata Mukherjee acknowledges the limitations of the study but writes that there is enough biological plausibility in the relationship so that “it would make sense to limit or to eliminate the use of PFOA and its congeners in industry through legislation and regulation while improving water purification and treatment techniques to try and remove this potentially toxic chemical from our water supply.” But, he warns concerns about PFOA “should not dissuade us from aggressively managing known existing risk factors for CVD such as dyslipidemia, smoking, hypertension, diabetes, obesity, and lack of regular physical activity.”
Click to continue reading…

What Is The Benefit Of Adding CRP To Risk Factor Assessment? Reply

In recent years controversy has swirled around the role of inflammation in cardiovascular disease and the relative worth of measuring novel risk factors like CRP. Now, in a new paper published in the New England Journal of Medicineresearchers from the Emerging Risk Factors Collaboration provide detailed calculations that estimate the benefits of adding two of these inflammatory markers to risk factor models.

In an analysis containing nearly a quarter million people enrolled in 52 studies, the investigators examined the effect of adding CRP and fibrinogen to a model including age, sex, smoking status, blood pressure, history of diabetes, and total cholesterol. They concluded that the effect of CRP and fibrinogen when added to the model were each roughly similar to the effect of HDL cholesterol when added to the model. In a secondary analysis, they found that CRP and fibrinogen improved risk prediction in men but not in women and had more predictive power in smokers than in nonsmokers.

The authors concluded that “targeted assessment of CRP in people at immediate risk for a cardiovascular event could help to prevent one additional event over the course of 10 years for every 440 people so screened.” Here’s how they calculated this conclusion:

In a population of 100,000 adults 40 years of age or older, with an age profile similar to that in the European standard population and with age-specific and sex-specific incidences of cardiovascular events that are assumed to be the same as those observed in the current study… 15,025 persons would initially be classified as having a predicted risk of cardiovascular disease of 10% to less than 20% over a period of 10 years when the risk is calculated with conventional risk factors alone…. Assuming that allocation to statin treatment would be conducted according to the ATPIII guidelines (i.e., persons with a predicted risk of ≥20% and those with risk factors, such as diabetes, irrespective of their predicted 10-year risk), 13,199 participants at intermediate risk would currently not be eligible for statin treatment. Additional assessment of CRP in these 13,199 participants would reclassify 690 participants (5.2%) to a predicted risk of 20% or more, of whom approximately 151 would be expected to have a cardiovascular event within 10 years; Assuming that persons reclassified as being at a predicted risk of 20% or more would begin statin therapy, in accordance with the ATPIII criteria, such targeted assessment of CRP could help to prevent about 30 (i.e., 0.20 × 151) additional cardiovascular events over a period of 10 years…

Meta-Analysis Links Stress At Work And Heart Disease Reply

A new study published in the Lancet provides the best evidence yet that work-related stress and, in particular, job strain– “the combination of high job demands and low control at work”– plays a small but important role in causing heart disease. In order to address the limitations of previous studies on this topic, including a publication bias which might exaggerate the effect, European investigators performed a large collaborative meta-analysis of published and unpublished studies.

The IPD-Work (individual-participant-data meta-analysis in working populations) consortium found that 15% of nearly 200,000 participants in the analysis reported having job strain. With a mean followup of 7.5 years, job strain was significantly associated with heart disease. The effect was higher in published studies, though it still achieved significance in the unpublished studies:

  • Overall hazard ratio (HR) for job strain: 1.23,CI 1.10–1.37
  • HR in published studies: 1.43, CI 1.15−1.77
  • HR in unpublished studies: 1.16, CI 1.02−1.32

The investigators calculated that the population attributable risk for job strain was 3.4%, which, they noted, was substantially lower than the major risk factors of smoking, obesity, and physical inactivity.

“Our findings suggest that job strain is associated with a small, but consistent, increased risk of an incident event of cardiovascular heart disease,” they concluded.

In an accompanying comment, Bo Netterstrøm writes that “job strain is a measure of only part of a psychosocially damaging work environment, which implies that prevention of workplace stress could reduce incidence of coronary heart disease to a greater extent than stated in the authors’ interpretation of the calculated population-attributable risk for job strain.”
Click here to read the press release from the Lancet…

Cardiovascular Risk Prediction: Two More Studies, Little Progress Reply

Two studies published in JAMA provide new data — and, perhaps, some additional clarity — about using additional markers to help improve risk prediction for coronary heart disease (CHD) and cardiovascular disease (CVD).

In one study, Joseph Yeboah and colleagues used data from 1330 intermediate-risk participants in the Multi-Ethnic Study of Atherosclerosis (MESA)  to analyze the prognostic value of 6 risk markers: 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 CHD.

After a median follow-up of 7.6 years, four risk markers (CAC, ABI, CRP, and family history) were found to be independent risk factors for CHD. CAC provided “the highest improvement in discrimination” over traditional risk scores. “The present study,” wrote the authors, “provides additional support for the use of CAC as a tool for refining cardiovascular risk prediction in individuals classified as intermediate risk.” However, “broad recommendations” about CAC should not be made until the associated problems of radiation exposure and incidental findings are addressed, they cautioned.

In the other study, Hester Den Ruijter and colleagues focused on CIMT, performing a meta-analysis in which they analyzed individual patient data from 14 studies and 45,828 patients. They found that adding CIMT provided only a small improvement in net reclassification which, they concluded, was “unlikely to be of clinical importance.”

In an accompanying editorial, J. Michael Gaziano and Peter Wilson write that “although there has been a great deal of work on the improvement in prediction modeling, less work has been done in 2 areas: the cost and risk in the screened population and risk prediction over time.” Using the example of an intermediate-risk patient who is a possible candidate for lipid-lowering therapy, they note that although CAC improves classification “at a single point in time,” most physicians evaluate patients over time and will often repeat tests to track trends over time. In this context, radiation exposure and costs may limit the utility of CAC.

Click to continue reading…

ESC Position Paper Advocates Population-Based Strategies To Reduce Cardiovascular Deaths Reply

About half of all cardiovascular deaths could be prevented by implementing population-level changes, according to a position paper from the European Society of Cardiology published in the European Journal of Preventive Cardiology. Torben Jørgensen and colleagues maintain that population-level interventions are much more effective than current strategies that seek to reduce individual risk.

Population-based strategies include taxation, legislation, and environmental changes. The authors call the move away from individual risk and toward a population-based strategy “a paradigm shift in CVD prevention.”

The authors argue that the change is necessary because “societal changes during the last decades have led to the present harmful environment with high calorie intake, low degree of physical activity, continuous smoking, and high alcohol intake.” Further, they note, efforts to promote a healthy lifestyle “routinely face opposition by commercial vested interest from corporations (e.g. food, tobacco, alcohol).”

Addressing a common criticism of population-based strategies, the authors counter the allegation that the “‘nanny state’ hinders the free choice of people” with the observation that “people today are nudged in the wrong direction by corporations’ de facto setting of the default option. Yet corporations do not have responsibility for population health – this is the responsibility of governments.”

”Population interventions make the environment healthier and change happens automatically whereas with an individual approach you need an active response,” said Professor Simon Capewell, a co-author of the paper, in an ESC press release.

Here are several of the paper’s major recommendations:

•    Healthy dietary habits will be supported by changes in agricultural policies, tax on products with free sugar and saturated fat and subsidies for fruit and vegetables, reduction of salt and trans-fatty acids in processed foods, clear labelling of foods, and limiting advertising for junk food.
•    Completely smoke-free environments are the only way to protect non-smokers. Smoking and second-hand smoking can be regulated by taxation, restrictions in sale and use, banning advertising, plain packaging, and warning labels.
•    Physical activities should be integrated in daily life by subsidies to public transport and re-allocating of road space to cycle and footpath lanes. Changes in schools, worksites, and built environment can make physical activity a more natural part of daily life.
•    Alcohol intake can be reduced by taxation, low availability, regulation of advertising, and low social and legal tolerance of drink driving.

Click here to read the press release from the ESC…

Is Chronic Kidney Disease A CHD Risk Equivalent? Reply

A new study published in the Lancet provides new data about whether chronic kidney disease (CKD) should, like diabetes, be considered a coronary heart disease (CHD) risk equivalent.

Marcello Tonelli and colleagues analyzed data from a population of 1.25 million people in Alberta, Canada. During a median followup of 4 years, 11,340 people were admitted to the hospital for MI. People with a previous MI were at higher risk for MI admission than people with either diabetes or CKD:

  • MI history: 18.5 per 1000 person-years (CI 17.4–19.8)
  • Diabetes: 5.4 per 1000 person-years (5.2–5.7)
  • CKD: 6.9 per 1000 person-years (6.6–7.2)
After adjustment for other variables, the relative rate of MI was lower in the CKD group than in the diabetes group (rate and adjusted relative rate for MI admission):
  • Previous MI: 7.7%, RR 3.8 (CI 3.5-41)
  • Diabetes and CKD: 6%, RR 2.7 (2.5-2.9)
  • CKD: 2.8%, RR 1.4 (1.3-3.5)
  • Diabetes: 2.4%, RR 2.0 (1.9-2.1)
  • No diabetes or CKD: 0.5%, RR 1 (reference)

The authors write that their “data show that diabetes alone and chronic kidney disease alone… do not increase the rate of myocardial infarction to the same extent as does a history of coronary disease, and therefore do not support the use of the term coronary heart disease risk equivalent for either disorder.” However, they concluded that CKD should “be added to the list of criteria defining people at highest risk of future coronary events.”

In an accompanying comment, Tamar Polonsky and George Bakris write that “despite negative findings for the primary outcome, compelling reasons are provided to consider lipid-lowering therapy in patients with chronic kidney disease.”
Click here to read the Lancet press release…

This Week In Medicine: Stop Exercising and Eat Chocolate! 5

It’s been a terrific few days of medical news for lazy people and chocoholics.

First, a study in PLoS One provided ammunition to the exercise-averse crowd by claiming that exercise can actually be bad for some healthy people. As an added bonus, a story about the study was carried on the front page of the New York Times.

Less than a day later, in a moment that will be long treasured by chocoholics, a study in BMJ calculated that people with metabolic syndrome could reduce their risk of serious cardiovascular events like heart attacks and strokes by eating dar chocolate every day.

Let’s take a quick look at each study:

The exercise study used data from 1,687 people who participated in one of six different exercise studies and found that a surprisingly large percentage of people had a significant adverse change in one of several important risk factors:
Click to continue reading…

The Y Chromosome May Explain Why Men Have Earlier Coronary Disease 1

The earlier onset of coronary artery disease in men has long provoked speculation and research. Now a new study in the Lancet suggests that common variations in the Y chromosome (which is transmitted directly from father to son and does not undergo recombination) may play an important role in the increased risk seen in men.

Using genetic information on the Y chromosome, an international team of researchers identified 9 different ancient lineages– haplogroups– in 3,233 British men. Two of the haplogroups accounted for nearly  90% of the subjects and men in one of these haplogroups, haplogroup I, had a 50% increase in the risk of coronary artery disease compared to  men with other haplotypes. This increase in risk was independent of other known risk factors. The investigators noted that haplogroup I appeared to exert a powerful effect on genes relating to inflammation and immunity. They further noted that haplotype I is generally more prevalent in northern than in southern Europe, and that this distribution is paralleled by an increased risk of coronary artery disease in northern Europe.

In an accompanying comment, Virginia Miller writes that the results of the study are “exciting because they identify a genetic haplotype linking response to infection (adaptive immunity) rather than innate immunity with perhaps an exaggerated inflammatory response and cardiovascular disease in men.”

Click here to read the press release from the Lancet…