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Better control of cholesterol levels and blood pressure and a decline in smoking have contributed to a 74% drop in the risk of heart attack among nearly 10,000 civil servants working in London over a 20-year period, according to new research. However, the reduction would have been even greater were it not for the fact that more people became fatter during this time, and this rise in body mass index (BMI) accounted for an estimated 11% increased risk of heart attack over the same period.

In a paper published online today in the European Heart Journal [1], researchers report that, among 9453 people taking part in the long-running Whitehall II study in London (UK), there was a substantial reduction (74%) in the chances of a first heart attack (myocardial infarction) among both men and women between 1985 and 2004. This corresponded to an annual average decline of 6.5%.

Over half of this reduction in heart attack rates could be explained by improvements in four of the main risk factors for heart attack: declining levels of “bad” non-HDL cholesterol levels, an increase in “good” HDL cholesterol, reduced blood pressure, and a reduction in the number of people who smoked. There was also a modest but statistically insignificant contribution from increased consumption of fruit and vegetables. Together, these five risk factors accounted for 56% of the reduction in the risk of heart attack.

Trends in physical activity, alcohol and bread consumption had no notable impact. However, there was a steady annual rise in BMI for both men and women, and this was associated with an increase in the risk of heart attack of 11% over the 20-year period.

The research, led by Ms Sarah Hardoon, a senior research associate, and Dr Eric Brunner, a Reader in Epidemiology and Public Health, at University College London Medical School (London, UK), suggests that the increase in BMI could have led to an increase in the incidence of heart attacks during the period of the study, were it not for the favourable trends seen in the other risk factors.

“The substantial decline in myocardial infarction over two decades to 2004, of which more than half could be attributed to favourable trends in well-known risk factors, highlights what can be achieved and emphasises the value of the measures taken to combat risky levels of cholesterol and blood pressure, and to promote healthier lifestyles. However, although these favourable trends seem to have outweighed the negative contribution of rising BMI over recent decades, continued increases in BMI may reduce further, and even reverse, the decline in the incidence of heart attacks in the future. Therefore, the rising BMI in the UK and in other countries needs urgent attention,” said Ms Hardoon.

More research is required to understand what other factors may account for the rest of the reduction in heart attacks that is not explained by these five risk factors. Ms Hardoon said there were a number of possible explanations.

“It could well be that we have underestimated the contribution of various risk factors. There may be some imprecision in the measurements, particularly for those that derive from questionnaires, such as diet, physical activity and alcohol consumption. Also, we have not captured the small fluctuations in the risk factors that occur. Had the risk factors all been measured precisely and we had captured the fluctuations in them, we might have explained a greater portion of the decline. Alternatively, there may have been favourable trends in other contributory factors not measured here, such as early treatment.”

The researchers say that the reduction in non-HDL (“bad”) cholesterol had the greatest single impact on the incidence of heart attacks, and this may reflect the increased use of cholesterol-lowering drugs such as statins, as well as healthier lifestyles. Statin use rose during the 20-year period and, by 2004, 11% of the civil servants were taking them.

Notes:

[1] “Rising adiposity curbing decline in the incidence of myocardial infarction: 20-year follow-up of British man and women in the Whitehall II cohort”. European Heart Journal. doi:10.1093/eurheartj/ehr142

[2] The Whitehall II Study is supported by grants from the Medical Research Council, the British Heart Foundation, Health and Safety Executive, Department of Health, Stroke Association, National Heart Lung and Blood Institute, National Institute on Aging, Agency for Health Care Policy Research, and the John D and Catherine T MacArthur Foundation.

Overweight and obese people looking to drop some pounds and considering one of the popular low-carbohydrate diets, along with moderate exercise, need not worry that the higher proportion of fat in such a program compared to a low-fat, high-carb diet may harm their arteries, suggests a pair of new studies by heart and vascular researchers at Johns Hopkins.

“Overweight and obese people appear to really have options when choosing a weight-loss program, including a low-carb diet, and even if it means eating more fat,” says the studies’ lead investigator exercise physiologist Kerry Stewart, Ed.D.

Stewart, a professor of medicine and director of clinical and research exercise physiology at the Johns Hopkins University School of Medicine and its Heart and Vascular Institute, says his team’s latest analysis is believed to be the first direct comparison of either kind of diet on the effects to vascular health, using the real-life context of 46 people trying to lose weight through diet and moderate exercise. The research was prompted by concerns from people who wanted to include one of the low-carb, high-fat diets, such as Atkins, South Beach and Zone, as part of their weight-loss program, but were wary of the diets’ higher fat content.

In the first study, scheduled to be presented June 3 at the annual meeting of the American College of Sports Medicine in Denver, the Hopkins team studied 23 men and women, weighing on average 218 pounds and participating in a six-month weight-loss program that consisted of moderate aerobic exercise and lifting weights, plus a diet made up of no more than 30 percent of calories from carbs, such as pastas, breads and sugary fruits. As much as 40 percent of their diet was made up of fats coming from meat, dairy products and nuts. This low-carb group showed no change after shedding 10 pounds in two key measures of vascular health: finger tip tests of how fast the inner vessel lining in the arteries in the lower arm relaxes after blood flow has been constrained and restored in the upper arm (the so-called reactive hyperemia index of endothelial function), and the augmentation index, a pulse-wave analysis of arterial stiffness.

Low-carb dieters showed no harmful vascular changes, but also on average dropped 10 pounds in 45 days, compared to an equal number of study participants randomly assigned to a low-fat diet. The low-fat group, whose diets consisted of no more than 30 percent from fat and 55 percent from carbs, took on average nearly a month longer, or 70 days, to lose the same amount of weight.

“Our study should help allay the concerns that many people who need to lose weight have about choosing a low-carb diet instead of a low-fat one, and provide re-assurance that both types of diet are effective at weight loss and that a low-carb approach does not seem to pose any immediate risk to vascular health,” says Stewart. “More people should be considering a low-carb diet as a good option,” he adds.

Because the study findings were obtained within three months, Stewart says the effects of eating low-carb, higher-fat diets versus low-fat, high-carb options over a longer period of time remain unknown.

However, Stewart does contend that an over-emphasis on low-fat diets has likely contributed to the obesity epidemic in the United States by encouraging an over-consumption of foods high in carbohydrates. He says high-carb foods are, in general, less filling, and people tend to get carried away with how much low-fat food they can eat. More than half of all American adults are estimated to be overweight, with a body mass index, or BMI, of 26 or higher; a third are considered to be obese, with a BMI of 30 or higher.

Stewart says the key to maintaining healthy blood vessels and vascular function seems – in particular, when moderate exercise is included — less about the type of diet and more about maintaining a healthy body weight without an excessive amount of body fat.

Among the researchers’ other key study findings, to be presented separately at the conference, was that consuming an extremely high-fat McDonald’s breakfast meal, consisting of two English muffin sandwiches, one with egg and another with sausage, along with hash browns and a decaffeinated beverage, had no immediate or short-term impact on vascular health. Study participants’ blood vessels were actually less stiff when tested four hours after the meal, while endothelial or blood vessel lining function remained normal.

Researchers added the McDonald’s meal challenge immediately before the start of the six-month investigation to separate any immediate vascular effects from those to be observed in the longer study. They also wanted to see what happened when people ate a higher amount of fat in a single meal than recommended in national guidelines. Previous research had suggested that such a meal was harmful, but its negative findings could not be confirmed in the Johns Hopkins’ analysis. The same meal challenge will be repeated at the end of the study, when it is expected that its participants will still have lost considerable weight, despite having eaten more than the recommended amount of fat.

“Even consuming a high-fat meal now and then does not seem to cause any immediate harm to the blood vessels,” says Stewart. However, he strongly cautions against eating too many such meals because of their high salt and caloric content. He says this single meal — at over 900 calories and 50 grams of fat — is at least half the maximum daily fat intake recommended by the American Heart Association and nearly half the recommended average daily intake of about 2,000 calories for most adults.

All study participants were between the age of 30 and 65, and healthy, aside from being overweight or obese. Researchers say that in the first study, because people were monitored for the period they lost the same amount of weight, any observed vascular differences would be due to what they ate.

Funding for the study was provided by the National Institute of Diabetes and Digestive and Kidney Diseases, part of the National Institutes of Health (NIH), with additional assistance from the Johns Hopkins Bayview Institute for Clinical Translational Research, also funded by the NIH. Besides Stewart, other Johns Hopkins researchers who took part in the studies were Sameer Chaudri, M.D.; Devon Dobrosielski, Ph.D.; Harry Silber, M.D., Ph.D.; Sammy Zakaria, M.D., M.P.H.; Edward Shapiro, M.D.; and Pamela Ouyang, M.B.B.S.

ROCHESTER, Minn. – One of the largest studies of its kind has found that people with coronary artery disease who have even a modest beer belly or muffin top are at higher risk for death than people whose fat collects elsewhere. The effect was observed even in patients with a normal Body Mass Index (BMI). The findings of this Mayo Clinic analysis are published in the May 10 issue of the Journal of the American College of Cardiology.

Researchers analyzed data from 15,923 people with coronary artery disease involved in five studies from around the world. They found that those with coronary artery disease and central obesity, measured by waist circumference and waist-to-hip ratio, have up to twice the risk of dying. That is equivalent to the risk of smoking a pack of cigarettes per day or having very high cholesterol, particularly for men.

The findings refute the obesity paradox, a puzzling finding in many studies that shows that patients with a higher BMI and chronic diseases such as coronary artery disease have better survival odds than normal-weight individuals.

“We suspected that the obesity paradox was happening because BMI is not a good measure of body fatness and gives no insight into the distribution of fat,” says Thais Coutinho, M.D., the study’s lead author and a cardiology fellow at Mayo Clinic. “BMI is just a measure of weight in proportion to height. What seems to be more important is how the fat is distributed on the body,” she says.

Francisco Lopez-Jimenez, M.D., the project’s lead investigator and director of the Cardiometabolic Program at Mayo Clinic, explains why this type of fat may be more harmful: “Visceral fat has been found to be more metabolically active. It produces more changes in cholesterol, blood pressure and blood sugar. However, people who have fat mostly in other locations in the body, specifically, the legs and buttocks, don’t show this increased risk.”

The researchers say physicians should counsel coronary artery disease patients who have normal BMIs to lose weight if they have a large waist circumference or a high waist-to-hip ratio. The measure is very easy to use, Dr. Coutinho says: “All it takes is a tape measure and one minute of a physician’s time to measure the perimeter of a patient’s waist and hip.”

The research subjects were diverse, coming from studies in the U.S. (Rochester, Minn. and San Francisco, Calif.), Denmark, France and Korea. The inclusion of different ethnic groups makes the study more applicable to the real world, Dr. Coutinho says.

Other members of the research team are Kashish Goel, M.D.; Daniel Correa de Sa, M.D.; Randal Thomas, M.D.; Veronique Roger, M.D., MPH; and Virend Somers, M.D., Ph.D., of Mayo Clinic; Charlotte Kragelund, M.D., Ph.D.; Lars Kober, M.D., Ph.D.; and Christian Torp-Pedersen, M.D., Ph.D., from Rigshaspitalet, Copenhagen, Denmark; Alka Kanaya, M.D. of the University of California, San Francisco, California; Jong-Seon Park, M.D.; Sang-Hee Lee, M.D.; and Young-Jo Kim, M.D., of Yeungnam University Hospital, Daegu, Korea; and Yves Cottin, M.D., Ph.D.; and Luc Lorgis, M.D., from CHU Bocage, Dijon, France.

University of Granada researchers have proven that melatonin –a natural hormone produced by the body– helps in controlling weight gain –even without reducing the intake of food–, improves blood lipid profile –as it reduces triglicerids–, increases HDL cholesterol and reduces LDL cholesterol.

Melatonin is found in small quantities in some fruits and vegetables as mustard, Goji berries, almonds, sunflower seeds, cardamom, fennel, coriander and cherries. Thus, the intake of this kind of food might help in controlling weight gain and preventing heart diseases associated to obesity and dyslipidemia.

Trials with rats

University of Granada researchers have analyzed in young Zucker diabetic obese rats the effects of melatonin on obesity, dyslipidemia and high blood pressure associated to obesity. Melatonin was found to be beneficial for young rats that had not still developed any methabolic or heart disease. Researchers think that melatonin might help in preventing heart diseases associated to obesity and dyslipidemia.

Finally, authors state that, if this finding is confirmed in humans, administration of melatonin and intake of food containing melatonin might be a useful tool to fight obesity and the risks associated to it.

A collaborative study

This study was partially funded and supported by the Research Plan of the University of Granada, by the research group CTS-109 (Junta de Andalucía), Spain and the Erasmus Mundus programme (European Council). University of Granada researchers –from the Institute for Neuroscience of the Department of Pharmacology of the Faculty of Medicine–, conducted this research in collaboration with the Clinical Trial Service of the University Hospital San Cecilio, Granada, the department of Physiology and Pharmacology of the University of Salamanca, the department of Pharmacology of the University of Jordan and the Service of Endocrinology of the Hospital Carloss III, Madrid.

The authors of this study are professors Ahmad Agil, Miguel Navarro, Rosario Ruiz, Sausan Abuamada, Yehia El-Mir and Gumersindo Fernández. They are certain that, in the light of the results obtained, a reduction of conditions associated to obesity and diabetes (heart diseases mainly) can be expected, which are good news, since these conditions reduce obese patients’ quality of life and life expectancy.

The results obtained in this study have been partially published in the prestigious Journal of Pineal Research.

NEW YORK (March 30, 2011) — In the longest study of its kind, bariatric surgery has been shown to reduce the risk of heart attack and stroke in patients with diabetes. These results and other groundbreaking research were presented at the 2nd World Congress on Interventional Therapies for Type 2 Diabetes, hosted by NewYork-Presbyterian Hospital and Weill Cornell Medical College.

“This is a watershed moment for diabetes care. With 20 years of data, we can really see how the surgery can improve a spectrum of health measures — notably cardiovascular risk,” says Dr. Francesco Rubino, director of the Congress and director of gastrointestinal metabolic surgery at NewYork-Presbyterian Hospital/Weill Cornell Medical Center.

While Type 2 diabetes is not technically a cardiovascular disease, experts say it might as well be one, given the corrosive effects of unregulated blood sugar on the heart. According to the American Heart Association, at least 65 percent of people with diabetes die of some form of heart disease or stroke.

Dr. Lars Sjöström, professor at the Institute of Medicine in Göteborg, Sweden, presented new data gleaned from the Swedish Obese Subjects (SOS) study. He reported on 20 years of data comparing 2,010 bariatric surgeries with 2,037 non-surgical patients who received medical treatment or lifestyle modification for obesity.

“Type 2 diabetes has always been considered a chronic, lifelong disease, but the long-term data show remission in 70 percent of patients after two years of follow-up,” he says. “Thirty percent are still in remission 15 years after bariatric surgery. Even more remarkable, 20 years out, we have seen that bariatric surgery has reduced new cases of diabetes by 80 percent among obese patients who did not have the disease at the start of the study.”

Dr. Sjöström concludes that the surgery’s preventive effect seems to be even stronger and more long-lasting than its ability to sustain long-term remission. Equally striking, the incidence of new cardiovascular events — either heart attack or stroke — has been at least 30 percent lower among postsurgical patients than their conservatively treated counterparts.

A Utah-based study presented similar clinical outcomes. After gastric bypass surgery, patients were seen to have greater reductions in blood pressure, heart rate, triglycerides, low-density lipoprotein (LDL) cholesterol, and insulin resistance than did patients in the group of severely obese patients who were treated via medication and lifestyle modification. The surgical group also experienced favorable changes in heart function and “geometry” — a subtle remodeling of the heart’s components leading to greater efficiency. The study’s principal investigator, Dr. Ted Adams of the University of Utah School of Medicine, believes the new data support the use of bariatric surgery to prevent the cardiovascular complications associated with obesity and Type 2 diabetes.

The GI Tract: A New Target for Treatment and Research

“The idea that the gastrointestinal tract can be targeted for the treatment of diabetes is highly promising. It also represents an entirely new way to treat and think about a disease that is notoriously difficult to control,” says Dr. Rubino, who also serves as associate professor of surgery at Weill Cornell Medical College.

Bariatric surgery, especially procedures that involve the rerouting as opposed to restriction of the gastrointestinal (GI) tract, appears to change the hormonal secretions of the gut, explains Dr. Rubino. These changes may be responsible for the surgery’s impressive success in improving or even resolving the disease in a majority of patients.

In bypassing portions of the jejunum or duodenum — the upper part of the small intestine right below the stomach — rerouting procedures such as gastric bypass seem to work via a mechanism of action that occurs too quickly to be related to weight loss. Although scientists are still engaged in lively debate around how and why the surgery works, there is growing consensus that anatomical changes in the GI tract play a far greater role in the control of diabetes than was previously believed.

Dr. Lee Kaplan, a renowned authority on obesity medicine and Congress presenter, elaborates: “The pharmaceutical and biotechnology industries have been developing novel diabetes drugs that target the GI tract, but the process is still at a relatively early stage.

“Recently, for example, we have seen the emergence of a new class of drugs designed to alter the action of gut-based hormones such as incretins, which play an important role in the production of insulin. However, the molecular character of the upper intestine still remains to be mapped and understood,” adds Dr. Kaplan, who is associate professor of medicine at Harvard Medical School and director of the Obesity Research Center at Massachusetts General Hospital.

The Congress also featured presentations by Nobel laureates Michael S. Brown and Joseph L. Goldstein. Their keynote lecture focused on the role of the gastrointestinal hormone ghrelin in regulating key biochemical processes implicated in energy metabolism. Ghrelin has been linked to obesity, mainly because of its ability to stimulate growth hormone release.

Beyond the details of that discussion, adds Dr. Rubino, the entire idea of the GI tract as an endocrine organ — one that could be responsible for the hormonal misfiring seen in diabetes — is still being tested, both in academic medical circles and by industry. At stake are new drugs, new devices and improved surgical methods for people living with and all too often dying from diabetes. “Some of us anticipate a paradigm shift in our understanding of the disease while others question such a shift,” says Dr. Rubino. “But there can be no doubt of how much we’re learning at this Congress about the clinical benefits of diabetes surgery and the basic science that underpins its success.”

Separate and combined associations of body-mass index and abdominal adiposity with cardiovascular disease:

collaborative analysis of 58 prospective studies

The Emerging Risk Factors Collaboration ‡
The Lancet, Early Online Publication, 11 March 2011
doi:10.1016/S0140-6736(11)60105-0

Summary

Background

Guidelines differ about the value of assessment of adiposity measures for cardiovascular disease risk prediction when information is available for other risk factors. We studied the separate and combined associations of body-mass index (BMI), waist circumference, and waist-to-hip ratio with risk of first-onset cardiovascular disease.

Methods

We used individual records from 58 cohorts to calculate hazard ratios (HRs) per 1 SD higher baseline values (4·56 kg/m2 higher BMI, 12·6 cm higher waist circumference, and 0·083 higher waist-to-hip ratio) and measures of risk discrimination and reclassification. Serial adiposity assessments were used to calculate regression dilution ratios.

Results

Individual records were available for 221 934 people in 17 countries (14 297 incident cardiovascular disease outcomes; 1·87 million person-years at risk). Serial adiposity assessments were made in up to 63 821 people (mean interval 5·7 years [SD 3·9]). In people with BMI of 20 kg/m2 or higher, HRs for cardiovascular disease were 1·23 (95% CI 1·17—1·29) with BMI, 1·27 (1·20—1·33) with waist circumference, and 1·25 (1·19—1·31) with waist-to-hip ratio, after adjustment for age, sex, and smoking status. After further adjustment for baseline systolic blood pressure, history of diabetes, and total and HDL cholesterol, corresponding HRs were 1·07 (1·03—1·11) with BMI, 1·10 (1·05—1·14) with waist circumference, and 1·12 (1·08—1·15) with waist-to-hip ratio.

Addition of information on BMI, waist circumference, or waist-to-hip ratio to a cardiovascular disease risk prediction model containing conventional risk factors did not importantly improve risk discrimination (C-index changes of −0·0001, −0·0001, and 0·0008, respectively), nor classification of participants to categories of predicted 10-year risk (net reclassification improvement −0·19%, −0·05%, and −0·05%, respectively). Findings were similar when adiposity measures were considered in combination. Reproducibility was greater for BMI (regression dilution ratio 0·95, 95%

CI 0·93—0·97) than for waist circumference (0·86, 0·83—0·89) or waist-to-hip ratio (0·63, 0·57—0·70).

Interpretation

BMI, waist circumference, and waist-to-hip ratio, whether assessed singly or in combination, do not importantly improve cardiovascular disease risk prediction in people in developed countries when additional information is available for systolic blood pressure, history of diabetes, and lipids.

Funding

British Heart Foundation and UK Medical Research Council.

Obesity is a killer in its own right, irrespective of other biological or social risk factors traditionally associated with coronary heart disease, suggests research published online in Heart.

Increasing weight is associated with a higher prevalence of known risk factors for coronary artery disease, such as diabetes, high blood pressure and cholesterol. And it has been assumed that these have been responsible for the increased risk of heart disease seen in obesity, say the authors.

The research team tracked the health of more than 6,000 middle aged men with high cholesterol, but no history of diabetes or cardiovascular disease, for around 15 years.

After excluding men who had cardiovascular problems or died within two years of the start of monitoring, to correct for any bias, 214 deaths and 1,027 non-fatal heart attacks/strokes occurred during the whole period.

The risk of a heart attack was compared across categories of increasing body mass index (BMI), using two different approaches.

One simply corrected for any differences in the age or smoking status of the men, while the second corrected for cardiovascular risk factors such as high cholesterol and blood pressure, deprivation and any medications the men were taking.

Not unexpectedly, the results showed that the higher a man’s weight, the higher was his likelihood of having other risk factors for cardiovascular disease. And there was no increased risk of a non-fatal heart attack with increasing BMI, (when using either approach)

But the risk of death was significantly higher in men who were obese – a BMI of 30 to 39.9 kg/m2.

In the model simply correcting for age and smoking, this risk was 75% higher. And despite correcting for known cardiovascular risk factors, medication, and deprivation in the second model, the risk was still 60% higher.

Inflammation is a strong factor in fatal cardiovascular disease, and obesity is increasingly being recognised as an inflammatory state, which may partly explain how obesity is linked to heart disease, say the authors. This has implications for treatment and prevention, they add.

In an accompanying podcast, which expands on the findings, lead author Dr Jennifer Logue, of the British Heart Foundation Cardiovascular Research Centre, at the University of Glasgow, cautions that the number of obese men in the sample was small, so the results need to be replicated elsewhere.

But she says, this is mainly because when the study started 20 years ago, the prevalence of obesity was low. But all that has now changed.

“The obesity generation is coming of age. We are going to see more and more complications from obesity, and coming at an earlier age,” she warns.