Study shows so-called 'healthy obesity' is harmful to cardiovascular health

Clinicians are being warned not to ignore the increased cardiovascular health risks of those who are classed as either 'healthy obese' or deemed to be 'normal weight' but have metabolic abnormalities such as diabetes.
Academics at the University of Birmingham's Institute of Applied Health Research carried out the largest study of its kind to date comparing weight and metabolic status to cardiovascular disease risks, published today (September 11th) in the Journal of the American College of Cardiology.

14 sept 2017--The study showed that individuals who are 'metabolically healthy obese' (MHO) - those who are obese but do not suffer metabolic abnormalities such as diabetes, high blood pressure and high cholesterol - have an increased risk of cardiovascular disease events compared to those who are normal weight without metabolic abnormalities.
The academics used electronic health records of 3.5 million British adults who were all initially free of cardiovascular disease (CVD). They then revisited each patient's record, at an average of 5 years and four months later, in order to assess whether they had gone on to develop each of four kinds of CVD events - coronary heart disease (CHD), cerebrovascular disease (in particular strokes), heart failure, or peripheral vascular disease (PVD).
Patients were divided into four 'body size phenotypes' using Body Mass Index (BMI), which is calculated by dividing body weight (kg) by height (m) squared:
1. Underweight (BMI less than 18.5)
2. Normal weight (more than 18 but less than 25)
3. Overweight (more than 25 but less than 30)
4. Obese (more than 30).
Three metabolic abnormalities were taken into consideration during the study: diabetes, hypertension and hyperlipidaemia. A metabolically healthy person was classified as having no metabolic abnormalities.
The results showed that those who were MHO had a 49 per cent higher risk of coronary heart disease, seven per cent higher risk of cerebrovascular disease and a 96 per cent increased risk of heart failure than normal weight metabolically healthy individuals.
Importantly, it also showed that 'normal' weight individuals with one or more metabolic abnormalities had an increased risk of CHD, cerebrovascular disease, heart failure and PVD compared to normal weight individuals without metabolic abnormalities.
The research results raise questions around the concept of 'healthy obesity'. Whether metabolically healthy obesity is associated with excess risk of cardiovascular disease has remained a subject of debate for many years due to limitations in previous studies. Academics at the University of Birmingham sought to address these limitations in the largest prospective study of its kind.
Lead author and epidemiologist Dr Rishi Caleyachetty, of the Institute of Applied Health Research University of Birmingham, said: "In our study, we had unprecedented statistical power to examine body size phenotypes by the number of metabolic abnormalities, potentially reflecting several definitions of the 'metabolically healthy' phenotype in relation to a range of CVD events.
"Obese individuals with no metabolic risk factors are still at a higher risk of coronary heart disease, cerebrovascular disease and heart failure than normal weight metabolically healthy individuals.
"So-called 'metabolically healthy' obesity is clearly not a harmless condition and the term should no longer be used in order to prevent misleading individuals that obesity can be healthy."
Senior author Professor Neil Thomas, also of the University of Birmingham, said it was important that clinicians took on board the research findings.
"The finding that normal weight individuals with metabolic abnormalities also had similar risk of cardiovascular disease events than normal weight metabolically healthy individuals has important implications." he added.
"In many countries it is currently recommended that clinicians in primary care settings use overweight and obesity as the main criteria to screen adults for cardiovascular risk factors as part of cardiovascular risk assessment. Our research suggests that this could result in the failure to identify metabolic abnormalities, such as diabetes, high blood pressure and high cholesterol, in many normal weight patients."
Senior author and Public Health physician Dr Krish Nirantharakumar, also of the University of Birmingham, said: "We conclude that obese patients, irrespective of their metabolic status, should be encouraged to lose weight and that early detection and management of normal weight individuals with metabolic abnormalities will be beneficial in the prevention of CVD events."

More information: Metabolically healthy obese and incident cardiovascular disease events among 3.5 million men and women, Journal of the American College of Cardiology (2017). DOI: 10.1016/j.jacc.2017.07.763


Provided by University of Birmingham

Dark chocolate with olive oil associated with improved cardiovascular risk profile

Dark chocolate enriched with extra virgin olive oil is associated with an improved cardiovascular risk profile, according to research presented today at ESC Congress.

04 sept 2017--"A healthy diet is known to reduce the risk of cardiovascular disease," said lead author Dr Rossella Di Stefano, a cardiologist at the University of Pisa, Italy. "Fruits and vegetables exert their protective effects through plant polyphenols, which are found in cocoa, olive oil, and apples. Research has found that the Italian Panaia red apple has very high levels of polyphenols and antioxidants."
This study tested the association between consumption of dark chocolate enriched with extra virgin olive oil or Panaia red apple (table 1) with atherosclerosis progression in healthy individuals with cardiovascular risk factors.
The randomised crossover study included 26 volunteers (14 men, 12 women) with at least three cardiovascular risk factors (smoking, dyslipidaemia, hypertension, or family history of cardiovascular disease) who received 40 grams of dark chocolate daily for 28 days. For 14 consecutive days it contained 10 percent extra virgin olive oil and for 14 consecutive days it contained 2.5 percent Panaia red apple. The two types of chocolate were given in random order.
Progression of atherosclerosis was assessed by metabolic changes (levels of carnitine and hippurate), lipid profile, blood pressure and levels of circulating endothelial progenitor cells (EPCs). EPCs are critical for vascular repair and maintenance of endothelial function.
Urine and blood samples were collected at baseline and after the intervention. Urine samples were analysed by proton nuclear magnetic resonance spectroscopy for endogenous metabolites. Circulating EPC levels were assessed with flow cytometry. Smoking status, body mass index, blood pressure, glycaemia and lipid profile were also monitored.
After 28 days, the researchers found that the chocolate enriched with olive oil was associated with significantly increased EPC levels and decreased carnitine and hippurate levels compared to both baseline and after consumption of apple-enriched chocolate. Olive oil-enriched chocolate was associated with significantly increased high-density lipoprotein ("good") cholesterol and decreased blood pressure compared to baseline. There was a non-significant decrease in triglyceride levels with apple-enriched chocolate.
Dr Di Stefano said: "We found that small daily portions of dark chocolate with added natural polyphenols from extra virgin olive oil was associated with an improved cardiovascular risk profile. Our study suggests that extra virgin olive oil might be a good food additive to help preserve our 'repairing cells,' the EPC."


Provided by European Society of Cardiology

Three-five cups of coffee per day may reduce CVD mortality risk by up to 21 percent, report says

Credit: George Hodan/public domain

Drinking 3-5 cups of coffee per day could cut an individual's cardiovascular disease (CVD) mortality risk by up to 21%, according to research highlighted in a EuroPRevent session report published by the Institute for Scientific Information on Coffee (ISIC), a not-for-profit organisation devoted to the study and disclosure of science related to coffee and health1.

27 jun 2015--The finding is significant given that coronary heart disease and stroke remain the primary cause of death across Europe, responsible for 51% of all deaths in women and 42% of all deaths in men.2 Over four million people die from CVD annually in Europe and overall, CVD is estimated to cost the EU economy €196 billion every year.3

The ISIC session report highlights the research presented at a Satellite Symposium held during the European Association for Cardiovascular Prevention & Rehabilitation's 2015 congress in Lisbon, Portugal, on the subject of 'Coffee and CVD Mortality'. Leading researchers in this field presented on the role of lifestyle factors in CVD mortality risk reduction, the epidemiological evidence on coffee and CVD mortality, and the conclusions from meta-analyses on coffee and CVD mortality.

Key highlights:

• The lowest CVD mortality risk is seen at an intake of approximately 3 cups of coffee per day, with a percentage risk reduction of up to 21%.1
• Two 2014 meta-analyses suggest an association between coffee consumption and CVD risk, proposing a 'U-shaped' pattern whereby optimal protective effects were achieved with 3-5 cups of coffee per day.3,4
• Drinking 3-4 cups of coffee per day is associated with an approximate 25% lower risk of developing type 2 diabetes compared to consuming none or less than 2 cups per day.5 People with diabetes typically have a higher CVD mortality risk, therefore this association may be linked to a decreased CVD risk.6
• In males, a combination of 5 healthy behaviours (a healthy diet, moderate alcohol consumption (10 to 30 g/ day), no smoking, being physically active and having no abdominal adiposity) could prevent 79% of myocardial infarction events.7
• Half of CVD cases in women could be avoided by modifying lifestyle choices, as approximately 73% of CHD cases and 46% of clinical CVD are attributable to an unhealthy lifestyle.8

The report concludes that recent research supports the view that moderate coffee consumption at approximately 3 - 5 cups per day may have a protective effect against CVD mortality risk. The mechanisms of action behind the associations are unclear, however areas of interest for future research include the anti-inflammatory and antioxidant properties of coffee, and the known association between coffee consumption and type 2 diabetes risk reduction as CVD mortality is typically higher in this group. It is important to note that results differ between varying populations; it is suggested that 2 cups of coffee per day may offer the greatest protection in a Japanese population, whilst 3 cups may provide the greatest protection in UK and US populations.

Prof. Doutor António Vaz Carneiro of the Faculdade de Medicine da Universidade de Lisboa commented: "It is important to acknowledge factors which might have a protective effect against CVD mortality. Moderate coffee consumption could play a significant role in reducing CVD mortality risk which would impact health outcomes and healthcare spending across Europe."

The session report details the key scientific research presented by Assoc. Prof. Esther Lopez-Garcia, Prof. Alicja Wolk, and Prof. Carlo La Vecchia during a session titled: Coffee and CVD Mortality Risk, which took place on 14th May in Lisbon, Portugal.

More information: References:

1. Crippa A. et al. (2014) Coffee consumption and mortality from all causes, cardiovascular disease, and cancer: a dose-response meta-analysis. Am J Epidemiol. 180(8):763-75

2. Nichols M. et al. (2014) Cardiovascular disease in Europe 2014: epidemiological update. European Heart Journal. 35(42):2950-9

3. European Heart Network, 'European Cardiovascular Disease Statistics 2012' Available at: www.ehnheart.org/ cvd-statistics.html

4. Ding M. et al (2014) Long-term coffee consumption and risk of cardiovascular disease: a systematic review and a dose-response meta-analysis of prospective cohort studies. Circulation. 129(6):643-59

5. Huxley R. et al. (2009) Coffee, Decaffeinated Coffee, and Tea Consumption in Relation to Incident Type 2 Diabetes Mellitus. Archives of Internal Medicine. 169:2053-2063

6. Huxley R. et al. (2009) Coffee, decaffeinated coffee, and tea consumption in relation to incident type 2 diabetes mellitus: a systematic review with meta-analysis. Arch Intern Med. 169(22):2053-63

7. Akesson A. et al. (2014) Low-Risk Diet and Lifestyle Habits in the Primary Prevention of Myocardial Infarction in Men - A Population-Based Prospective Cohort Study. J Am Coll Cardiol. 64(13):1299-1306

8. Chomistek A.K. et al. (2015) Healthy lifestyle in the primordial prevention of cardiovascular disease among young women. J Am Coll Cardiol. 65(1):43-51

Provided by Institute for Scientific Information on Coffee

Prognostic value of lipoprotein (a) with low cholesterol unclear

25 nov 2013—Lipoprotein (a) (Lp[a]) has utility in assessing cardiovascular risk in patients with coronary artery disease (CAD); however, the prognostic value of Lp(a) in patients with low cholesterol levels remains unclear, according to a study published online Oct. 23 in the Journal of the American College of Cardiology.

Michelle O'Donoghue, M.D., from Brigham and Women's Hospital in Boston, and colleagues combined data from three studies of patients with CAD (6,762 participants) and eight previously published studies in which plasma Lp(a) was measured (for a total of 18,979 patients).

The researchers found that increasing levels of Lp(a) were not associated with cardiovascular event risk when modeled as a continuous variable (OR, 1.03) or by quintile (OR Q5:Q1, 1.05), based on data from the three studies. Utilizing the total combined data, subjects with Lp(a) levels in the highest quintile were at increased risk of cardiovascular events (OR, 1.40); however, there was significant between-study heterogeneity (P = 0.001). The association between Lp(a) and cardiovascular events, when stratified on the basis of low-density lipoprotein (LDL) cholesterol, was significant in studies in which average LDL cholesterol was ≥130 mg/dL (OR, 1.46; P < 0.001), whereas this relationship was not significant for studies with an average LDL cholesterol <130 .="" br="">

"Lp(a) is significantly associated with the risk of cardiovascular events in patients with established CAD; however, there exists marked heterogeneity across trials," O'Donoghue and colleagues conclude. "In particular, the prognostic value of Lp(a) in patients with low cholesterol levels remains unclear."

Several authors disclosed financial ties to the pharmaceutical industry, including companies that funded some studies included in the meta-analysis.

More information: Full Text (subscription or payment may be required)

Depression in postmenopausal women may increase diabetes and cardiovascular disease risk

Postmenopausal women who use antidepressant medication or suffer from depression might be more likely to have a higher body mass index (BMI), larger waist circumference and inflammation—all associated with increased risk for diabetes and cardiovascular disease, according to a study led by University of Massachusetts Medical School investigator Yunsheng Ma, PhD, MD, MPH, and published in the June 13 issue of the American Journal of Public Health.

16 jun 2013--The UMass Medical School study investigated whether elevated depressive symptoms and antidepressant use are associated with biomarkers for glucose dysregulation and inflammation, BMI and waist circumference. The three main findings indicate that both elevated depressive symptoms and antidepressant use are each significantly associated with higher BMI and waist circumference; elevated depressive symptoms are associated with increased levels of insulin and insulin resistance; and antidepressant use is associated with increased C-reactive protein (CRP) levels, a marker of inflammation, which increases the risk of type-2 diabetes and cardiovascular disease.

"It may be prudent to monitor post-menopausal women who have elevated depression symptoms or are taking antidepressant medication to prevent diabetes and cardiovascular disease," said Dr. Ma, associate professor of medicine, who with UMMS colleagues analyzed data from the landmark Women's Health Initiative (WHI).

Postmenopausal women were recruited into the WHI from 1993 to 1998, and data for this analysis were collected at regular intervals through 2005. Using data from 1,953 women who completed all relevant WHI assessments, the study found that elevated depressive symptoms were found to be significantly associated with increased insulin levels and measures of insulin resistance. Significantly, throughout the entire 7.6 years on average that women were enrolled in the WHI, those who had elevated depressive symptoms or were using antidepressants had higher average BMI and waist circumference than did women not using antidepressants or without depressive symptoms among 71,809 women. However, the associations were stronger for waist circumference.

Analysis of data from 2,242 women showed that both elevated depressive symptoms and antidepressant use was associated with higher CRP levels, a marker of inflammation.

"Identifying these markers in women is important for diabetes prevention because they can be monitored for possible action before progression to full-blown diabetes," said Ma.

Few studies have examined the association of BMI, waist circumference and biomarkers of glucose dysregulation and inflammation with depression, antidepressant medication use, or both. The UMMS study included a large, racially and ethnically diverse sample of post-menopausal women. Because the analysis was epidemiological, it could not determine a causal relationship, so further study is needed to confirm the results through clinical trials.

"Given that diabetes and cardiovascular disease can be effectively prevented or delayed in high-risk individuals with lifestyle modifications or pharmacological interventions, our findings indicate the prudence of monitoring BMI, waist circumference, along with established biomarkers for diabetes and cardiovascular risk including serum glucose, insulin resistance, and CRP among women with elevated depression symptoms, or who are taking antidepressant medication, to prevent diabetes and cardiovascular disease," adds Simin Liu, MD, MS, MPH, ScD, professor of epidemiology and medicine at Brown University, a WHI investigator and study coauthor. "Further intervention trial is needed to confirm our findings and identify the specific patterns of change associated with diabetic and cardiovascular disease risk markers and individual antidepressants and depression."

Provided by University of Massachusetts Medical School

Polyphenol-rich diet could reduce cardiovascular risk

19 dec 2011-- A diet high in polyphenols could help reduce the risk of cardiovascular disease and associated health risks, according to a new study by the University of Glasgow.

Researchers in the Institute of Cardiovascular and Medical Sciences (ICAMS) and Mosaique Diagnostics recruited 39 overweight volunteers, with a body mass index greater than 25, and gave half of them a fruit drink rich in polyphenols – naturally-occurring chemicals found in many plants – and the other half a placebo.

The drink used in the study was specially developed by the scientists and The Coca-Cola Company to contain polyphenolic compounds from a range of sources, including: green tea, grape seed, lemons and apples.

After two weeks, scientists took urine samples from the participants and subjected them to proteomic analysis.

Proteomics is a developing field of medicine which seeks to identify a range of proteins produced in the body which can be monitored to identify the development of particular disease states, long before symptoms are evident.

By knowing which proteins – or biomarkers – change when a disease is in its early stages of development, doctors might be able to prevent or reverse the disease’s progress, or to begin therapeutic treatment earlier.

The research found a total of 27 proteins that were significantly different between the two groups, including five that are associated with reduced risk cardiovascular disease.

Professor Harald Mischak, Professor of Proteomics and founder of Mosaique Diagnostics, said: “While the epidemiological data supports the idea that a diet rich in fruit and vegetables is beneficial to health, clinical studies have generally not adequately confirmed this. Our data indicates that proteomic analysis can be a powerful tool to assess potential positive effects of dietary products.

“Our pilot study suggests that as far as polyphenol-containing fruit drinks go, there are possible benefits for cardiovascular health, which deserve further consideration in longer term trials.

“Given the recommended daily intake of five 80g portions of fruit and vegetables a day is taken by around just a quarter of Britons and less than half of Americans, fruit juices and juice drinks fortified with polyphenols represent a potential way for some consumers to meaningfully increase their intake of such potentially beneficial compounds, although the long term effects remain to be elaborated.”

Dr William Mullen, Director of Biomarker Research at the University of Glasgow, said: “The long-term goal of clinical proteomics is to identify biomarkers for a range of diseases that would allow early detection and treatment.

“However, finding a single ‘ideal’ compound that can do this is an unlikely prospect, but by using a ‘fingerprint’ of a number of proteins we can identify pre-symptomatic development of a range of diseases, from coronary artery disease to chronic kidney disease and diabetes. We have developed a range of biomarkers from urine samples for clinical diagnostics that are highly sensitive and selective for a range of diseases. These biomarkers are in effect ‘urinary fingerprints’ of diseases.

“This technology and approach also has potential for use in nutrition and health research, as our study has demonstrated.

“This study was small and did not allow the testing of all proteomics data so we need larger, more in-depth studies to develop this potential further, and we need longer term studies to link patterns to disease outcomes.

“The technology of this method has been found to be acceptable for use in clinical studies by the US Food & Drug Administration and many diseases can be analysed with just one urine sample.”

The research, published in the Journal of Agricultural and Food Chemistry, was led by Professor Naveed Sattar and funded by The Coca-Cola Company.

Provided by University of Glasgow

Sugar-sweetened beverages may increase cardiovascular risk in women

Drinking two or more sugar-sweetened beverages a day may expand a woman's waistline and increase her risk of heart disease and diabetes, according to research presented at the American Heart Association's Scientific Sessions 2011.

14 nov 2011--In this study, researchers compared middle-aged and older women who drank two or more sugar-sweetened beverages a day, such as carbonated sodas or flavored waters with added sugar, to women who drank one or less daily. Women consuming two or more beverages per day were nearly four times as likely to develop high triglycerides, and were significantly more likely to increase their waist sizes and to develop impaired fasting glucose levels. The same associations were not observed in men.

"Women who drank more than two sugar-sweetened drinks a day had increasing waist sizes, but weren't necessarily gaining weight," said Christina Shay, Ph.D., lead author of the study and assistant professor at the University of Oklahoma Health Sciences Center in Oklahoma City. "These women also developed high triglycerides and women with normal blood glucose levels more frequently went from having a low risk to a high risk of developing diabetes over time."

The Multi-Ethnic Study of Atherosclerosis (MESA) included food frequency surveys in 4,166 African-American, Caucasian, Chinese-Americans and Hispanic adults 45 to 84 years old. At the beginning of the study the participants didn't have cardiovascular disease.

Researchers assessed risk factors in three follow-up exams spanning five years starting in 2002. Participants were monitored for weight gain, increases in waist circumference, low levels of high density lipoproteins (HDL "good" cholesterol), high levels of low density lipoproteins (LDL "bad" cholesterol), high triglycerides, impaired fasting glucose levels, and type 2 diabetes.

"Most people assume that individuals who consume a lot of sugar-sweetened drinks have an increase in obesity, which in turn, increases their risk for heart disease and diabetes," said Shay, formerly of Northwestern University's Department of Preventive Medicine in Chicago, where the study was conducted. "Although this does occur, this study showed that risk factors for heart disease and stroke developed even when the women didn't gain weight."

Women may have a greater chance for developing cardiovascular disease risk factors from sugar-sweetened drinks because they require fewer calories than men which makes each calorie count more towards cardiovascular risk in women, Shay said.

Researchers have yet to determine exactly how sugar-sweetened beverages influence cardiovascular risk factors such as high triglycerides in individuals who do not gain weight, Shay said, but further work is planned to try and figure that out.

Provided by American Heart Association

Systolic and diastolic blood pressures together more useful for predicting cardiovascular risk

Irvine, Calif., 19 feb 2009 – Individuals with diastolic blood pressure under 70 mm Hg coupled with an elevated systolic blood pressure may have a greater risk of heart attack and stroke than indicated by the systolic blood pressure values alone, according to a UC Irvine study.

Dr. Stanley Franklin and colleagues at the UC Irvine Heart Disease Prevention Program in conjunction with researchers at the Framingham Heart Study reviewed blood pressure data from 9,657 participants in the Framingham Heart Study who had not received antihypertensive treatment and found that the combination of low diastolic and high systolic numbers to be a superior predictor of future adverse cardiovascular events.

"Systolic blood pressure as a single blood pressure component is usually superior to diastolic blood pressure in predicting cardiovascular risk in middle-aged and older individuals," Franklin said. "But a very high or very low diastolic blood pressure can add to the risks identified by systolic blood pressure alone."

Currently, physicians diagnose hypertension with systolic and diastolic readings of 140/90 and above. This study suggests that doctors should give even greater consideration to systolic blood pressure when the diastolic blood pressure is low.

Franklin said, however, that a diastolic number under 70 mm Hg when combined with a systolic blood pressure less that 120 mm Hg indicates normal values with no increased cardiovascular risk; the low diastolic blood pressure must be coupled with an elevated systolic reading to indicate increased risk. This combination of blood pressure components is an indicator of increased stiffening of arteries, which is a strong risk factor for future heart attacks and strokes.

###

Study results appear in Circulation, a journal of the American Heart Association.

Metabolic Syndrome Not Useful in Predicting Cardiovascular Risk

By Todd Neale
GLASGOW, Scotland, 24 may 2008-- A diagnosis of metabolic syndrome is strongly associated with a risk of developing diabetes, but not cardiovascular disease, researchers here concluded.
They reported the results of two prospective studies -- the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER) and the British Regional Heart Study -- online this week in The Lancet.
In PROSPER, metabolic syndrome was not associated with increased risk of cardiovascular disease (HR 1.07, 95% CI 0.86 to 1.32) but was associated with a greater risk of diabetes (HR 4.41, 95% CI 3.33 to 5.84), Naveed Sattar, M.B.Ch.B., of the University of Glasgow, and colleagues found.
On the basis of initial findings in PROSPER, they conducted the British Regional Heart Study and found that metabolic syndrome was "modestly associated" with cardiovascular disease risk (HR 1.27, 95% CI 1.04 to 1.56) and strongly associated with risk of diabetes (HR 7.47, 95% CI 4.90 to 11.46).
"Our clear finding in both studies of substantial differing diabetes versus cardiovascular disease associations of metabolic syndrome and its components should aid better general understanding of differing risk patterns for these two diseases, which therefore should not be considered together," the researchers said.
The clinical usefulness of a diagnosis of metabolic syndrome in predicting risk of cardiovascular disease and diabetes is debated, according to the researchers.
To explore the issue, they first enrolled 4,812 men and women ages 70 to 82 in the PROSPER trial. To "corroborate and generalize" those findings, they enrolled 2,737 males ages 60 to 79 in the British Regional Heart Study. All participants were free from diabetes at baseline.
In PROSPER, after a mean follow-up of 3.2 years, there were 772 cases of incident cardiovascular disease and 287 cases of diabetes.
Overall, about 28% of participants met the criteria for metabolic syndrome.
Metabolic syndrome and each of its components were significantly associated with an increased risk of diabetes, with a fasting glucose of 6.1 mmol/L or higher most strongly predicting risk (HR 18.42, 95% CI 13.86 to 24.49).
Neither metabolic syndrome nor any of its components were significantly associated with risk of cardiovascular disease.
In the British Regional Heart Study, after a mean follow-up of seven years, there were 440 cases of cardiovascular disease and 105 cases of diabetes.
Overall, 27% of patients met the criteria for metabolic syndrome.
As in PROSPER, metabolic syndrome and each of its components were significantly associated with an increased risk of diabetes, with a fasting glucose of 6.1 mmol/L or higher representing the component that most strongly predicted risk (HR 5.97, 95% CI 4.07 to 8.76).
Metabolic syndrome (HR 1.27) and the components of low HDL cholesterol (HR 1.46, 95% CI 1.17 to 1.81) and high blood pressure (HR 1.68, 95% CI 1.26 to 2.24) were associated with risk of cardiovascular disease. The other three components of metabolic syndrome were not.
"These findings suggest that the pattern of risk factors for new-onset diabetes differs in many respects to that which predicts vascular events in elderly people," the researchers said.
"Our findings concur with data in middle-age populations for whom criteria for metabolic syndrome are inferior to, and do not enhance conventional methods for, risk prediction of coronary heart disease," they said.
In an accompanying comment, Richard Kahn, Ph.D., of the American Diabetes Association in Alexandria, Va., wrote that the findings of the study "put yet another nail in the coffin of the metabolic syndrome," noting that a simple, inexpensive test for fasting plasma glucose would be a better predictor of diabetes than the expensive procedure of diagnosing the syndrome.
"What seems to make the most sense is for clinicians to focus on global risk assessment that takes into account all the well-established cardiometabolic risk factors, and then to treat each abnormality appropriately," he said.
"Also," he said, "more research is needed to understand the cause of risk-factor clustering and the pathogenesis of insulin resistance. Both actions would better serve the health of those at risk of diabetes and cardiovascular disease than seeking a diagnosis of the metabolic syndrome."
The authors listed several limitations to the studies, including the lack of oral glucose tolerance tests, the use of BMI instead of waist circumference in PROSPER, and the potential weakening of associations by attrition bias.
The metabolic syndrome analysis for PROSPER was funded by a Diabetes U.K. project grant and the British Regional Heart Study is a British Heart Foundation Research Group. The study authors and Dr. Kahn declared no conflicts of interest.
Primary source: The LancetSource reference:Sattar N, et al "Can metabolic syndrome usefully predict cardiovascular disease and diabetes? Outcomes data from two prospective studies" Lancet 2008; DOI: 10.1016/S0140-6736(08)60602-9.

Biomarkers Improve Cardiovascular Risk Stratification

By Charles Bankhead ,
UPPSALA, Sweden,15 may 2008-- In older men, a panel of biomarkers associated with heart and kidney disease significantly improved risk stratification for cardiovascular death, investigators here said.
Incorporating four biomarkers into a hazards model that included traditional risk factors improved overall risk prediction (P<0.001) whether the men had cardiovascular disease at baseline or not, Johan Arnlov, M.D., Ph.D., of the University of Uppsala, and colleagues reported in the May 15 issue of the New England Journal of Medicine.
Predictive ability remained significant when the model was evaluated by different statistical methods.
"If these results are validated, the incorporation of these [biomarkers] in clinical practice for the prediction of death from cardiovascular causes could be accomplished quickly, since the measurement of these biomarkers is already well established for diagnostic use," the authors concluded.
Conventional cardiovascular risk factors, such as hypertension and hypercholesterolemia, do not directly reflect clinical conditions associated with an increased risk of cardiovascular death. These conditions include myocardial cell damage, left ventricular dysfunction, renal failure, and inflammation.
Several biomarkers have been shown to increase the risk of cardiovascular events independently of established risk factors, the authors noted. However, the markers have not demonstrated the ability to improve risk stratification of individual patients by area under the receiver-operating-characteristic curve (AUC).
So the researchers sought to determine whether combining four biomarkers with conventional risk factors would improve risk assessment.
The biomarkers chosen were troponin I, N-terminal pro-brain natriuretic peptide, cystatin C, and C-reactive protein.
The study involved 1,135 participants in the Uppsala Longitudinal Study of Adult Men, a community-based cohort of men born from 1920 through 1924. Data for the study came from the third examination cycle of the cohort, when participants' age was approximately 71. Blood samples were obtained at baseline (1991 through 1995) and stored for an average of 11 years.
During a median follow-up of 10 years, 315 participants died; 136 of the deaths were cardiovascular in nature. Investigators found that including the biomarkers in the hazards model improved risk stratification from an AUC of 0.664 with risk factors alone to 0.766 (P<0.001) for the entire cohort.
A separate analysis of 661 men who were free of cardiovascular disease at baseline demonstrated an improvement in AUC from 0.688 to 0.748 (P=0.03).
The authors cautioned that the findings "should not be construed as implying a direct benefit of a reduction in the biomarkers." In contrast to data supporting modification of conventional cardiovascular risk factors, "there is currently little evidence that reducing the levels of the biomarkers will reduce the risk," they said.
The findings indicate that "measurable progress with the use of biomarkers could be possible," James A. de Lemos, M.D., of the University of Texas in Dallas, and Donald M. Lloyd-Jones, M.D., of Northwestern University in Chicago, said in an accompanying editorial.
The study improved on previous attempts to use biomarkers for risk stratification by use of better markers, Drs. de Lemos and Lloyd-Jones said. Each of the four biomarkers used in the study more accurately reflects renal and heart impairment and tissue damage compared with markers examined in previous studies.
The precision of the biomarker panel requires additional work, the editorialists continued. For example, the model inappropriately reclassified 69 patients who did not have cardiovascular disease at baseline.
"These findings need to be validated in younger cohorts of men and women that include only patients who are free of cardiovascular disease and should be updated iteratively as newer and better biomarkers emerge from discovery research programs," Drs. de Lemos and Lloyd-Jones concluded.
The study was supported by grants from the Swedish Research Council, Swedish Heart-Lung Foundation, theErik, Karin, och Gosta Selander Foundation, the Loo och Hans Osterman Foundation, the Ernfors Foundation, the Thuring Foundation, Stiftelsen Sigurd och Elsa Goljes Minne, and Uppsala University. Reagents and assay instruments were supplied by Beckman Coulter and Roche Diagnostics.
Dr. Arnlov reported no conflicts of interest. Dr. de Lemos disclosed grant support and consulting fees from Biosite/Inverness and consulting fees from Roche Diagnostics.
Primary source: New England Journal of MedicineSource reference:Zethelius B, et al "Use of multiple biomarkers to improve the prediction of death from cardiovascular causes" N Engl J Med 2008; 358: 2107-2116. Additional source: New England Journal of MedicineSource reference: de Lemos JA, Lloyd-Jones DM "Multiple biomarker panels for cardiovascular risk assessment" N Engl J Med 2008; 358: 2172-2174.

Knowing "Cardiovascular Age" May Help Patients Get to Lipid Targets, Follow Medical Advice

November 28, 2007 — Simple ways of informing patients about their cardiovascular risk can make them more likely to adhere to medical advice and reach lipid goals, a new study suggests [1]. In particular, the easily understandable concept of "cardiovascular age" might strike a chord with patients, particularly those at the highest risk of developing cardiovascular disease (CVD) but who don't yet have overt symptoms.
"We've been doing this for many years at the McGill Cardiovascular Health Improvement Program," lead author on the study, Dr Steven A Grover (McGill University, Montreal, QC), told heartwire. "Over a dozen years ago we started showing patients what their risk profiles were and how much they were changing when they lost weight, exercised, or took drugs for their lipids. So we were quite convinced from our own personal experiences that this was a useful way to guide patients about the progress of their treatments, particularly for asymptomatic conditions like blood pressure and cholesterol, when you're trying to convince the patients that they need to embark on some sort of therapy, whether it's lifestyle or drugs, and yet they don't feel that anything is wrong and they certainly don't notice any differences when you make changes."
Grover and colleagues report the results of their 3053-patient Cardiovascular Health Evaluation to Improve Compliance and Knowledge Among Uninformed Patients (CHECK-UP) study in the November 26, 2007 issue of the Archives of Internal Medicine.
Percent risk and cardiovascular age
For the study, 230 primary-care physicians enrolled more than 3000 patients, of whom 2687 were still in the study after 12 months. All patients underwent risk-factor screening at baseline, which generated a one-page computer printout detailing their probability of developing cardiovascular disease. For people with preexisting CVD, this was calculated using a CV life-expectancy model; for people with no CVD, their risk estimate was expressed as a percent risk of developing CVD over the next eight years, using Framingham risk estimates, and as a CV life expectancy. As the authors describe, this second tool — validated in earlier studies — expresses a patient's risk as their "cardiovascular age," calculated as the patient's age minus the difference between his or her estimated remaining life expectancy, taking into account coronary and stroke risk and the average remaining life expectancy of Canadians of the same age and sex. Study participants were then randomized to either usual care or to be shown the computer printout with their risk-profile results. Over the subsequent 12 months, patients had their lipids and blood pressure measured and met with their physicians at three-month intervals throughout the year. All patients were regularly encouraged to meet and maintain their lipid goals, but only patients in the intervention group were shown their risk-profile printouts during the visits.
After 12 months and after adjustment for baseline lipid levels, patients who had been shown their risk profiles throughout the study had greater, statistically significant, reductions in low-density lipoprotein (LDL) cholesterol levels and total-cholesterol/high-density lipoprotein (HDL) cholesterol ratios, although the differences between the two groups were small. Patients who regularly saw their risk-profile changes were also more likely to reach their lipid goals — a finding particularly marked in patients who had the worst lipid profiles at baseline.
According to Grover, cardiovascular age was one of the strongest predictors of reaching lipid targets, even stronger than Framingham risk. "While we can't say definitively, the thing that came up the most strongly was age gap: in other words, how far was your cardiovascular age from your chronological age? There appeared to be a dose response: the bigger the age gap, the bigger the impact on risk profile. But when we looked at high, medium, or low risk by Framingham, the impact was less. The thing that really seemed to motivate patients was seeing this one line about their cardiovascular age."
Understanding cardiovascular risk
Two editorials accompanying the CHECK-UP study explore the nuanced problem of cardiovascular risk communication. According to Dr Rod Jackson and Sue Wells (University of Auckland, New Zealand) [2], the concept of managing risk, not risk factors, is poorly grasped by doctors, let alone patients. "Most physicians are still taught to diagnose and treat hypertension and hyperlipidemia, whereas risk-based approaches dispense with these entrenched yet clinically irrelevant diagnoses. Also, most treatments are designed to target individual risk factors, so it is difficult for physicians not to focus on measuring and treating blood pressure or blood lipid levels."
A major hurdle, however, is time; the time allotted in the CHECK-UP study to calculate cardiovascular risk and convey it to patients at regular intervals would be difficult for many busy physicians to invest. As such, computerized systems that link risk calculations to patient medical records can expedite the process. In New Zealand, they point out, the PREDICT computerized system is already doing this for 45,000 patients.
Jackson and Wells also suggest that Grover et al's concept of cardiovascular age will prove to be "the right metric to translate predicted cardiovascular risk into something meaningful to patients and physicians" and should be further explored.
In a second editorial [3], Dr Charles B Eaton (Brown University, Pawtucket, RI) points out that the CHECK-UP study also indirectly validates the role of regular physician visits. Indeed, the fact that the difference between the two study groups for the study end points was not larger than that reported by the authors might be due to the fact that even patients in the nonintervention group were in regular contact with a physician urging them to meet treatment goals. Still, Eaton notes, "only 45% to 66% of these high-risk cardiovascular patients had reached their respective lipid targets after one year, and thus, a large treatment gap still persisted."
Hope for the aging heart
Acknowledging the gap, Grover told heartwire that his study is at least a step in the right direction. He believes that finding new ways of involving patients is paramount. "We know for certain that the drugs that work well in clinical trials don't do nearly as well in real life. So clearly, the treatment paradigms for chronic asymptomatic medical conditions have to go beyond what we're doing now," he said. "In a chronic-care situation, patients become their own experts—they know what makes them better and what makes them worse. If we're talking about an asymptomatic condition, they know what behaviors bring their lipids under control and what behaviors make them go out of control. To engage the patient so that you can leverage that knowledge is potentially a very powerful instrument."
In fact, Grover thinks the notion of cardiovascular age also holds profound resonance for doctors. His group has offered cardiovascular-age assessments in the exhibition hall at Canadian Cardiovascular Society meetings for the past 10 years. "Health professionals come back year after year to see how their numbers are changing, which shocks me," he told heartwire. "I always believed health professionals would probably have a gut sense of how they are doing and really weren't interested. But that's really not the case at all; they'll line up to get it done."
Pfizer sponsored the CHECK-UP study. Some of the study authors have disclosed various financial relationships with Pfizer, Sanofi Aventis, AstraZeneca, and Orynx.
Drs. Jackson, Wells, and Eaton have disclosed no relevant financial relationships.
Sources
Grover SA, Lowensteyn I, Joseph L, et al. Patient knowledge of coronary risk profile improves the effectiveness of dyslipidemia therapy: the CHECK-UP study: A randomized controlled trial. Arch Intern Med. 2007;167:2296-2303.
Eaton CB. Using cardiovascular age equivalent to close the treatment gap for dyslipidemia. Arch Intern Med. 2007;167:2288.
Jackson R, Wells S. Prediction is difficult, particularly about the future. Arch Intern Med. 2007;167:2286-2287.

Any Degree of Albuminuria Signals Increased Cardiovascular Risk

November 26, 2007 — Albuminuria, even in low levels within the "normal" range, is an independent predictor of cardiovascular and all-cause mortality, a new analysis of the Prevention of Events with an ACE inhibitor (PEACE) trial shows.
The study, published online November 19, 2007 in Circulation and scheduled for its December 4, 2007 issue, was conducted by a group led by Dr Scott Solomon (Brigham and Women's Hospital, Boston, MA).
Solomon commented to heartwire: "We found that virtually any degree of albuminuria, even albumin below the level we call microalbuminuria, placed a patient at significantly higher risk of cardiovascular events. A number of other studies have been suggestive of this — HOPE [Heart Outcomes Prevention Evaluation] in higher-risk vascular disease patients and LIFE [Losartan Intervention for End Point Reduction] in hypertension patients — but ours was a particularly low-risk population, so we've extended the findings to this low-risk group with stable CHD [coronary heart disease]. We should stop thinking about cut-off values for microalbuminuria. If albumin is detectable in the urine, the patient is at increased risk."
A new window to the health of the vasculature
Solomon explained that as such low levels of albumin cannot be detected with a dipstick test, they used a spot assay that measures the urinary albumin-to-creatinine ratio (ACR), which gives a more accurate measure of albumin status, as it takes into account the fact that the concentration of albumin in urine varies, depending on the amount of water consumed. "This is still a very easy, noninvasive, and cheap test. All you need is a urine sample. We do many far more invasive and expensive tests than this to risk-stratify patients. This test gives us a new window to the health of the vasculature that we should take advantage of," he added.
Noting that a previous analysis of the PEACE population had shown that a reduced glomerular filtration rate (GFR) was also associated with increased cardiovascular risk, Solomon said: "We have now shown that both measures of kidney function are markers of increased risk. If either one is compromised, then risk is increased, and if both are affected, then risk is very much increased. These two studies are telling us that we cardiologists need to pay more attention to kidney function in our patients and to understand that these are not patients who will ever come to dialysis or even necessarily see a nephrologist, but they do have mild kidney disease that puts them at increased risk for a cardiovascular event."
He pointed out that whether or not patients with minor renal dysfunction should be treated differently is open to debate but added: "There is a fair amount of evidence that inhibitors of the renin angiotensin system and ACE [angiotensin-converting enzyme] inhibitors in particular are of benefit to CHD patients with reduced renal function. So I would say that if you are undecided about whether to give an ACE inhibitor or not, this test could help you make that decision."
A measure of treatment efficacy
In the paper, the authors also note that microalbuminuria may represent an early marker of diffuse vascular endothelial dysfunction, and clinicians should consider serial quantification of ACR as a marker of risk, because its reduction may be a metric of treatment efficacy.
The main PEACE trial evaluated the effects of trandolapril vs placebo in 8290 patients with stable coronary artery disease and normal left ventricular ejection fraction. In the current analysis, the urinary ACR was assessed in a core laboratory in 2977 patients at baseline and in 1339 patients at follow-up (mean 34 months). The majority of patients (73%) had a baseline ACR within the normal range (<17 µg/mg for men and <25 µg/mg for women).
Results showed that independent of the estimated GFR and other baseline covariates, a higher ACR, even within the normal range, was associated with increased risks for all-cause mortality (p<0.001) and cardiovascular death (p=0.01). An increase in ACR over time was also associated with increased risk of cardiovascular death.
While the effect of trandolapril therapy on outcomes was not modified significantly by the level of albuminuria, trandolapril therapy was associated with a significantly lower mean follow-up ACR (12.5 vs 14.6 µg/mg, p=0.0002). Solomon suggested that the power of this analysis may have been insufficient to show an effect of trandolapril on outcomes. "We did see an effect of the drug on albuminuria and a definite relationship between degree of albuminuria and outcomes, but we probably had too few patients to show an actual relationship between trandolapril and outcomes," he commented to heartwire.
Source
Solomon S D, Lin J, Solomon C G et al. Influence of albuminuria on cardiovascular risk in patients with stable coronary artery disease. Circulation. 2007. Published online before print. November 19. DOI: 10.1161/CIRCULATIONAHA.107.723270

Resting Heart Rate Directly Related to Risk of Cardiovascular Disease

By Will Boggs, MD
NEW YORK (Reuters Health) Aug 30 - Higher resting heart rates are associated with an increased risk of cardiovascular disease, according to a review in the August 28th Journal of the American College of Cardiology.
"I hope that as a consequence of the article physicians consider why a healthy person has a high heart rate and search for causes, such as anemia, thyrotoxicosis, etc.," Dr. Kim Fox told Reuters Health. "In an otherwise healthy person, I think we are a long way off suggesting pharmacological intervention to improve outcome."
Dr. Fox from Royal Brompton Hospital, London, and colleagues reviewed the data associating resting heart rate and mortality, the possible pathophysiological basis of this association, and the likelihood utility of therapeutic heart rate slowing in improving cardiovascular outcomes for a wide range of patients.
Epidemiological data regarding both the general population and patients with various cardiovascular diseases reveal significant associations between resting heart rate and all-cause and cardiovascular mortality, the authors report.
Lowering of resting heart rate, they note, has proven beneficial in preventing exercise-induced angina and ischemia and reducing mortality in patients with coronary artery disease and with heart failure.
Heart rate appears to have direct effects on the status of the arterial wall, the investigators say, as a result of mechanical pulsatile stress and possibly through proinflammatory actions of such stresses on the vascular endothelium. Heart rate also influences whether ischemic episodes trigger serious arrhythmias.
A relatively high heart rate is likely both causative and indicative of important pathophysiological processes, the researchers note, but exactly what heart rate is optimal remains uncertain.
"From the epidemiologic data presented previously," the investigators write, "it seems desirable to maintain heart rate in the normal rather than in the high range, and specifically, to maintain resting heart rate substantially below the traditionally defined tachycardia threshold of 90 or 100 beats per minute."
"We have designed and are running two very large-scale trials in coronary disease with various degrees of left ventricular impairment," Dr. Fox said. "We are looking at the effect of pure heart rate reduction in these patients who are otherwise well, treated with therapies such as beta blockers, ACE inhibitors/ARBs, statins, and aspirin."
"Clearly, if our studies in coronary disease are proven to show that reducing heart rate improves outcome, then this should be introduced into clinical practice," Dr. Fox concluded.
J Am Coll Cardiol 2007;50:823-830.

IAS: HIV Treatment Requires Cardiac Assessment

SYDNEY, July 24 -- As the long-term prognosis for patients with HIV improves, it becomes more important to assess the patient's risk for cardiovascular disease and other health issues, researchers suggested here.
"In settings where antiretroviral therapy is readily accessible, the long-term prognosis for people living with HIV/AIDS has dramatically improved," Judith Currier, M.D., of the University of California, Los Angeles, told attendees at an industry-sponsored symposium held in conjunction with the International AIDS Society meeting.
"Clinical management of HIV infection now needs to include provision of screening and interventions to reduce morbidity and mortality from other chronic diseases such as cardiovascular disease," she said.
Dr. Currier reviewed a series of clinical studies that attempted to tease out the question of whether HIV itself is responsible for increased risk of cardiovascular disease; whether the problem is rooted in the treatment of HIV disease with highly active antiretroviral therapy (HAART); and which of the components of HAART might be the culprit for increasing the risk of heart disease in patients.
She said that one of the surprising results of the SMART study was that patients with HIV who were assigned to a regimen in which treatment was guided by levels of CD4-positive cells and were able to take less medication actually had worse cardiovascular disease outcomes than did patients who never stopped taking the HAART regimen. (See Interrupting HIV Treatment Raises Cardio Risk)
On the other hand, she noted, data from the DAD study indicated that use of protease inhibitors increased HIV patients' risk of myocardial infarction by about 16% a year. (See Protease Inhibitors Linked to Increased Heart Attack Risk)
Dr. Currier also noted that treatment of cardiovascular disease requires that the physician be aware of interactions between statins and protease inhibitors. For example, fluvastatin and pravastatin appear safe for use in HIV patients, but lovastatin and simvastatin are contraindicated. The other statins have to be used with caution, she said.
While there is reason to consider the cardiovascular risk profile of a patient with HIV, Dr. Currier noted, "The absolute risk of cardiovascular disease in the HIV population remains low (about 2%). Modification of coronary heart disease risk and use of antiretroviral agents less likely to cause metabolic disturbances may be warranted when patients have many options, but the fear of coronary heart disease should not preclude the use of effective HAART," she said.
Peter Reiss, M.D., of the Academic Medical Centre, in Amsterdam, illustrated how the choices of treatment fit into selection of therapy for a patient, noting that the risk of heart disease could be reduced by selecting specific HIV drugs.
However, he said, the best way to get his patient to dramatically reduce his Framingham Heart Score was to get the individual to quit smoking.
"Cardiovascular risk assessment has become an integral component of the care for persons with HIV infection," Dr. Reiss said. "Careful choice of antiretroviral regimens may contribute to optimization of lipid profile. Cardiovascular disease risk reduction, however, involves much more than just paying attention to lipids."
The symposium was sponsored by Bristol-Myers-Squibb.
The International AIDS Society does not require presenters to identify possible financial conflicts of interest. Dr. Currier said she has possible conflicts with Abbott, Bristol-Myers Squibb, GlaxoSmithKline, Merck and Tibotec. Dr. Reiss did not list conflicts, nor did symposium chairman Andrew Carr, MD, professor of medicine at the University of New South Wales, Sydney.Primary source: IAS Conference on HIV Pathogenesis and TreatmentSource reference: "HIV and Cardiovascular Disease -- Minimizing the Risk;" Conference Programme 4th IAS Conference on HIV Pathogenesis, Treatment and Prevention incorporating the 19th ASHM Conference, 22-25 July 2007, Sydney, Australia, p 199.