Obesity and cardiovascular disease: risk factor, paradox, and impact of weight loss.
TL;DR: The adverse effects of obesity on CV disease risk factors and its role in the pathogenesis of various CV diseases are summarized, the obesity paradox and potential explanations for these puzzling data are reviewed, and a discussion regarding the current state of weight reduction in the prevention and treatment of CV diseases is discussed.
About: This article is published in Journal of the American College of Cardiology.The article was published on 2009-05-26 and is currently open access. It has received 2054 citations till now. The article focuses on the topics: Obesity paradox & Risk factor.
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TL;DR: In this paper, a randomized clinical trial was conducted to evaluate the effect of preterax and Diamicron Modified Release Controlled Evaluation (MDE) on the risk of stroke.
Abstract: ABI
: ankle–brachial index
ACCORD
: Action to Control Cardiovascular Risk in Diabetes
ADVANCE
: Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation
AGREE
: Appraisal of Guidelines Research and Evaluation
AHA
: American Heart Association
apoA1
: apolipoprotein A1
apoB
: apolipoprotein B
CABG
: coronary artery bypass graft surgery
CARDS
: Collaborative AtoRvastatin Diabetes Study
CCNAP
: Council on Cardiovascular Nursing and Allied Professions
CHARISMA
: Clopidogrel for High Athero-thrombotic Risk and Ischemic Stabilisation, Management, and Avoidance
CHD
: coronary heart disease
CKD
: chronic kidney disease
COMMIT
: Clopidogrel and Metoprolol in Myocardial Infarction Trial
CRP
: C-reactive protein
CURE
: Clopidogrel in Unstable Angina to Prevent Recurrent Events
CVD
: cardiovascular disease
DALYs
: disability-adjusted life years
DBP
: diastolic blood pressure
DCCT
: Diabetes Control and Complications Trial
ED
: erectile dysfunction
eGFR
: estimated glomerular filtration rate
EHN
: European Heart Network
EPIC
: European Prospective Investigation into Cancer and Nutrition
EUROASPIRE
: European Action on Secondary and Primary Prevention through Intervention to Reduce Events
GFR
: glomerular filtration rate
GOSPEL
: Global Secondary Prevention Strategies to Limit Event Recurrence After MI
GRADE
: Grading of Recommendations Assessment, Development and Evaluation
HbA1c
: glycated haemoglobin
HDL
: high-density lipoprotein
HF-ACTION
: Heart Failure and A Controlled Trial Investigating Outcomes of Exercise TraiNing
HOT
: Hypertension Optimal Treatment Study
HPS
: Heart Protection Study
HR
: hazard ratio
hsCRP
: high-sensitivity C-reactive protein
HYVET
: Hypertension in the Very Elderly Trial
ICD
: International Classification of Diseases
IMT
: intima-media thickness
INVEST
: International Verapamil SR/Trandolapril
JTF
: Joint Task Force
LDL
: low-density lipoprotein
Lp(a)
: lipoprotein(a)
LpPLA2
: lipoprotein-associated phospholipase 2
LVH
: left ventricular hypertrophy
MATCH
: Management of Atherothrombosis with Clopidogrel in High-risk Patients with Recent Transient Ischaemic Attack or Ischaemic Stroke
MDRD
: Modification of Diet in Renal Disease
MET
: metabolic equivalent
MONICA
: Multinational MONItoring of trends and determinants in CArdiovascular disease
NICE
: National Institute of Health and Clinical Excellence
NRT
: nicotine replacement therapy
NSTEMI
: non-ST elevation myocardial infarction
ONTARGET
: Ongoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial
OSA
: obstructive sleep apnoea
PAD
: peripheral artery disease
PCI
: percutaneous coronary intervention
PROactive
: Prospective Pioglitazone Clinical Trial in Macrovascular Events
PWV
: pulse wave velocity
QOF
: Quality and Outcomes Framework
RCT
: randomized clinical trial
RR
: relative risk
SBP
: systolic blood pressure
SCORE
: Systematic Coronary Risk Evaluation Project
SEARCH
: Study of the Effectiveness of Additional Reductions in Cholesterol and
SHEP
: Systolic Hypertension in the Elderly Program
STEMI
: ST-elevation myocardial infarction
SU.FOL.OM3
: SUpplementation with FOlate, vitamin B6 and B12 and/or OMega-3 fatty acids
Syst-Eur
: Systolic Hypertension in Europe
TNT
: Treating to New Targets
UKPDS
: United Kingdom Prospective Diabetes Study
VADT
: Veterans Affairs Diabetes Trial
VALUE
: Valsartan Antihypertensive Long-term Use
VITATOPS
: VITAmins TO Prevent Stroke
VLDL
: very low-density lipoprotein
WHO
: World Health Organization
### 1.1 Introduction
Atherosclerotic cardiovascular disease (CVD) is a chronic disorder developing insidiously throughout life and usually progressing to an advanced stage by the time symptoms occur. It remains the major cause of premature death in Europe, even though CVD mortality has …
7,482 citations
TL;DR: A Report of the American College of Cardiology Foundation/AmericanHeart Association Task Force on Practice Guidelines, and the AmericanCollege of Physicians, American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for CardiovascularAngiography and Interventions, and Society of ThorACic Surgeons
Abstract: Jeffrey L. Anderson, MD, FACC, FAHA, Chair
Jonathan L. Halperin, MD, FACC, FAHA, Chair-Elect
Alice K. Jacobs, MD, FACC, FAHA, Immediate Past Chair 2009–2011 [§§][1]
Sidney C. Smith, Jr, MD, FACC, FAHA, Past Chair 2006–2008 [§§][1]
Cynthia D. Adams, MSN, APRN-BC, FAHA[§§][1]
Nancy M
2,469 citations
TL;DR: The development of the present guideline involved a process of partial adaptation of other guideline statements and reports and supplemental literature searches, which confirmed that in patients with atherosclerotic vascular disease, comprehensive risk factor management reduces risk as assessed by a variety of outcomes.
Abstract: Since the 2006 update of the American Heart Association (AHA)/American College of Cardiology Foundation (ACCF) guidelines on secondary prevention,1 important evidence from clinical trials has emerged that further supports and broadens the merits of intensive risk-reduction therapies for patients with established coronary and other atherosclerotic vascular disease, including peripheral artery disease, atherosclerotic aortic disease, and carotid artery disease. In reviewing this evidence and its clinical impact, the writing group believed it would be more appropriate to expand the title of this guideline to “Secondary Prevention and Risk Reduction Therapy for Patients With Coronary and Other Atherosclerotic Vascular Disease.” Indeed, the growing body of evidence confirms that in patients with atherosclerotic vascular disease, comprehensive risk factor management reduces risk as assessed by a variety of outcomes, including improved survival, reduced recurrent events, the need for revascularization procedures, and improved quality of life. It is important not only that the healthcare provider implement these recommendations in appropriate patients but also that healthcare systems support this implementation to maximize the benefit to the patient.
Compelling evidence-based results from recent clinical trials and revised practice guidelines provide the impetus for this update of the 2006 recommendations with evidence-based results2–165 (Table 1). Classification of recommendations and level of evidence are expressed in ACCF/AHA format, as detailed in Table 2. Recommendations made herein are largely based on major practice guidelines from the National Institutes of Health and updated ACCF/AHA practice guidelines, as well as on results from recent clinical trials. Thus, the development of the present guideline involved a process of partial adaptation of other guideline statements and reports and supplemental literature searches. The recommendations listed in this document are, whenever possible, evidence based. Writing group members performed these relevant supplemental literature searches with key search phrases including but not limited …
1,825 citations
TL;DR: In this large, community-based sample, increased body-mass index was associated with an increased risk of heart failure and strategies to promote optimal body weight may reduce the population burden ofheart failure.
1,388 citations
TL;DR: The updated understanding of the antigluconeogenic action of met formin in the liver and the implications of the discoveries of metformin targets for the treatment of diabetes mellitus and cancer are discussed.
Abstract: Metformin has been the mainstay of therapy for diabetes mellitus for many years; however, the mechanistic aspects of metformin action remained ill-defined. Recent advances revealed that this drug, in addition to its glucose-lowering action, might be promising for specifically targeting metabolic differences between normal and abnormal metabolic signalling. The knowledge gained from dissecting the principal mechanisms by which metformin works can help us to develop novel treatments. The centre of metformin's mechanism of action is the alteration of the energy metabolism of the cell. Metformin exerts its prevailing, glucose-lowering effect by inhibiting hepatic gluconeogenesis and opposing the action of glucagon. The inhibition of mitochondrial complex I results in defective cAMP and protein kinase A signalling in response to glucagon. Stimulation of 5'-AMP-activated protein kinase, although dispensable for the glucose-lowering effect of metformin, confers insulin sensitivity, mainly by modulating lipid metabolism. Metformin might influence tumourigenesis, both indirectly, through the systemic reduction of insulin levels, and directly, via the induction of energetic stress; however, these effects require further investigation. Here, we discuss the updated understanding of the antigluconeogenic action of metformin in the liver and the implications of the discoveries of metformin targets for the treatment of diabetes mellitus and cancer.
972 citations
References
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TL;DR: In this paper, the authors compared a lifestyle intervention with metformin to prevent or delay the development of Type 2 diabetes in nondiabetic individuals. And they found that the lifestyle intervention was significantly more effective than the medication.
Abstract: Background Type 2 diabetes affects approximately 8 percent of adults in the United States. Some risk factors — elevated plasma glucose concentrations in the fasting state and after an oral glucose load, overweight, and a sedentary lifestyle — are potentially reversible. We hypothesized that modifying these factors with a lifestyle-intervention program or the administration of metformin would prevent or delay the development of diabetes. Methods We randomly assigned 3234 nondiabetic persons with elevated fasting and post-load plasma glucose concentrations to placebo, metformin (850 mg twice daily), or a lifestyle modification program with the goals of at least a 7 percent weight loss and at least 150 minutes of physical activity per week. The mean age of the participants was 51 years, and the mean body-mass index (the weight in kilograms divided by the square of the height in meters) was 34.0; 68 percent were women, and 45 percent were members of minority groups. Results The average follow-up was 2.8 years. The incidence of diabetes was 11.0, 7.8, and 4.8 cases per 100 person-years in the placebo, metformin, and lifestyle groups, respectively. The lifestyle intervention reduced the incidence by 58 percent (95 percent confidence interval, 48 to 66 percent) and metformin by 31 percent (95 percent confidence interval, 17 to 43 percent), as compared with placebo; the lifestyle intervention was significantly more effective than metformin. To prevent one case of diabetes during a period of three years, 6.9 persons would have to participate in the lifestyle-intervention program, and 13.9 would have to receive metformin. Conclusions Lifestyle changes and treatment with metformin both reduced the incidence of diabetes in persons at high risk. The lifestyle intervention was more effective than metformin.
17,333 citations
TL;DR: Type 2 diabetes can be prevented by changes in the lifestyles of high-risk subjects by means of individualized counseling aimed at reducing weight, total intake of fat, and intake of saturated fat and increasing intake of fiber and physical activity.
Abstract: Background Type 2 diabetes mellitus is increasingly common, primarily because of increases in the prevalence of a sedentary lifestyle and obesity. Whether type 2 diabetes can be prevented by interventions that affect the lifestyles of subjects at high risk for the disease is not known. Methods We randomly assigned 522 middle-aged, overweight subjects (172 men and 350 women; mean age, 55 years; mean body-mass index [weight in kilograms divided by the square of the height in meters], 31) with impaired glucose tolerance to either the intervention group or the control group. Each subject in the intervention group received individualized counseling aimed at reducing weight, total intake of fat, and intake of saturated fat and increasing intake of fiber and physical activity. An oral glucose-tolerance test was performed annually; the diagnosis of diabetes was confirmed by a second test. The mean duration of follow-up was 3.2 years. Results The mean (±SD) amount of weight lost between base line and the end of ye...
10,178 citations
"Obesity and cardiovascular disease:..." refers background in this paper
...Clearly lifestyle interventions, including exercise training and at least mild weight reduction with caloric restriction, showed a nearly 60% reduction in the risk of developing DM, which was considerably better than that noted in patients treated with metformin (73, 74 )....
[...]
TL;DR: The increases in the prevalences of obesity and overweight previously observed continued in 1999-2000, and increases occurred for both men and women in all age groups and for non-Hispanic whites, non- Hispanic blacks, and Mexican Americans.
Abstract: ContextThe prevalence of obesity and overweight increased in the United States
between 1978 and 1991. More recent reports have suggested continued increases
but are based on self-reported data.ObjectiveTo examine trends and prevalences of overweight (body mass index [BMI]
≥25) and obesity (BMI ≥30), using measured height and weight data.Design, Setting, and ParticipantsSurvey of 4115 adult men and women conducted in 1999 and 2000 as part
of the National Health and Nutrition Examination Survey (NHANES), a nationally
representative sample of the US population.Main Outcome MeasureAge-adjusted prevalence of overweight, obesity, and extreme obesity
compared with prior surveys, and sex-, age-, and race/ethnicity–specific
estimates.ResultsThe age-adjusted prevalence of obesity was 30.5% in 1999-2000 compared
with 22.9% in NHANES III (1988-1994; P<.001).
The prevalence of overweight also increased during this period from 55.9%
to 64.5% (P<.001). Extreme obesity (BMI ≥40)
also increased significantly in the population, from 2.9% to 4.7% (P = .002). Although not all changes were statistically significant,
increases occurred for both men and women in all age groups and for non-Hispanic
whites, non-Hispanic blacks, and Mexican Americans. Racial/ethnic groups did
not differ significantly in the prevalence of obesity or overweight for men.
Among women, obesity and overweight prevalences were highest among non-Hispanic
black women. More than half of non-Hispanic black women aged 40 years or older
were obese and more than 80% were overweight.ConclusionsThe increases in the prevalences of obesity and overweight previously
observed continued in 1999-2000. The potential health benefits from reduction
in overweight and obesity are of considerable public health importance.
6,523 citations
"Obesity and cardiovascular disease:..." refers background in this paper
...Obesity has now become a critical problem in the U.S., with the prevalence among adults increasing by nearly 50% during the 1980s and 1990s ( 5 ); now, nearly 70% of adults are classified as overweight or obese compared with fewer than 25% 40 years ago (5‐7)....
[...]
...has shifted in a skewed fashion such that the proportion of the population with morbid obesity has increased by a greater extent than overweight and mild obesity (1,2, 5 ,7)....
[...]
TL;DR: Bariatric surgery for severe obesity is associated with long-term weight loss and decreased overall mortality.
Abstract: Background Obesity is associated with increased mortality. Weight loss improves cardiovascular risk factors, but no prospective interventional studies have reported whether weight loss decreases overall mortality. In fact, many observational studies suggest that weight reduction is associated with increased mortality. Methods The prospective, controlled Swedish Obese Subjects study involved 4047 obese subjects. Of these subjects, 2010 underwent bariatric surgery (surgery group) and 2037 received conventional treatment (matched control group). We report on overall mortality during an average of 10.9 years of follow-up. At the time of the analysis (November 1, 2005), vital status was known for all but three subjects (follow-up rate, 99.9%). Results The average weight change in control subjects was less than ±2% during the period of up to 15 years during which weights were recorded. Maximum weight losses in the surgical subgroups were observed after 1 to 2 years: gastric bypass, 32%; vertical-banded gastropl...
4,297 citations
"Obesity and cardiovascular disease:..." refers background in this paper
...Obesity surgery may reduce arterial pressure over the short term (2 to 3 years), but may not have a long-term (e.g., 6 to 8 years) effect to reduce HTN ( 82 ,86)....
[...]
TL;DR: Intervention in obesity, in addition to the well established risk factors, appears to be an advisable goal in the primary prevention of CVD.
Abstract: The relationship between the degree of obesity and the incidence of cardiovascular disease (CVD) was reexamined in the 5209 men and women of the original Framingham cohort. Recent observations of disease occurrence over 26 years indicate that obesity, measured by Metropolitan Relative Weight, was a significant independent predictor of CVD, particularly among women. Multiple logistic regression analyses showed that Metropolitan Relative Weight, or percentage of desirable weight, on initial examination predicted 26-year incidence of coronary disease (both angina and coronary disease other than angina), coronary death and congestive heart failure in men independent of age, cholesterol, systolic blood pressure, cigarettes, left ventricular hypertrophy and glucose intolerance. Relative weight in women was also positively and independently associated with coronary disease, stroke, congestive failure, and coronary and CVD death. These data further show that weight gain after the young adult years conveyed an increased risk of CVD in both sexes that could not be attributed either to the initial weight or the levels of the risk factors that may have resulted from weight gain. Intervention in obesity, in addition to the well established risk factors, appears to be an advisable goal in the primary prevention of CVD.
3,771 citations