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  • In 2002, 2.4 million deaths were reported in the United States. This is a 42% decrease in the overall age-adjusted death rate compared with 1950. This graph shows that the decline is due to the decrease in mortality for some of the leading causes of death including heart disease, stroke, and unintentional injuries. Centers for Disease Control and Prevention. Health, United States, 2005: With chartbook on Trends in the Health of Americans. Available at: hus05.pdf. Accessed July 4, 2006.
  • In the 2006 update of Heart Disease and Stroke Statistics , published by the American Heart Association, cardiovascular disease (CVD) was listed as the number 1 killer of men and women in the United States. Since 1900, CVD has been the number 1 killer in the United States every year except 1918. Nearly 2500 Americans die of CVD each day, an average of 1 death every 35 seconds. CVD claims more lives each year than the next 4 leading causes of death combined, which are cancer, chronic lower respiratory diseases, accidents, and diabetes mellitus. The cost of CVD and stroke in the United States for 2006 is estimated at $403.1 billion. This figure includes health expenditures and lost productivity resulting from morbidity and mortality. American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics—2006 update. Circulation. 2006;1-69. Centers for Disease Control and Prevention. Available at: hus05.pdf. Accessed July 4, 2006.
  • The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) provided new guidelines for hypertension prevention and management. This slide summarizes major CVD risk factors and target-organ damage. Hypertension, diabetes mellitus, high low-density lipoprotein (LDL)/total cholesterol or low high-density lipoprotein (HDL), and obesity are components of the metabolic syndrome. It is also noted that being overweight (body mass index [BMI] between 25 and 29.9 kg/m 2 ]) is a risk factor, as is obesity. Target organs affected by CVD include the heart, brain, and kidneys. These cardiovascular (CV) risk factors and concomitant disorders affect prognosis and can guide treatment. Chobanian AV, Bakris GL, Black HR, et al, and the National High Blood Pressure Education Program Coordinating Committee. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 Report. JAMA . 2003; 289:2560-2572 (C). Segura J, Campo C, Ruilope LM. Proteinuria: an underappreciated risk factor in cardiovascular disease. Curr Cardiol Rep . 2002;4:458-462 (A). Wilson PWF, D’Agostino RB, Sullivan L, Parise H, Kannel WB. Overweight and obesity as determinants of cardiovascular risk: the Framingham experience. Arch Intern Med. 2002;162:1867-1872 (B).
  • Key points: Smoking is another risk factor (besides hypertension and elevated cholesterol) that has decreased substantially over the past 30-40 years. However, the prevalence of obesity (as seen in the previous slide) and diagnosed diabetes has increased dramatically. Incidence of both have doubled during this period. Between 1976-1980 and 1999-2000, the prevalence of total (diagnosed and undiagnosed) diabetes increased by 55%. Gregg et al. JAMA . 2005;293:1868-1874.
  • The importance of systolic BP elevation as a cause of CVD mortality is emphasized by the Prospective Studies Collaboration, a meta-analysis involving 120,000 deaths among 1 million participants in 61 cohorts, the largest meta-analysis of its kind. Individuals with pre-existing vascular disease were excluded from the meta-analysis, limiting any effects of disease on BP (ie, reverse causality). During 12.7 million person-years at risk, there were about 56,000 vascular deaths (12,000 stroke, 34,000 ischemic heart disease [IHD], 10,000 other vascular) from ages 40 to 89 years. This slide shows the relationship between BP and stroke and IHD mortality for different age groups. A “doubling” or log scale has been used for mortality rates. Throughout middle age, each difference of 20 mm Hg usual systolic BP (usual BP at the start of each decade) — or approximately equivalently 10 mm Hg usual diastolic BP — is associated with a more than 2-fold difference in the stroke death rate. Because stroke is much more common in old age than in middle age, the absolute annual differences in stroke death associated with a given BP difference are greater in old age. Similarly, each 20 mm Hg difference in usual systolic BP was associated with 2-fold differences in the death rate from IHD. All of the proportional differences found in vascular mortality were reduced by half in the 80 to 89 year group. Age-specific associations for men and women were similar. The data from this large study indicate that usual BP is directly and significantly related to vascular mortality, with no threshold evident down to 155/75 mm Hg at minimum. Prospective Studies Collaboration. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet . 2002;360:1903-1913.
  • BP Reductions as Small as 2 mmHg Reduce the Risk of CV Events by Up to 10% Data from a meta-analysis of 61 prospective, observational studies have also provided powerful evidence that throughout middle and old age, BP is strongly and directly related to vascular mortality. 7 Perhaps most striking are the practical implications of these data: even a small, 2 mmHg fall in mean systolic BP would be associated with large absolute reductions in premature deaths and disabling strokes. 7 As shown here, a 2 mmHg lower mean systolic BP could lead to a 7% lower risk of ischemic heart disease (IHD) death and a 10% lower risk of stroke death. 7 Prospective Studies Collaboration. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet. 2002;360:1903-1913.
  • Figure 1. Global Mortality and Burden of Disease Attributable to Cardiovascular Diseases and Their Major Risk Factors for People 30 y of Age and Older The size of each circle is proportional to the number of deaths (left) or burden of disease (right; measured in disability-adjusted life years) (in millions). Overweight and obesity affect non-cardiovascular diseases, including diabetes, endometrial and colon cancers, post-menopausal breast cancer, and osteoarthritis, shown as the portions of yellow circles that fall outside the cardiovascular disease circle [57]. The mortality estimates exclude osteoarthritis, which results in morbidity but not direct deaths. Disease burden does include nonfatal health outcomes associated with diabetes and osteoarthritis (hence the larger size of the circle for overweight and obesity relative to those for blood pressure and cholesterol). Source: re-analysis of data from Ezzati et al. [57,58]. DOI: 10.1371/journal.pmed.0020133.g001 Background Cardiovascular diseases and their nutritional risk factors—including overweight and obesity, elevated blood pressure, and cholesterol—are among the leading causes of global mortality and morbidity, and have been predicted to rise with economic development. Methods and Findings We examined age-standardized mean population levels of body mass index (BMI), systolic blood pressure, and total cholesterol in relation to national income, food share of household expenditure, and urbanization in a cross-country analysis. Data were from a total of over 100 countries and were obtained from systematic reviews of published literature, and from national and international health agencies. BMI and cholesterol increased rapidly in relation to national income, then flattened, and eventually declined. BMI increased most rapidly until an income of about I$5,000 (international dollars) and peaked at about I$12,500 for females and I$17,000 for males. Cholesterol’s point of inflection and peak were at higher income levels than those of BMI (about I$8,000 and I$18,000, respectively). There was an inverse relationship between BMI/cholesterol and the food share of household expenditure, and a positive relationship with proportion of population in urban areas. Mean population blood pressure was not correlated or only weakly correlated with the economic factors considered, or with cholesterol and BMI. Conclusions When considered together with evidence on shifts in income–risk relationships within developed countries, the results indicate that cardiovascular disease risks are expected to systematically shift to low-income and middle-income countries and, together with the persistent burden of infectious diseases, further increase global health inequalities. Preventing obesity should be a priority from early stages of economic development, accompanied by population-level and personal interventions for blood pressure and cholesterol.
  • This was a cover story a couple of years ago. There have now been many other cover stories about obesity.
  • Key points: This slide shows trends for three of the cardiovascular risk factors: overweight/obesity, hypertension, and elevated serum cholesterol for adults age 20–74. Overweight (BMI ≥ 25) increased from 48% to 65%, and obesity (BMI of ≥ 30) increased from 15% to 31% for the time period shown. Obesity has increased dramatically, and as a risk factor, influence CV morbidity and mortality accordingly. Prominent nutrition issues in the US recently begun to place greater focus overconsumption and unsound food choices, which have had an impact on the increase in overweight and obesity. Briefel, RR et al. Annu Rev Nutr . 2004; 24: 401–431
  • NHANES III 1988-1994 Prevalence of Elevated Blood Pressure in Diabetic Adults Reference: Geiss LS, Rolka DB, Engelgau MM. Elevated blood pressure among U.S. adults with diabetes, 1988-1994. Am J Prev Med. 2002;22(1):42-48.
  • The slide shows the risk of a cardiovascular event over the next 5 years in men and women without diabetes, according to age (50 to 70 years), smoking status, and ratio of total cholesterol to high-density lipoprotein (HDL) cholesterol. A cardiovascular event is defined as a death related to coronary disease, nonfatal myocardial infarction, new angina, fatal or nonfatal stroke or transient ischemic attack, or the development of congestive heart failure or peripheral vascular disease. The charts are from the National Heart Foundation of New Zealand and are based on a Framingham Heart Study prognostic algorithm. Jackson R. Updated New Zealand cardiovascular disease risk-benefit prediction guide. BMJ. 2000;320:709-710. Anderson KM, Odell PM, Wilson PW, Kannel WB. Cardiovascular disease risk profiles. Am Heart J. 1991;121(1 pt 2):293-298.
  • The slide shows the risk of a cardiovascular event over the next 5 years in men and women with diabetes, according to age (50 to 70 years), smoking status, and ratio of total cholesterol to high-density lipoprotein (HDL) cholesterol. The charts are from the National Heart Foundation of New Zealand and are based on a Framingham Heart Study prognostic algorithm. This and the previous slide show the dramatic increase in risk associated with diabetes. Jackson R. Updated New Zealand cardiovascular disease risk-benefit prediction guide. BMJ. 2000;320:709-710. Anderson KM, Odell PM, Wilson PW, Kannel WB. Cardiovascular disease risk profiles. Am Heart J. 1991;121(1 pt 2):293-298.
  • Diabetes is currently the most common cause of ESRD. The number of patients with ESRD maintained on dialysis is predicted to double over present levels by 2010, and the major contributor to this exponential increase is chronic renal failure associated with diabetes. United States Renal Data System. Annual data report. 2000. Available at: Accessed April 25, 2001.
  • Consequences of Obesity Although diabetes, hypertension and dyslipidemia are the most important comorbidities of obesity leading to CVD, many other systems in the body can be affected. Obesity is associated with osteoarthritis, 1 cholelithiasis, 1 stroke, 1 sleep apnea, hormonal abnormalities, 2 hyperuricemia, 2 gout 2 and even cancer. 1 References: 1. National Institutes of Health. Clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults — the evidence report. Obes Res. 1998; 6(suppl 2):51S – 209S. 2. World Health Organization. Obesity: preventing and managing the global epidemic. Report of a WHO consultation on obesity, Geneva, June 3 – 5, 1997. Geneva: WHO; 1998.
  • Obesity: Body Mass Index (BMI) When a relative index of weight over height is used, a linear or curvilinear relationship is observed between relative weight and the presence of comorbidities such as type 2 diabetes and cardiovascular disease. The most commonly used index is the body mass index (BMI), which is expressed as body weight in kg divided by height in m 2 . When populations are examined, higher BMI values are associated with a greater prevalence of comorbidities. However, in clinical practice, physicians have been perplexed by the fact that equally obese individuals may or may not be characterized by the expected comorbidities of obesity. Twenty-five years ago, the reason for such heterogeneity was unclear. Reference: World Health Organization. Obesity: Preventing and Managing the Global Epidemic: Report of a WHO Consultation. WHO Technical Report Series, No. 894. Geneva: WHO; 2000.
  • Comorbid Conditions and BMI As BMI increases, the prevalence of comorbid conditions such as hypertension, dyslipidemia and type 2 diabetes also increases. Fully 65% of patients age 25 or older with a BMI  27 have at least one comorbidity. 56% of patients with hypertension, 47% of patients with dyslipidemia and 70% of patients with type 2 diabetes have a BMI  27. Reference: Data on file (Reference 038-014). Analysis of data from the National Center for Health Statistics NHANES III (National Health and Nutrition Examination Survey III), 1988 – 1994.
  • Relation Between BMI and Comorbidities Two large-scale studies, the Nurses ’ Health Study and the Health Professionals Follow-up Study, followed large groups of subjects for several years. Among these subjects, the risk of various diseases was closely related to BMI. Cholelithiasis, hypertension and coronary heart disease all increased at comparable rates — a person with a BMI of 30 had approximately 3 – 4 times the risk of a person with a BMI of 21. Risk of type 2 diabetes, however, increased much more sharply. Reference: Willett WC, Dietz WH, Colditz GA. Guidelines for healthy weight. N Engl J Med. 1999;341:427 – 434.
  • During 24 years of follow-up, 10,282 deaths occurred—2370 from cardiovascular disease, 5223 from cancer, and 2689 from other causes. Mortality rates increased monotonically with higher body-mass-index values among women who had never smoked ( P for trend <0.001). In combined analyses of all participants, adiposity predicted a higher risk of death regardless of the level of physical activity. Higher levels of physical activity appeared to be beneficial at all levels of adiposity but did not eliminate the higher risk of death associated with obesity. As compared with women who were lean (i.e., they had a body-mass-index lower than 25) and active (they spent 3.5 or more hours exercising per week), the multivariate relative risks of death were 1.55 (95 percent confidence interval, 1.42 to 1.70) for lean and inactive women, 1.91 (95 percent confidence interval, 1.60 to 2.30) for women who were obese (defined as a body-mass-index of 30 or higher) but active, and 2.42 (95 percent confidence interval, 2.14 to 2.73) for inactive, obese women. Even modest weight gain during adulthood, independent of physical activity, was associated with a higher risk of death.
  • Do You Know Your Own BMI? BMI is a vital sign. It should be recorded as routinely as blood pressure or pulse. BMI can be easily determined with a chart such as this one. BMI, although invaluable for evaluating obesity, is not the only tool available. Fat mass and the distribution of body fat are also important, and no measurement can be a substitute for the clinician ’ s judgment.
  • Discrimination: The Pain of Obesity According to a survey of 47 former severely obese patients who had lost 100 pounds or more, the subjective experience of morbid obesity is extremely distressful. When asked whether they would prefer a given disability to being obese again, the patients overwhelmingly said they would choose the other disabilities, and even said they would rather choose to forego several million dollars than to be obese. The authors speculated that these striking results reflect the social discrimination against obese people. Reference: Rand CSW, Macgregor AMC. Successful weight loss following obesity surgery and the perceived liability of morbid obesity. Int J Obes. 1991;15:577 – 579.
  • Android (Apple) vs. Gynoid (Pear) Obesity A key factor responsible for the heterogeneity of obesity as a clinical entity is body fat distribution. Professor Jean Vague from the University of Marseille in France was the first to suggest, more than half a century ago, that the complications of obesity were not dependent upon excess body fat mass per se but were the consequence of the regional distribution of body fat. Vague coined the term “android” or male-type obesity to characterize the form of overweight and obesity observed among his patients with diabetes or clinical signs of cardiovascular disease, whereas he proposed that “gynoid” or the lower-body form of obesity, frequently found in premenopausal obese women, was mostly benign. These remarkable clinical observations did not receive immediate attention from the medical community, and more than 35 years passed before Vague’s hypothesis received further support from “modern” prospective epidemiological studies. Reference: Vague J. La différenciation sexuelle, facteur déterminant des formes de l'obésité. Presse Med. 1947;30:339-340.
  • Intra-abdominal (Visceral) Fat: The Dangerous Inner Fat A cross-sectional image of the abdomen is obtained by computed tomography and usually by scanning the abdomen at the level of L4–L5. Computed tomography was a specialized equipment found in academic centers 2 or 3 decades ago. It has now become available even in regional hospitals, which makes the measurement of visceral adiposity fairly easy for the patient and the physician. Because of differences in the attenuation values of adipose, muscle, and bone tissue, it is very easy to distinguish fat from muscle and bone on the image. The intra-abdominal, or visceral, adipose tissue is highlighted in white. Studies have indicated that among equally overweight or obese individuals, an excess of intra-abdominal, or visceral, adipose tissue is predictive of increased risk of the expected abnormalities of obesity. Reference: Lemieux l, Pascot A, Almeras N, Lamarche B, Bergeron J, Despres JP. Obesity in the 21(St) century: new approaches? Ann Endocrinol. (Paris) 2001;62:255-261.
  • Visceral Fat Is an Independent Predictor of All-Cause Mortality in Men Recently, Professor Robert Ross and colleagues from Queen’s University in Kingston, Ontario, Canada have provided evidence that an increased visceral adipose tissue accumulation was associated with an increased mortality risk. Reference: Kuk JL, Katzmarzyk PT, Nichaman MZ, Church TS, Blair SN, Ross R. Visceral fat is an independent predictor of all-cause mortality in men. Obesity (Silver Spring). 2006;14:336-341.
  • Waist circumference has a high correlation with visceral adiposity and is particularly appealing because it can be easily assessed in the clinic. The CT scan shown here demonstrates the relative volumes of visceral and subcutaneous fat. This graphic suggests that waist circumference might be a better surrogate measure than BMI. It shows the correlation between waist circumference and visceral fat as measured by CT of the abdomen. Obviously, a CT scan is not a very efficient screening method, and waist circumference might serve as a surrogate marker for obesity. Reference: Despres JP, Lemieux I, Prud'homme D. Treatment of obesity: need to focus on high risk abdominally obese patients. BMJ. 2001;322(7288):716-720.
  • Features of the Metabolic Syndrome Commonly Found among Viscerally Obese Patients Additional metabolic studies conducted in several laboratories around the world have shown that among equally obese patients, subjects with an excess of visceral adipose tissue have the most deteriorated metabolic risk profile. These subjects show insulin resistance and compensatory hyperinsulinemia as a sign of insulin resistance. Among genetically susceptible individuals, insulin resistance favors the development of glucose intolerance and eventually leads to type 2 diabetes when the insulin resistant state is accompanied by a relative deficit in insulin secretion. However, it is important to point out that even in the absence of glucose intolerance and marked hyperglycemia, the presence of visceral obesity and insulin resistance have been associated with a very typical dyslipidemic profile that includes hypertriglyceridemia, low HDL-C concentration, elevated apolipoprotein B as a marker of an increased concentration of atherogenic lipoproteins, and an increased concentration of small, dense LDL particles. In addition to the dyslipidemic insulin resistant profile of viscerally obese patients, these individuals are characterized by an impaired fibrinolysis, an increased susceptibility to thrombosis, an endothelial dysfunction (as an early sign of endothelial damage) and an inflammatory profile. HDL: high-density lipoprotein LDL: low-density lipoprotein Reference: Adapted from Lemieux I, Despres JP. Obesity and hyperlipidemia. In: Kopelman P, ed. Management of Obesity and Related Disorders. London: Martin Dunitz Ltd.; 2001:45-64.
  • There is a lack of up-to-date well-validated data in many countries, creating an urgent need to establish prevalence data for waist circumference and associated risk factors. The most recent well-standardized data available from a large sample is from the NHANES database in the USA. The table below provides the prevalence of risk factors associated with high waist circumference in the USA. Prevalence of High Waist Circumference Associated with Low HDL High TG High FPG High BP > 3 Risk Factors 22% 18% 12% 24% 9.8%
  • [Click to reveal patient’s results] This patient has the metabolic syndrome. A recent article estimates that 87% of US adults with diabetes >50 years of age have the metabolic syndrome. ATP III. JAMA . 2001;285;2486-2497. Alexander CM. Diabetes. 2003;52:1210-1214.
  • According to ATP III, the metabolic syndrome consists of a constellation of risk factors that place patients at risk for both the development of type 2 diabetes and atherosclerotic disease. The hallmarks of the syndrome are: Abdominal obesity Atherogenic dyslipidemia – characterized by elevated triglycerides, small LDL particles, and low HDL Elevated blood pressure Insulin resistance with or without glucose intolerance A prothrombotic state A proinflammatory state Lipid and nonlipid risk factors of metabolic origin not only increase the risk of type 2 diabetes, but enhances the risk for coronary heart disease at any given LDL cholesterol level. Reference: Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA. 2001;285:2486-2497.
  • Abdominal obesity and increased risk of cardiovascular events This analysis from the Heart Outcomes Protection Evaluation (HOPE) study evaluated the effects of abdominal obesity (tertiles of waist circumference) on the risk of all-cause or cardiovascular death, or myocardial infarction in 6620 men and 2182 women followed for an average of 4.5 years. Results were a djusted for BMI, age, smoking, sex, previous MI, stroke, peripheral arterial disease, microalbuminuria, use of antiplatelet agents, diuretics, lipid-lowering agents, and anti-hypertensives, history of hypertension, diabetes, or total cholesterol >5.2 mmol/L, or HDL <0.9 mmol/L. The risk of cardiovascular death, MI, or death from any cause increased in line with increasing tertiles of waist circumference. These data from this major intervention study add to the growing database of evidence linking high waist circumference with a clinically significant increase in the risk of an adverse cardiovascular outcome. Dagenais GR, Yi Q, Mann JF, Bosch J, Pogue J, Yusuf S. Prognostic impact of body weight and abdominal obesity in women and men with cardiovascular disease. Am Heart J 2005;149:54-60.
  • Different components of the NCEP metabolic syndrome predict CHD: NHANES Although the metabolic syndrome predicts both type 2 diabetes and CHD, different components within the metabolic syndrome predict these two major outcomes of the metabolic syndrome. In this analysis of NHANES data, low HDL-C, blood pressure, and type 2 diabetes were associated with a high prevalence of CHD. Impaired fasting glucose, high triglycerides, and obesity were not associated with a high prevalence of CHD. When the individual components of the metabolic syndrome were included in a multiple logistic regression model, the metabolic syndrome did not add additional predictive power. The last observation has not universally been found in other reports. Reference: Alexander CM, Landsman PB, Teutsch SM, Haffner SM. NCEP-defined metabolic syndrome, diabetes, and prevalence of coronary heart disease among NHANES III participants age 50 years and older. Diabetes 2003;52:1210-1214.
  • Fitness–fatness and CVD mortality in men: ACLS Examining combinations of fitness and fatness in men from the ACLS, Wei et al. reported that in normal-weight, overweight and obese individuals, low fitness was associated with substantially increased risk of CVD mortality. It was also observed that men who were overweight or obese but fit were at lower risk of CVD mortality than men who were normal weight but unfit. This finding suggested that for CVD mortality risk, it is more important to be fit than to be normal weight. This report received considerable press coverage and led many patients to question their doctors about the importance of losing weight compared with just becoming active. Reference: Wei M, Kampert JB, Barlow CE, Nichaman MZ, Gibbons LW, Paffenbarger RS Jr, Blair SN. Relationship between low cardiorespiratory fitness and mortality in normal-weight, overweight, and obese men. JAMA 1999;282:1547-1553.
  • CVD mortality risk by fitness level in individuals with diabetes: ACLS It is well known that individuals with diabetes are at very high risk for CVD events and mortality. Regular physical activity is not only important for preventing diabetes, but it is also important for reducing the risk of CVD in those with diabetes. We reported a steep inverse relationship between level of fitness and risk of CVD mortality in men with diabetes (n=2,316; 179 CVD deaths). Note the steep drop-off associated with the lower levels of fitness and the flattening of the curve with the higher levels of fitness, once again supporting the importance of even a minimal level of activity. Reference: Church TS, LaMonte MJ, Barlow CE, Blair SN. Cardiorespiratory fitness and body mass index as predictors of cardiovascular disease mortality among men with diabetes. Arch Intern Med 2005;165:2114-2120.
  • Inflammation and Cardiovascular Disease: Is Abdominal Obesity the Missing Link? The reason for this close relationship between the expanded waistline and the elevated C-reactive protein (CRP) levels could result from evidence of macrophage infiltration in adipose tissue of abdominally obese patients. These macrophages can become the source of production for inflammatory cytokines such as tumor necrosis factor- α (TNF- α ) and interleukin-6 (IL-6), which could have a local impact on adipose tissue metabolism as well as systemic effects. This can exacerbate the dysmetabolic profile noted among patients with an excess of visceral adipose tissue. For instance, the TNF-α could make the adipose tissue insulin resistant, and it also has an inhibitory effect on the production of adiponectin (an important adipose tissue-derived cytokine that has been suggested to have anti-atherogenic and anti-diabetic properties). In addition, the release of IL-6 by fat cells is known to stimulate the production of CRP through the liver. Reference: Despres JP. Inflammation and cardiovascular disease: is abdominal obesity the missing link? Int J Obes Relat Metab Disord . 2003;27:S22-S24.
  • Potential Contribution of Ectopic Fat Deposition to the Cardiometabolic Risk Profile of Viscerally Obese Patients Although the “portal free fatty acid (FFA) hypothesis” has been suggested to explain some of the metabolic abnormalities associated with excess adipose tissue accumulation, the hyperlipolytic state of the expanded visceral depot cannot, by itself, explain all of the metabolic abnormalities observed in viscerally obese patients. However, if the exciting new findings indicating that adipose tissue is an important endocrine organ and a site of production for inflammatory cytokines (such as interleukin-6 [IL-6] and tumor necrosis factor-α [TNF-α]) and a potentially protective cytokine (such as adiponectin, which is reduced in visceral obesity) are considered, the comprehensive alterations in the metabolic profile observed in viscerally obese patients can now be reconciled. Therefore, the hyperlipolytic state and pro-inflammatory profile of visceral obesity could explain the constellation of metabolic abnormalities found in viscerally obese patients. LPL: lipoprotein lipase PAI-1: plasminogen activator inhibitor-1 Reference: Despres JP. Is visceral obesity the cause of the metabolic syndrome? Ann Med. 2006;38:52-63.
  • Classical and emerging risk factors increase cardiometabolic risk We have understood for decades the roles of “classical” risk factors – elevated LDL-cholesterol, hypertension, dysglycaemia and smoking – in the pathogenesis of cardiovascular disease. More recent research is continuing to define the contribution of emerging risk factors to the risk of developing type 2 diabetes and cardiovascular disease, particularly in the setting of insulin resistance. Abdominal obesity, and associated hypertriglyceridaemia and low HDL-cholesterol are key features of the metabolic syndrome. In addition, atherosclerosis is increasingly regarded as an inflammatory condition.
  • Intensive management of patients’ risk factors, through pharmacotherapy and lifestyle modifications, can prevent catastrophic consequences, such as heart attack, stroke, heart failure, and end-stage renal disease. The physician has many options, from broad improvements such as weight loss for overweight patients and exercise for sedentary patients to drugs targeted at specific risk factors.
  • Saving and Overconsuming Energy Before addressing the question of which anthropometric index is most appropriate for use in clinical practice to assess the risks associated with obesity, the reason(s) for the current epidemic of obesity and type 2 diabetes should be pondered. “Mother Nature” has engineered humans to be quite efficient from an energy standpoint. Ancestors of humans had to survive very difficult environments, in which energy from food was sometimes limited yet the energy requirements of daily life were rather high. While the exponential development of equipment and devices have made life quite comfortable, the level of energy expenditure has been substantially reduced. Meanwhile, an increasing proportion of our population is exposed to energy dense food of poor nutritional value. Thus, for these simple and rather obvious reasons, there is currently a worldwide epidemic of obesity and no evidence that this phenomenon will plateau in the near future.
  • Black.ppt

    1. 1. <ul><li>HYPERTENSION AND OBESITY </li></ul><ul><li>AS CLUSTERED RISK FACTORS: CONSIDERATIONS AND GOALS FOR SUCCESS IN THE COMPLEX PATIENT </li></ul><ul><li>Henry R. Black, M.D. </li></ul><ul><li>NYU School of Medicine </li></ul><ul><li>Center for the Prevention of Cardiovascular Disease </li></ul><ul><li>Oct. 30, 2007 </li></ul>
    2. 2. Achievements in Public Health, 20 th Century Age-adjusted to the 2000 US population.; Sources: NHLBI, Morbidity and Mortality Chart Book 2000 CDC, Health, United States 2001 Total cardiovascular diseases Diseases of the heart Coronary heart disease Stroke
    3. 3. Leading Causes of Death for All Ages United States CLRD=chronic lower respiratory diseases. Centers for Disease Control and Prevention. Available at: hus05.pdf. Accessed July 4, 2006. SGR VA STUDY DIURETICS STATINS 1950 1960 1970 1980 1985 1990 1995 2002 100 10 1000 10,000 Year Deaths per 100,000 Population (log scale) Unintentional injuries Stroke Cancer CLRD Heart disease All causes
    4. 4. Cardiovascular disease mortality trends for males and females ( United States: 1979-2004). Source: NCHS and NHLBI. 0
    5. 5. Deaths in Thousands A Total CVD B Cancer C Accidents D Chronic Lower Respiratory Diseases E Diabetes Mellitus F Alzheimer’s Disease Leading causes of death for all males and females (United States: 2004). Source: NCHS and NHLBI.
    6. 6. Leading causes of death: both sexes (United States: 2004). Source: NCHS and NHLBI. Deaths All Ages <85 85+
    7. 7. Leading causes of death: females (United States: 2004). Source: NCHS and NHLBI. Deaths < 85 All Ages 85+
    8. 8. Impact of Cardiovascular Disease <ul><li>CVD No 1 killer in US </li></ul><ul><ul><li>$403.1 billion </li></ul></ul><ul><li>2500 CVD deaths each day ~ 1 death every 35 seconds </li></ul><ul><li>CVD claims more lives each year than the next 3 leading causes of death combined </li></ul>AHA Statistics Committee and Stroke Statistics Subcommittee. Circulation . 2006;1-69. Deaths per 100,000 CVD Cancer Respiratory Disease Trauma
    9. 9. Prevalence of cardiovascular diseases in adults age 20 and older by age and sex (NHANES: 1999-2004). Source: NCHS and NHLBI. These data include coronary heart disease, heart failure, stroke and hypertension.
    10. 10. Percentage breakdown of deaths from cardiovascular diseases (United States:2004) Source: NCHS and NHLBI. Coronary Heart Disease Heart Failure Diseases of the Arteries Defects Rheumatic Fever/ Rheumatic Heart Disease Stroke High Blood Pressure Congenital Cardiovascular Other
    11. 11. Cardiovascular Risk Factors JNC 7 LDL=low-density lipoprotein; HDL=high-density lipoprotein; GFR=glomerular filtration rate; UAE=urinary albumin excretion; LVH=left ventricular hypertrophy; MI=myocardial infarction; CKD=chronic kidney disease; JNC 7=The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure . *Components of the metabolic syndrome. Chobanian et al. JAMA. 2003;289:2560-2572 (C); Segura et al. Curr Cardiol Rep . 2002;4:458-462 (A). Major Risk Factors Hypertension Age (>55 years, ♂, >65 years, ♀) Diabetes mellitus ↑ LDL/ total cholesterol, or ↓HDL Estimated GFR <60 mL/min Family history of premature CVD (<55 years, ♂, <65 years ♀) Microalbuminuria (UAE=30-300 mg/d) Obesity* (BMI ≥30 kg/m 2 ) Physical inactivity Tobacco usage Target-Organ Damage Heart LVH Angina/prior MI Prior coronary revascularization Heart failure Brain Stroke or transient ischemic attack CKD Peripheral arterial disease Retinopathy
    12. 12. Trends in CV Risk Factors, US Adults Aged 20-74 Years (NHES: 1960-1962; NHANES: 1971-1975 to 1999-2000) Gregg EW, et al. JAMA . 2005;293:1868-1874. High total cholesterol was defined as ≥ 240 mg/dL; hypertension was defined as ≥140/90 mm Hg. NHES=National Health Examination Survey.
    13. 13. Multiple Risk Factors Are Prominent in Residents Across the United States CDC. MMWR Morbid Mortal Wkly Rep . 2005;54:113-117. Percentage With  2 Risk Factors 20%–29% 30%–39% >40% Risk factors included high BP, high cholesterol, diabetes, and smoking. Risk Factors for Heart Disease and Stroke, 2003
    14. 14. Stroke and IHD Mortality vs Usual Systolic BP by Age IHD = ischemic heart disease. Prospective Studies Collaboration. Lancet . 2002;360:1903-1913. Mortality (Floating absolute risk and 95% CI) Usual Systolic BP (mm Hg) 50-59 years 60-69 years 70-79 years 80-89 years Stroke Age at risk: 256 128 64 32 16 8 4 2 1 0 120 140 160 180 IHD Usual Systolic BP (mm Hg) 50-59 years 60-69 years 70-79 years 80-89 years Age at risk: 40-49 years 256 128 64 32 16 8 4 2 1 0 120 140 160 180
    15. 15. Prospective Studies Collaboration <ul><li>“ Throughout middle and old age, usual blood pressure is strongly and directly related to vascular (and overall) mortality, without any evidence of a threshold down to at least 115/75 mm Hg .” </li></ul>Lancet 2002; 360:1903
    16. 16. BP Reductions as Small as 2 mmHg Reduce the Risk of CV Events by Up to 10% <ul><li>Meta-analysis of 61 prospective, observational studies </li></ul><ul><li>1 million adults </li></ul><ul><li>12.7 million person-years </li></ul>Prospective Studies Collaboration. Lancet. 2002;360:1903-1913. 2 mmHg decrease in mean SBP 10% reduction in risk of stroke mortality 7% reduction in risk of IHD mortality
    17. 17. CV mortality risk SBP/DBP (mm Hg) 0 1 2 3 4 5 6 7 8 115/75 135/85 155/95 175/105 CV Mortality Risk Doubles With Each 20/10 mm Hg BP Increment* CV, cardiovascular; DBP, diastolic blood pressure; SBP, systolic blood pressure. *Individuals aged 40-69 years, starting at BP 115/75 mm Hg. Lewington S et al. Lancet . 2002;360:1903-1913. Chobanian AV et al. JAMA. 2003;289:2560-2572.
    18. 18. Global Mortality and Burden of Disease Attributable to CVD and Major Risk Factors for People Aged  30 Years <ul><li>Ezzati M, et al. PLoS Med . 2005;2:e133. </li></ul>M=million. 16M 7.8M 4.3M 128M 2.3M 30M 39M 59M Mortality Burden of Disease All CV High BP High cholesterol Overweight and obesity
    19. 19. <ul><li>&quot;I see one third of a nation </li></ul><ul><li>ill-housed, </li></ul><ul><li>ill-clad, and </li></ul><ul><li>ill-nourished.” </li></ul><ul><li>FDR, Second Inaugural, Jan. 1937 </li></ul>
    20. 20. Welcome to Cape Cod!
    21. 21. Age-adjusted prevalence of obesity ( BMI > 30.0) in adults ages 20-74 by sex and survey NHES, 1960-62; NHANES, 1971-74, 1976-80, 1988-94 and 2001-2004) . Source: Health, United States, 2006, unpublished data. NCHS
    22. 23. Prevalence of overweight among students in grades 9-12 by race/ethnicity and sex (YRBS: 2005). Source: BMI 95 th percentile or higher. MMWR. 2006 55: No. SS-5. NH – non-Hispanic.
    23. 24. Trends in prevalence of overweight among U.S. children and adolescents by age and survey (NHANES, 1971-74, 1976-80, 1988-94 and 2001-2004). Source: Health, United States, 2006, unpublished data. NCHS.
    24. 25. Prevalence of Overweight & Obesity in School-Children (10-16 yr-old), Defined by BMI, 2001-2002 <ul><li>Source: International Association for the Study of Obesity </li></ul><ul><li>Published in the Br Med J , June 21, 2005 </li></ul>USA
    25. 26. Trends in Age-Adjusted Prevalence of Health Conditions, US Adults Aged 20-74 Years (NHANES: 1971-1974 to 1999-2000) Briefel RR, et al. Annu Rev Nutr . 2004;24:401-431. NHANES=National Health and Nutrition Examination Survey.
    26. 27. OBESITY AND HYPERTENSION RISK PERCENT OF PATIENTS WITH SYSTOLIC BP > 140 mm Hg % BMI Levels Canadian Guidelines for Healthy Weights. Cat No. H39-134/1989E; 1988:69
    27. 28. PREVALENCE OF OBESITY AND DIABETES AMONG US ADULTS, 1991 AND 2001 Mokdad: JAMA 2001, 286: 1195-1200; Sacks FM et al. Am J Cardiol. 2002;90(suppl 2):165-167 Obesity Diabetes
    28. 29. Prevalence of Non-Insulin-Dependent (Type 2) diabetes in Adults age 18+ by Race/Ethnicity, and Years of Education (NHANES: 1999-2004). Source: NCHS and NHLBI.
    29. 30. NHANES III 1988-1994 Prevalence of Elevated Blood Pressure* in Diabetic Adults Non-Hispanic White , Total Men Women Total Population, Total Men Women Percent Non-Hispanic Black, Total Men Women Mexican American , Total Men Women Geiss LS et al. Am J Prev Med . 2002;22:42-48. NHANES III=Third US National Health and Nutrition Examination Survey (1988-1994) *  130/85 mm Hg or current use of prescription medication for hypertension
    30. 31. Association of Systolic BP and Cardiovascular Death in Type 2 Diabetes Cardiovascular mortality rate/10,000 person-yr Stamler J et al. Diabetes Care . 1993;16:434-444. Systolic blood pressure (mm Hg) Non-diabetic patients Diabetic patients 250 200 150 100 50 0 <120 120–139 140–159 160–179 180–199  200
    31. 32. Percent Chance of Cardiovascular Event in 5 Years: No Diabetes 4 5 6 7 8 4 5 6 7 8 Men Women Nonsmoker Smoker Total Chol.:HDL-C Age 70 Nonsmoker Smoker Total Chol.:HDL-C Age 60 180/105 160/95 140/85 120/75 180/105 160/95 140/85 120/75 Age 50 180/105 160/95 140/85 120/75 4 5 6 7 8 4 5 6 7 8 Jackson R. BMJ. 2000;320:709-710. BP (mm Hg) >20% 15-20% 10-15% 5-10% 2.5-5% <2.5%
    32. 33. Percent Chance of Cardiovascular Event in 5 Years: Diabetes Jackson R. BMJ. 2000;320:709-710. >20% 15-20% 10-15% 5-10% 2.5-5% Age 70 Age 60 180/105 160/95 140/85 120/75 180/105 160/95 140/85 120/75 Age 50 180/105 160/95 140/85 120/75 BP (mm Hg) Men Women Nonsmoker Smoker Total Chol.:HDL-C Nonsmoker Smoker Total Chol.:HDL-C 4 5 6 7 8 4 5 6 7 8 4 5 6 7 8 4 5 6 7 8
    33. 34. Causes of ESRD in the United States Primary Diagnosis for Patients Who Start Dialysis Glomerulonephritis 13% Other 10% United States Renal Data System . Annual data report. 2000. No. of patients Projection 1984 1988 1992 1996 2000 2004 2008 0 100 200 300 400 500 600 700 r 2 =99.8% 243,524 281,355 520,240 No. of dialysis patients (thousands) Diabetes 50.1% Hypertension 27%
    34. 35. Consequences of Obesity Cardiovascular disease Respiratory disease Gallbladder disease Hormonal abnormalities Hyperuricemia Gout Stroke Diabetes Osteoarthritis Cancer
    35. 36. Body Mass Index (BMI) Adapted from the World Health Organization. Obesity: Preventing and Managing the Global Epidemic. Geneva: WHO; 2000. Weight (kg) Height (m 2 ) BMI = BMI (kg/m 2 ) Risk of Comorbidities Healthy weight 18.5 – 24.9 Normal Overweight 25.0 – 29.9 Increased Obese Class I 30.0 – 34.9 High Obese Class II 35.0 – 39.9 Very High Obese Class III > 40.0 Extremely High
    36. 37. Correlation Between Increased Body Mass Index and Risk of Mortality Image courtesy of George A. Bray, MD. Clinical Obesity BMI (kg/m 2 ) 15 20 25 30 35 40 0 .5 1.0 2.5 3.0 Overweight Mortality Ratio Digestive and Pulmonary Disease CV Gallbladder Diabetes Mellitus Age at Issue 20–29 y 30–39 y Very Low Risk Low Risk Moderate Risk High Risk Very High Risk 1.5 2.0 Pre-overweight BMI=body mass index.
    37. 38. Comorbid Conditions and BMI <ul><li>Comorbid conditions that increase as BMI increases </li></ul><ul><ul><li>Hypertension (56%) </li></ul></ul><ul><ul><li>Dyslipidemia (47%) </li></ul></ul><ul><ul><li>Type 2 diabetes (70%) </li></ul></ul>Adapted from NHANES III data. Patients With BMI  27 Comorbidity 65% No Comorbidity 35%
    38. 39. Willett WC, et al. N Engl J Med. 1999;341:427–434. Relation Between BMI and Comorbidities 4 Body Mass Index Relative Risk Women Men Body Mass Index 4 6 5 3 2 1 0 6 5 3 2 1 0 Type 2 diabetes Cholelithiasis Hypertension Coronary heart disease <21 22 23 24 25 26 27 28 29 30 <21 22 23 24 25 26 27 28 29 30 (kg/m 2 ) (kg/m 2 )
    39. 40. Relative Risk of Type 2 Diabetes Nurses Health Study (N Engl J Med 2001;345:790-7) 61% of diabetes cases had BMI of 25 or higher Body Mass Index Relative Risk
    40. 41. RELATIONSHIP OF BMI AND MORTALITY Hu FB et al. N Engl J Med. 2004;351:2694-2703. 8.00 6.00 4.00 2.00 0.00 <2.10 21.0-22.9 23.0-24.9 25.0-26.9 30.0-32.9 33.0-34.9 35.0-39.9 ≥ 40.0 11.86 Death from Cardiovascular Disease (684 cases) A Body-Mass Index Relative Risk of Death 27.0-29.9 3.00 2.50 1.50 0.50 0.00 3.62 Death from Cancer (1740 cases) B Relative Risk of Death <2.10 21.0-22.9 23.0-24.9 25.0-26.9 33.0-34.9 35.0-39.9 ≥ 40.0 Body-Mass Index 2.00 1.00 30.0-32.9 27.0-29.9
    41. 42. RELATIONSHIP OF BMI AND MORTALITY Hu FB et al. N Engl J Med . 2004;351:2694-2703. We estimate that excess weight (defined as a BMI of 25 or higher) and physical inactivity (less than 3.5 hours of exercise per week) together could account for 31% of all premature deaths, 59% of deaths from CVD, and 21% of deaths from cancer among nonsmoking women.
    42. 43. BMI and risk for Type 2 Diabetes, Hypertension and CVD 5'4&quot; Height Weight (lbs) 5'2 &quot; 5'0&quot; 5'10&quot; 5'8&quot; 5'6&quot; 6'0&quot; 6'2&quot; 120 130 150 160 170 180 190 200 210 220 230 240 250 140 260 270 280 290 300 6'4&quot;  40 Extreme Obesity Extremely high risk 15-18.9 Very low risk 19-24.9 Normal Low risk 25-29.9 Overweight Moderate risk 30-39.9 Obesity Very high risk
    43. 44. Impact of 5-unit BMI increase on CHD risk Meta-analysis of 21 studies; N = 302,296 Bogers RP et al. Arch Intern Med . 2007;167;1720-8. Adverse effects of overweight on BP and cholesterol could account for ~45% of the ↑ C HD risk RR = relative risk CI = confidence interval RR (95% CI) Adjusted for age, sex, physical activity, smoking RR (95% CI) Additionally adjusted for BP and cholesterol P All studies 1.29 (1.22-1.35) 1.16 (1.11-1.21) <0.001
    44. 45. Discrimination: The Pain of Obesity <ul><li>Former severely obese patients: </li></ul><ul><ul><li>Leg amputation was preferred by 91.5% and blindness by 89.4% </li></ul></ul><ul><ul><li>100% preferred to be deaf, dyslexic, diabetic or have heart disease or bad acne than to be obese again </li></ul></ul><ul><ul><li>100% preferred to be a normal weight person rather than a severely obese multimillionaire </li></ul></ul>Rand CSW, Macgregor AMC. Int J Obes . 1991;15:577-579.
    45. 46. Android (Apple) vs. Gynoid (Pear) Obesity Jean Vague (1947) A Tribute to a Pioneer: Vague J. Presse Med 1947;30:339 – 340.
    46. 47. Intra-abdominal (Visceral) Fat: Subcutaneous adipose tissue Front Visceral adipose tissue Lemieux l, et al. Ann Endocrinol. 2001;62:255-261.
    47. 48. Visceral Fat Is an Independent Predictor of All-Cause Mortality in Men Kuk JL, et al. Obesity (Silver Spring). 2006;14:336-341. Visceral Fat (kg) 1 Subject A Subject B 6 5 4 3 2 1 0 Risk of Death Subject B is at a 2-fold higher risk for mortality 0 0.5 1.5 Visceral fat in red
    48. 49. Waist Circumference as a Surrogate Marker <ul><li>Amount of visceral fat, as seen on the computed tomography scan of the abdomen, has an excellent correlation with waist circumference as shown by the adjoining graph </li></ul><ul><li>Correlation coefficient (r=0.80) </li></ul>Despres JP, et al. BMJ. 2001;322:716-720.
    49. 50. Features of the Metabolic Syndrome Commonly Found among Viscerally Obese Patients Genetic susceptibility to hypertension, type 2 diabetes, and coronary heart disease ultimately affects the clinical features of the metabolic syndrome. Adapted from Lemieux l , Després JP. In: Management of Obesity and Related Disorders. 2001:45-63. <ul><li>Hypertriglyceridemia </li></ul><ul><li>Insulin resistance </li></ul><ul><li>Low HDL cholesterol </li></ul><ul><li>Hyperinsulinemia </li></ul><ul><li>Elevated apolipoprotein B </li></ul><ul><li>Glucose intolerance </li></ul><ul><li>Small, dense LDL particles </li></ul><ul><li>Impaired fibrinolysis </li></ul><ul><li>Inflammatory profile </li></ul><ul><li>Endothelial dysfunction </li></ul>
    50. 51. Abdominal obesity is linked to multiple cardiometabolic risk factors Patients with abdominal obesity often present with one or more additional CV risk factors (NCEP ATP-III Criteria ) NHANES 1999–2000 cohort (data on file) National Cholesterol Education Panel/Adult Treatment Panel III (2002) CV risk factor Parameters Increased waist circumference Men ≥ 102cm (40in) Women ≥ 88cm (35in) Elevated triglycerides  1.7 mmol/L ( > 150 mg/dL) Low HDL-cholesterol Men <1.03 mmol/L (<40 mg/dL) Women <1.30 mmol/L (<50 mg/dL) Hypertension Blood pressure  130/85 mm Hg Elevated fasting glucose  6.1 mmol/L ( > 110 mg/dL)
    51. 52. Abdominal Obesity – Better Predictor of Development of the Metabolic Syndrome than BMI Han TS et al. Obes Res . 2002;10:923-931. Janssen I et al. Arch Intern Med . 2002;162:2074-2079. Waist Waist? Top of right iliac crest Horizontal
    52. 53. ATP III: The Metabolic Syndrome (  3 risk factors are required for diagnosis) Modifications as of 10/2005 <40 mg/dL or Rx <50 mg/dL or Rx Men Women >40 in (37-39 gen. predisp; 35 for As. Am) >35 in (31-35 gen. predisp; 31 for As. Am) Men Women  100 mg/dL Fasting glucose  130 or  85 mm Hg or Rx for  BP Blood pressure HDL-C  150 mg/dL or Rx TG Abdominal obesity (Waist circumference * ) Defining Level Risk Factor Grundy SM et al. Circulation . 2005;28:2289-2304.
    53. 54. The Metabolic Syndrome and its Consequences Visceral obesity  Insulin resistance Raised blood pressure Atherogenic dyslipidemia Proinflammatory state Prothrombotic state Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA . 2001;285:2486-2497. Type 2 Diabetes Cardiovascular Disease
    54. 55. Mortality rates in U.S. adults, age 30-75, with metabolic syndrome (MetS), with and without diabetes mellitus (DM) and pre-existing CVD (NHANES II: 1976-80 Follow-up Study). Average of 13 years of follow-up. Source: Malik et al., Circulation. 2004;110:1245-50.
    55. 56. Adverse Cardiovascular Prognosis in Metabolic Syndrome. Population-Based Observational Study in 1209 Men Lakka et al. JAMA 2002;288:2709-2716 15 10 5 0 0 2 4 6 8 10 12 Cardiovascular Disease Mortality RR (95% Cl), 3.55 (1.98-6.43) Metabolic Syndrome Yes No Cumulative Hazard, % Follow-up, y
    56. 57. Abdominal Obesity and Increased Risk of Cardiovascular Events Dagenais GR et al. Am Heart J . 2005;149:54-60. Adjusted relative risk 1 1 1 1.17 1.16 1.14 1.29 1.27 1.35 0.8 1 1.2 1.4 CVD death MI All-cause deaths Adjusted for BMI, age, smoking, sex, CVD disease, DM, HDL-C, total-C The HOPE Study Tertile 1 Tertile 2 Tertile 3 Men Women <95 95–103 >103 <87 87–98 >98 Waist circ. (cm):
    57. 58. Elevated BP: One of the Most Prevalent Risk Factors in Metabolic Syndrome Wong ND, et al. Am J Cardiol. 2003;91:1421-1426. Patients With Metabolic Syndrome, % Prevalence of Selected Risk Factors Among Patients With Metabolic Syndrome
    58. 59. Different Components of the NCEP the Metabolic Syndrome Predict CHD: NHANES *Significant predictors of prevalent CHD. Prediction of CHD Prevalence using Multivariate Logistic Regression Alexander CM et al. Diabetes . 2003;52:1210-1214. Variable Odds Ratio Lower 95% Limit Upper 95% Limit Waist circumference 1.13 0.85 1.51 Triglycerides 1.12 0.71 1.77 HDL-cholesterol* 1.74 1.18 2.58 Blood pressure* 1.87 1.37 2.56 Impaired fasting glucose 0.96 0.60 1.54 Diabetes* 1.55 1.07 2.25
    59. 60. The Problem
    60. 62. Note: “Currently recommended levels” is defined as activity that increased their heart rate and made them breathe hard some of the time for a total of at least 60 minutes/day on 5 or more of the 7 days preceding the survey. Prevalence of students in grades 9-12 who met currently recommended levels of physical activity during the past 7 days by race/ethnicity and sex Source: MMWR. 2006;55:No. SS-5. NH – non-Hispanic.
    61. 63. Prevalence of leisure-time physical inactivity among adults age 18 and older by race/ethnicity, and sex. Source: MMWR, 2005;54:No. 39. NH – non-Hispanic.
    62. 64. Fitness–Fatness and CVD Mortality in Men Overweight Obese Normal Weight Risk for Death Wei M et al. JAMA 1999;282:1547-1553. Unfit Fit 5.0 1.6 1.5 4.5 Reference 3.1
    63. 65. CVD Mortality Risk by Fitness Level in Individuals with Diabetes <7 7.0– 7.9 8.0– 8.9 9.0– 9.9 10.0– 10.9 11.0– 11.9 12.0– 12.9  13.0 Risk for CVD Mortality Maximal METs Church TS et al. Arch Intern Med 2005;165:2114-2120. Reference
    64. 66. Cardiovascular Disease and Abdominal Obesity and Inflammation Després JP. Int J Obes Relat Metab Disord. 2003;27:S22-S24. Atherogenic, insulin resistant “dysmetabolic milieu” Adipose Tissue IL-6 ? TNF-  ? ?  Risk of acute coronary syndrome  CRP
    65. 67. Potential Contribution of Ectopic Fat Deposition to the Cardiometabolic Risk Profile of Viscerally Obese Patients Després JP. Ann Med. 2006;38:52-63.  Insulin  Glucose LIVER  Triglyceride  Apolipoprotein B  Visceral adipose tissue  Hepatic lipase Lipid deposition SKELETAL MUSCLE Insulin-resistant subcutaneous adipose tissue  LPL Insulin resistance CORONARY ATHEROSCLEROSIS UNSTABLE PLAQUE  Systemic FFAs Altered Cardiometabolic Risk Profile <ul><li>PAI-1 </li></ul><ul><li>IL-6 </li></ul><ul><li>TNF-  </li></ul><ul><li> Adiponectin </li></ul> Portal FFAs ? FFAs = Free Fatty Acids
    66. 68. Cardiometabolic Risk Inflammatory markers High TG Insulin resistance Low HDL-C Abdominal adiposity High BP Smoking Dysglycaemia High LDL-C CV disease Type 2 diabetes
    67. 69. Algorithm for Treatment of Hypertension Not at Goal Blood Pressure (<140/90 mmHg) (<130/80 mmHg for those with diabetes or chronic kidney disease) Initial Drug Choices Lifestyle Modifications Drug(s) for the compelling indications Other antihypertensive drugs (diuretics, ACEI, ARB, BB, CCB) as needed. With Compelling Indications Not at Goal Blood Pressure Optimize dosages or add additional drugs until goal blood pressure is achieved. Consider consultation with hypertension specialist. Stage 2 Hypertension (SBP > 160 or DBP > 100 m mHg) 2-drug combination for most (usually thiazide-type diuretic and ACEI, or ARB, or BB, or CCB) Stage 1 Hypertension (SBP 140 –159 or DBP 90–99 mmHg) Thiazide-type diuretics for most. May consider ACEI, ARB, BB, CCB, or combination. Without Compelling Indications
    68. 70. GOAL OF ANTIHYPERTENSIVE THERAPY <ul><li>< 140 mm Hg and < 90 mm Hg for most patients </li></ul><ul><li>< 130 mm Hg and < 80 mm Hg for diabetics , patients with HF and those with CRF and any day now for those with CAD </li></ul><ul><li>Goal is not dependent on age, gender or co-morbidity </li></ul><ul><li>THE GOAL IS THE CEILING, NOT THE FLOOR. </li></ul>
    69. 71. Appropriate Intensive Risk Factor Management Today, Protect Patients Against Consequences Tomorrow Manage Risk Factors Intensively Today Protect Patients Against Consequences Tomorrow Ezetimibe Elevated LDL Statins Medication Compliance Weight Loss Exercise Smoking Cessation Lifestyle & Dietary Modifications Hypertensive Renal Failure Stroke CHD Heart Failure Diabetic Renal Disease End Stage Renal Disease Statins Thrombosis Risk ASA Clopidogrel Warfarin ARBs ACEIs Combination Therapy Diuretics Elevated BP Ca Channel Blockers  -Blocker
    70. 72. Saving and Overconsuming Energy