C l i n i c a l F e at u r e s

Prevention of Cardiovascular Disease: Updating the Immensity of the Challenge and the Role of Risk Factors

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DOI: 10.3810/hp.2014.02.1096

Richard Kones, MD, FAHA, FESC, FRSM, FRSH, FCP 1 Umme Rumana, MBBS 1 1 The Cardiometabolic Research Institute, Houston, TX

Abstract: Despite remarkable decreases in the mortality of coronary heart disease, there is concern that continued high levels of cardiovascular risk in the population may reverse these gains. By 2015, the prevalence of cardiovascular disease in the United States will be 37.8%. Obesity, hypertension, dyslipidemia, diabetes mellitus (DM), metabolic syndrome, and inflammation are the primary components driving cardiovascular risk. Approximately 70% of adults are overweight or obese, yet diet quality continues to deteriorate and authoritative information is insufficiently promoted. More than half of US adults have lipid abnormalities; 27% of US adults have high values of low-density lipoprotein cholesterol, 23% have low values of high-density lipoprotein cholesterol concentrations, and 30% have high triglyceride levels. Approximately 34% of adults have hypertension; 40% of these adults are unaware of the diagnosis. In patients with hypertension who are treated, 54% remain uncontrolled. The prevalence of hypertension in elderly patients has increased from 35% to 41%. In addition, 30% of adults have prehypertension. The burden of hypertension alone accounts for approximately 1000 deaths per day. Trends in the prevalence of glucose intolerance are similar. The prevalence of DM is approximately 12%, with 27% of cases remaining undiagnosed. Thirty-five percent of US adults aged . 20 years have prediabetes and 7.3% of adults are unaware of the diagnosis. If the present trends continue, 1 in 3 of US adults will have DM by 2050. Participation in exercise has been low and a “straight line” for . 2 decades. Accelerometer data indicate that individuals who attain minimal exercise goals are only a fraction of the often quoted levels of . 35%. Control of risk factors in primary prevention, although improved, remains decidedly incomplete. Lowering the burden of cardiovascular risk factors at the population level has been exceptionally difficult. For reasons outlined, the solution to this problem is multifaceted and extends well beyond the delivery of medical care into the structure of society and the environment. Keywords: coronary heart disease; cardiovascular prevention; lipoproteins; hypertension; diabetes mellitus; metabolic syndrome

Introduction: Defining the Problem

Correspondence: Richard Kones, MD, FAHA, FESC, FRSM, FRSH, FCP, Cardiometabolic Research Institute, 7505 Fannin St, Suite 210, Houston, TX 77054. E-mail: [email protected]

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An ominous cloud of rising cardiovascular risk is casting its shadow around the globe, eclipsing and possibly reversing the striking gains made in some prevention and treatments during the last decades. A shift to a Western lifestyle and diet, associated with high rates of obesity, hypertension, dyslipidemia, diabetes mellitus (DM), metabolic syndrome (MetS), smoking, and physical inactivity, together with urbanization and increasing age of the population, is considered the major cause of coronary heart disease (CHD). Additionally, there is evidence that this plague is mutating somewhat before our eyes. As obesity, overweight, and glucose intolerance have become the “new normal,” the pathophysiology and presentations of patients have also changed.

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Prevention of CVD

From 1970 through 2000, American life expectancy gained a total of 6 years, and greater survival from cardiovascular disease (CVD) added 3.9 of those years; in the period from 1999 to 2009 the overall CVD mortality rate dropped 32.7% in the United States. To be sure, there has been remarkable progress in managing heart disease, with approximately half of the reduction in the CVD mortality rate due to a fall in risk factors, reflected in a lower incidence of acute coronary syndrome, and the remainder of the drop due to advances in treatment, reflected by lower rates of mortality, with the edge on the side of the former.1 Documentation of improved mortality rates from CHD are also provided in the European Union and elsewhere.2,3 The portion attributable to primary and secondary prevention is due, in large part, to classical risk factors identified in the INTERHEART study4 and other reports. In the decade from 1998 to 2008, mortality from CVD fell 31% in the United States, but at the end of this period CVD was still responsible for approximately one third of all deaths, and approximately half of those were due to CHD,5 which incurred a cost of approximately $444 billion in 2010. However, the declines in hospitalizations for acute myocardial infarction (MI) are uneven across demographic groups.6,7 Improvements in control of risk factors, largely due to the use of statin drugs and better treatment of glycemia, along with newer revascularization procedures and efficiency in acute care, have contributed to this change in the epidemiology of CHD.8 Nevertheless, the high burden of ­­CVD menaces most countries with associated oppressive morbidity and mortality. Every 26 seconds, another individual experiences an acute MI in the United States and approximately 45% of patients are aged , 45 years; many of these incidents are the initial manifestation of the disease. About 83% of all MIs are first occurrences, and all other MIs are recurrent events. Of MIs that are fatal, approximately two-thirds occur as sudden deaths and approximately 45% of all sudden cardiac deaths occur in patients without known heart disease. The epidemic in cardiovascular risk factors, recently termed “stark and far-reaching” in an issue of Lancet in which an editorial and commentary reviewed the content and import of 3 papers,9,10 has reached remarkable proportions throughout the world and shows no sign of abating. Despite the impressive number of publications, rising awareness, and calls for action, there is no large-scale, evidence-based initiative in place capable of reversing this trend in the United States or elsewhere. Formerly regarded as a disease of developed nations, the number of deaths from CVD is far higher in developing

countries, which have fewer resources to invest in prevention and care. In India, for instance, CHD is the leading cause of death (Table  1); globally, ischemic heart disease is responsible for . 12% of all deaths and accounts for approximately one third of all deaths in women worldwide. All told, approximately 80% of all global cardiovascular deaths in 2005 occurred in low- and middle-income countries. Individuals who experience major cardiovascular events may also be younger in such nations.11,12 For these reasons, cooperative efforts to lower the risk of noncommunicable diseases are ongoing.12–14 Reducing the burden of cardiovascular risk is the most important challenge in public health today. It has been said that rather than preventing heart disease, it is being made less lethal through modern therapies, but the ever-increasing level of high cardiovascular risk predicts dire consequences for the future.15 Eventually, the ability to identify patients who will benefit most, and to provide the services they need, will be overwhelmed by the tsunami of risk even in developed nations. Trends in risk factors indicate that improvements in CHD mortality rates may be increasingly offset by the current epidemics of obesity and DM and their consequences. Less than one third of our population is not yet overweight, and with most new reports from the Centers for Disease Control and Prevention (CDC), this population contracts. Remarkably and an often forgotten fact, the current epidemic of atherothrombotic disease is a recent phenomenon in human history and largely related to modern Table 1.  Leading Causes of Death in the United States and Worldwidea Position

Cause of death worldwide (2008)

Position

Cause of death in the US (2010)

1 2

CHD Cerebrovascular diseases Lower respiratory infections Chronic obstructive lung disease Diarrheal diseases

1 2

CHD Cancer

3

HIV/AIDS Trachea, bronchus, lung cancers Tuberculosis

6 7

Chronic lower respiratory disease Stroke (cerebrovascular disease) Unintentional injuries (accidents) Alzheimer’s disease DM

DM Motor vehicle accidents

9 10

3 4 5 6 7 8 9 10

4 5

8

Nephritis, nephrotic syndrome, nephrosis Influenza and pneumonia Suicide

Data from Murphy et al18 and Shanthi et al.11 Abbreviations: CHD, coronary heart disease; DM, diabetes mellitus; HIV/AIDS, human immunodeficiency virus/acquired immunodeficiency syndrome.

a

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Richard Kones and Umme Rumana

lifestyle and diet; up to 90% cases of CVD are preventable and reversible.2,4,5,12 Due to the westernization of the globe, the causes of death worldwide are becoming similar to those in the United States. Indeed, reduction of cardiovascular morbidity and mortality through prevention is arguably the major current public health challenge in both American and global medicine today.

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Need for Changes in Approach: Cardiovascular Health Has Deteriorated and Is Presently Poor

The state of health in the United States from 1980 to 2010 was summarized in an annual report from the National Center for Health Statistics by the CDC.16 Life expectancy was slightly higher in 2010 from prior values in 2007 and 1988–2008 of 76.8 to 77.9 years, respectively. This year, in a National Vital Statistics Report, the CDC released state-specific updates of life expectancy at age 65 years, quoting 2010 data.17 The good news is that for 2011 the preliminary US estimate of life expectancy from birth remains at 78.7 years, the same as it was in 2010.18 Importantly, longevity gaps between men and women have been decreasing since 1979. In contrast with life expectancy, the current prevalence of major risk factors, even with improvements in control of hypercholesterolemia, hypertension, and inpatient mortality from acute atherothrombotic disease, needs additional attention. Mean body mass index (BMI) and obesity rates have risen substantially, with approximately 70% of adults now overweight (BMI 25.0–29.9) or obese (BMI 30.0–39.9; a BMI $ 35 is sometimes termed severe obesity, a BMI $  35 with related health issues or BMI $ 40–44.9 is termed morbid obesity, and a BMI $ 45 or 50 is sometimes termed super obesity). In Health United States 2011, the CDC reported that the rates of all grades of obesity (a BMI $ 30 ranging to . 40) increased, but more rapidly among the very obese.18 Further, . 50% of ­A mericans have high levels of visceral fat, with ­projections of further increases to come. Some signs of a modest plateau in the rate of rise of nonmorbid obesity are encouraging, but most US adults are already obese or overweight, still leaving an oppressive burden. Some reports underestimate the prevalence, severity of obesity, and dire health consequences. More telling is the steep rise in the prevalence of extreme obesity (BMI $ 40) and adults $ 100 pounds (45.4 kg) overweight, which has increased 350% since the late 1970s to 2009 and 2010.19 Minimizing the adverse effects, overemphasizing a “protective effect,” or even the outright denial of the health

dangers of obesity is a disservice to the populace. Nearly 1 in 5 deaths among US adults aged 40 to 85 years are indirectly attributable to obesity; 27% of black women die prematurely because of obesity. The hazard ratios (HRs) for mortality and obesity in women are as follows: white women, aged 45, HR 1.25, and aged 65, HR 2.0; black women, aged 45, HR 0.7, and aged 65, HR 1.5.20 Most unfavorable is that none of the many preventive programs that have been introduced have been successful in slowing the relentless progression of obesity and DM in the general population. Additional figures of interest, state by state, appear in the annual F as in Fat: How Obesity Threatens America’s Future 2013 report, issued jointly by the Trust for America’s Health and the Robert Wood Johnson Foundation.19 In the United States, approximately 33% of adults have hypertension and . 39% of these adults remain unaware of the diagnosis. In the 69.9% of adults with hypertension who are treated, 54% of hypertension cases remain uncontrolled. An analysis of telephone survey data from 2005 to 2009, in which only 24% of contacts had landline telephone service and median state response rates were just 28%,21 found that about 1 in 5 (20.4%) US adults with high blood pressure were unaware of their diagnosis. Prevalence of hypertension in elderly patients has increased from 35% to 41%. The burden of hypertension alone accounts for approximately 1000 deaths per day, but does not take into account the 31% of adults with prehypertension. Globally, 40% of adults have hypertension, and in 53.3% of adults with hypertension, it is undiagnosed. Of patients aware that they have high blood pressure, 87.5% receive some medication, but 32.5% of patients continue to experience uncontrolled blood pressure. Multiplying these fractions, a small percentage of all patients with hypertension are controlled.22 One billion people have hypertension worldwide and the condition is implicated in 9.4 million deaths annually. Because these data were generated on the basis of occasional blood pressure measurements, rather than the newer standard of ambulatory blood pressure monitoring, and because the accuracy of office-based measurements has been challenged, the reported prevalence and usefulness of blood pressure recordings for risk stratification are likely to change. The National Health and Nutrition Examination Survey (NHANES) 2003 to 2006 data indicate that approximately 53% of US adults have lipid abnormalities, 27% have high levels of low-density lipoprotein cholesterol (LDL-C), 23% have low levels of high-density lipoprotein cholesterol (HDL-C), and 30% have high triglyceride (TG) levels. The ongoing fall in mean cholesterol concentrations, attrib-

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Prevention of CVD

uted in part to a doubling of the use of statins, is expected to continue, but clinical achievement of goals remains a challenge. The vexing problem of residual risk, the risk that remains after which patients are aggressively managed with statins, is appreciable and there is no clear solution. The prevalence of DM is approximately 12% and 27% of cases remain undiagnosed. Diabetes mellitus is the primary cause of death for 71 382 US adults each year, but it contributes to the death of 231 404 patients annually. If present trends continue, 1 in 3 of US adults will have DM by 2050. Thirtyfive percent of US adults aged . 20 years have prediabetes and 7.3% are unaware of the diagnosis. In reviewing the prevalence of each classic risk factor, the true burden of risk is not fully appreciated, because of both the extent of “pre-disease” in ostensibly healthy individuals and the clustering of subclinical and clinical risk factors. Prehypertension is closely associated with elevations in BMI,23 plasma glucose, and glycated hemoglobin levels24 in the absence of clinical disease. Both prehypertension and prediabetes act as coaccelerants for risk.25 Men and women with coexisting prehypertension and prediabetes26 have a higher mean BMI, particularly visceral adiposity (waist circumference), and show high levels of insulin, TG, and markers of inflammation, as well as generally lower levels of HDL-C. Inflammation alone is capable of inducing prehypertension and visceral adiposity; lone prediabetes is associated with endothelial dysfunction and subsequent raised cardiovascular risk. Metabolic syndrome, the best known cluster of risk factors, is defined by the presence of 3 of the following components: (1) fasting glucose $  100  mg/dL; (2) blood pressure $ 130/85 mm Hg; (3) TG $ 150 mg/dL; (4) HDL-C level , 50 mg/dL in women or , 40 mg/dL in men; and (5) waist circumference $ 88 cm (35 in) in women, $ 102 cm (40 in) in men, or, if Asian American, $ 80 cm (32 in) in women and $ 90 cm (35 in) in men. As of NHANES data from 1999 to 2006, the prevalence of MetS in the United States was approximately 35% and was higher for adults aged . 50 years, figures which are expected to increase. The 3 variables that confer the most risk together are visceral adiposity, hypertension, and insulin resistance, but a high level of C-reactive protein is also associated with a poor prognosis, although it is not a core component.27 This observation is not unexpected, given the chronic adipose tissue dysregulation and significant adipokine secretions that contribute to the proinflammatory phenotype. Finally, discordance between LDL-C and other lipid measurements, especially the size or number of LDL particles, may raise cardiovascular risk as

much as 50% even after multivariate adjustment for HDL-C and TG levels, but may remain unrecognized. For all risk factors, the prevalence is too high, patient awareness of the diagnosis is too low, the percentages of patients under active care and treatment intensity are too low, patient adherence is abysmal, and overall control is less than ideal. A CDC analysis of NHANES data from 1999 to 2004 reported that approximately 17% of the US population aged . 20 years had chronic kidney disease, and 12% of US adults had been diagnosed with CVD. Another accounting of lifestyle and risk factors in 2000 found that only 23% of the US population consumed $ 5 servings of fruits and vegetables daily, 22% engaged in regular physical activity, 24% smoked, and 40%—now 30%—maintained a healthy weight.28 Because these data were self-reported, the actual figures may have been considerably worse. Even so, the most striking finding was that only 3% of adults had a healthy lifestyle (ie, followed all 4 healthy lifestyle characteristics), even though the requirements were not stringent. Trends in risk factors are mixed but unfavorable. Vasan et al29 analyzed data from the third NHANES conducted between 1988 and 1994. Fewer than 1% of men aged 35 and 74 years had all CHD risk factors of interest in an optimal range (systolic blood pressure , 120 mm Hg, diastolic blood pressure , 80 mm Hg; LDL-C level , 100 mg/dL, HDL-C level . 59 mg/dL; fasting glucose level , 110 mg/dL or 2-hour glucose level , 140 mg/dL; and never smoking). Just 8.9% of women aged 35 to 44 years had all risk factors in the optimal range, but those aged between 55 and 74 years (when clinical disease would be more evident), , 1% of women had all risk factors in the optimal range. The Behavioral Risk Factor Surveillance System, a large, ongoing telephone health survey system sponsored by the CDC, found a flat line in physical activity performance from 1986 to 2000, which clearly demonstrated that promoting exercise had not worked. In the release of Health United States 2010, the number of individuals who reported sufficient aerobic or strength training exercise was 20.4%, including 39% of individuals aged 18 to 24 years, and the number of adults aged . 65 years who exercised insufficiently was . 90%. When self-reported, 40% to 50% of adults may meet recommended levels of physical activity, but when accelerometer verification is employed, just 5% of adults meet guideline-directed requirements. Similarly, there is substantial underreporting of total caloric intake during telephone and similar surveys.

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During the same period, the daily consumption of $ 5 servings of vegetables and fruits fell from 42% to 26%, moderate alcohol intake rose from 40% to 51%, and smoking rates were essentially unchanged at 26.5%. Taken together, adherence to all 5 health behaviors dropped from 15% to 8% during the 18 year study. There was no better adherence to healthy habits among patients who were aware of their heart disease or DM, a situation that continues today. A further review of NHANES data revealed that 45% of US adults had $ 1 of 3 illnesses—hypertension, dyslipidemia, or DM—1 in 8 (13%) adults had 2 illnesses, and 3% of US adults had all 3 conditions. Approximately 1 in 7 (14%) adults had $ 1 of these conditions undiagnosed.30

Multiple Comorbidities Compound Risk But May Be Delayed With Prevention

Because many cardiovascular risk factors are also considered individual illnesses, when all entities (CHD, DM, dyslipidemia, hypertension, MetS, renal disease, obesity, stroke, fatty livers) are totaled, they constitute the largest category of chronic disease. A concern among health officials has been the inordinate burden of chronic multiple diseases; deleterious effects of risk factors in primary and secondary prevention are amplified by comorbidities. Often this involves direct pathophysiology, as with DM or renal insufficiency, but visual or auditory impairment, sarcopenia, and cognitive loss may significantly impair self-care. Prevalence of multiple chronic conditions in the United States has risen steadily since 1996, when 41% of US adults had $ 1 chronic illness. In 2005, this number had increased to 44%, a rise of approximately 0.33% annually. These trends are also confirmed through examination of medical expenditure data.31 The national percentage of patients with $ 3 chronic illnesses increased from 13% in 1966 to 22% in 2005 in adults aged 45 to 64 years, and to 45% for adults aged 65 to 79 years. For all ages, individuals with $ 3 diseases rose from 7% to 13%.31 In general, the current health care system is more oriented to single acute diseases of the past rather than the multiple chronic illnesses of today.32 The extent and consequences of an inexorable rise in the prevalence of comorbid chronic diseases were presented in detail by the US Department of Health and Human Services (DHHS) in 2010.33 The report emphasized that . 25% of Americans had $ 2 chronic conditions. For adults aged . 65 years, approximately 66% had multiple chronic illnesses, and for those aged . 80 years, approximately 75% suffered with multiple conditions. Approximately 66% of

resources were directed to the care of 27% of Americans with multiple chronic conditions. As the population ages, the number of such patients is expected to increase 42% to 81 million by 2020, which will create a strain of devastating proportions.5,11,12,33 The immensity of the problem is amplified because a higher number of people are living longer but are sicker, less able to care for themselves, and require more intensive, technologically advanced care. According to the strategy report, multiple chronic diseases lead to more polypharmacy (as a higher number of physicians prescribe medications), poorer adherence, under- and overtreatment, more emergency department visits, more hospitalizations, more testing, duplication of services, and greater risk of conflicting care with potential adverse reactions.33 This situation may obtain even when guidelines are followed, because guidelines do not address multiple conditions, which may be therapeutically complex because of competing priorities. Much of this scenario is preventable by reducing the risk factor burden in the population. An international survey conducted by Deloitte Center for Health Solutions in April 2011 found that 55% of Americans said they had $ 1 chronic illness, as did 41% of people in the United Kingdom and 52% of Canadians. Although 57% of Americans took $ 1 prescription drug, and half of them took $ 3 drugs, 61% said they were in good or excellent health, compared with 56% of those in the United Kingdom and 55% of Canadians. Considering data from other sources, many of the respondents were in denial about their health— overestimating healthy behaviors and underestimating the negative.34 In surveys concerning behavior, discrepancies between perception and reality are common. Specifically, however, Americans do suffer poorer health when ranked against 17 high-income countries in most areas, including higher incidence of CHD, obesity, and DM; this is a situation that the Institute of Medicine and other health officials find embarrassing, alarming, and unacceptable.35 Although an immediate response includes the proportion of uninsured Americans and access to care, there is much more to be considered because the wealthy, white, and highly educated US population also experiences inferior health compared with its overseas counterparts. Analysts cite the inefficiency and ineffectiveness of the US system, which addresses only a fraction of the determinants of health. The Institute of Medicine report35 opined that even reforms in medical care delivery will not improve public health sufficiently. Changes in ­public policies to support alterations in the physical and social environment must be added, clear thinking (eg, clearing the deck of widespread health misinformation) must prevail, and

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Prevention of CVD

individual attitudes about 30% of health behaviors must be addressed.36,37 Unfortunately, confronting these hard truths remains unpopular among most stakeholders.

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Obesity and DM Epidemics Threaten Gains Achieved in CHD Mortality

Ford and colleagues38 analyzed the reasons for the decline in CVD mortality in the United States from 1980 to 2000 with respect to risk factors and improved treatment. There were 341 745 fewer deaths from CHD in 2000 than in 1980. The authors attributed 20% of the reduction to lowered systolic blood pressure, 24% to decreased total cholesterol, and 12% to smoking cessation (Table 2). These reductions were offset by increased CVD mortality, 8% of which was due to greater prevalence of obesity and 10% to a rise in the prevalence of DM. Separately, the authors established that postponed deaths due to improved treatment of CHD resulted in an additional 6.9 years of life, but deaths postponed due to lowered prevalence of risk factors doubled the yield to an additional 13.7 years of life.39 Mathematical models quantitating health benefits through greater use of 9 clinical preventive services were studied for the years 2000 to 2010.40 Optimal use defining improvements in dyslipidemia, hypertension, tobacco use, and physical activity would have resulted in 51 000 fewer deaths from heart disease. However, these gains Table 2.  Control of Risk Factors From 1980 to 2000a Risk variable

% change

Risk-attributed deaths (estimate)

BMI DM Totalb

+2.6 +2.9

+25 900 +33 470 +59 370

Risk variable

% change

Deaths postponed (estimate)

Smoking SBP Lack of physical activity Total cholesterol Totalc Net gaind

-11.7 -5.1 -2.3 -0.34

-39 930 -68 800 -17 450 -82 800 -208 980 -149 610

a Deaths were postponed (negative values, bottom), but the rise in prevalence of obesity and diabetes (positive values, top) offset the gains.37 b Value calculated by adding the number of risk-attributed deaths from BMI and from DM. c Value was calculated by adding the number of postponed mortalities from each of the 4 controlled variables: smoking, SBP, lack of physical activity, and total cholesterol. d Net gain denotes the amount of averted deaths and was calculated by adding the values from each total. Abbreviations: BMI, body mass index; DM, diabetes mellitus; SBP, systolic blood pressure.

were offset by 32 000 additional deaths due to the rise in prevalence of obesity and DM (Table 2). Imagine if these latter deaths could be converted to gains, added to the estimated annual mortality benefit from optimal pharmacological control of cholesterol, hypertension, and use of aspirin prophylaxis—totaling 100 000 deaths in patients aged , 80 years, and as many as 40 000 deaths in patients aged , 65 years.40 Because of the deaths attributable to increasing burdens of obesity and DM, by the year 2030 the rate of acute MI may again rise by as much as 16.6%.5 Despite prodigious work on the physiological, behavioral, and social aspects of obesity, there is no definitive, evidence-based long-term medical treatment available. One popular current approach is environmental control, but ultimately all perturbations that affect weight do so through changes in energy balance.41 Calories do count, and emphasizing food choices, portion control, and meal planning remain pertinent, so individual participation in any successful program is critical. Continuing their work, these investigators pooled data from 4 NHANES conducted from 1999 to 2004 and compared an index of low risk among adult participants during the different time periods in order to determine any trend in the prevalence of low CVD risk factor burden.42 The index was composed of the following behaviors and factors: not currently smoking, total cholesterol , 200 mg/dL (, 5.17 mmol/L) without using cholesterol medications, systolic/diastolic blood pressure , 120/80 mm Hg without medication, BMI , 25 kg/m2, and no diagnosis of DM. The age-adjusted prevalence of individuals with low risk factors in all 5 metrics recorded increased from 4.4%, 5.7%, and to 10.5% during the first 3 NHANES, but fell to 7.5% in the last survey (Table 3). Smoking had improved between the third and fourth study, and cholesterol levels were flat, but blood pressure, BMI, and DM all increased. On balance, overall cardiovascular health was in decline, even without examining physical activity and nutritional quality, which were also deteriorating during this period as noted by other sources. Commenting on the strikingly low level of cardiovascular health, the authors emphasized the huge potential for preventing cardiovascular disease not yet realized. However, a number of prior studies estimated the level of low cardiovascular risk at approximately 5%, depending on the variables used, as mentioned. From 1971 to 1994, CVD risk in the population improved, reflected in a rise in the percent of individuals with low values of 5 CVD risk factors. Reversal of this trend during the last NHANES from 1999 to 2004 was attributed to the

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rise in prevalence of obesity, DM, and hypertension.42 Taken together, the data summarized in Tables 2 and 3 identify obesity and DM as the current drivers of CVD. Significantly, in order for the candidate program to be successful in reducing CVD risk, it must simultaneously address the obesity epidemic because adiposity is associated with hypertension, MetS, DM, and dyslipidemia. On the other hand, the same data suggest that if preventive measures are implemented, there is enormous promise for improving cardiovascular health.

Important Cardiovascular Risk Goals in the Healthy People 2010 Program Were Not Met

Healthy People 2000, a comprehensive, nationwide health promotion and disease prevention agenda begun in 1990 by the DHHS, reported an overall 60% success rate in achieving 319 preventive objectives, but upon closer examination of cardiovascular risk factors alone during the same period, the risk factor burden was mixed.43 Notably, although there was some overlap, NHANES data during this same time found deterioration in risk factors that Healthy People reported to be improved. Although the results of the Healthy People 2010 initiative showed attainment of some 18% of 467 objectives, the goals for important lifestyle behaviors were not realized. Objectives for healthy weight, physical activity, prevalence of DM, consumption of fruits and vegetables, dietary salt intake, and tobacco use were far from being attained. For example, approximately 18% of women and 2% of men aged between 40 and 59 years consumed , 2400 mg salt per day at completion of the program. These were low percentages in view of the newly revised recommendation from the American Heart Association (AHA) of 1500 mg per day and the high background burdens of hypertension, heart, and kidney disease during the survey. Currently only 0.6% of Americans consume , 1500 mg salt per day, , 2% ingest the minimum recommended amount of 4.7 g potassium daily, and 0.015% satisfy both requirements. Yet if all the risk Table 3.  Variation in Low CV Risk From 4 Sequential NHANESa % with all 5 low CV risk factors

Survey

Years conducted

4.4 5.7 10.5 7.5

NHANES I NHANES II NHANES III NHANES IV

1971–1975 1976–1980 1988–1994 1999–2004

Data from Ford et al.41 Abbreviations: CV, cardiovascular; NHANES, National Health and Nutrition Examination Survey. a

factor goals in the Healthy People 2010 initiative were in fact attained, it could halve the death rate from heart disease.44 Healthy People 2020 was launched in December 2010.45 In future health surveys, the current crop of obese children and adolescents will be added, and by that time, their inescapable burden of DM, hypertension, CHD, and kidney disease will dampen efforts made to achieve risk goals in Healthy People 2020 and beyond. Because a prodigious amount of planning and effort was invested in these initiatives, it appears that the enemy was underestimated, and drastic improvements in cardiovascular health promotion and in the environment involving food and physical activity will be necessary. Among the traditional risk factors on the rise are obesity, dyslipidemia (including low levels of HDL-C and high TG concentrations), hypertension, and DM, which are largely amenable to dietary improvements. Overall, the smoking rate in adults has not fallen in recent years and appears to have stabilized at approximately 21% in adults (men, 23.5%; women, 17.9%) and approximately 20% in adolescents;46 the rate may now be slightly lower, as noted.18 The reliability of data for physical activity may be the most influenced by selfreporting, and progress in this category has been particularly dismal by any standard. Despite several worthy initiatives, efforts to promote physical activity have been ineffective, with reported participation unimproved since 1986; actual levels are probably even lower. Beneficial pleiotropic effects of physical activity are underappreciated; graded exercise and fitness are associated with greater longevity and improved quality of life in healthy individuals and in patients with CVD, DM, and MetS.47

Lifestyle Factors Strongly Affect Cardiovascular Events and Mortality

In 1999, Stamler et al48 published a trial of 366 000 participants in which age-adjusted risks of CHD mortality were 72% to 92% lower in cohorts of individuals with none of 4 risk factors (use of tobacco, absence of DM, total cholesterol , 200 mg/dL, systolic/diastolic blood pressure # 120/80 mm Hg) compared with a cohort of individuals with $ 1 risk factor. Those without any major CHD risk factors experienced all-cause mortality rates 40% to 58% lower than their counterparts with higher risk. With as much as 5.8 to 9.5 years added to life in lowrisk individuals, these ­investigators concluded that there were impressive rewards for those who reached middle age without any major risk factors. Using NHANES data from 1988 to 2006, King et  al49 noted that obesity (BMI . 30 kg/m2) rose by 8 percentage

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Prevention of CVD

points from 24% to 36%, reported physical activity (12 times/month) decreased from 53% to 43%, consumption of $ 5 servings of fruits and vegetables daily fell from 42% to 26%, moderate use of alcohol rose from 40% to 51%, and the rate of smoking remained nearly unchanged, from 26.9% to 26.1%. The number of people adhering to all 5 behaviors fell from 15% to 8%, and the numbers were lower in minorities. Following a healthy lifestyle was no more frequent in patients who were aware of their diagnosis and needs than in those without the illnesses. During this same period of 18 years, Ford and colleagues50 examined the relationship between 4 low-risk behaviors—never smoked, healthy diet, adequate physical activity, and moderate alcohol intake—and mortality in Americans. In agreement with earlier work, they found that few participants followed all 4 behaviors. In contrast, those who did follow all 4 behaviors were 63% less likely to die, an effect that was graded according to the number of healthy behaviors adopted. Again, the data were self-reported, with physical activity and number of servings of produce consumed vulnerable to overreporting. In the large Nurse’s Health Study, women aged 34 to 59 years were followed for 24 years with respect to 5 lifestyle factors: smoking, being overweight, deficient amounts of moderate to vigorous physical activity, no light to moderate alcohol intake, and a low diet quality score.51 Each of these factors independently and significantly predicted mortality. For 5 compared with no lifestyle risk factors, the relative risks were 3.26 for cancer mortality, 8.17 for cardiovascular mortality, and 4.31 for all-cause mortality. If all of the participants were in the no risk factor group, 72% of cardiovascular mortality, 55% of all-cause mortality, and 44% of cancer mortality would have been eliminated. Most certainly, these data also indicate that adherence to simple lifestyle recommendations are amply rewarded in several ways.

Conclusion

Cardiovascular prevention, represented by otherwise mundane numbers about populations, is so well accepted in principle that it is tempting to consider it with a nod of acknowledgment and understanding; however, implementation of prevention is resisted at every level. Common risk factors strongly drive nonfatal events and mortality; the most ominous factors are obesity, DM, and MetS. Simultaneously, these statistics actively reflect the cardiovascular health of the population, predict future events, and in part represent our ­collective success in practice. Attainment of recommended risk factor goals could result in lowering CHD mortality by 50% and cut deaths from CVD (CHD, stroke, and hyperten-

sion) by $ 25%. Many cardiovascular deaths are avoidable through simple, low-tech methods available to everyone. Although the factors that influence the high burden of risk include many nonmedical issues, physicians are in a unique position to provide authoritative information and to motivate and treat patients to minimize the risk.

Conflict of Interest Statement

Richard Kones, MD, FAHA, FESC, FRSM, FRSH, FCP, and Umme Rumana, MBBS, have no conflicts of interest to declare.

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Prevention of cardiovascular disease: updating the immensity of the challenge and the role of risk factors.

Despite remarkable decreases in the mortality of coronary heart disease, there is concern that continued high levels of cardiovascular risk in the pop...
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