- AHA Scientific Statements
- endothelium, vascular
- peripheral arterial disease
- vascular diseases
- vascular stiffness
- venous thromboembolism
On behalf of the American Heart Association (AHA) and American Stroke Association, I am privileged to welcome this esteemed group of scientists, healthcare providers, educators, and trainees from all over the globe. Thank you for joining us and thank you for all the work you are doing to save and improve lives.
Today, I would like to talk to you about the burden of vascular disease and the urgent reasons we must act to preserve vascular health. As a specialist in vascular medicine, I have devoted my career to investigating vascular diseases and, most importantly, to caring for patients with these disabling and often fatal conditions of the arteries and veins.
The importance of the vascular system was noted some 2500 years ago by Hippocrates, when he made this observation about the blood vessels: “They are the sources of human nature and are like rivers that purl through the body and supply the human body with life.”1 It is a compelling metaphor. Rivers are sources of life, vitality, and connectivity. When a river becomes obstructed or damaged, everything around it suffers, sometimes with grave consequences. The same occurs with the rivers and tributaries that are our blood vessels. When they are damaged, everything downstream is in peril. That is precisely the problem millions of Americans are facing today—their damaged vessels put their bodies in dire jeopardy.
Just over a century ago, William Osler said: “Life’s tragedies are usually arterial.”2 And indeed today, 2 significant vascular disorders, atherosclerosis and thrombosis, are the principal underpinnings of the 2 leading causes of death in the world: heart disease and stroke. These disorders also cause peripheral artery disease (PAD), which affects between 8 and 10 million people in the United States.
PAD limits a person’s ability to walk, may require revascularization, or worse yet, can result in the loss of a limb. But PAD is not simply a disease of the legs. It is a clinical manifestation of a systemic disease, often associated with heart attacks, strokes, life-threatening kidney and intestinal problems, and other serious health issues. Tragic outcomes can also occur when veins are affected. Up to 600 000 people are affected by venous thromboembolism each year, and it is the cause of >40 000 deaths.3
The burden of vascular diseases goes beyond lives lost and changed. There is also a fiscal toll. Costs in this country for vascular-related complications in patients with PAD is >$20 billion a year.4 Healthcare costs for venous thromboembolism are >$7.5 billion.5 Clearly, the unrecognized epidemic of vascular disease requires our attention. And that is why I would like to focus not only on the extent of this crisis, but also on the importance of using what we know to treat it and prevent it, and the urgency of intensifying our research efforts to better understand it.
For me, vascular disease is personal. My father, Nathaniel Creager, had PAD, possibly because of decades of smoking. He grew up when smoking was the norm, and even encouraged by some physicians. It was a lot like the hit TV series Mad Men, with everybody lighting up everywhere all the time. My dad fired through 3 packs of unfiltered Chesterfields a day for >30 years. He quit when he was 50 years old, ≈10 years after the Surgeon General’s landmark report on Smoking and Health.6 But, by age 62, he had developed increasingly severe leg claudication, and then severe hypertension caused by renal artery stenosis.
Yet we were fortunate. My father had access to quality care, and a son who recognized his symptoms and sent him to physicians who understood the disease. They helped him live a fulfilling and independent life with my mother, until he died just last year at age 91. Although we were blessed with his extra years, the disease left its mark. His legs fatigued easily. He developed renal failure and endured dialysis for >5 years. Truly, my father illustrates both the struggle of living with PAD and the benefit offered by diagnosis and treatment.
My father was 1 of >200 million people across the globe affected by PAD.7 The disease is prevalent not only in high-income countries, but in low- and middle-income countries as well.7 It affects both men and women. Importantly, the risk of PAD is increased by tobacco use, diabetes mellitus, and high cholesterol, and prevalence increases dramatically as we age. PAD is also disproportionately present in some minority populations. For example, there is a greater prevalence in blacks than whites,8 which is consistent with the troubling fact that blacks face an overall higher burden of heart disease and stroke.
Socioeconomic factors also play an important role with PAD. When my colleague Reena Pande and I investigated the US National Health and Nutrition Examination Survey (NHANES) database, we found the highest prevalence among people in the lowest income brackets or with the lowest education levels (Figure 1).9 These findings were largely independent of traditional risk factors.
Prevalence of peripheral artery disease (PAD) by poverty-income ratio (PIR) category. PIR is a ratio of self-reported household income relative to a family’s poverty threshold. A PIR value <1.0 indicates family income below the poverty threshold. PIR was categorized as <1.0, 1.0 to 1.99, 2.0 to 2.99, 3.0 to 3.99, 4.0 to 4.99, and ≥5.0. Reprinted from Pande and Creager.9 Copyright © 2014, American Heart Association, Inc.
Why is this important? Because the risk of death is at least doubled in comparison with patients who do not have PAD.10 And the risk of cardiovascular death, myocardial infarction, stroke, and hospitalization among people with PAD exceeds that of patients who already have had a heart attack or established cerebrovascular disease.11 Yet PAD is a health crisis that is largely unnoticed. One survey found that 75% of the public is unaware of PAD. This is highlighted by a Wall Street Journal story in which a 71-year-old retired social worker in Minnesota described the excruciating pain in his leg this way: “I thought it was a bad charley horse, so I sat down to have a smoke … and the cramps went away.”12
Even physicians often fail to consider PAD, chalking up leg pain to age or arthritis. In 1 study, physicians missed the diagnosis of PAD half the time.13 And even when physicians diagnose PAD, they often do not treat it adequately.
When my research group examined the NHANES database, we found that risk factor–modifying therapies and antiplatelet drugs were being prescribed for <30% of PAD patients who did not have previously established coronary or cerebrovascular disease (Figure 2).14,15 This oversight is not trivial. When studied in patients with PAD, antiplatelet drugs and statin therapy each reduced the risk of heart attack, stroke, and cardiovascular death by ≈25%. Among symptomatic patients, therapy such as supervised exercise training can double walking distance.16 This option is not considered if the diagnosis is missed. And it is rarely instituted even with the diagnosis, largely because of a lack of reimbursement.
Use of preventive therapies in patients with peripheral artery disease (PAD)* and no other known cardiovascular disease, based on an ankle-brachial index ≤0.90, from the National Health and Nutrition Examination Survey, 1999 to 2004. *Defined as patients with known history of PAD. ACEi indicates angiotensin-converting enzyme inhibitors; and ARB, angiotensin receptor blockers. Modified from Pande et al14 and reproduced from Bonaca and Creager.15 Copyright © 2015, American Heart Association, Inc.
To illustrate what a difference supervised exercise can make, one of my middle-aged patients was putting in 30 minutes a day on the treadmill and doing quite well. Her conditioning improved so much that she was able to spend 6 hours per day over several days at Disney World in Orlando with her 5-year-old granddaughter. In a letter to me afterward, she called it “the most wonderful vacation of my life.” She said “the joy of seeing my granddaughter’s face light up…was well worth all the hours I have spent exercising.” She summed it up by saying, “Thank you for giving me back the will to continue walking.” It was one of those moments we are all grateful for—when we see our work change people’s lives. It is moments like those that underscore our need to address vascular diseases.
Indeed, our ability to diagnose and treat vascular diseases has never been greater. The field of vascular biology has virtually exploded in recent years. Our understanding of the pathophysiology underlying atherosclerosis and thrombosis is being translated into novel therapies for prevention and treatment. The application of genomics and proteomics to the development of more precise therapies is being realized.
Consider the promise of the proprotein convertase subtilisin–kexin type 9 (PCSK9) inhibitors. These drugs evolved from the recognition of a genetic mutation in families predisposed to hypercholesterolemia and premature atherosclerosis. This led to a better understanding of a protein involved in regulating low-density lipoprotein (LDL) cholesterol levels by targeting the liver’s LDL receptors for degradation and, from there, to a fragment of a monoclonal antibody to block that protein and dramatically lower LDL cholesterol.17,18
Similarly, novel oral antithrombotic drugs to treat venous thrombosis and prevent pulmonary embolism have entered the marketplace. And new antiplatelet drugs have the potential to reduce the limb complications of PAD.19
Advances in technology are also leading to innovative approaches with optical coherence tomography, intravascular ultrasonography, positron emission tomography–computed tomography, contrast-enhanced magnetic resonance imaging, and other modalities to image plaques and to assess their vulnerability for rupture. Innovative bioengineering also is leading to the application of fenestrated stents to treat aneurysmal disease. And drug-coated balloons and bioresorbable vascular scaffolds hold the promise to reduce restenosis, preserve vascular patency, and improve outcomes following endovascular treatment of critical lesions.
As you can see, there are many ways to treat vascular diseases. But we still have a long way to go in awareness, treatment, and prevention to preserve vascular health, and so we must continually seek new and creative solutions.
We took a stride forward a few months ago when the AHA convened a group of leading vascular disease experts to discuss ways to boost awareness and knowledge and to generate a road map for AHA initiatives to tackle atherosclerotic peripheral vascular diseases, aortic aneurysms, and venous thromboembolism (Figure 3).20 The outcomes of this summit include plans for increased public awareness, improved professional education, enhanced quality initiatives to address vascular health on a large scale, and more.
Our efforts to preserve vascular health must be considered early in life. In fact, endothelial function, a measure of vascular health, begins to decline well before clinical manifestations of cardiovascular disease. In light of Robert Furchgott’s Nobel Prize–winning identification of nitric oxide as an important vasodilator released from the endothelium,21 my group studied endothelial function in healthy adults by measuring the blood flow response to methacholine (Figure 4).22 We used the age range of 20 to 29 years as a reference. Even by age 30 to 39 years, the age of many early career professionals in this audience, we saw a ≈30% decrease in endothelial function. For ages 40 to 49 years, about the age of midcareer professionals, the drop was 50%. And for people >50 years of age, which includes many of us senior clinicians and scientists, the decline was even greater.
The future of vascular disease, as depicted at the American Heart Association Vascular Disease Thought Leaders Summit. Reprinted from Creager et al.20 Copyright © 2015, American Heart Association, Inc.
Age-related changes in endothelium-dependent vasodilation depicted as the calculated slope of the methacholine dose response for each of the 5 decades studied. Endothelium-dependent vasodilation declined with each decade. Values represent mean±standard error. Reprinted from Gerhard et al.22 Copyright © 1996, American Heart Association, Inc.
Superimposed on the aging process, endothelial function is further impaired by smoking, high cholesterol, hypertension, and diabetes mellitus.23,24 And abnormal endothelial function precedes and contributes to atherosclerosis.25,26 The blood vessels also stiffen as we age. This phenomenon is linked to systolic hypertension, stroke, atrial fibrillation, and heart failure. Mechanisms responsible for increased vascular stiffness and the underlying changes in the structure of the blood vessel wall include accumulation of abnormal amounts of collagen, elastin degradation, and vascular smooth muscle infiltration. Importantly, excess sodium intake and elevated blood sugar contribute to increased vascular stiffness and, on the other hand, regular exercise can reduce stiffness.27,28
Considering the importance of improving these health factors, the AHA has set a goal of improving the cardiovascular health of all Americans by 20%, and reducing deaths from cardiovascular diseases and stroke by 20% by the year 2020.29 The World Health Organization is also working to reduce premature deaths from noncommunicable diseases, including cardiovascular diseases, by 25% by the year 2025.30 Addressing vascular diseases is a critical component to reaching these goals. The good news is that we are making progress. Through the first half-decade of work toward the AHA’s 2020 goal of a 20% drop in cardiovascular disease deaths, we have already seen a decrease of 13.7%.3,31
People are living longer, and the 75 million people in the baby boomer generation are projected to see an average life span of 83 years. But what will that extended lifespan look like? Will we have more good years or just more years? The concern is whether we will experience difficulty walking, congestive heart failure, stroke, and dementia, and all of these resulting from vascular disease.
To help people age successfully, we must put forth bold initiatives to benefit vascular health, and consequently, our hearts, our brains, and our limbs. One way that the AHA is doing this is by firmly embracing the concept of “building a culture of health.” This simply means creating environments where the healthy choice is the easy choice. We believe we can make a difference by helping people make healthy decisions wherever they are—at work, at school, at home, and at play. We are building this culture on a number of fronts. We are advocating at the national, state, and local levels, and we are helping communities address their specific health needs.
The AHA is fighting tobacco through support of taxes on cigarettes, clean-air laws, and easier access to smoking cessation programs. In addition, the AHA strongly opposes marketing campaigns promoting electronic cigarettes to youth.
The AHA is also making it easier to find healthier food and drink options. We are advocating for a healthier food supply, including reduced sodium content, lower saturated fat and trans fat, and improved nutrition in schools. A culture of health means healthy choices are affordable and available for everyone. That is why the AHA is encouraging innovative community development in low-income areas, more access to healthy foods, and safe places to exercise. And, as suggested in a recent AHA scientific statement on the social determinants of risk and outcomes, we must address health disparities by developing strategies that are linguistically and culturally sensitive.32
A culture of health is necessary at work, too, because people spend so much time there. The AHA is helping companies by encouraging comprehensive workplace health programs.
And finally, a culture of health is one where everyone has access to high-quality health care. The Affordable Care Act is helping more people get insurance, and the AHA’s quality improvement programs are helping healthcare providers ensure the proper standard of care.
Our healthcare system is striving to meet people where they are through ancillary systems of care using digital technology. At the Dartmouth-Hitchcock Medical Center, we are initiating a program with a leading technology company in which patients’ data can be gathered by using biometric sensors, instantly sent to the cloud, and continuously monitored by healthcare professionals. Critical treatment adjustments can be made promptly, without the patient ever leaving home. Innovations in digital technology also are transforming the way we conduct science, with new opportunities to acquire, analyze, and interpret big data.
Although it is exciting to witness these tremendous advances, we are not seeing enough clinical research in vascular diseases. Consider this—of the nearly 41 000 interventional trials registered in ClinicalTrials.gov in a 3-year stretch ending in late 2010, <700 involved peripheral vascular diseases.33 That is <2%.
Research funding is crucial, which is why the AHA funds more cardiovascular disease and stroke research than any US organization outside the federal government. This past fiscal year alone, we funded nearly 1000 new projects and increased our funding to $145 million.
The AHA also continues to push ahead with new research initiatives, such as our Institute for Precision Cardiovascular Medicine.34 The research funded by the institute integrates the precision of molecular analysis into long-term population studies to increase our understanding of cardiovascular health and disease, and direct us toward better-targeted, safer, and more effective treatments. And we are funding Strategically Focused Research Networks on Prevention, Hypertension, Disparities in Cardiovascular Disease, and Cardiovascular Health in Women.
The AHA also strongly supports the National Institutes of Health. Like many of you, I am grateful for the funding I have received from both the AHA and the NIH. Sadly, research funding for the NIH continues to decline in terms of real dollars, so I urge all my US colleagues to advocate for more federal research support. It is also critical that we advocate for a healthier environment and for improved systems of care. One impactful way you can do all of this is to join the AHA’s You’re the Cure Network. For our international colleagues, consider working with health organizations like ours in your own country.
Earlier, I discussed Hippocrates comparing blood vessels with rivers that supply life to the human body. As you leave here today, and as you navigate Sessions this week, I ask each of you to remember that imagery of a journey down a vibrant river. All of us are on this journey of life. But you, here in this room, are uniquely qualified to change that journey for so many people and to save and improve lives. I challenge you to make a difference for others sharing this journey. Use your skills, knowledge, and influence to help our patients, families, friends, and colleagues improve their own vascular health, to find their way to a culture of health, and to enjoy richer, fuller lives.
Thank you, and enjoy the meeting.
Footnotes
Presented at the 2015 Scientific Sessions of the American Heart Association, November 7 to 11, Orlando, FL.
- © 2016 American Heart Association, Inc.
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- The Crisis of Vascular Disease and the Journey to Vascular Health
