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African-American Smokers at Higher Risk for PAD (CME/CE)

Action Points

  • Among a large cohort of African-Americans, cigarette smoking was associated with measures of peripheral artery disease (PAD) in a dose-dependent manner.
  • Note that these findings support the evaluation of smoking-cessation efforts to reduce the impact of PAD in this population.

CME Author: Zeena Nackerdien

Study Authors: Donald Clark III, Loretta Cain, et al.

Target Audience and Goal Statement: Cardiologists and primary care physicians

The goal was to evaluate the relationship between cigarette smoking and peripheral artery disease (PAD) in African-Americans in the Jackson Heart Study (JHS), the largest single-site, prospective, epidemiologic investigation of cardiovascular disease among African-Americans ever undertaken.

Question Addressed:

  • What was the relationship between cigarette smoking and smoking intensity with measures of subclinical PAD in the JHS?
  • Was there an association between abdominal aortic calcification and smoking behaviors among study participants?

Synopsis and Perspective:

The large, population-based, longitudinal JHS, based in Jackson, Mississippi, of cardiovascular disease among African-Americans is also the largest investigation of the genetic factors that affect high blood pressure, heart disease, strokes, diabetes, and other major diseases in that group.

Key findings from the study to date include the following:

  • A gene variant in African-Americans that doubles the risk of heart disease
  • Even small spikes in blood pressure can lead to a higher risk of death
  • A sickle cell trait is linked to a higher risk of kidney disease

Americans have an estimated 1.5 million heart attacks and strokes each year. PAD — atherosclerosis of the abdominal aorta and arteries of the lower extremities — is known to affect one in 20 Americans over the age of 50 and 202 million people worldwide. PAD increases the risk of heart attack and stroke and is almost three times more prevalent in African-Americans compared with non-Hispanic whites. Many African-American men (approximately 44%) and women (48%) have some form of CVD that includes heart disease and stroke.

Endothelial dysfunction, dyslipidemia, inflammatory and immunologic factors, plaque rupture, and tobacco use are among the risk factors known to contribute to the pathophysiology of PAD. Compared with non-Hispanic whites with PAD, African-Americans with PAD have more severe disease and a greater reduction in walking distance, speed, and stair climbing, according to the authors of a 2012 review. Moreover, African-American PAD patients are also at higher risk for disease progression and deterioration in lower limb function.

Cigarette smoking, especially, is a powerful predictor for PAD. Tobacco use was a major contributor to the three leading causes of death among African-Americans — heart disease, cancer, and stroke. Patterns of tobacco use vary among the races, with African-American adults smoking fewer cigarettes but starting at a later age compared with white adults. But African-American children and adults were more likely to be exposed to secondhand smoke than any other racial or ethnic group. In addition, abdominal aortic calcification, known to be highly prevalent and a predictor of CVD mortality, and aortoiliac calcium burden were also evaluated in this analysis.

Donald Clark III, MD, of the University of Mississippi Medical Center in Jackson, and colleagues, explained that because the role of cigarette smoking in PAD among African-Americans has not been well studied, the new analysis was designed to fill this unmet need.

Study participants (n=5,306; ages 21 to 84) were stratified into categories of current, past (smoked at least 400 cigarettes/life), and never-smokers. Self-reported smoking status was identified for a total of 5,258 participants (3,579 [68%] never smokers, 986 [19%] past smokers, and 693 [13%] current smokers).

Measures of PAD included an assessment of ankle-brachial index (ABI), which assesses the ratio of the systolic blood pressure (SBP) measured at the ankle to that measured at the brachial artery. Computed tomography (CT) measurements of aortic and aortoiliac calcium were also recorded. Correlations were drawn between baseline smoking status and intensity and ABI measures (visit 1) and calcium measures (visit 2). The results were compared against never smokers as the reference group.

After adjustment for covariates, the researchers found that current smokers had an increased risk of an ABI <1 (odds ratio, 2.2, 95% CI 1.5–3.3) and increased risk of abdominal aortic (odds ratio, 8.4, 95% CI 5.8–12.0) and aortoiliac calcium (odds ratio, 9.6, 95% CI 6.7–13.7). African-Americans smoking more than 20 cigarettes per day (i.e., one pack) had a higher likelihood of having subclinical PAD by all of the study measures versus those who smoked fewer cigarettes, suggesting a dose-dependent relationship.

However, “despite strong associations between smoking and PAD, for example, the findings do not establish a causal link,” Clark cautioned in a news release from the National Heart, Lung, and Blood Institute, which funded the study with the National Institute of Minority Health and Health Disparities. “Nor can [the results] be generalized to people of African descent from other regions or countries, since the Jackson Heart Study was conducted in a single community of African-Americans.”

The cross-sectional design of the study, reliance on self-reporting of tobacco use, and the long (5.5-year) delay between baseline determination of smoking status and the second assessment were also cited by the researchers as study limitations.

Source Reference: Journal of the American Heart Association, Jan. 23, 2019; 8: e010674

Study Highlights: Explanation of Findings

Current and past smokers made up 13% and 19%, respectively, of this community-based black cohort. “Among current smokers, there was a dose-dependent response whereby those smoking ≥20 cigarettes per day and higher pack-year smoking exposure demonstrated considerably higher odds of subclinical PAD compared with those smoking one to 19 cigarettes per day,” Clark and co-authors wrote.

In addition, current smokers had 2.2 times the likelihood of having subclinical lower-extremity PAD and >8 times the likelihood of a high aortic calcium burden, the study showed.

The strong association between smoking and abdominal aorta and aortoiliac calcium burden demonstrated in the study is in keeping with evidence from the literature identifying smoking as a dominant risk factor for abdominal aortic calcification, the researchers noted. Current evidence suggests that multiple environmental, genetic, and epigenetic factors may play a role in the predilection for abdominal aortic pathology in smokers.

Obesity, diabetes, hypertension, and cardiovascular disease occur disproportionately among African-Americans. Similarly, past reports have highlighted a significantly higher prevalence of PAD among Africans compared with other racial groups. Taken together, the study findings demonstrate a high degree of association among cigarette smoking, smoking intensity, and measures of subclinical PAD in the Jackson Heart Study cohort.

“Our findings add to the mountain of evidence showing the deleterious effects of smoking in the African-American population,” Clark emphasized to MedPage Today.

“This type of research can be useful in the development of clear messages targeted to our African-American population to underscore the real physical costs of tobacco product use,” Mariell Jessup, MD, chief science and medical officer of the American Heart Association, said in a press statement about the study.

PAD and its associated morbidity, including claudication, exercise intolerance, decreased quality of life, infection, and amputation, are alarming health consequences for all patients, Clark and co-authors said. “Additionally, the high burden of infrarenal aortic calcium among smokers may suggest concomitant renovascular atherosclerosis, potentially mechanistically linking smoking and progressive renal function decline.”

Future studies, the team said, should also look at the relationships among smoking, PAD, and chronic kidney disease.

  • Reviewed by
    Robert Jasmer, MD Associate Clinical Professor of Medicine, University of California, San Francisco
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