In Smokers, Peripheral Artery Disease Risk Climbs Faster Than CHD, Stroke Risks

Batya Swift Yasgur MA, LSW

July 24, 2019

Smoking is well known as a risk factor for clinical vascular disease, notably coronary heart disease (CHD) and stroke, but its effect on peripheral vascular disease (PAD) may be underappreciated, say researchers based on their look at the community-based ARIC longitudinal study cohort.

Their analysis saw a dose–response relationship between pack-years of smoking and incident CHD, stroke, and PAD in more than 13,000 initially middle-aged adults tracked for a median of 26 years.

The greatest increase in risk was seen for PAD, which went up at least twice as sharply as the risk for either CHD or stroke.

Moreover, a longer period of smoking cessation was consistently related to lower risk for all three types of vascular disease. But the risks for PAD and CHD remained elevated for decades after the participants quit smoking, up to 30 and 20 years, respectively.

"Policy statements regarding smoking have been mainly focusing on the impact of smoking on coronary disease and stroke, and thus may have underestimated its impact," Kunihiro Matsushita, MD, PhD, Johns Hopkins School of Medicine, Baltimore, told | Medscape Cardiology.

"Our study suggests the importance of recognizing the impact of smoking on PAD as well," said Matsushita. He is senior author on the ARIC analysis published July 22 in the Journal of the American College of Cardiology, with lead author Ning Ding, MBBS, SCM, also of Johns Hopkins.

Smoking Cessation "Underutilized" in PAD

It is an "elegantly performed study," outcomes researcher Kim Smolderen, PhD, University of Missouri and Saint Luke's Mid-America Heart Institute, Kansas City, commented to | Medscape Cardiology.

Smolderen, not involved with the research, advised clinicians to be aware of the "potential risk of PAD and leg symptoms in patients with a smoking history or in patients who are currently smoking."

The study encourages clinicians to promote greater "access to evidence-based strategies to support smoking cessation." Smoking cessation support in PAD is "underutilized," she said, and "relapse rates are also high."

Why the magnitude and durability of the smoking–PAD association are stronger than for the other vascular diseases "cannot be discerned from this report," contends an accompanying editorial by Nancy A. Rigotti, MD, Massachusetts General Hospital and Harvard Medical School, Boston, and Mary M. McDermott, MD,, Northwestern University Feinberg School of Medicine, Chicago.

"However, the findings are consistent with the hypothesis that traditional atherosclerotic risk factors have distinct effects on different arterial beds, thus suggesting that atherosclerosis is not a homogeneous process and that the pathophysiology of atherosclerosis may differ across distinct arterial beds," they write.

A Hole in the Evidence

The analysis tries to address a hole in the evidence base about smoking's broad vascular effects, Matsushita noted.

"It has been recognized that PAD is especially strongly related to smoking. However, to our knowledge, there were no prospective studies quantifying the impact of smoking on three major atherosclerotic diseases — CHD, stroke, and PAD," he said.

"Also, we were particularly interested in evaluating how long the contribution of smoking to PAD may last," he said.

He and his colleagues looked at 13,355 participants in ARIC initially 45 to 64 years of age, of whom 56% were women. They were required not to have known PAD, CHD, or stroke at baseline.

One-fourth of the cohort were current smokers, 31% were former smokers, and 44% were never-smokers, the group writes.

Compared with never-smokers, current smokers who smoked for at least 35 years showed the following hazard ratios [HRs] for the three types of vascular disease:

  • PAD: 5.56 (95% CI, 4.26 - 7.26)

  • CHD: 2.30 (95% CI, 1.98 - 2.66)

  • Stroke: 1.91 (95% CI, 1.57 - 2.31)

The association between pack-years and vascular disease was significantly greater for PAD than for CHD and stroke (< .001).

Compared with never-smokers, those with 25 to less than 40 pack-years of smoking showed a PAD risk increased 4.13 times, but it was increased by 1.73 for CHD and 1.64 for stroke.

The associations of pack-years with PAD were found to be largely consistent across subgroups. Of note, the association between pack-years and PAD was stronger in those without diabetes than in those with diabetes.

Compared with lower-intensity smokers, current smokers of at least one pack per day showed the following HRs by type of vascular disease:

  • PAD: 5.36 (95% CI, 4.16 - 6.91),

  • CHD: 2.38 (95% CI, 2.08 - 2.73)

  • Stroke: 1.88 (95% CI, 1.57 - 2.26)

The corresponding association with CHD was stronger among people initially 55 years or younger, in women, and for those without diabetes compared with younger participants (age, ≤55 years), women, and those without diabetes — compared with older participants, men, and those with diabetes, respectively.

"Smoking usually starts in adolescence or early adulthood, and thus it's important for young people to understand that smoking can have unfavorable consequences that may last for a few decades," Matsushita stated.

The majority of ever-smokers started smoking at age 20 or younger. But regardless of age when they started, ever-smokers showed a significantly higher risk for all three vascular diseases, the group found.

Compared with current smokers, those who quit at a younger age showed lower risks for all three vascular outcomes; the finding was stronger for PAD (P for trend < .001) than for CHD or stroke (P for trend > .7 for both).

The risks for all three atherosclerotic diseases fell within 5 years of smoking cessation, although the decrease for PAD reached only borderline significance, "likely due to the smaller number of events." For any period of smoking cessation 5 years or longer, the group writes, the risk fell furthest for PAD, compared with current smokers.

Hazard Ratios* (95% CI) for PAD, CHD, and Stroke by Years Since Cessation Compared With Current Smokers
End Point Shorter-term Cessation, 5 to <10 Years (95% CI) Long-term Cessation, ≥30 Years (95% CI)
PAD 0.43 (0.29–0.65) 0.22 (0.16–0.31)
CHD 0.71 (0.58–0.89) 0.47 (0.40–0.56)
Stroke 0.62 (0.45–0.84) 0.49 (0.39–0.62)
*Adjusted for age, race, sex, education level, body mass index, total cholesterol, high-density-lipoprotein cholesterol, drinking status, physical activity, systolic blood pressure, diastolic blood pressure, blood-pressure-lowering medication use, cholesterol-lowering medication use, estimated glomerular filtration rate, diabetes status, and smoking intensity as packs per day.

"It is important to recognize that the risk of the atherosclerotic diseases started to decline after smoking cessation in a short timeframe of <5 years, which would be encouraging to persons attempting or considering quitting smoking," the authors write.

Overall, observe Rigotti and McDermott, the findings "reinforce the existing public health message for smokers: it is never too early or too late to benefit from quitting. It is never too late because of the relatively rapid reversal of CVD risk after smoking cessation and never too early because complete risk reversal requires decades — even longer for PAD than for myocardial infarction or stroke, as this report demonstrates."

Also, the findings "support including information about PAD risk and its consequences (e.g., limb loss, mobility impairment) in public health messages that target CVD risk reduction."

Matsushita discloses receiving research funding and personal fees from Fukuda Denshi unrelated to the current work. Ding reports no relevant conflicts. Disclosures for the other authors are in the report. Rigotti reports receiving royalties from UpToDate, consulting for Achieve Life Sciences, and receiving travel reimbursement from Pfizer. McDermott discloses receiving research support from Chromadex, ReserveAge, Hershey Company, and ViroMed. Smolderen reports support through unrestricted research grants from Abbott Vascular, Boston Scientific, and Terumo, and that she is cofounder of Dynamo Health LLC.

J Am Coll Cardiol. Published online July 22, 2019. Abstract, Editorial

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