PARIS—A strong association exists between reduced lung function and two serious cardiovascular conditions, new French and Swedish studies have shown.[1,2] One study found a link between diminished peak expiratory flow (PEF) and carotid atherosclerosis in older patients; the other established an association between decreased forced expiratory volume in one second (FEV1) and ventricular arrhythmias.

In the French study, the relationship between diminished PEF and carotid atherosclerosis persisted even after adjustment for smoking and other known cardiovascular risk factors. “We need further studies to explain this association,” lead investigator Mahmoud Zureik, MD, PhD, told PULMONARY REVIEWS. “But our findings document that it is not an artifact.” Dr. Zureik is a researcher in the Unit of Cardiovascular and Metabolic Epidemiology at the National Institute of Health and Medical Research in Paris.

The Swedish study suggests that the link between reduced lung function and ventricular arrhythmias may have prognostic significance: Among the patients with ventricular arrhythmias, the increased risk of myocardial infarction (MI) and death was limited mainly to those with reduced lung function.

The French study included 656 adults (ages 59 to 71 years). All subjects underwent three PEF tests at baseline; the highest result was used in the subsequent analyses. In addition, each subject’s relative PEF value was calculated by comparing the actual measurement with age- and gender-specific predicted values.

At baseline and two- and four-year follow-up, the subjects underwent ultrasonography to check for evidence of carotid atherosclerosis. The examinations included scanning of the common carotid arteries, carotid bifurcations, and first 2 cm of the internal carotid arteries.

Carotid atherosclerosis was defined as the development of one or more plaques in a formerly normal vessel segment or the appearance of new plaques in a previously atherosclerotic segment. “The presence of plaques was defined as localized echo structures encroaching into the vessel lumen,” the investigators remarked. The distance between the media–adventitia interface and the internal side of the lesion had to be at least 1 mm, they added.

Overall, 110 (16.8%) of the subjects were found to have carotid atherosclerosis during follow-up. When the patients were stratified according to relative PEF values, a surprising finding emerged: The relationship between lung function and atherosclerosis risk is linear—albeit inverse. The odds ratio for carotid atherosclerosis was three times higher in the patients in the lowest quintile of relative PEF than in those in the highest quintile (Figure 1). The increase in risk presented by diminished lung function was independent of known risk factors for cardiovascular disease, including smoking, increased body mass index, hypertension, diabetes, and hypercholesterolemia.

Figure 1 Effect of Pulmonary Function on the Risk of Carotid Atherosclerosis

* Adjusted for age, gender, body mass index, hypertension, hypercholesterolemia, diabetes, smoking habits, alcohol consumption, common carotid artery intima-media thickness, and the presence of carotid plaques at baseline (when applicable). CI, confidence interval. Data extracted from Zureik et al. Arch Intern Med. 2001.[1]

Subgroup analyses showed that the link between decreased PEF and increased atherosclerosis risk was present in both men and women. Perhaps most intriguing was the fact that this link was found even in subjects who had never smoked and in subjects with known respiratory disease at baseline. This is, to the investigators’ knowledge, the first study to associate reduced lung function with carotid atherosclerosis development. Thus, they suggest that measurement of lung function, which is both simple and inexpensive, could help to identify patients at increased risk of atherosclerosis and coronary heart disease.

VENTRICULAR ARRHYTHMIAS AND FEV1

Lung function tests may also be useful in assessing the prognostic significance of ventricular arrhythmias, the second study indicates. Gunnar Engström, MD, and coworkers from Malmö University Hospital in Sweden examined 402 men, all of whom were 68 years old and none of whom had a history of MI or stroke.

The subjects underwent ambulatory 24-hour electrocardiographic recordings. Ventricular arrhythmias, if detected, were categorized by number and type and by Lown grade. Both FEV1 and static vital capacity (VC) were also measured; the results were adjusted for body height and presented as a percentage of predicted. For each value, the best of two measurements was used; if necessary, subjects were retested until two acceptable measurements were obtained. Follow-up lasted from baseline until death or December 31, 1996. The median follow-up was about 13 years.

Of the 402 subjects, 28 (7%) had no ventricular arrhythmias, 231 (57%) had Lown grade 1 arrhythmias (fewer than 720 ventricular ectopic beats per 24 hours), and 143 (36%) had Lown grade 2 to 5 arrhythmias (frequent or complex ventricular arrhythmias).

A total of 87 men had a coronary event—fatal or nonfatal MI or death from ischemic heart disease—during follow-up, and 181 died. Both the coronary event and death rates were markedly higher in the subjects with arrhythmias of Lown grade 2 to 5 than in those with less frequent or no arrhythmias.

Engström et al then stratified the men into quartiles based on pulmonary function. In doing so, they found that the occurrence of frequent or complex ventricular arrhythmias was significantly—but inversely—associated with FEV1. Forty-five percent of the subjects in the lowest quartile of FEV1 had such ventricular arrhythmias, compared with only 29% of those in the highest quartile.

Furthermore, among the men with Lown grade 2 to 5 arrhythmias, mortality was almost three times higher in those with an FEV1 below median than in those with higher values (71.5 vs 26.8 deaths per 1,000 person-years). And, the coronary event rate was more than twice as high in the men with an FEV1 below median (37.7 vs 18.0 events per 1,000 person-years).

These associations remained significant even after adjustment for confounders, such as tobacco and alcohol use, physical activity level, and the presence of angina pectoris or diabetes mellitus. Among the subjects with Lown grade 2 arrhythmias, a similar inverse relationship was found between the coronary event and death rates and FEV1/VC. In contrast, no significant association emerged between any measurement of diminished lung function and the outcomes studied among subjects with Lown grade 1 arrhythmias.

LUNG FUNCTION SHOULD BE CONSIDERED

Engström et al acknowledge that the lung function–ventricular arrhythmia link could reflect an etiologic factor common to both, such as smoking. However, their analysis controlled for both smoking status and level of tobacco consumption, and neither factor influenced the results, which diminishes the likelihood of this possibility. Thus they, like their French colleagues, believe that reduced lung function may be an independent marker for cardiovascular disease. “Lung function should be considered when assessing the prognostic significance of ventricular arrhythmia,” they concluded.

—Timothy Begany

References
1. Zureik M, Kauffmann F, Touboul P-J, et al. Association between peak expiratory flow and the development of carotid atherosclerotic plaques. Arch Intern Med. 2001;161:1669-1676.
2. Engström G, Wollmer P, Hedblad B, et al. Occurrence and prognostic significance of ventricular arrhythmia is related to pulmonary function: a study from “Men Born in 1914,” Malmö, Sweden. Circulation. 2001;103:3086-3091.

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