doi: 10.1161/01.CIR.0000028402.47626.62
(Circulation. 2002;106:e42.)
© 2002 American Heart Association, Inc.
Correspondence |
Plasma Leptin Levels and Coronary Heart Disease
Università degli Studi di Milano, Cattedra di Medicina Interna, Ospedale San Paolo, Divisione di Medicina 2°, Ospedale San Raffaele, Divisione di Medicina, Milano, Italy
To the Editor:
In the West of Scotland Coronary Prevention (WOSCOP) study, Wallace et al1 show that plasma leptin levels predict coronary heart disease (CHD), and they interpret this finding on the basis of the known relationships between leptin and several facets of the metabolic syndrome, including high body mass index (BMI), insulin resistance, arterial hypertension, and of the relationship between leptin and C-reactive protein, a marker of inflammation and a predictor of CHD events.1 Other interpretations are possible. We analyzed BMI, serum leptin levels, and the QT interval (QTc) in 45 morbidly obese subjects, and we found that loss of weight obtained through laparoscopic adjustable gastric banding (from 44.6±1.01 kg/m2 to 35.6±0.89 kg/m2 in one year) is accompanied by a significant decrease of leptin levels (from 36.9±2.94 ng/mL to 19.7±2.04 ng/mL) and of the QTc (from 407.7±3.69 ms to 391.9±3.57 ms). Considering basal values, as well as values registered under basal conditions and after one year, we found significant relationships between BMI and leptin (r=0.63, P<0.001; r=0.72, P<0.001, respectively), and between leptin and QTc (r=0.57, P<0.001; r=0.52, P<0.001, respectively).
A long QTc, frequent in obese and in hypertensive subjects, is a risk factor for ventricular arrhythmia and sudden death2; in addition, leptin levels correlate with heart rate in healthy individuals,3 in heart-transplant recipients, 4 and with blood pressure. 1 Indeed, in the WOSCOP study, subjects with CHD events had higher systolic and diastolic blood pressure than subjects without events1; however, no data were given for their heart rate, nor whether cases were fatal or nonfatal. Leptin acts in the central nervous system, via interaction with several neuromediators in the hypothalamus, and may represent a partial link between excess weight gain and increased sympathetic activity5; in turn, increased sympathetic activity can lead to increased heart rate and long QTc. In summary, it is tempting to speculate that leptin can be involved in increased heart rate and in long QTc, thus amplifying the risk for CHD and sudden death.
References
1. Wallace AM, McMahon AD, Packard CJ, et al. Plasma leptin and the risk of cardiovascular disease in the west of Scotland coronary prevention study (WOSCOPS). Circulation. 2001; 104: 3052–3056.
2. Frank S, Colliver JA, Frank A. The electrocardiogram in obesity: statistical analysis of 1029 patients. J Am Coll Cardiol. 1986; 7: 295–299.[Abstract]
3. Narkiewicz K, Kato M, Phillips BG, et al. Leptin interacts with heart rate but not sympathetic nerve traffic in healthy male subjects. J Hypertens. 2001; 19: 1089–1094.[CrossRef][Medline] [Order article via Infotrieve]
4. Winnicki M, Phillips BG, Accurso V, et al. Independent association between plasma leptin levels and heart rate in heart transplant recipients. Circulation. 2001; 104: 384–386.
5. Hall JE, Hildebrandt DA, Kuo J. Obesity hypertension: role of leptin and sympathetic nervous system. Am J Hypertens. 2001; 14: 103–115.
Response
Departments of Pathological Biochemistry, Cardiology, Clinical Trials Unit Glasgow Royal Infirmary, Glasgow, Scotland, UK
Robertson Center for Biostatistics, University of Glasgow, Glasgow, Scotland, UK
We thank Pontiroli and colleagues for their interesting comments in relation to our paper1 on leptin as a novel risk factor for coronary heart disease (CHD). We accept that mechanisms other than those proposed in our article, including increased heart rate and long QTc, may link leptin to CHD. Fortunately, such parameters were measured at baseline in the West of Scotland Coronary Prevention Study (WOSCOPS) and we have therefore examined the relationship between leptin and the above parameters. In the 783 control subjects with leptin measurements, log leptin did not correlate with heart rate (r=0.03, P=0.39) but did so positively with QTc (r=0.10, P=0.005). However, body mass index (BMI) also correlated with QTc (r=0.15, P<0.001) and the association of leptin with QTc was lost with adjustment for BMI (r=0.018, P=0.62). This observation contrasts with findings for established risk factors such as C-reactive protein and triglyceride that do correlate with leptin independently of BMI. These data suggest that total adiposity rather than fat mass per se is linked to increased QTc.
References
1. Wallace AM, McMahon AD, Packard CJ, et al. Plasma leptin and the risk of cardiovascular disease in the west of Scotland coronary prevention study (WOSCOPS). Circulation. 2001; 104: 3052–3056.
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