Exercise cardiac power and the risk of myocardial infarction and fatal coronary heart disease events in men

Cardiorespiratory fitness (CRF) is a predictive marker of cardiovascular capacity; however, it does not take into account possible differences in cardiovascular resistance and cardiac afterload between the subjects. Exercise cardiac power (ECP) is defined as the ratio of directly measured VO_2max with peak systolic blood pressure (SBP) during exercise test. We aimed to explore whether ECP was a risk predictor of acute myocardial infarction (AMI) and fatal coronary heart disease (CHD) events.

Hence, we investigated the association of ECP (mL/mmHg) by integrating surrogates of preload (VO_2max) and afterload (SBP) during exercise test with the risk of AMI and fatal CHD events in a population based sample of men.

Subjects were participants in the Kuopio Ischaemic Heart Disease Risk Factor Study, designed to investigate risk factors for cardiovascular diseases and related outcomes in a population-based, randomly selected sample of men.^1,2 Examinations were conducted on 2682 men aged 42 to 61 years between March 1984 and December 1989 at baseline. The study was approved by the Research Ethics Committee, University of Kuopio. Each participant gave written informed consent. Complete data on ECP was available on 1798 subjects with no CHD at baseline. Subjects were divided into quartiles based on ECP levels.

The standardized testing protocol comprised an increase in the workload of 20 W/min with the direct analyses of respiratory gases. The VO_2max was defined as the highest value or the plateau of oxygen uptake. Blood pressure was measured every 2 min during the test. The maximal SBP was the highest value achieved during the test. Use of medications and diagnosis of diseases were collected at baseline examination. ¹ Left ventricular hypertrophy (LVH; Sokolow–Lyon index) and blood pressure were recorded at rest. Elevated resting SBP was >130 mmHg. Alcohol consumption was assessed using the Nordic Alcohol Consumption Inventory. Blood specimens collection and measurement of serum lipids and lipoproteins, insulin, smoking, resting blood pressure and type 2 diabetes and body mass index (BMI) have been described elsewhere.^2,3

The diagnostic classification of coronary events were based on symptoms, electrocardiographic findings and cardiac enzyme elevations. Each suspected coronary event was coded according to Ninth or Tenth (code numbers 410–414, I20–I25) International Classification of Diseases.

Risk factors for main outcomes were analysed with a multivariate Cox hazards models. To characterize the shape of the association between ECP and risk of AMI and CHD, hazard ratios were calculated within quartiles. The Kaplan–Meier cumulative survival curves from AMI according to the presence of ECP are shown in Figure 1.

Figure 1.

The age and examination year adjusted survival curves of acute myocardial infarction in men according to quartiles of exercise cardiac power.

The mean age was 52.2 years (range 42 to 61 years) and the mean ECP was 12.4 mL/mmHg (standard deviation (SD), 3.09 mL/mmHg, range 3.58 to 29.57 mL/mmHg). At baseline, men with low ECP were older, smoked more, and had higher serum LDL cholesterol, SBP, higher prevalence of diabetes and were less physically active and consumed more alcohol as compared with those with higher ECP. During an average follow-up of 25 years 260 cases of AMI and 161 of CHD deaths occurred.

One SD increase in ECP was associated with a decrease in AMI by 28% (95% confidence interval (CI) 37% to 16%). Low ECP was associated with a 2.1-fold (<8.7 mL/mmHg, lowest quartile) risk of AMI (Table 1) and 3.9-fold risk of CHD death after adjustment for age, examination year, the use of the use of antihypertensive medication, smoking, alcohol, BMI, energy expenditure of physical activity, diabetes, C-reactive protein, serum low-density lipoprotein (LDL) and high-density lipoprotein cholesterol as compared with men who had high ECP (>16.1 mL/mmHg, highest quartile). After further adjustment for LVH, men with low ECP had increased risk of CHD death (hazard ratio 3.7, 95% CI 1.98 to 6.82, p<0.001).

Table 1.

The hazard ratios of acute myocardial infarction and fatal coronary heart disease events in the quartiles of exercise cardiac power in men at baseline ^a .

Risk factor	Acute myocardial infarctionn=260					Coronary heart disease deathn=161
Exercise cardiac power	HR (95% CI) a	p value	HR (95% CI) b	p value	No. of cases	HR (95% CI) a	p value	HR (95% Cl) b	p value	No. of cases
>16.47 mL/mmHg (first quartile) n=449	1.00		1.00		41	1.00		1.00		16
11.21–16.47 mL/mmHg (second quartile) n=450	1.30(0.83–1.91)	0.229	1.28(0.86–1.93)	0.230	55	1.68(0.91–3.09)	0.095	1.42(0.70–2.89)	0.328	30
8.78–11.20 mL/mmHg (third quartile) n=450	1.81(1.22–2.67)	0.002	1.63(1.10–2.42)	0.014	73	2.57(1.44–4.57)	0.001	2.84(1.49–5.39)	0.001	46
<8.77 mL/mmHg (fourth quartile) n=449	2.55(1.73–3.75)	<0.001	2.14(1.44–3.18)	<0.001	91	4.10(2.34–7.2)	<0.001	3.92(2.08–7.40)	<0.001	69

^aAdjusted for age and examination year.

^bAdjusted for age, examination year, the use of antihypertensive medication, cigarette smoking, alcohol consumption, body mass index, the energy expenditure of physical activity, type 2 diabetes, C-reactive protein and serum high-density lipoprotein and low-density lipoprotein cholesterol.

HR: hazard ratio; Cl: confidence interval.

Combination of low ECP and elevated SBP at rest was related to 2.3-fold (95% CI 1.02 to 5.31, p=0.045) risk of AMI and 3.9-fold (95% CI 1.64 to 5.99, p= 0.001) for fatal CHD events as compared with men with high ECP and low resting SBP.

Exercise cardiac power, a novel marker of peak cardiac output during exercise, was associated with an increased risk of AMI events in a population-based study of men. The integration of afterload and preload with VO_2max and peak SBP during exercise test emphasizes the role of ergospirometry in the risk prediction of AMI and fatal CHD events and gives prognostic information in addition to that obtained by conventional methods.

The novelty is that ECP provides incremental prognostic power on AMI event risk assessment, despite taking into account established risk factors such as smoking, lipids, hypertension, LVH and diabetes. A continuous increase in ECP (3.2 mL/mmHg) corresponds to 28% decrease in the risk for AMI. ECP, a function of cardiac output (VO_2max) and peripheral resistance (SBP), may improve the predictive value of VO_2max alone. Studies have suggested that low CRF is comparable to other conventional risk factors for CHD.^4–7 In addition to resting SBP, exercise-induced elevation of SBP and exercise capacity have been found to be independent predictors of CHD and mortality.^8,9 Based on our study, ECP may provide a more valuable tool for the risk prediction for AMI than CRF alone during exercise stress test. Cardiac function during exercise may be caused by dynamic coronary artery stenosis as a result of vessel constriction, endothelial dysfunction, spasm and thrombosis. ¹⁰

Incidence of AMI and fatal CHD events can be reduced by a combination of several approaches and hence preventing their occurrence. VO_2max may be preserved among subjects with medications lowering afterload despite the reduced pumping capacity. As ECP is a function of cardiac output and peripheral resistance, it may improve the predictive value of VO_2max alone. Our findings suggest that it may be useful to assess the level of ECP although further studies are needed showing ECP as a prognostic measure in different sexes.

In conclusion, this prospective study provides evidence that low ECP is associated with an increased risk of AMI and fatal CHD events. ECP during exercise testing may provide valuable information on the evaluation of AMI risk and fatal CHD events.