The results of the present study demonstrate an association between high levels of sPAP and a one- and five-year mortality rate after AMI in a cohort of elderly patients, all aged 80 or older at baseline. After multivariate adjustment, sPAP with a threshold ≥ 40 mmHg was a strong independent predictor with a two-fold increased risk for all-cause mortality rate at one and five years. Each 5 mmHg increase in sPAP was associated with a 17 and 15% increased relative risk of all-cause mortality at one and five years, respectively.
To our knowledge, the present study is the first to analyze the impact of sPAP on the prognosis at one and five years after AMI in a sample of elderly patients, ≥ 80 years old. However, the impact of sPAP on survival after AMI has been demonstrated in several studies in recent years.14,15,16,17, but these studies compared to the present study were conducted in much younger patients with shorter follow-up periods. The results of the present study add more data to the available evidence supporting the impact of sPAP on short- and long-term survival and in all patient age groups, including patients ≥ 80 years old.
Interestingly, sPAP was a stronger predictor for both short-term and long-term mortality, compared to LVEF which showed no statistically significant impact in multivariate Cox regression models. These results indicate that sPAP as a marker of hemodynamic dysfunction21 after AMI is a stronger prognostic predictor, compared to LVEF as a marker of structural LV dysfunction.
Cox multivariate proportional hazards regression models found sPAP ≥ 40 mmHg to be the only independent predictor of one-year all-cause mortality after AMI. While independent predictors of increased five-year all-cause mortality, besides sPAP ≥ 40 mmHg, were also diabetes mellitus and atrial fibrillation and eGFR ≤ 35 ml/min, while treatment with PCI had a protective effect on survival. These results indicate that patients with high sPAP have a high risk of impaired survival from the first year and these patients should be identified and matched for secondary preventive care as soon as possible.
Pathophysiological mechanisms of elevated pulmonary arterial pressure after AMI
AMI can lead to decreased left ventricular (LV) pumping function and thus increased LV filling pressures. Increased LV filling pressures transmit backward into the pulmonary circulation, resulting in increased pulmonary arterial pressure (PAP). Elevated PAP is frequently associated with a reactive increase in pulmonary vascular resistance (PVR), leading to a further increase in PAP22. Thus, pulmonary circulation after AMI is characterized by elevated PAP and PVR, which increases right ventricular (RV) afterload and may contribute to RV dysfunction and possibly RV failure.23.
The mechanism underlying pulmonary vasoconstriction after AMI is not fully understood, but may involve alterations in angiotensin-II24,25,26as well as endothelial dysfunction22.
The pulmonary vascular endothelium is the predominant site of angiotensin converting enzyme which hydrolyzes angiotensin-I to angiotensin-II. The pulmonary circulation is very sensitive to the vasoconstrictor and proliferative effects of angiotensin-II24,25,26therefore, after AMI develops progressive PHT and RVH with extensive lung structural remodeling characterized by proliferation of myofibroblasts and a vicious cycle of cardiopulmonary dysfunction26.
Another reason for the high PAP level could be ischemic mitral valve regurgitation, which is a common complication after AMI and often associated with a poor prognosis.27,28,29.
The evidence and mechanisms mentioned above indicate that patients with elevated sPAP after AMI could benefit from personalized and intensive treatment with angiotensin enzyme inhibitors and angiotensin receptor blockers, to prevent the development of post-AMI heart failure and thus improve survival.
Elevated sPAP was an independent risk factor for all-cause mortality at one and five years after AMI in very elderly patients, and sPAP appears to be a better prognostic predictor of all-cause mortality than LVEF. The risk of all-cause mortality after AMI increased with increasing sPAP.
Strengths and limitations
Data for the present study was collected from medical records at one of the two largest heart centers in Gothenburg. All echocardiography studies were performed by an echocardiography specialist in the Department of Clinical Physiology and all echocardiography reports were reviewed by the authors. However, in this observational study, medical records were reviewed retrospectively. Additionally, despite our efforts to gather as much information as possible, some patient data was not available. Moreover, despite the adjustment, we cannot rule out residual confounding of unmeasured variables. The sample size was relatively small and included both STEMI and non-STEMI patients. There were a limited number of patients with adequate sPAP data. Nevertheless, the study showed a significant association between elevated sPAP and mortality in patients 80 years or older who had suffered a myocardial infarction.
In addition, the estimation of sPAP by echocardiography includes an approximation of the right atrial pressure using the width of the inferior vena cava and its respiratory variation. The gold standard would be right heart catheterization for the measurement of pulmonary arterial pressure, a data that was not available in our current study.
In clinical practices after AMI, sPAP can be used as a marker of poor prognosis and a target in secondary preventive care to reduce mortality and morbidity rates. As a secondary preventive management after AMI, treatment with renin-angiotensin-aldosterone system (RAAS) inhibitors may improve prognosis in patients with elevated sPAP after AMI. However, this is pure speculation. ACEI/ARB treatment had no significant impact on survival in the present study, which may be due to the study patients having relatively low doses of ACEI/ARB.