The high incidence of AMI in older and males may be due to an increased incidence of metabolic diseases, such as hypertension and diabetes as well as smoking in men. Indonesian health survey in 2018 found that 10.9% and 34.1% of the population had diabetes mellitus and hypertension respectively, and that these percentages increase with age. For example, the prevalence of hypertension was 45.3% among 45–54 years old and increased to 63.2% among 65–74 years old. In addition, 31.3% of the hypertension sufferers were male. Meanwhile, the World Health Organisation (2015) show that 24.1% of male and 20.1% of female worldwide had high blood pressure. There was an increase in the number of hypertensive patients from 594 million in 1975 to more than 1.13 billion in 2015 [7, 8].
Birry K et al. (2012) found that the mean age of acute coronary syndromes (ACS) patients ware 56.24 ± 11.18 years, and 67.3% were male; these demographics are almost the same as those in the present study. Similarly, in Zulkifli et al. (2017) study, the mean age of ACS patients was 59.97 ± 10.62 years, and 72.5% were male [9, 11].
The incidence of MACE in this study was 15.8%. This result is higher than that of previous studies conducted at RSCM. Diah et al. (2018) and Anastasia et al. (2019) conducted studies on ACS patient populations and found that 9.6% and 11.9%, respectively had MACE. Diah found 25%, 36.5%, and 38% of patients had unstable angina pectoris, STEMI, and NSTEMI, respectively. For the same conditions, Anastasia's results were 37.5%, 37.5%, and 25%, respectively. In the present study, which only focused on AMI patients with STEMI or STEMI, 62.5% had STEMI, and 37.5% had NSTEMI. The large proportion of patients with STEMI led to a higher prevalence of MACE in the sample population because, as shown in the literature, the risk of MACE in the acute period of STEMI is much greater than in NSTEMI or unstable angina pectoris [9,10,11].
The average BPV value in the present study was slightly lower than the value identified by Mancia (2007), who studied non-AMI patients who died from cardiovascular events. The mean SD-SBP and SD-DBP in Mancia’s study were15.3 ± 3.9 mmHg and 12.7 ± 3.4 mmHg, respectively. Meanwhile, systolic and diastolic ARV was 8.6 ± 1.4 mmHg and 9.9 ± 1.6 mmHg, respectively. This difference between Mancia’s and the present study may be due to close monitoring of BP and immediate pharmacological intervention in the intensive care unit. In contrast, BPV assessments of people who are not hospitalized, the control and supervision of BP is highly dependent on individual awareness [12, 13].
Hassan et al. (2017), conducted a prospective cohort study with 200 samples and found a significant correlation between a high BPV and the incidence of MACE in AMI patients who were observed for the first seven days of hospitalization. In Hassan’s study, a weighted standard deviation of blood pressure (wSD-BP) and the standard deviation of the 24-hour systolic-diastolic blood pressure (SD-SBP/SD-DBP) was used to measure BPV. Hassan et al. found a significant correlation between the high wSD-BP group (>12.6mmHg) and the high SD-SBP group (>13.5 mmHg) and the incidence of MACE (r=0.56, p=0.003). The present study findings indicate that BPV and MACE did not have a significant relationship in the first five days of AMI patient hospitalization. However, the average BPV value in the MACE group was higher than in the non-MACE group. The result is in line with the finding in Hassan et al study [14].
The non-significance relationship between BPV and MACE found in the present study could be due to the study population, which included patients with various cardiovascular risk factors. The BPV characteristics in each comorbid disease affected the average BPV of the entire study population and affected the relationship between BPV and MACE.
Variations in blood pressure mainly cause mechanical responses in the form of shear stress and circular stretch on the endothelium and blood vessel walls. These pressure and stretch forces cause deformity of the vessel structure consisting of cells and connective tissue, which in turn, stimulate the release of biochemical reactants. On physiological conditions, there is a balance between mechanical and chemical stimuli with biological responses which maintain the hemostatic function of blood vessels. In vitro studies have shown that an increased acute stress load immediately induces signaling sequences and remodeling of the endothelium. This series of responses include activation of nuclear factor-κβ (NF-κβ), intercellular adhesion molecules-1 (ICAM-1), monocyte chemoattractant protein-1 (MCP-1), tissue factor, platelet-derived growth factor-B (PDGF-B), transforming growth factor (TGF-β1), cyclooxygenase-2 (COX-2), endothelial nitric oxide synthase (eNOS) and manganese superoxide dismutase. The aforementioned biological processes lead to the release of NO and prostacyclin, which are the main vessels vasodilators [15, 16].
Regarding mechanobiological response, chronic stress and strain decrease the production of eNOS, endothelin-1(ET-1), and PDGF-B. In addition, lead to a decrease in the production of prostaglandin vasodilators and an increase in oxidative stress production, the activation of platelet and erythrocyte aggregation, and cell hypertrophy as well as an increase in the density of actin-myosin filaments. The mechanobiological response above predisposes patients to atherosclerosis, prothrombotic conditions, and chronic systemic inflammation, which in turn have a pathological effect on the cardiovascular system and future MACE risk [15, 16].
The non-significant relationship between BPV and MACE in the presents study may also be because the stress and strain loading caused by BPV tends to lead to chronic low-grade inflammation response. Traditional factors, such as the location and extent of the infarct, the number and location of the coronary vessels involved, and the functional capacity of the heart before the attack, seem to be the primary determinants of the incidence of MACE during the acute period of AMI. According to the study finding, the acute inflammation that occurs in AMI which is exacerbated by the vascular inflammatory process in response to pressure and strain loads, is not strong enough to induce MACE in AMI. Duplication of the inflammatory response due to AMI, increase ventricular load and myocardial oxygen demand caused by high BPV that could be associated with the incidence of MACE in the acute period of AMI, was not supported.
As previously mentioned, the systolic BPV in AMI patients with hypertension who experienced MACE was significantly higher than in patients without hypertension who experienced MACE. This was probably caused by the underlying disease suffered by the patients. Previous studies have shown that BPV tends to be higher in the hypertensive population than in the non-hypertensive population. The occurrence of AMI followed by an increased sympathetic activity and baroreceptor dysfunction further increase BPV in the hypertensive population [17,18,19].
Furthermore, high BPV in hypertensive patients is amplified by increased sympathetic activity and heart rate during AMI. This pathological condition is further exacerbated by the high sympathetic activity, vasoactive-vasodilator imbalance, renin-angiotensin aldosterone system activation, and chronic inflammation that was already present in hypertensive patients. A high BPV value and the accompanying pathological consequences are likely to have a large resultant effect on target organs and the emergence incidence of MACE in hypertensive AMI patients [17, 18].
The effect of hypertension on the incidence of MACE was further strengthened by the results of the multivariate analysis conducted on existing cardiovascular risk factors. It was found that the following variables influence the incidence of MACE; hypertension (OR=7.452), smoking (OR=3.902), and previous cardiovascular disease (OR=2.832). The significant difference in BPV values in patients with hypertension who experience MACE compared with patients without hypertension who experience MACE illustrates the important role of BPV in hypertensive patients in terms of MACE complications during AMI. The identification of hypertension as a major risk factor for MACE raises questions for further research on the effect of BPV on the incidence of MACE in patients with hypertension.
As a retrospective study, technical errors in BP measurement for some patients cannot be avoided. To the best of our’s knowledge, this is the first study in Indonesia to investigate the effect of BPV on the incidence of MACE. As such, we hope that this study will increase literacy about BPV and its relation to MACE and improve standard management for AMI patients.
