Percutaneous coronary intervention (PCI) is an acceptable option in octogenarian patients, especially those with refractory angina. However, gender related differences in admission and outcome after PCI in female and male are not well recognized. Moreover, for octogenarians PCI is a higher risk of adverse outcomes secondary to procedural complications owing to a high prevalence of associated comorbid conditions such as anaemia [1]. Anaemia is common in elder people and geriatric hospitalized population [2,3]. Increasing age was found to be significantly associated with haemoglobin levels [4]. Elderly people might easily suffer from anaemia because haematological function declines with aging [5,6]. Shortened erythrocytes survival, decreased erythropoietin secretion, and concurrent deficiencies of iron, pyridoxine (vitamin B6) and folic acid may contribute to anaemia [7]. Anaemia has the potential to worsen the myocardial ischemia in acute coronary syndrome (ACS), both by decreasing the oxygen content of the blood supplied to the distressed myocardium and by increasing myocardial oxygen demand through necessitating a higher cardiac output to maintain adequate systemic oxygen delivery [8]. In this paper, admission haemoglobin levels and the factors related to haemoglobin concentrations and in-hospital outcomes were analysed at PCI for the management of ACS in female and male octogenarian patients.

Study population

We analyzed data of 2.256 consecutive patients who underwent PCI with bare metal and/or drug eluting stent implantation since March 2006 at our institution. There were 50 octogenarians (mean age: 82.5 ± 3.1 years), of whom 22 (44%) presented with unstable angina pectoris (USAP), 21 (42%) presented with non-ST segment myocardial infarction (NSTEMI), and 7 (14%) with ST segment elevation myocardial infarction (STEMI). The patients with active bleeding during admission were not included in this study. Some patients were receiving angiotensin-converting enzyme inhibitor, angiotensin II receptor blocker, beta blocker, calcium channel blocker, statin, clopidogrel and warfarin (2 female) for hypertension, diabetes mellitus, hyperlipidemia, atrial fibrillation, coronary artery or peripheral artery disease. Admission international normalized ratio (INR) levels were <1.5. Their baseline clinical characteristics, angiographic data, procedural details, clinical outcomes in hospital were analysed Table 1 and 2. Patient data and outcomes were collected from their medical archive. STEMI was determined by the presence of >30 min of continuous chest pain, a new or presumed new ST-segment elevation ≥2 mm on at least 2 contiguous electrocardiography leads, and creatine kinase-MB >3 times normal. NSTEMI was diagnosed by the presence of chest pain and a positive cardiac biochemical marker of necrosis (troponin or creatine kinase-MB) without new ST-segment elevation. USAP was diagnosed in the absence of ST-elevation and serum biochemical markers when patient complaints suggested an ACS. Chronic renal failure was defined as a baseline serum creatinine value ≥1.8 mg/dL. Anaemia was defined when haemoglobin concentrations fall below 12 g/dL for non-pregnant female, and 13 g/dL for male [2]. Left ventricular ejection fraction was measured by echocardiography (A Vivid 3 cardiovascular ultrasound system [3S sector probe (1.5-3.6 MHz), GE] or ventriculography during the hospitalization.

Table 1: Baseline characteristics, biochemical and hematologic values between male and female.

Table 2: Angiographic characteristics and procedural details.

Laboratory measurements

Blood samples were taken from the antecubital vein. Serum glucose, urea, creatinine, uric acid, cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL) and triglyceride levels were measured using an Abbott C8000 (Abbott, Japan) automatic analyzer. Serum creatine kinase, creatine kinase-MB and troponin I levels were measured with the use of a quantitative electro chemiluminescence immunoassay. D-dimer was assessed in plasma with the use of a quantitative and automated immunoassay. Thyroid stimulating hormone was measured with Immulite 2000 (DPC; Los Angeles, USA) by chemiluminescent immunometric assay. Plasma levels of BNP (ADVIA Centaur BNP Assay, USA) was measured using a competitive enzyme immunoassay. Blood cells were counted on the HMX (Beckman Coulter, USA) analyzer.

Procedure

Contemporary PCI was performed after obtaining written, informed consent. The interventional strategy and stent selection was at the discretion of the operators. Either the femoral artery or brachial artery approach was used. Patients received single or multiple bare metal stent or drug eluting stent for various lesions with or without predilatation. Intravascular ultrasound guided the procedure in about 30% of the cases. After stent implantation, angiographic optimization was performed by high pressure dilation to achieve an acceptable angiographic result with <30% residual stenosis by visual estimate. All patients received aspirin 300 mg/day ≥24 hr before the procedure and continued indefinitely. Additional antiplatelet therapy with clopidogrel, 75 mg/day (after a loading dose of 300-600 mg), was instituted in all the patients and advised to continue for ≥1 years. Intraprocedural anticoagulation was ensured using unfractionated heparin with or without glycoprotein IIb/IIIa inhibitors to achieve an activated clotting time of >250 sec in all patients.

Study end points

End points included major adverse cardiac events in-hospital. Major adverse cardiac events were defined as a composite of death, new myocardial infarction, or repeat revascularizations. Also, we noted the bleeding complications. The severity of bleeding complications was classified according to the Thrombolysis In Myocardial Infarction (TIMI) bleeding classification [9]. Major bleeding was defined as either intracranial haemorrhage or clinically overt bleeding of ≥5 g/dl decrease in the haemoglobin concentration, whereas minor bleeding was a 3 to 5 g/dl decrease, and minimal bleeding as a <3 g/dl decrease.

Statistical analysis

Statistics were obtained using the ready-to-use programme of SPSS version 8.0. Data are expressed as mean ± SD for continuous variables and as percentages for categorical variables. Nonparametric (Mann- Whitney u) test was used to compare continuous variables and the chi-square test or Fischer’s exact test was used to compare categorical variables between male and female. Pearson correlation analysis was used between haemoglobin and clinical, angiographic, procedural characteristics, biochemical and hematologic values. p value <0.05 was considered to indicate statistical significance.

Fifty octogenarian patients (mean age: 82.5 ± 3.1 years) enrolled in this study. 24 (48%) patients were male and 26 (52%) patients were female. With regard to indications for PCI, 22 (44%) had USAP, 21 (42%) had NSTEMI, and the remaining 7 (14%) had STEMI. No patient had chronic renal failure. Clinical baseline characteristics, biochemical and hematologic values between male and female are presented in Table 1, angiographic and procedural characteristics in Table 2. 80% of the procedures were elective; 34% of the patients had 2 or 3 vessel disease; 66% had only 1 vessel treated (with lesions of type B/C in 90% of cases); 2 female patients had left main artery disease. The mean diameter of stents were 2.80 ± 0.31 mm, the mean length of stents were 21.50 ± 6.54 mm. 64% were drug-eluting stents and the remainder were the bare metal type. The intra-aortic balloon pump was used in 3 patients (2 female). The overall procedural success rate was 98%. There was one mortality (female patient) in hospital. The causes of death included myocardial infarction complicating ventricular fibrillation. Stent thrombosis (with drug eluting stent) had developed 2 female patients; but no patient had any problem after re-intervention with balloon angioplasty. Bleeding risk is a major concern in older patients, especially when they are treated with dual antiplatelet agents (acetylsalicylic acid and clopidogrel) during the post-intervention period. Six patients (3 female) had minor bleeding complication from gastrointestinal system. Also 3 (2 female) patients had femoral artery pseudoaneurysm. Baseline mean haemoglobin levels were significantly elevated in male octogenarian patients as compared with female octogenarian patients (12.10 ± 1.37 mg/dl, 11.24 ± 1.03 mg/dl, p=0.02, respectively). Pearson correlation analysis between haemoglobin and clinical, angiographic, procedural characteristics, biochemical and hematologic values showed that haemoglobin only correlated negatively with leukocytes (r=-0.35; p=0.01).

In this paper, admission haemoglobin levels and the factors related to haemoglobin concentrations and in-hospital outcomes were analysed at PCI for the management of ACS in octogenarian patients. Mean admission haemoglobin levels were significantly elevated in male octogenarian patients as compared with female octogenarian patients (12.10 ± 1.37 mg/dl, 11.24 ± 1.03 mg/dl, p=0.02, respectively). Only blood leukocyte levels were found to be significantly associated with haemoglobin concentration.

Anaemia decreases oxygen delivery to tissues and causes increased cardiac output in order to meet the demand. Also, several mechanisms such as increased stroke volume and decreased peripheral vascular resistance and blood pressure have been proposed [10]. When haemoglobin, as a main oxygen carrier, concentration decreases, body may increase cardiac output to maintain the normal metabolic demands of tissues, which increases cardiac work, and result in myocardial damage [11,12]. The relationship between haemoglobin concentrations and cardiovascular outcomes has been reported in a broad cohort of patients with ACS [13,14]. But the exact underlying patho-mechanisms between low haemoglobin concentrations and adverse cardiovascular outcomes are not well recognized. Nikolsky et al. [15] showed that anaemia predicted death in patients with myocardial infarction treated with primary angioplasty. Recently, Pilgrim et al. [16] demonstrated that severe anaemia is common among patients undergoing PCI with the unrestricted use of drug eluting stent. Also, anaemia is associated with overall definite stent thrombosis (hazard ratio, 2.59; 95% confidence interval, 1.48-4.54; P=0.00089) and adversely affects long-term prognosis, including survival. The worse outcomes in patients with anaemia and ACS could be explained by the theory that anaemia could decrease oxygen delivery to tissues, therefore attenuate the ability of coronary collateral flow from nearby patent vessels to limit the extent of myocardial ischemia, meanwhile anaemia increase myocardial oxygen demand through necessitating a higher work load [8].

Haemoglobin levels may also be linked with other conditions that limit survival, such as like inflammatory, pulmonary or bone marrow disease. Accordingly, our data indicate negative correlation between haemoglobin levels and increased blood leukocytes levels, which suggest increasing inflammatory process [17]. Elevated leukocytes may predict incident cardiovascular events. It may influence the development of ACS some possible patho- physiological mechanisms including endothelial cell injury caused by proteolytic enzymes, vessel plugging, decreased perfusion, increased expression of monocyte tissue factors, activation of coagulation system, increased thrombus formation, and involvement in hematologic stress syndrome [18,19]. Among other links leukocytosis with ACS outcomes, it is hypothesized that elevated count of leukocytes may reflect a more severe condition or an association with other comorbidities that convey increased risk of adverse outcomes, such as infection, malignancy, trauma, and inflammation commonly linked to anaemia [17].

In conclusion, admission haemoglobin concentrations were significantly elevated in male octogenarian patients as compared with female octogenarian patients. Only blood leukocyte levels were found to be significantly associated with haemoglobin concentration. Therefore, anaemia and leucocytosis may be associated with worse in-hospital outcomes at PCI for the management of ACS in female octogenarian patients. For this reason, in such patients additional precautions may be useful such as during procedure.

Limitations of this Study

As this is a retrospective study, some potential limitations of this study should be considered. The cause of anaemia in patients in the present study was not known, the different causes might have residual confounding. Because the active bleeding during admission was not included in this study, the anaemia exactly means chronic anaemia. Also, these conclusions may not extend to the great population. Therefore, the results of this study will need confirmation in larger studies.