Yoram Neuman

Mortality and Coronary Heart Disease in Euthyroid Patients

BACKGROUND Subclinical thyroid dysfunction is associated with increased mortality and cardiovascular risk. It is unknown whether this association remains within normal thyroid function range. METHODS The study was conducted using the computerized database of the Sharon-Shomron district of Clalit Health services. Included were subjects aged ≥40 years with normal thyroid function. Patients with a history of thyroid or cardiovascular diseases or diabetes were excluded. The primary end points were all-cause mortality and the need for coronary revascularization with either percutaneous coronary intervention or coronary artery bypass grafting. RESULTS The 42,149 participants were stratified into 3 groups of equal thyrotropin intervals (0.35-1.6, 1.7-2.9, and 3-4.2 mIU/L). During a mean follow-up of 4.5±2.1 years, 4239 (10.1%) participants died and 1575 (3.7%) underwent coronary revascularization. For both women and men, the lowest mortality rates were observed in the intermediate thyrotropin group. Nevertheless, only for the low thyrotropin group, mortality risk remained significantly higher as compared with the intermediate thyrotropin group, even following multivariate model adjusted for the conventional cardiovascular risk factors, in both women (odds ratio 1.22; 95% confidence interval, 1.09-1.36 for the low thyrotropin group, compared with the intermediate group) and men (odds ratio 1.14; 95% confidence interval, 1.01-1.3 for the low thyrotropin group, compared with the intermediate group). There was no significant difference in the need for coronary revascularization among the 3 thyrotropin groups in both men and women. CONCLUSIONS Low thyrotropin level within the reference range is associated with increased risk for all-cause mortality.

USage of chitosan for Femoral (USF) haemostasis after percutaneous procedures: a comparative open label study.

AIMS To test the efficacy and safety of a chitosan pad for femoral haemostasis as an adjunct to manual compression. Haemostasis of the femoral artery after coronary angiography by manual compression is time consuming and uncomfortable for the patient. Closure devices are costly and do not reduce vascular complication rate. The HemCon(r) pad is used by the US army to control traumatic bleeding. It consists of chitosan, a positively charged carbohydrate that attracts the negatively charged blood cells and platelets and promotes clotting. METHODS AND RESULTS Patients undergoing percutaneous coronary angiography were 1:1 randomised for manual compression with regular or HemCon(r) pad. All patients were catheterised with 6 Fr sheath and received 2500 u of heparin. Time to haemostasis, incidence of minor and major bleeding, haematoma size, post-procedural stay at the hospital and level of satisfaction were compared between the two groups. Seventy patients in the HemCon group and 66 patients in the regular pad groups were recruited. Activated clotting time (ACT) before manual compression was similar, 183.9 ± 43.4 and 178.3 ± 34.2 seconds in the HemCon(r) and regular pad groups respectively. Time to haemostasis was 5.6 ± 2.1 and 8.4 ± 3.5 minutes in the HemCon® and regular pad groups, respectively (p<0.001). Haematoma developed in 6% and 14.8% of patients in the HemCon(r) and regular pad group, respectively (p=0.14). CONCLUSIONS The HemCon(r) pad significantly decreased time-to-haemostasis compared to the regular pad. The total incidence of haematoma tended to be lower in the HemCon(r) pad compared to the regular pad group.

Comparison of lipid control in patients with coronary versus peripheral artery disease following the first vascular intervention.

Peripheral arterial disease (PAD) is a strong risk factor for cardiovascular morbidity and mortality. Therefore, target low-density lipoprotein (LDL) cholesterol level in patients with PAD is ≤70 mg/dl, similar to patients with coronary artery disease (CAD). However, despite their high cardiovascular risk, patients with PAD less frequently achieve LDL cholesterol goals compared to patients with CAD. We aimed to compare LDL cholesterol control in patients after first coronary or peripheral vascular intervention. Included were patients ≥18 years of age without a history of cardiovascular disease who underwent first coronary or peripheral vascular intervention from 2004 through 2010. Primary end points were percentage of patients who achieved the LDL cholesterol goal of <100 and <70 mg/dl. Of 9,138 patients available for analysis, 7,512 (82.2%) underwent first coronary revascularization and 1,626 (17.8%) underwent first peripheral revascularization. Patients after first coronary revascularization were treated more frequently with any statin and with highly potent statins. Furthermore, they more frequently achieved the LDL cholesterol goals compared to patients after first peripheral intervention. This was true for the LDL cholesterol goal of <100 mg/dl (65% and 46.7%, p <0.0001) and for the lower LDL cholesterol goal of <70 mg/dl (23.3% and 13.3%, p <0.0001). Differences in LDL cholesterol control between the 2 groups remained statistically significant after multivariate adjustment. In conclusion, lipid control in patients with PAD is poor and significantly inferior to that of patients with CAD even after the first vascular intervention.

Prevalence and Significance of Unrecognized Renal Dysfunction in Patients with Acute Coronary Syndrome

BACKGROUND Unrecognized renal insufficiency, defined as estimated glomerular filtration rate <60 mL/min/1.73 m(2) in the presence of normal serum creatinine, is common among patients with acute coronary syndrome. We aimed to determine the prevalence and clinical significance of unrecognized renal insufficiency in a large unselected population of patients with acute coronary syndrome. METHODS The study population consisted of patients with acute coronary syndrome included in the Acute Coronary Syndrome Israeli biennial Surveys during 2000-2013. The estimated glomerular filtration rate was calculated using the simplified Modification of Diet in Renal Disease formula. Patients were stratified into 3 groups: 1) normal renal function (estimated glomerular filtration rates ≥60 mL/min/1/73 m(2)); 2) unrecognized renal insufficiency (estimated glomerular filtration rates <60 mL/min/1/73 m(2) with serum creatinine ≤1.2 mg/dL); and 3) recognized renal insufficiency (estimated glomerular filtration rates <60 mL/min/1/73 m(2) with serum creatinine ≥1.2 mg/dL). The primary endpoint was all-cause mortality at 1 year. RESULTS Included in the study were 12,830 acute coronary syndrome patients. Unrecognized renal insufficiency was present in 2536 (19.8%). Patients with unrecognized renal insufficiency were older and more frequently females. All-cause mortality rates at 1 year were highest among patients with recognized renal insufficiency, followed by patients with unrecognized renal insufficiency, with the lowest mortality rates observed in patients with normal renal function (19.4%, 9.9%, and 3.3%, respectively, P <.0001). Despite their increased risk, patients with renal insufficiency were less frequently referred for coronary angiography and were less commonly treated with guideline-based cardiovascular medications. CONCLUSIONS Acute coronary syndrome patients with unrecognized renal insufficiency should be considered as a high-risk population. The question of whether this group would benefit from a more aggressive therapeutic approach should still be evaluated.

Comparison of mortality in patients with coronary or peripheral artery disease following the first vascular intervention.

ObjectivesPatients with peripheral artery disease (PAD) less frequently achieve secondary prevention goals compared with patients with coronary artery disease (CAD). We aimed to compare mortality rates in patients with PAD and CAD following first vascular intervention. Patients and methodsPatients 18 years of age or older without a history of cardiovascular disease, who underwent first coronary or lower limb vascular intervention between 2002 and 2010, were included in this study. The primary endpoint was all-cause mortality. ResultsOf the 9950 participants, 8242 (82.8%) underwent first coronary revascularization and 1708 (17.2%) received first peripheral vascular intervention. During a mean follow-up period of 5.6±2.3 years, 1283 (12.9%) participants died. Compared with CAD patients, patients with PAD had significantly worse long-term prognosis with an increased risk for all-cause mortality (hazard ratio=2.95, 95% confidence interval 2.6–3.3, P<0.0001). This association remained statistically significant following a multivariable analysis (hazard ratio=1.86, 95% confidence interval 1.6–2.1, P<0.0001). Furthermore, PAD patients were less frequently treated with cardioprotective medications including statins, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, aspirin, and clopidogrel (P<0.001). ConclusionPatients with PAD have worse outcome compared with patients with CAD, even in the specific group of patients following first vascular intervention. These findings demand more effort to improve secondary prevention guidelines in all patients with cardiovascular diseases, but especially in PAD patients.

Admission plasma glucose levels within the normal to mildly impaired range and the outcome of patients with acute coronary syndrome.

Background: Elevated admission plasma glucose levels >140 mg/dl are associated with adverse clinical outcomes in both diabetic and non-diabetic patients admitted with acute coronary syndrome (ACS). We aimed to evaluate the association between admission plasma glucose levels <140 mg/dl and the outcome of non-diabetic patients admitted with acute coronary syndrome. Methods: The study population consisted of patients with acute coronary syndrome included in the Acute Coronary Syndrome Israeli Survey during 2000–2013. Diabetic patients were excluded. The primary endpoint was all-cause mortality at one year. Results: The 4520 patients had a mean age of 61.7±13.5 years and were stratified into four quartiles according to admission plasma glucose (60–94, 95–105, 106–119, 120–140 mg/dl). Patients with higher admission plasma glucose were older and included a higher percentage of smokers. In addition, the higher the glucose so also did they have a poorer risk factor profile including a higher body mass index, total and low-density lipoprotein cholesterol and triglyceride levels, and lower high-density lipoprotein cholesterol levels. During the first year 5.2% of patients died. A comparison of one-year mortality according to admission plasma glucose quartiles demonstrated a significant and progressive increase in mortality risk as admission plasma glucose rose (3.5%, 4.1%, 6.1%, 6.4%, respectively, p=0.001). However, this association lost its clinical significance following a multivariate analysis (p=0.08). Conclusions: High admission plasma glucose levels within the normal to mildly impaired range are associated with increased one-year mortality in non-diabetic acute coronary syndrome patients. However, the higher glucose level is probably not the cause for the adverse outcome but rather a marker for high risk. Our findings support the definition of 140 mg/dl as the cutoff for clinically acceptable admission glucose levels in patients with acute coronary syndrome.

The Effect of Admission Renal Function on the Treatment and Outcome of Patients with Acute Coronary Syndrome

Background: Chronic kidney disease is a frequent comorbidity among patients with acute coronary syndrome (ACS). We aimed to evaluate treatment characteristics in ACS patients according to their renal function and to assess the effect of differences in therapy on clinical outcomes. Methods: Included were patients with ACS enrolled in the biennial Acute Coronary Syndrome Israeli Surveys (ACSIS) during 2000-2013. Excluded were patients with cardiogenic shock at presentation. The estimated glomerular filtration rate (eGFR) was calculated using the simplified Modification of Diet in Renal Disease (MDRD) formula. The distribution of the eGFRs was divided into 4 categories (<45, 45-59.9, 60-74.9, and ≥75 mL/min/1.73 m2). The primary endpoint was all-cause mortality at 1 year. Results: A total of 13,194 patients with ACS were included. Patients with a reduced eGFR were less likely to be admitted to a coronary care unit and had lower rates of coronary angiograms and subsequent percutaneous coronary interventions. Furthermore, as the eGFR was lower, the patients were less frequently treated with aspirin, clopidogrel, β-blockers, and ACE inhibitors/angiotensin receptor blockers. We demonstrated an inverse association between renal function and 1-year mortality, with the highest mortality rates observed in the group with the lowest eGFR (HR = 3.8, 95% CI 2.9-4.9, p < 0.0001). Differences in mortality remained significant following a multivariate analysis for all the baseline characteristics as well as for invasive and medical treatment (HR = 2.7, 95% CI 1.9-3.7, p < 0.0001). Conclusions: ACS patients with chronic kidney disease represent a high-risk group with an increased mortality risk. Despite this high risk, these patients are less frequently selected for an invasive treatment strategy and are less commonly treated with guideline-based medications. However, reduced renal function was associated with higher mortality regardless of the variations in therapy.