Sadi Gulec

Urinary Sodium and Potassium Excretion, Mortality, and Cardiovascular Events

BACKGROUND The optimal range of sodium intake for cardiovascular health is controversial. METHODS We obtained morning fasting urine samples from 101,945 persons in 17 countries and estimated 24-hour sodium and potassium excretion (used as a surrogate for intake). We examined the association between estimated urinary sodium and potassium excretion and the composite outcome of death and major cardiovascular events. RESULTS The mean estimated sodium and potassium excretion was 4.93 g per day and 2.12 g per day, respectively. With a mean follow-up of 3.7 years, the composite outcome occurred in 3317 participants (3.3%). As compared with an estimated sodium excretion of 4.00 to 5.99 g per day (reference range), a higher estimated sodium excretion (≥ 7.00 g per day) was associated with an increased risk of the composite outcome (odds ratio, 1.15; 95% confidence interval [CI], 1.02 to 1.30), as well as increased risks of death and major cardiovascular events considered separately. The association between a high estimated sodium excretion and the composite outcome was strongest among participants with hypertension (P=0.02 for interaction), with an increased risk at an estimated sodium excretion of 6.00 g or more per day. As compared with the reference range, an estimated sodium excretion that was below 3.00 g per day was also associated with an increased risk of the composite outcome (odds ratio, 1.27; 95% CI, 1.12 to 1.44). As compared with an estimated potassium excretion that was less than 1.50 g per day, higher potassium excretion was associated with a reduced risk of the composite outcome. CONCLUSIONS In this study in which sodium intake was estimated on the basis of measured urinary excretion, an estimated sodium intake between 3 g per day and 6 g per day was associated with a lower risk of death and cardiovascular events than was either a higher or lower estimated level of intake. As compared with an estimated potassium excretion that was less than 1.50 g per day, higher potassium excretion was associated with a lower risk of death and cardiovascular events. (Funded by the Population Health Research Institute and others.).

Prevalence of a Healthy Lifestyle Among Individuals With Cardiovascular Disease in High-, Middle- and Low-Income Countries The Prospective Urban Rural Epidemiology (PURE) Study

IMPORTANCE Little is known about adoption of healthy lifestyle behaviors among individuals with a coronary heart disease (CHD) or stroke event in communities across a range of countries worldwide. OBJECTIVE To examine the prevalence of avoidance or cessation of smoking, eating a healthy diet, and undertaking regular physical activities by individuals with a CHD or stroke event. DESIGN, SETTING, AND PARTICIPANTS Prospective Urban Rural Epidemiology (PURE) was a large, prospective cohort study that used an epidemiological survey of 153,996 adults, aged 35 to 70 years, from 628 urban and rural communities in 3 high-income countries (HIC), 7 upper-middle-income countries (UMIC), 3 lower-middle-income countries (LMIC), and 4 low-income countries (LIC), who were enrolled between January 2003 and December 2009. MAIN OUTCOME MEASURES Smoking status (current, former, never), level of exercise (low, <600 metabolic equivalent task [MET]-min/wk; moderate, 600-3000 MET-min/wk; high, >3000 MET-min/wk), and diet (classified by the Food Frequency Questionnaire and defined using the Alternative Healthy Eating Index). RESULTS Among 7519 individuals with self-reported CHD (past event: median, 5.0 [interquartile range {IQR}, 2.0-10.0] years ago) or stroke (past event: median, 4.0 [IQR, 2.0-8.0] years ago), 18.5% (95% CI, 17.6%-19.4%) continued to smoke; only 35.1% (95% CI, 29.6%-41.0%) undertook high levels of work- or leisure-related physical activity, and 39.0% (95% CI, 30.0%-48.7%) had healthy diets; 14.3% (95% CI, 11.7%-17.3%) did not undertake any of the 3 healthy lifestyle behaviors and 4.3% (95% CI, 3.1%-5.8%) had all 3. Overall, 52.5% (95% CI, 50.7%-54.3%) quit smoking (by income country classification: 74.9% [95% CI, 71.1%-78.6%] in HIC; 56.5% [95% CI, 53.4%-58.6%] in UMIC; 42.6% [95% CI, 39.6%-45.6%] in LMIC; and 38.1% [95% CI, 33.1%-43.2%] in LIC). Levels of physical activity increased with increasing country income but this trend was not statistically significant. The lowest prevalence of eating healthy diets was in LIC (25.8%; 95% CI, 13.0%-44.8%) compared with LMIC (43.2%; 95% CI, 30.0%-57.4%), UMIC (45.1%, 95% CI, 30.9%-60.1%), and HIC (43.4%, 95% CI, 21.0%-68.7%). CONCLUSION AND RELEVANCE Among a sample of patients with a CHD or stroke event from countries with varying income levels, the prevalence of healthy lifestyle behaviors was low, with even lower levels in poorer countries.

Elevated Whole-Blood Tissue Factor Procoagulant Activity as a Marker of Restenosis After Percutaneous Transluminal Coronary Angioplasty and Stent Implantation

Background—Experimental data suggest that tissue factor (TF) may induce neointimal hyperplasia after arterial injury. In this study, we investigated the hypothesis that elevated levels of TF in the circulation contribute to the development of restenosis after percutaneous transluminal coronary angioplasty (PTCA) or stent implantation. Methods and Results—Whole-blood TF procoagulant activity (TF-PCA) was measured using a previously described assay before, at 3 hours after, and at 24 hours after the intervention in 61 patients with stable angina undergoing PTCA (n=20) or stent implantation (n=41). Coronary angiography was performed 4 to 6 months after the intervention, and luminal narrowing ≥50% was defined as restenosis. Whole-blood TF-PCA levels did not correlate with intracellular monocyte tumor necrosis factor-&agr; expression, a marker of activation of these cells. Baseline levels and time course of whole-blood TF-PCA after the intervention were compared in patients who did or did not subsequently develop restenosis. Whole-blood TF-PCA levels did not change significantly in the 24 hours after either intervention. However, in both the PTCA and stent groups, initial TF-PCA was significantly higher in patients who subsequently developed restenosis (P =0.018 and 0.039 compared with those who did not develop restenosis for PTCA and stent groups, respectively). Conclusions—Higher baseline values of whole-blood TF-PCA may be a predictor of restenosis after PTCA and stent implantation.

Exercise-induced myocardial ischemia in patients with coronary artery ectasia without obstructive coronary artery disease

BACKGROUND Aetiology, clinical significance and treatment options for coronary artery ectasia/aneurysm is not clear. OBJECTIVE We sought to determine whether exercise can induce coronary ischemia in patients with coronary artery ectasia/aneurysm without significant coronary stenosis. METHODS Coronary artery ectasia was defined as 1.5-2-fold, aneurysm as >2-fold luminal dilatation of the adjacent normal segment. The study patients could have irregularities with ectatic coronaries but they did not have stenotic lesions >50% with visual assessment of two blinded observers. Patients having coronary artery ectasia or aneurysm with prior myocardial infarction, dilated cardiomyopathy, valvular heart disease, bundle branch block, significant ST-T changes were excluded. The control group was formed from a well matched population of 32 patients with normal coronary arteries who have not performed a treadmill test before coronary angiography. The study group underwent a symptom limited treadmill test if they did not have one before coronary angiogram, all control patients underwent treadmill test. RESULTS Thirty-three patients with coronary artery ectasia/aneurysm (ranging from one to three vessels) but without significant stenosis were derived from 4470 cardiac catheterization procedures between January 1998 and July 2000. In the study group, 17 of the patients had positive treadmill tests with respect to five patients in the control group (P = 0.004). In subgroup analysis, diffuse ectasia/aneurysm (involving 2-3 vessels) was found to be strongly related with ischemia (P = 0.005) with respect to local disease. CONCLUSION Coronary artery ectasia/aneurysm may lead to exercise induced ischemia, especially in the diffuse form.

Echocardiographic evaluation of left ventricular diastolic function in chronic cor pulmonale

In this study we hoped to understand the abnormalities of left ventricular filling dynamics in chronic cor pulmonale. Our findings showed a severe left ventricular diastolic impairment, directly related to a progressive increase in pulmonary hypertension itself, as expressed by correlation analysis between systolic pulmonary artery pressure and the following parameters: transmitral flow velocity in early/late diastole ratio (r = -0.69, p <0.001), isovolumic relaxation time (r = 0.54, p = 0.001), and transmitral flow velocity in early diastole (r = -0.59, p <0.01).

Elevated levels of C-reactive protein are associated with impaired coronary collateral development.

Background  In vitro studies have shown that C‐reactive protein (CRP) attenuates nitric oxide production and inhibits angiogenesis, which may result in impaired collateral development. The aim of this study was to investigate the association between high sensitivity CRP (hsCRP) levels and the extent of coronary collaterals.

A Stepwise Approach to the Treatment of Amiodarone-Induced Thyrotoxicosis

Amiodarone-induced thyrotoxicosis (AIT) is a complex therapeutic challenge. Two major forms have been described: type I and type II. Methimazole (MMI) and potassium perchlorate (KCLO(4)) is the treatment of choice for the former, whereas corticosteroids are used for the latter. However, mixed forms appear frequently and it is not easy to prescribe corticosteroids because of side effects. The present study investigated the validity of a stepwise therapeutic approach to AIT. Twenty patients with AIT were given 30-50 mg/d of MMI and 1000 mg/d of KCLO(4) initially for a month. Euthyroidism or a significant decrease in serum thyroid hormone levels could be achieved in 12 of the patients (7 with type I, 5 type II). Prednisolone, 40-48 mg/d was added for the 8 nonresponding patients (7 type I, 1 type II) and euthyroidism was achieved in all. The prednisolone dose was decreased when free thyroxine (T(4)) levels normalized, and MMI was titrated, maintaining euthyroidism until urinary iodine excretion normalized. Mixed forms of AIT may prevail in iodine-deficient areas. Initial classification of the patients may cause unnecessary corticosteroid use in a substantial number of patients with AIT. A stepwise approach is feasible; however, when the patient is gravely ill, MMI, KCLO(4), and prednisolone could be prescribed simultaneously.

Hyperhomocysteinemia and Restenosis

Objective This study was undertaken to assess the effect of plasma homocysteine level on angiographic restenosis 6 months after coronary angioplasty. Methods The plasma homocysteine level was measured in 100 consecutive patients at the time of coronary angioplasty, 56 patients who attended a 6-month follow-up angiogram being enrolled to the study; the 44 patients without a control coronary angiogram were not enrolled. Patients with and without angiographic restenosis were designated as groups A (n = 34) and B (n = 22) respectively. Results The baseline demographic (groups A and B), angiographic (groups A and B) and procedural characteristics were similar in both groups. The mean plasma homocysteine level (SD) was 15.2 (7.7) and 11.1 (2.5) μmol/l in groups A and B respectively (P = 0.007; 95% CI −6.9 to −1.1). With respect to the plasma homocysteine level, the upper and the lower thirds were compared by binary logistic regression (the lower third homocysteine level being < 10.6 μmol/l and the upper third homocysteine level > 14.1 μmol/l). The angiographic restenosis rate for the lower and upper tertiles was 47.4% and 89.5% respectively (P = 0.01; OR = 9.4; 95% CI 1.6−52.7). After adjustment for age and sex, the statistical significance did not change (P = 0.013; OR = 9.43; 95% CI 1.6-54.9). Even after adjustment for age, sex, smoking, hypertension, hypercholesterolemia, and diabetes mellitus, there was a statistically significant difference between the upper and lower tertiles (P = 0.008; OR = 41.3; 95% CI 2.6-635). Conclusion Increased plasma homocysteine level and diabetes mellitus were independent risk factors for angiographic restenosis after percutaneous transluminal coronary angioplasty and coronary stenting.

Value of ST-segment depression during paroxysmal supraventricular tachycardia in the diagnosis of coronary artery disease.

We evaluated 39 patients >45 years old with paroxysmal supraventricular tachycardia (SVT), 21 of whom had ST-segment depression during SVT. Treadmill exercise testing, including thallium stress scintigraphy, was performed in all patients and coronary angiography in 21 patients with ST-segment depression. Based on the presence of abnormal findings on exercise electrocardiogram and/or thallium in 7 of 21 patients (33%) with ST-segment depression, with additional corroboration by angiographic data, we conclude that myocardial ischemia and coronary artery disease is one, but not the only, mechanism involved in the genesis of ST-segment depression during paroxysmal SVT.

Relation between the insertion/deletion polymorphism of the angiotensin I converting enzyme gene and restenosis after coronary stenting.

Background Observations with intravascular ultrasound demonstrated that neointimal hyperplasia is the predominant factor responsible for in-stent restenosis. Experimental data suggest that angiotensin I converting enzyme (ACE) plays a role in the thickening of neointima after balloon denudation. Insertion/deletion (I/D) polymorphism of the ACE gene is significantly associated with plasma level of ACE and subjects with D/D genotype have significantly higher plasma levels of ACE than normal. Objective To investigate whether this polymorphism influences the risk of restenosis after coronary stenting. Methods We genotyped 158 patients who had undergone single-vessel coronary stenting for the ACE I/D polymorphism. Results Of the 158 patients, 56 (35%) had the D/D genotype, 71 (45%) had the I/D genotype and 31(20%) had the I/I genotype. Prevalences of genotypes were compatible with Hardy-Weinberg equilibrium and distributions of ACE genotype among patients and 132 healthy controls from the same geographic area did not differ. At follow-up (after a median duration of 5.4 months), overall rates of angiographic restenosis and of revascularization of target lesion (RTL) were 32.3 and 22.8%, respectively. Of 51 patients with angiographic restenosis, 31 (60.8%) had focal and 20 (39.2%) had diffuse patterns of restenosis. Diffuse in-stent restenosis was significantly more prevalent among patients with D/D genotype (P= 0.016). Multiple stepwise logistic regression analysis identified ACE I/D polymorphism as the independent predictor of angiographic restenosis and RTL. Relative risk of angiographic restenosis was 6.29 [95% confidence interval (CI), 1.80–22.05, P= 0.0004] for D/D genotype and 3.88 (95% CI 1.11–13.12, P= 0.029) for I/D genotype, whereas relative risk of RTL was 7.44 (95% CI 1.60–34.58, P= 0.01) for D/D genotype and 3.88 (95% CI 0.083–18.15, P= 0.085) for I/D genotype. Conclusions The ACE I/D polymorphism is significantly associated with risk of angiographic and clinical restenosis after coronary stenting. Angiographic pattern of restenosis is also significantly associated with I/D polymorphism, diffuse type being more prevalent among subjects with D/D genotype.