Systemic immune-inflammation index, and neutrophilto-lymphocyte and platelet-to-lymphocyte ratios can predict clinical outcomes in patients with acute coronary syndrome.

OBJECTIVE: Inflammatory mechanisms play an important role in the pathogenesis of atherosclerosis and myocardial infarction. The clinical and prognostic importance of inflammatory parameters, such as neutrophil-lymphocyte (NLR) and platelet-lymphocyte ratios (PLR) in complete blood counts in acute myocardial infarction and other cardiovascular diseases has been demonstrated. However, systemic immune-inflammation index (SII) calculated from neutrophils, lymphocytes and platelets in the complete blood cell count has not been studied sufficiently and is thought to provide a better prediction. This study investigated whether haematological parameters such as SII, NLR and PLR were associated with clinical outcomes in acute coronary syndrome (ACS) patients. METHODS: We included 1 103 patients who underwent coronary angiography for ACS between January 2017 and December 2021. The association between major adverse cardiac events (MACE) that developed in hospital and at 50 months of follow up and SII, NLR and PLR was compared. Long-term MACE were defined as mortality, re-infarction and target-vessel revascularisation. SII was calculated using the formula: NLR × total platelet count in the peripheral blood (per mm3). RESULTS: Of the 1 103 patients, 403 were diagnosed with ST-elevation myocardial infarction and 700 with non-STelevation myocardial infarction. The patients were divided into a MACE and a non-MACE group. In hospital and during the 50-month follow up, 195 MACE were observed. SII, PLR and NLR were found to be statistically significantly higher in the MACE group (p < 0.001). SII, C-reactive protein level, age and white blood cell count were independent predictors of MACE in ACS patients. CONCLUSIONS: SII was found to be a strong independent predictor of poor outcomes in ACS patients. This predictive power was greater than that of PLR and NLR.

High Triglyceride-Glucose Index is Associated With Poor Prognosis in Patients With Acute Coronary Syndrome in Long-Term Follow-Up.

The triglyceride-glucose (TyG) index is calculated from fasting triglycerides and fasting glucose levels and is an indicator of insulin resistance. The present study investigates whether the TyG index has a role in predicting clinical outcomes in cases of acute coronary syndrome (ACS). This retrospective study included 646 patients with ST-elevation myocardial infarction (STEMI) and 1048 patients with non-ST-elevation myocardial infarction (NSTEMI). The association between major adverse cardiac events (MACEs) that developed in-hospital and at 60 months of follow-up and TyG index values were compared. Patients were divided into 2 groups: TyG index values of ≥8.65 and <8.65. During the hospital stay and 60 months of follow-up, 303 MACEs occurred. In both the STEMI and NSTEMI groups, as the TyG index increased, an increase was observed in MACE rates. MACE rates were also found to be highest in the group with TyG index ≥8.65 (P < .001). TyG index, C-reactive protein, and age were independent predictors of MACEs in both the NSTEMI and STEMI groups. The present study found a significant association between higher TyG index values and increased risk of MACEs in ACS patients. The TyG index may prove useful to predict clinical outcomes in ACS patients.

Vitamin D Deficiency Is a Potential Risk for Blood Pressure Elevation and the Development of Hypertension.

Background and objectives: Hypertension is a global health problem and a major risk factor for cardiovascular diseases. Vitamin D deficiency is closely related to high blood pressure and the development of hypertension. This study investigated the relationship between the vitamin D and blood pressure status in healthy adults, and their 8-year follow-up was added. Materials and Methods: A total of 491 healthy middle-aged participants without any chronic illness, ages 21 to 67 at baseline, were divided into two groups as non-optimal blood pressure (NOBP) and optimal blood pressure (OBP). NOBP group was divided into two subgroups: normal (NBP) and high normal blood pressure (HNBP). Serum 25-hydroxy vitamin D levels were measured with the immunoassay method. 8-year follow-up of the participants was added. Results: The average vitamin D level was detected 32.53 ± 31.50 nmol/L in the OBP group and 24.41 ± 14.40 nmol/L in the NOBP group, and a statistically significant difference was found (p < 0.001). In the subgroup analysis, the mean vitamin D level was detected as 24.69 ± 13.74 and 24.28 ± 14.74 nmol/L in NBP and HNBP, respectively. Together with parathyroid hormone, other metabolic parameters were found to be significantly higher in the NOBP. During a median follow-up of 8 years, higher hypertension development rates were seen in NOBP group (p < 0.001). Conclusions: The low levels of vitamin D were significantly associated with NBP and HNBP. The low levels of vitamin D were also associated with the development of hypertension in an 8-year follow-up.

Low Serum Uric Acid Predicts Risk of a Composite Disease Endpoint.

Background and objectives: Mortality may increase in hypouricemia as well as inhyperuricemia. We assessed the predictive value of low serum uric acid (SUA) levels on the risk of overall mortality or a composite endpoint of death and nonfatal events. Materials and Methods: In 1013 community-based middle-aged adults, free of uncontrolled diabetes and coronary heart disease at baseline, the association of sex-specific SUA tertiles with defined outcomes was evaluated prospectively by logistic regression, stratified to gender and presence of type-2 diabetes, using recent criteria. Results: Totally, 43 deaths and additional incident nonfatal events in 157 cases were recorded at a median 3.4 years' follow-up. Multivariable linear regression disclosed SUA to be significantly associated among non-diabetic individuals positively with creatinine, triglycerides, and body mass index in women further with fasted glucose. In multivariable-adjusted logistic regression analysis, sex-specifically dichotomized baseline uric acid (<5.1 and <4.1 mg/dL vs. higher values) significantly predicted the non-fatal events in the whole sample (relative risk (RR) 1.51 [95% confidence interval (CI) 1.02; 2.26]), as well as in men, while composite endpoint in the whole sample tended to rise (RR 1.38). Compared with the intermediate one, the top and bottom SUA tertiles combined tended to confer mortality risk (RR 2.40 [95% CI 0.89; 6.51]). Adverse outcomes in diabetic women were predicted by tertiles 2 and 3. Conclusions: Inverse association of SUA with adverse outcomes, especially in men, is consistent with the involvement of uric acid mass in autoimmune activation. The positive association of uric acid with adverse outcomes in diabetic women is likely mediated by concomitant high-density lipoprotein dysfunction.

Population-based serum omentin-1 levels: paradoxical association with cardiometabolic disorders primarily in men.

AIM: The conflicting relationships of serum omentin with inflammation markers and cardiometabolic disorders were investigated. Results & methods: Unselected 864 population-based middle-aged adults were cross-sectionally studied by sex-specific omentin tertiles. Men in the lowest omentin tertile (T1) had lower systolic blood pressure, HbA1c and glucose values and tended in T3 to higher lipoprotein(a) levels. Logistic regression analysis, adjusted for four covariates, revealed significant independent associations with the presence of hypertension and diabetes only in men. Sex- and age-adjusted odds ratio in gender combined for T2 & T3 versus T1 was 1.34 (95% CI: 1.00-1.79) for metabolic syndrome. DISCUSSION & CONCLUSION: The elicited adverse relationships of omentin-1 support the notion of oxidative stress-induced proinflammatory conversion of omentin, rendering loss of anti-inflammatory properties.

Determinants of obstructive sleep apnea syndrome: Pro-inflammatory state and dysfunction of high-density lipoprotein.

OBJECTIVE: The goal of this study was to determine variables preceding and predicting incident obstructive sleep apnea syndrome (OSAS) in the population at large. METHODS: Anthropometric, lipid, and non-lipid variables in participants with newly developing OSAS (n = 131) were compared with those of a cohort sample (n = 2615) of the Turkish Adult Risk Factor study. Available values preceding (by a median of 32 mo) the development of OSAS were used in multivariable Cox regression models. RESULTS: Significant determinants of OSAS assessed by group differences were waist/neck circumference and fibrinogen. Fasting triacylglycerols, systolic blood pressure, and C-reactive protein in men and low sex hormone-binding globulin and elevated homeostatic model assessment in women were further significant covariates. Cox regression analysis for the risk of incident OSAS confirmed the independent predictive value of central obesity measures, especially neck circumference (having a twofold hazard ratio) and younger age. Age-adjusted former smoking status and-compared with the lowest tertile-the upper two tertiles of fibrinogen (relative risk = 1.66, 95% confidence interval: 1.05-2.63) were significant predictors. Elevated triacylglycerols in males and high apolipoprotein B and lowest high-density lipoprotein cholesterol tertile in females also predicted subsequent OSAS. Systolic blood pressure and total cholesterol did not prove to be independent predictors in multivariable adjusted Cox models in which partial sex-dependent independence of obesity measures of the previously stated five variables was essentially retained. CONCLUSIONS: An enhanced pro-inflammatory state appeared to be the underlying pathophysiologic mechanism for OSAS, whereas in men, the added factor of high-density lipoprotein dysfunction was suggested. Because it contributes to the pro-inflammatory state, discontinuance of smoking was another further significant predictor of OSAS.

Female and urban participants demonstrate an adverse trend in overall mortality in Turkey - and a report on the TARF survey 2016.

OBJECTIVE: This study is an examination of 1) overall mortality trend in the Turkish Adult Risk Factor (TARF) study stratified by sex and place of residence, and 2) brief report on main aspects of the 2016 survey. METHODS: The period of last 18 years was divided into 2 for trend analysis of data. Required information on deaths was obtained. Baseline age ≥40 years at the beginning of each period was the inclusion criterion. Cox regression analyses were performed. RESULTS: Among over 2500 participants in each, deaths were recorded in 281 and 334 individuals in Periods 1 and 2, respectively, and baseline mean age was 54.6 years and 56.4 years, respectively, in each period. Age-adjusted hazard ratio for mortality in Period 2 remained virtually the same for rural males, rose to borderline significance for urban males and rural females (p=0.06, p=0.09), and increased 1.72-fold for urban females (p=0.006), as compared to Period 1. Whereas males gained an average of 3.8 years of survival in the later period compared with the earlier period, females gained only 1.8 years. This narrowed the difference in mean age at death in favor of women from 2.5 years to 0.5 year. Of 1144 participants to be surveyed in the TARF 2016, 48 were lost to follow-up, 695 were examined, and 39 participants were ascertained to be deceased. In 362 cases, verbal information was obtained regarding health status. CONCLUSION: Gain in survival in Turkish women has distinctly stagnated compared with men, and hazard of death has risen significantly for women and urban residents in the past decade, suggesting interaction between female sex and urban residence. Both phenomena require recognition and adoption of appropriate measures.

Low acylation stimulating protein levels are associated with cardiometabolic disorders-secondary to autoimmune activation?

OBJECTIVE: We investigated the possible association of serum acylation stimulating protein (ASP) with cardiometabolic disorders and the evidence of autoimmune activation. METHODS: Population-based randomly selected 1024 participants were cross-sectionally and prospectively analyzed. ASP concentrations were measured with a validated ELISA kit. Correlations were sought separately in subjects with no cardiometabolic disorders (n=427) designated as "healthy." RESULTS: ASP was positively correlated with total testosterone and inversely correlated with platelet activating factor (PAF), PAF-acetylhydrolase (AH), in each gender, and positively correlated in "healthy" men with lipoprotein [Lp](a) and apolipoprotein B. Correlations of ASP with PAF values ≥22 nmol/L were abolished, contrasted to a strongly inverse one in subjects with PAF <22 nmol/L. In linear regression analyses in the whole sample, ASP was inversely associated independently with PAF and PAF-AH and, in men, positively with Lp(a) and sex hormone-binding globulin. Prevalent and (at 2.0 years' follow-up) incident metabolic syndrome (MetS, n=393), diabetes (n=154), and coronary heart disease (CHD, n=171) were analyzed by sex-, age-, and Lp(a)-adjusted logistic regression, using tertiles of ASP and PAF. The lower two (<42 nmol/L) ASP tertiles were a risk factor in combined sexes for MetS and diabetes. In women, incident CHD was predicted by either reduced or elevated ASP tertiles. CONCLUSION: Findings can be explained by the notion of operation of immune responses against both ASP and oxidized PAF-like lipids of Lp(a) to yield for "reduced" values and increased likelihood of cardiometabolic disorders.

Fasting glycemia and glycated hemoglobin categories: Relationship to serum lipoprotein(a) level and disparity in 2 geographic regional groups of Turkey.

OBJECTIVE: The goal of the present study was to determine covariates of serum lipoprotein (Lp) (a) within fasting glucose and glycated hemoglobin (HbA1c) categories, and to detect features that were different among covariates based on residence in Marmara and Central Anatolia (Marm-CA) regions or remaining 5 geographic regions of Turkey. METHODS: Data of randomly-selected group of 1167 men and women (mean age 61 years) who participated in biennial surveys of 2013 and 2015 were cross-sectionally analyzed in 6 categories. RESULTS: In multiple linear regression analysis of nondiabetic women, homeostatic model assessment (HOMA) index score was inversely associated with Lp(a) (ß coefficient 0.49; p=0.001); this was not true for men. In the whole sample, Lp(a) was significantly positively associated with female sex and with serum creatinine, and inversely in each sex with HOMA index (ß coefficient 0.63; p<0.001). Linear models within separate categories showed significant associations of Lp(a) only in individuals with no evidence of diabetes other than HbA1c >6.5%: in women, positive association with total cholesterol and inverse relationship with creatinine were found, and in men, positive association with apolipoprotein (apo) B was determined. Similar age, diastolic blood pressure, fasting glucose, triglyceride, uric acid, and C-reactive protein values were obtained from participants of 2 regional groups. Residents of the Marm-CA region who were nondiabetic exhibited significantly (by 23%) lower serum Lp(a) among individuals with HbA1c ≥5.7%, significantly higher HOMA index score, concentrations of apoB, and low-density lipoprotein cholesterol. CONCLUSION: Hallmark of prediabetic and diabetic glycemia/HbA1c categories seems to be an independent inverse association between Lp(a) protein (yet not of apoB) and HOMA score, this being primarily so in residents of Marm-CA region.

Gender-modulated risk of coronary heart disease, diabetes and coronary mortality among Turks for three major risk factors, and residual adiposity risk.

BACKGROUND: We determined the proportion of the effects of body mass index (BMI) or its categories on cardiometabolic outcomes mediated through systolic blood pressure (SBP), total cholesterol and fasting glucose. METHODS: Cox regression analyses were performed for incident outcomes among Turkish Adult Risk Factor study participants in whom the three mediators had been determined (n = 2158, age 48.5 ± 11 years). Over a mean 10.2-years' follow-up, new coronary heart disease (CHD) developed in 406, diabetes in 284 individuals, and 149 CHD deaths occurred. RESULTS: Hazard ratios (HR) of BMI for incident diabetes were no more than marginally attenuated by the 3 mediators including glucose, irrespective of gender. Compared to "normal-weight", sex- and age-adjusted RRs for incident CHD of overweight and obesity were 1.40 and 2.24 (95 % CI 1.68; 2.99), respectively, in gender combined. Only three-tenths of the excess risk was retained by BMI in men, six-tenths in women. No mediation of glycemia was discerned in males, in contrast to greatest mediation in females. HR of age-adjusted continuous BMI was a significant but modest contributor to CHD mortality in each gender. While the BMI risk of CHD death was abolished by mediation of SBP in men, HR strengthened to over two-fold in women through mediation of fasting glucose. CONCLUSIONS: Mediation of adiposity by 3 traditional factors exhibited among Turkish adults strong gender dependence regarding its magnitude for CHD risk and the mediation by individual risk factors. Retention of the large part of risk for diabetes in each sex and for CHD in women likely reflects underlying autoimmune activation.

Twenty-five years of the TARF study: The 2015 survey, and temporal trends in mortality and loss to follow-up.

OBJECTIVE: The aims of the present study were to examine, first, overall mortality in the Turkish Adult Risk Factor (TARF) 2015 survey, and second, distribution of cumulative mortality and temporal losses to follow-up in the 7 geographic regions of Turkey over 25 years. METHODS: Information on mode of death was obtained from first-degree relatives and/or primary health center personnel. Information regarding survivors was based on history, examination of the cardiovascular system, and Minnesota coding of electrocardiograms. RESULTS: Of the 1304 participants to be screened, 58 were lost to follow-up, 787 were examined, and 39 participants had died. In 420 subjects, verbal reporting alone was used to determine health status. Deaths were attributed to coronary heart disease in 16 subjects, and cerebrovascular event and cancer in 8 cases each. However, evidence suggested underlying autoimmune activation in 85% of cases. Cumulative 25-year assessment of the entire cohort, comprising 863 deaths over a mean follow-up of 20.5 years, corresponded to a rate of 11.4 per 1000 person-years. A significantly lower mortality rate was found in the Southeast. The 1992 participants lost to follow-up represented a rate of 22.5 per 1000 person-years. CONCLUSION: The generally high overall mortality in Turkey is similar among geographic regions, with the exception of a lower rate in Southeastern Anatolia. One of every 45 surviving participants is lost to follow-up each year.

Primary hyperparathyroidism in pregnancy: a case series and literature review.

Primary Hyperparathyroidism (PHP) in pregnancy constitutes a serious danger to mother and fetus. The diagnosis of PHP in pregnancy presents a challenge, and PHP commonly goes unidentified and untreated in pregnancy. We present four case reports about patients having PHP, which is very rare condition in pregnancy and their treatment modalities. Three patients, not to be controlled biochemically, denied the parathyroidectomy operation although they are informed about the details of their disease. They are followed up with medical therapy. The first one had no maternal or fetal complications, the second one acquired nephrolithiasis crisis in the last trimester and the third one gave birth to a premature baby who succumbed to tetany. The fourth patient who underwent parathyroidectomy operation in the second trimester had no maternal or fetal complications. PHP in pregnancy is a preventable cause of fetal and maternal mortality and morbidity. Thus, suspecting from PHP during the pregnancy and early diagnosis is critically important in terms of maternal and fetal wellness.

Advances in understanding gender difference in cardiometabolic disease risk.

Gender differences exist in cardiovascular or metabolic disease risk, beyond the protective effect of estrogens, mostly burdening the postmenopausal female. We aimed to review herein sex differences in pro-inflammatory states, the independence of inflammation from insulin resistance, differences in high-density lipoprotein dysfunction, in gene-environment interactions, and in the influence of current and former smoking on cardiometabolic risk. Sex differences in absorption of long-chain fatty acids are highlighted. Differences exist in the first manifestation of cardiovascular disease, men being more likely to develop coronary heart disease as a first event, compared to women who have cerebrovascular disease or heart failure as a first event. Autoimmune activation resulting from pro-inflammatory states, a fundamental mechanism for numerous chronic diseases in people prone to metabolic syndrome, is much more common in women, and these constitute major determinants. Therapeutic approaches to aspects related to sex difference are briefly reviewed.

[Turkish Adult Risk Factor survey 2014: Overall mortality and coronary disease incidence in Turkey's geographic regions]. / TEKHARF 2014 taramasi ve Türkiye'de cografi bölgelere göre ölüm orani ile koroner hastalik insidansi.

OBJECTIVE: This study aimed to examine the overall and coronary mortality in the 2014 Turkish Adult Risk Factor Study survey, and the distribution of cumulative mortality and incident coronary heart disease (CHD) across 7 geographic regions. METHODS: Information on mode of death was appropriately obtained. Information collected from survivors was based on history, examination of the cardiovascular system and the Minnesota coding of electrocardiograms. Cox regression analyses were performed. RESULTS: Of the 1.323 participants to be surveyed, 87 were lost to follow-up, 753 examined, and 35 ascertained as deceased. In 448 subjects, verbal information alone was obtained regarding health status. Nineteen deaths were of coronary and cerebrovascular origin. Cumulative 24-year assessment of the entire cohort in the age bracket 45-74 years disclosed high coronary mortality, at 7.3 per 1000 person-years in men and 3.8 in women, and recorded a limited decline of 18% since the year 2000. Age-adjusted Cox regression analysis, comprising 614 deaths and 482 incident CHD over a follow-up of 9.6 years, revealed higher mortality rates in the Mediterranean region and in men in the Black Sea and Marmara regions. The age-adjusted CHD incidence was significantly higher in males of the Mediterranean and females of the Southeast regions. An estimated 400-420.000 incident CHD cases develop currently each year in Turkey. CONCLUSION: The generally high age-adjusted overall mortality in Turkey displays significant differences across geographic regions. Age-adjusted CHD incidence is not regressing sufficiently, and is especially high among men of the Mediterranean and women of the Southeast regions.

Prediction by Low Plasma HbA1c of Mortality, Cardiac and Noncardiac Disease Risk: Modulation by Diabetic Status and Sex.

AIM: The aim of the study was to evaluate the predictive value of HbA(1c) for risk of overall mortality or a composite endpoint of death and nonfatal events. METHODS: Logistic regression retrospectively assessed the longitudinal association of measured HbA(1c) with outcome in 746 middle-aged adults, recruited from a tertiary health center and stratified to absence or presence of type 2 diabetes, using the recent American Diabetes Association criteria. RESULTS: A total of 70 deaths and additional incident nonfatal events in 82 cases were recorded at a median of 3.1-year follow-up. Multivariable linear regression revealed among nondiabetic individuals HbA(1c) to be significantly associated--independent of fasted glucose--inversely with triglycerides and high-density lipoprotein cholesterol, distinct from the diabetic sample. Sex and diabetes status differed in baseline HbA1c values with respect to the development of outcome. Nondiabetic men who subsequently died exhibited significantly lower HbA(1c), as did men and women with incident coronary heart disease. Similar difference was observed for incident hypothyroidism and nondiabetic subjects developing malignancy. In logistic regression analysis, adjusted for sex, age, and fasting glucose, each 0.7% (SD, 1) decrement of baseline HbA(1c) predicted the composite endpoint in the nondiabetic sample (risk estimates, 1.49%; 95% confidence interval, 1.07-2.04), but not in the diabetic sample, whereas overall mortality in the whole sample was increased (risk estimates, 1.51%; 95% confidence interval, 1.05-2.17). CONCLUSIONS: Inverse association of HbA(1c) with adverse outcomes in men and nondiabetic people indicates the involvement of HbA(1c) levels in autoimmune activation. The weaker inverse association with prevalent diabetes and in women is consistent with the operation of more pronounced confounding autoimmune processes.

Sex-Specific Predictors of Metabolic Syndrome Independent of Its Components.

To what extent is the metabolic syndrome (MetS) determined beyond its recognized components? In 1702, middle-aged men and women without MetS at baseline, MetS development was identified in 546 participants at a mean of 10.1-year follow-up. Participants subsequently developing MetS had, beyond higher values of MetS traits, significantly higher total and low-density lipoprotein cholesterol, apolipoprotein B, C-reactive protein (CRP), γ-glutamyl transferase (GGT), and lower high-density lipoprotein cholesterol. Females were significantly more frequent never smokers and males had lower values of total testosterone. In logistic regression analyses, adjusted for sex, age, and smoking status, MetS was predicted disparately in the sexes, whereas males exhibited, beyond abdominal obesity, CRP, GGT, and sex hormone-binding globulin (SHBG) as independent predictors, abdominal obesity was not an independent predictor in females in whom other than age, CRP conferred MetS risk, whereas SHBG was and current smoking tended to be protective. A surrogate of hepatic steatosis proved a major mediator of abdominal obesity in determining incident MetS (relative risk, 5.6 [95% confidence interval, 3.4-9.3]) in each sex. We confirm that GGT and SHBG are novel independent MetS determinants. Hepatic steatosis is the major predictor of MetS mediating adiposity in each sex. Abdominal obesity is not an independent determinant in Turkish women in whom autoimmune activation seems to prevail before MetS development.

[Turkish Adult Risk Factor survey 2013: rapid rise in the prevalence of diabetes]. / TEKHARF 2013 taramasi ve diyabet prevalansinda hizli artis

OBJECTIVES: To analyze (1) the sex-specific and age-bracket defined all-cause and coronary mortality in the 23-years' follow-up of the Turkish Adult Risk Factor Study, and (2) to determine the nation-wide prevalence of Type-2 diabetes and its recent trend. STUDY DESIGN: Information on the mode of death was obtained from first-degree relatives and/or health personnel of local heath office. Information collected in survivors was based on history, physical examination of the cardiovascular system and Minnesota coding of resting electrocardiograms. Diabetes was defined by criteria of the American Diabetes Association without the use of glycated hemoglobin. RESULTS: Of the 1370 participants to be surveyed, 768 were examined, in 452 subjects information was gathered, and 29 men, 18 women were ascertained to have died. Cumulative assessment of the entire cohort in the age bracket 45-74 years disclosed coronary mortality to be 7.5/1000 person-years in men and 3.74 in women, persisting to be high among the European countries. The recent decline observed in overall mortality seemed to halt as well. Of greatest concern was the finding in the past 12 years that the rate of rise in the age-controlled prevalence of Type-2 diabetes was as high as 5% annually. CONCLUSION: Overall and coronary mortality in Turkish adults continue to be high, while an elicited annual increase of 5% in the age-controlled prevalence of diabetes is virtually alarming and requires new public health policies.

Renal "hyperfiltrators" are at elevated risk of death and chronic diseases.

BACKGROUND: The definition of glomerular hyperfiltration has not been agreed upon and the pathophysiological mechanisms have not been well explored. Low serum creatinine concentrations may be associated with increased risk of coronary heart disease (CHD) or cardiopulmonary events the impact of which needs further study. METHODS: Consecutive applicants to a cardiovascular hospital free of moderate/severe chronic kidney disease (age 55.6 ± 8.2 years) were grouped into those without ("healthy", n = 469) and with CHD (320 stable and acute coronary syndrome cases) at baseline and into sex-specific quartiles of CKD-EPI equation-estimated glomerular filtration rate (eGFR). New or recurrent cardiovascular (myocardial infarction, stroke, heart failure [HF]) events, obstructive pulmonary disease (COPD) and death were determined during 3-years' follow-up. RESULTS: Among 25 deaths and 75 cardiopulmonary events, HF was the leading nonfatal event. Age, serum uric acid and left ventricular ejection fraction proved the best independent inverse covariates of eGFR in the "healthy" sample. The highest eGFR quartile ("hyperfiltrators"), exhibiting significantly lower serum LDL-cholesterol levels, significantly predicted the combined outcome (at a RR of 6) in "healthy" subjects, after adjustment for sex, age, body mass index, smoking status and presence of hypertension. This finding was paralleled by the highest eGFR quartile calculated also by the MDRD equation, replicating this also in the CHD group. CONCLUSION: Renal "hyperfiltrators" represent individuals with autoimmune activation (involving serum creatinine, partly escaping assay), are misclassified into optimal renal function and actually are at significantly higher risk of death, HF or cardiopulmonary events. Low serum creatinine levels may represent a clue to the existence of autoimmune activation.