Plasma viscosity as a cardiovascular risk marker in patients with proteinuria

Plasma viscosity is a major determinant of capillary blood flow. It has been suggested that alteration in plasma viscosity contributes to impaired blood flow and to increased cardiovascular risk. The aim of this study was to investigate the plasma viscosity levels and its possible role in the cardiovascular risk in patients with low grade nephrotic proteinuria. 20 patients with low-grade nephrotic proteinuria (mean age: 35+/-5 years) and 20 healthy controls (mean age: 33+/-4 years) were participated in the study. Plasma viscosity was measured by Harkness capillary viscometer. Biochemical analysis were measured by commercial enzymatic kits. Plasma viscosity, plasma levels of creatinine, fibrinogen and triglyceride were increased in patients with proteinuria than in the healthy controls (p<0.001, p<0.001, p<0.001, and p<0.001, respectively). The plasma levels of total protein and albumin were significantly lower in patients with low grade nephrotic proteinuria than in healthy controls (p<0.001 and p<0.001, respectively). Plasma viscosity was negatively correlated with plasma albumin (r= -0.835, p<0.001) and total protein (r= -0.862, p<0.001) in proteinuric patients. When the correlation analyses were performed a significant positive correlation was found between plasma viscosity and fibrinogen (r=0.636, p<0.001). In the stepwise multiple regression analysis plasma viscosity was found to be related with plasma total protein (t= -6.456, p<0.001) in the patients. When the stepwise multiple regression analysis were performed in healthy controls, the significant relationship was only found between plasma viscosity and fibrinogen (t= +2.202, p<0.01). These results suggested that altered plasma composition associated with low-grade nephrotic proteinuria may be involving the determination of plasma viscosity. Thus, the plasma viscosity in patients with low-grade nephrotic proteinuria may have a prognostic value in assessing cardiovascular risk in this group.     

Association of obesity and distribution of obesity with glucose tolerance and cardiovascular risk factors in the elderly.

The association of obesity and fat distribution with glucose tolerance and cardiovascular risk factor levels were investigated in a population-based study in East Finland including 396 non-diabetic men and 673 women aged from 65 to 74 years. Obese men and women (BMI greater than 27 kg/m2) had higher levels (P less than 0.001) of fasting and 2 h plasma glucose and insulin as well as total triglycerides and diastolic blood pressure, and lower levels of HDL cholesterol than normal weight men and women. Central fat distribution (the highest vs. the lowest tertile of waist-hip ratio) was associated independently of obesity with high fasting glucose (5.7 vs. 5.5 mmol/l in non-obese subjects, 5.9 vs. 5.7 mmol/l in obese subjects, P less than 0.05) and insulin levels (13.7 vs. 10.6 mU/l in non-obese subjects, 18.4 vs. 15.6 mU/l in obese subjects, P less than 0.01) and with adverse changes (P less than 0.05) in lipid and lipoprotein levels (triglycerides: 1.59 vs. 1.41 mmol/l in non-obese subjects, 1.92 vs. 1.69 mmol/l in obese subjects; HDL cholesterol: 1.33 vs. 1.43 mmol/l in non-obese subjects, 1.20 vs. 1.32 mmol/l in obese subjects). There were no marked differences in metabolic aberrations related to obesity between men and women. However, the association between waist-hip ratio and risk factors was non-linear in men whereas it was linear in women. In conclusion, obesity per se rather than its distribution was a more significant determinant of glucose and insulin as well as total triglyceride and HDL cholesterol levels in elderly subjects.     

Proteinuria as a predictor of risk of cardiovascular disease: a new insight

Mortality and morbidity due to cardiovascular disease is one of the fundamental health problems at present. Proteinuria is not only commonly recognized factor of progression of chronic renal diseases, but is also independent risk factor for cardiovascular complications. Lately, the value of albuminuria as a prognostic factor in the course of cardiovascular diseases has increased its significance. Not long ago, there was considered that only microalbuminuria (quantity of excreted albumins in urine above 30 to 300 mg daily) indicates on increased risk of complications of such diseases as arterial hypertension or diabetes. However, observational studies, as well as interventional studies lead us to verify that view. It turned out that in the general population the number of cardiovascular complications leading to death increases in proportion to the quantity of albumins excreted in urine. Moreover, it was found that the relationship is continuous in a wide range of albuminuria even at value below the lower limits accepted now as normal levels, i.e., 30 mg per day corresponding with urinary albumin concentration 20 mg/L. It means that not only the quantity of excreted albumins but also the presence of albumin in urine indicate a higher risk of cardiovascular death. It may be assumed therefore that the presence of albumin in urine gives the evidence of unfavorable functional state of the circulatory system followed by fatal consequences. Therefore, the presence of albuminuria ought to be considered in quality and quantity aspects.     

Monocyte cyclooxygenase-2 overactivity: a new marker of subclinical atherosclerosis in asymptomatic subjects with cardiovascular risk factors?

AIMS: Cyclooxygenase-2 (COX-2)-mediated prostaglandin production by activated macrophages is associated with inflammation and atherosclerosis. We investigated the relationship between COX-2-mediated prostaglandin-E2 (PGE2) release, cardiovascular risk factors, and carotid atherosclerosis in apparently healthy subjects. METHODS AND RESULTS: PGE2 release by lipopolysaccharide-stimulated blood monocytes was measured by ELISA in 291 subjects (76.5% men, mean age 58) who underwent global vascular risk assessment and carotid ultrasonography. COX-2 expression (real-time RT-PCR) was analysed in a subgroup of 100 subjects (76% men, mean age 59). Inducible PGE2 production was associated with smoking and diabetes (P<0.05), but not with arterial hypertension, dyslipidaemia, or obesity. Subjects in the highest tertile of PGE2 (>8.1 ng/mL) had significantly higher mean carotid intima-media thickness (IMT) than those in the lowest tertile (P<0.01). No significant differences among tertiles were observed in the levels of inflammatory markers (C-reactive protein, fibrinogen, and von Willebrand factor). The association between PGE2 and carotid IMT remained statistically significant (P=0.012) after adjustment for a number of cardiovascular and inflammatory risk factors. A correlation between COX-2 expression and PGE2 production was observed (P<0.005). CONCLUSIONS: COX-2-mediated PGE2 overproduction by stimulated monocytes might provide a new marker of subclinical atherosclerosis in asymptomatic subjects exposed to cardiovascular risk factors.     

C-reactive protein: a new golden marker of cardiovascular risk.

The need for new cardiovascular risk factors, due to the limitations of traditional factors, is pointed out. Recent views regarding the role of inflammation in the evolution of the atherosclerotic process, namely in the formation of the atheroma plaque, its progression and rupture, and initiation of acute coronary events, are briefly summarized. These events point to the possibility that inflammatory markers could constitute new markers of cardiovascular risk. Amongst them, C-reactive protein (CRP)--particularly high sensitivity CRP (hsCRP)--has been found to be a 'golden marker' in this field. Data are presented indicating that CRP, rather than being merely an epiphenomenon of inflammation, in fact constitutes a pathogenic agent of the atherosclerotic process. The importance of CRP elevation in acute coronary events, in revascularization interventions, in other situations of cardiovascular risk and even in apparently healthy individuals is outlined. The performance of CRP is then compared with that of traditional risk factors. Finally, the need for studies to discover whether a decrease in CRP levels, as obtained with several pharmacological agents, is accompanied by a simultaneous reduction of cardiovascular risk is emphasized.     

Therapy insight: weight-loss surgery and major cardiovascular risk factors

Weight-loss surgery is an effective treatment for severe, medically complicated and refractory obesity. It reverses, eliminates or significantly ameliorates major cardiovascular risk factors related to obesity. In a large proportion of patients, the therapy produces significant weight loss, reduces the risk of disability and premature death, and improves quality of life. Surgical treatment by gastric-restrictive and malabsorptive procedures started several decades ago in the US. Since the 1970s, accrued clinical experience and advances in technology, particularly in minimally invasive surgical approaches, have changed this therapy. Some procedures have evolved, whereas others have become obsolete. Today's weight-loss operations are safe, effective and potentially life-saving options for severely obese cardiology patients. This review describes weight-loss surgery procedures and their effects on cardiovascular risk factors.     

Weight cycling and cardiovascular risk factors in obesity

OBJECTIVE: To assess the relationship between weight cycling and some cardiovascular risk factors in a wide sample of obese subjects. DESIGN: Cross-sectional study with retrospective evaluation of weight and dieting history. SUBJECTS: In all, 459 obese subjects, 340 women and 119 men (age: 19-65 y; BMI: 30-69 kg/m2). MEASUREMENTS: Body composition and fat distribution (by bioelectrical impedance analysis and anthropometry), systolic and diastolic blood pressure, plasma glucose, total and HDL cholesterol, triglycerides, insulin and insulin resistance by HOMAir, various weight cycling indices. RESULTS: A positive correlation between weight cycling indices, BMI and percent body fat was found in both genders. Also, the maximum absolute amount of weight regained following a single diet episode was significantly associated to insulin and HOMAir in both genders. However, these correlations disappeared when the data were controlled for age and BMI. CONCLUSION: In obese subjects of both genders weight cycling, and in particular weight regain, does not appear to be associated with adverse effects on body composition, fat distribution or cardiovascular risk factors in an independent manner, but rather in relation to fat accumulation over years.     

Association between C-reactive protein, metabolic cardiovascular risk factors, obesity and oral contraceptive use in young adults

OBJECTIVE: This study sought to determine the relationship between levels of the inflammatory marker, C-reactive protein (CRP), cardiovascular risk factors and oral contraceptive use in young adults. DESIGN: Cross-sectional study of a community cohort. SUBJECTS: A total of 822 men and women aged 26 y. MEASUREMENTS: CRP, body mass index (BMI), blood pressure, lipid and lipoprotein levels, smoking status, socioeconomic status, health status, and hormonal contraceptive use in women. RESULTS: Multiple regression analysis showed that obesity was independently related to CRP with an increase in ratio CRP of 1.03 (95% CI 1.01, 1.05) for men and 1.07 (1.05, 1.09) for women associated with a 1 kg/m(2) increase in BMI. In women, combined oral contraceptive use was associated with a ratio change in CRP of 1.52 (1.27, 1.82) compared with nonusers. Other independent determinants of CRP in men and women were apolipoprotein B level, systolic blood pressure and apolipoprotein A1 in men. Univariate analysis showed that the relationship between CRP and BMI, systolic blood pressure and apolipoprotein B was significantly stronger in women than men. CONCLUSION: These findings suggest that obesity is associated with inflammation independent of other cardiovascular risk factors that may contribute to an increased risk for cardiovascular disease in men and women. Elevated CRP related to combined oral contraceptive use may influence the rate of cardiovascular events in young women.     

Plasma viscosity, an early cardiovascular risk factor in women with subclinical hypothyroidism

OBJECTIVE: It is controversial, if subclinical hypothyroidism increases cardiovascular risk. Plasma viscosity is a hemorheological parameter, which is accepted as an early cardiovascular risk factor. We investigated the alterations in plasma viscosity in women with subclinical hypothyroidism. DESIGN: 40 female patients with subclinical hypothyroidism and 31 age- and weight-matched healthy women were included. Free thyroxine (FT4), thyroid stimulating hormone (TSH), lipid parameters, fibrinogen, C-reactive protein (CRP) levels, hematocrit and plasma viscosity were measured in all subjects. MAIN OUTCOME: Plasma viscosity, total cholesterol and low density lipoprotein were significantly increased and high density lipoprotein was significantly decreased in patients with subclinical hypothyroidism. No significant correlation was found among the parameters. CONCLUSION: Increased plasma viscosity in patients' group suggests that cardiovascular risk might be increased in patients with subclinical hypothyroidism. As far as we could reach, this is the first study concerning plasma viscosity in subclinical hypothyroidism.     

Association between diet, lifestyle, metabolic cardiovascular risk factors, and plasma C-reactive protein levels

Increased C-reactive protein (CRP) levels have been associated with several of the components of the metabolic syndrome, but the direct influence of diet and lifestyle factors on CRP levels remains largely unknown. The purpose of the present study was to investigate the association between CRP and diet and lifestyle factors. Plasma CRP levels were determined by a highly sensitive enzyme-linked immunosorbent assay (ELISA) in 760 participants in the beta-Blocker Cholesterol-Lowering Asymptomatic Plaque Study (BCAPS). In accordance with previous findings, increased levels of CRP were associated with high body mass index (BMI) (P = .012), triglycerides (P = .001), systolic blood pressure (P = .019), cholesterol/high-density lipoprotein (HDL) ratio (P = .009), and low HDL cholesterol (P = .001). CRP was also increased in smokers (P = .023) and in subjects with a low vitamin C intake (P = .018). When men and women were analyzed together, there were no significant associations between CRP and dietary intake of total calories, total fat, saturated fat, monounsaturated fat, polyunsaturated fat, n-3 polyunsaturated fatty acids, n-6 polyunsaturated fatty acids, fiber, vitamin E, carotene, or selen, or in physical activity. However, in the female subgroup weak inverse relations were observed between CRP and the intake of total fat (r = -0.13, P = .011), saturated fat (r = -0.13, P = .011), monounsaturated fat (r = -0.13, P = .010), polyunsaturated fat (r = -0.14, P = .007), and n-3 PUFA (r = -0.14, P = .004). Stratified factor analyses in smoking subgroups, obese, and in under-reporters of energy, largely confirmed the results although in male never-smokers a combination of high fiber vitamin C/beta carotene intake was associated with low CRP levels. These observations suggest that CRP levels are only marginally associated with individual dietary and lifestyle factors. Surprisingly, a higher intake of fat tended to be associated with lower CRP values among women.     

Goiter and pregnancy: a new insight into an old problem.

Evidence is presented that pregnancy constitutes a goitrogenic stimulus, particularly in conditions with a restricted or even a marginally low iodine intake. In a series of studies carried out in a large cohort of pregnancies in the Brussels area, the authors show that an increase in thyroid volume is observed in a majority of pregnant women, leading to goiter formation at delivery in 9% of the cases. Furthermore, increments in thyroid volume were correlated with biochemical evidences of functional stimulation of the thyroid, such as an elevation in serum TG levels, preferential T3 secretion, and slight increases in basal TSH at delivery. Hence, the association of biochemical features of thyroidal stimulation with volumetric changes in the gland strongly suggests that pregnancy truly induces goitrogenesis rather than vascular swelling ("intumescence") alone, at least in conditions with a low iodine intake. Finally, preliminary data from this laboratory, as well as recently published data from other investigators, suggest that goiter formation during pregnancy can easily be prevented by increasing the iodine supply during pregnancy.     

Association between plasma renin activity and metabolic cardiovascular risk factors in essential hypertension

Objectives. To study the relationships between plasma renin activity and metabolic cardiovascular risk factors in patients with essential hypertension.
Subjects and design. Patients with uncomplicated essential hypertension ( n =36) with a diastolic blood pressure of 95–115 mmHg were studied. Assessment of plasma renin activity (PRA) related to urinary sodium excretion was used to define subgroups with high ( n =12), medium ( n =16) and low renin profiles ( n =8).
Main outcome measures. Fasting plasma lipid levels were determined. Glucose, insulin and C-peptide responses to standard oral glucose tolerance test (OGTT) were measured.
Results. Patients with high PRA had higher levels of plasma cholesterol (6.13±0.81 versus 4.67±0.7 mmol L^-1, P <0.05) and triglycerides (2.14±0.18 versus 0.98±0.13 mmol L^-1, P <0.05), than the low PRA group. HDL-cholesterol levels were lower in the high renin group than in the low renin group (1.05±0.04 versus 1.26±0.09 mmol L^-1, P <0.05). Insulin and C-peptide sums were higher in high PRA group (33.8±1.2 versus 25.1±0.9 and 2.6±0.3 versus 1.9±0.4 ng L^-1, P <0.05), than in the low PRA group.
Conclusions. Essential hypertensive patients with a high renin profile display more pronounced dyslipidaemia and higher levels of plasma insulin than patients with a low renin profile. This may be one explanation for higher incidence of cardiovascular disease previously reported in high PRA group.     

Fibrinogen, plasma viscosity and blood viscosity in obesity. Relationship with insulin resistance

Plasma viscosity (PV) and blood viscosity (BV) have been scarcely evaluated in morbid obese patients with no other concomitant cardiovascular risk factors. Contradictory results have been published regarding the influence of insulin resistance on these rheological parameters in obesity. In 67 severe or morbid obese patients without other cardiovascular risk factors (51 women and 11 men, aged 34+/-11 years), fibrinogen, PV and BV at native (nBV) and corrected 45% hematocrit (cBV) have been determined, and insulin resistance has been calculated with homeostasis model assessment (HOMA) index, in basal conditions and after a three month diet period. The same determinations were performed in 67 healthy volunteers (45 women, 22 men, aged 32+/-10 years) at baseline and three months later. When cases and controls were compared, obese patients showed higher fibrinogen levels (P<0.001), PV (P=0.050) and cBV (P=0.035), and showed a higher insulin resistance than the control group (P<0.001). Differences in PV were maintained after adjusting for BMI (P=0.001), but disappeared after adjusting for HOMA (P=0.391) fibrinogen (P=0.367) and LDL-chol (P=0.097). Differences between obese patients and the control group for cBV disappeared after adjusting for BMI (P=0.739), HOMA (P=0.744), fibrinogen (P=0.907), LDL-chol (P=0.283) and PV (P=0.112). The achieved weight loss (8.7+/-3.53%) was not accompanied by any changes in these rheological parameters (P>0.050). Obese patients show increased fibrinogen levels, PV and cBV. These rheological disturbances seem to be associated with insulin resistance and the metabolic syndrome, and do not seem to improve with moderate weight loss.     

Microalbuminuria, an integrated marker of cardiovascular risk in essential hypertension

This paper reviews the existing epidemiological and clinical evidence about the relationships of non-diabetic microalbuminuria with cardiovascular risk factors such as elevated blood pressure (BP), systolic particularly, cardiac hypertrophy, adverse metabolic status, smoking habits, elevated angiotensin II levels, endothelial dysfunction, acute and perhaps subclinical inflammation. Because of that unique property of reflecting the influence of so many clinically relevant parameters, microalbuminuria may legitimately be defined as an integrated marker of cardiovascular risk, an unique profile among the several prognostic predictors available to stratify risk in hypertensive patients. Recent cohort studies also showed associations with cardiovascular morbidity and mortality independently from conventional atherogenic factors. This behaviour, whose understanding still needs further elucidation, suggests to measure albuminuria and to screen patients at a higher absolute risk in whom preventive treatment is expected to be more beneficial than in those with a lower absolute risk.     

Association of myeloperoxidase with cardiovascular disease risk factors in prediabetic subjects

IntroductionPrediabetes is a chronic low-grade inflammatory disease and considered as a risk factor for the development of diabetes mellitus and cardiovascular disease. Myeloperoxidase (MPO) is a leukocyte-derived enzyme, linked to both oxidative stress and inflammation and has been proposed as a possible mediator of atherosclerosis, the major cause of cardiovascular disease. The objective of the present study was to evaluate the level of MPO in prediabetic subjects and correlate it with other cardiovascular disease risk factors.Materials and methodsIn this cross-sectional study, a total of 400 subjects were recruited. Of them, 200 were prediabetic subjects and 200 were age and gender-matched controls. For each subject, blood pressure, weight, height, waist circumference, hip circumference and lipid parameters were measured. In addition, MPO was determined.ResultsMPO was significantly increased in prediabetic subjects as compared to controls. In correlation analysis, MPO was found to be significantly and positively correlated with all the cardiovascular disease risk factors i.e. age, body mass index (BMI), waist-to-hip ratio (WHR), blood pressure [both systolic blood pressure (SBP) and diastolic blood pressure (DBP)], lipid parameters except high density lipoprotein (HDL) to which it was negatively correlated.ConclusionIn conclusion, MPO is well correlated with cardiovascular disease risk factors in prediabetes. Hence, MPO could be used to detect cardiovascular risk among prediabetic subjects and also can be used as an early biomarker of oxidative stress and inflammation in prediabetes.     

Low-carbohydrate diets,obesity, and metabolic risk factors for cardiovascular disease

Given the increased prevalence of obesity in the United States (and its associated cardiovascular risk) despite reduced fat intake, there has been increasing interest in the effect of low-carbohydrate diets on obesity. Recent prospective trials have demonstrated equivalent weight loss on low-carbohydrate versus low-fat diets, but with significantly different effects on metabolic risk factors for cardiovascular disease. Low-carbohydrate diets have more favorable effects on metabolic abnormalities found in insulin resistance syndromes, including serum triglyceride levels, high-density lipoprotein cholesterol levels, and small, dense low-density lipoprotein particles. The translation of these different metabolic effects on cardiovascular disease and events requires future studies. These studies should take into consideration that patients with insulin resistance syndromes would be the most likely group to benefit from carbohydrate restriction.