Subclinical thyroid dysfunction as a risk factor for cardiovascular disease

BACKGROUND: There have been few large epidemiological studies examining the association between thyroid dysfunction and cardiovascular disease. In particular, it is uncertain if subclinical hypothyroidism is a risk factor for cardiovascular disease. METHODS: Serum thyrotropin and free thyroxine concentrations were measured in 2108 archived serum samples from a 1981 community health survey in Busselton, Western Australia (Busselton Health Study). In a cross-sectional study, we examined the prevalence of coronary heart disease in subjects with and without subclinical thyroid dysfunction. In a longitudinal study, we examined the risk of cardiovascular mortality and coronary heart disease events (fatal and nonfatal combined) to the end of 2001 (excluding subjects who had coronary heart disease at baseline). RESULTS: In the cross-sectional analysis, subjects with subclinical hypothyroidism (n = 119) had a significantly higher prevalence of coronary heart disease than euthyroid subjects (n = 1906) (age- and sex-adjusted prevalence odds ratio, 1.8; 95% confidence interval, 1.0-3.1; P = .04). In the longitudinal analysis of subjects with subclinical hypothyroidism (n = 101), there were 21 cardiovascular deaths observed compared with 9.5 expected (age- and sex-adjusted hazard ratio, 1.5; 95% confidence interval, 1.0-2.4; P = .08) and 33 coronary heart disease events observed compared with 14.7 expected (age- and sex-adjusted hazard ratio, 1.7; 95% confidence interval, 1.2-2.4; P < .01). The increased risk of coronary heart disease events remained significant after further adjustment for standard cardiovascular risk factors. Subjects with subclinical hyperthyroidism (n = 39) had no adverse outcomes. CONCLUSION: Subclinical hypothyroidism may be an independent risk factor for coronary heart disease.     

Subclinical hypothyroidism is an independent risk factor for atherosclerosis and myocardial infarction in elderly women: the Rotterdam Study

BACKGROUND: Overt hypothyroidism has been found to be associated with cardiovascular disease. Whether subclinical hypothyroidism and thyroid autoimmunity are also risk factors for cardiovascular disease is controversial. OBJECTIVE: To investigate whether subclinical hypothyroidism and thyroid autoimmunity are associated with aortic atherosclerosis and myocardial infarction in postmenopausal women. DESIGN: Population-based cross-sectional study. SETTING: A district of Rotterdam, The Netherlands. PARTICIPANTS: Random sample of 1149 women (mean age +/- SD, 69.0 +/- 7.5 years) participating in the Rotterdam Study. MEASUREMENTS: Data on thyroid status, aortic atherosclerosis, and history of myocardial infarction were obtained at baseline. Subclinical hypothyroidism was defined as an elevated thyroid-stimulating hormone level (>4.0 mU/L) and a normal serum free thyroxine level (11 to 25 pmol/L [0.9 to 1.9 ng/dL]). In tests for antibodies to thyroid peroxidase, a serum level greater than 10 IU/mL was considered a positive result. RESULTS: Subclinical hypothyroidism was present in 10.8% of participants and was associated with a greater age-adjusted prevalence of aortic atherosclerosis (odds ratio, 1.7 [95% CI, 1.1 to 2.6]) and myocardial infarction (odds ratio, 2.3 [CI, 1.3 to 4.0]). Additional adjustment for body mass index, total and high-density lipoprotein cholesterol level, blood pressure, and smoking status, as well as exclusion of women who took beta-blockers, did not affect these estimates. Associations were slightly stronger in women who had subclinical hypothyroidism and antibodies to thyroid peroxidase (odds ratio for aortic atherosclerosis, 1.9 [CI, 1.1 to 3.6]; odds ratio for myocardial infarction, 3.1 [CI, 1.5 to 6.3]). No association was found between thyroid autoimmunity itself and cardiovascular disease. The population attributable risk percentage for subclinical hypothyroidism associated with myocardial infarction was within the range of that for known major risk factors for cardiovascular disease. CONCLUSION: Subclinical hypothyroidism is a strong indicator of risk for atherosclerosis and myocardial infarction in elderly women.     

Association between subclinical hypothyroidism and severe diabetic retinopathy in Korean patients with type 2 diabetes

The association between subclinical hypothyroidism (SCH) and microvascular complications of type 2 diabetes is unclear. We examined whether SCH is associated with diabetic retinopathy or nephropathy in Korean patients with type 2 diabetes. Data from 489 patients who visited the diabetes clinic at a university hospital between 2001 and 2007 were analyzed retrospectively. Participants were evaluated for glycemic control, thyroid function, and diabetic retinopathy and nephropathy. Diabetic retinopathy was classified into five grades. Diabetic nephropathy was assessed by the presence of albuminuria. Patients in the SCH group had a higher proportion of women, older age, longer duration of diabetes, higher systolic and diastolic blood pressure, and higher insulin resistance index compared with the euthyroid group. No significant difference in family history of diabetes or body mass index was found between groups. The prevalence of severe diabetic retinopathy (severe nonproliferative diabetic retinopathy or proliferative diabetic retinopathy) was significantly higher in the SCH group than the euthyroid group (32.8% vs. 19.6%, P = 0.036), whereas no between-group difference was found in the prevalence of diabetic nephropathy. After adjustment for potential confounding factors (HbA1c, BMI, duration of diabetes, diabetic nephropathy, and hypertension) by multivariate logistic regression analysis, SCH remained significantly associated with severe diabetic retinopathy (odds ratio 2.086 (95% CI, 1.010-4.307), P = 0.047). These results suggest that SCH was independently associated with severe diabetic retinopathy in patients with type 2 diabetes. Further prospective studies are required to confirm the association between SCH and diabetic retinopathy.     

2型糖尿病患者中亚临床甲状腺功能减退症与糖尿病血管并发症关系的研究

对382例2型糖尿病患者的临床资料进行回顾性分析,发现2型糖尿病患者中亚临床甲状腺功能减退症(甲减)合并率为15.7%,合并亚临床甲减组心血管疾病和糖尿病肾病的发病率高于无亚临床甲减组(P<0.05),亚临床甲减是糖尿病肾病的独立危险因素[OR=1.9(95%CI:1.0～3.6),P<0.05].     

Cardiovascular risk profile and morbidity in subjects affected by type 2 diabetes mellitus with and without diabetic foot

Diabetic foot syndrome (DFS) is the most frequent cause of hospitalization of diabetic patients and one of the most economically demanding complications of diabetes. People with diabetes have been shown to have higher mortality than people without diabetes. On this basis, the aim of our study was to evaluate the possible role of diabetic foot as a cardiovascular risk marker in patients with type 2 diabetes mellitus. We enrolled 102 consecutive patients with type 2 diabetes mellitus with diabetic foot and 123 patients with type 2 diabetes mellitus without limb lesions to compare the prevalence of main cardiovascular risk factors, subclinical cardiovascular disease, previous cardiovascular morbidity, and incidence of new vascular events on a 5-year follow-up. Diabetic patients with diabetic foot were more likely to have a higher prevalence of cardiovascular risk factors such as hypercholesterolemia, hypertriglyceridemia, hyperuricemia, and microalbuminuria or proteinuria, a higher prevalence of a previous cardiovascular morbidity (coronary artery disease, transient ischemic attack/ischemic stroke, diabetic retinopathy), and a higher prevalence of subclinical cardiovascular disease. Furthermore, diabetic patients with foot ulceration showed, on a 5-year follow-up, a higher incidence of new-onset vascular events (coronary artery disease, transient ischemic attack/ischemic stroke, diabetic retinopathy). At multivariate analysis, duration of diabetes, age, hemoglobin A1c, and DFS maintained a significant association with cardiovascular morbidity; but DFS presence showed the highest hazard ratio.     

Effect of Tight Blood Glucose Control Versus Conventional Control in Patients with Type 2 Diabetes Mellitus: A Systematic Review with Meta‐Analysis of Randomized Controlled Trials

Tight control of blood glucose reduces cardiovascular events and total mortality is conflicting. To summarize clinical effects of tight versus conventional glucose control in patients with type 2 diabetes. We systematically searched MEDLINE, EMBASE, Cochrane Library, and ISI Web of Knowledge with no limits of language and time. Further trials were searched from the reference lists of identified studies. We included randomized controlled comparing different levels of blood glucose control intensity in type 2 diabetic patients. Two independent reviewers extracted data of eligible studies using standard case report forms. We investigated total mortality, cardiovascular and microvascular events, and hypoglycemia in patients with type 2 diabetes. We used random‐effects models to obtain relative risks (RR) with 95% confidence intervals (CI). We included 6 trials involving 27,654 patients. There was no significant effect of tight blood glucose control on all‐cause mortality (RR 1.03; 95% CI 0.90–1.17) or cardiovascular mortality (RR 1.04; 95% CI 0.83–1.29). Tight glucose control reduced the risk for nonfatal MI (RR 0.85; 95% CI 0.76–0.95), although had no effect on the incidence of nonfatal stroke (RR 1.02; 95% CI 0.88–1.17). For microvascular events, tight glucose control reduced the risk progression of retinopathy (RR 0.80; 95% CI 0.71–0.91), incidence of peripheral neuropathy (RR 0.94; 95% CI 0.89–0.99), and progression of nephropathy (RR 0.55; 95% CI 0.37–0.80), but had not significant effect on the incidence of nephropathy (RR 0.69; 95% CI 0.42–1.14). The risk of severe hypoglycemia increased with tight glucose control (RR 2.39; 95% CI 1.79–3.18). Tight blood glucose control reduces the risk for some macrovascular and microvascular events, without effect on all‐cause mortality and cardiovascular mortality. Tight glucose control increases the risk of severe hypoglycemia.     

Mortality and vascular outcomes in patients treated for thyroid dysfunction

CONTEXT: There are limited studies describing mortality and morbidity in patients treated for hyperthyroidism, and no data exist for people with treated hypothyroidism. OBJECTIVE: The objective of the study was to describe all-cause mortality and vascular mortality and morbidity in patients after treatment for hyperthyroidism and hypothyroidism. DESIGN: This was a population-based cohort study from 1994 to 2001. SETTING: The study was conducted in Tayside, Scotland. PATIENTS: All patients were treated for thyroid dysfunction. INTERVENTION(S): Event rates among patients with thyroid dysfunction were compared with rates in the general population. We measured standardized mortality ratio and standardized incidence ratio (SIR). MAIN OUTCOME MEASURE(S): The primary outcome was all-cause mortality. The secondary outcome was serious vascular event, the composite end point of nonfatal myocardial infarction, nonfatal stroke, or vascular death. RESULTS: There were 15,889 primary hypothyroid and 3,888 hyperthyroid patients. There were 3,116,719 patient-years of follow-up in 524,152 subjects in the general population. No increase was found in all-cause mortality or serious vascular events in patients with treated hypothyroidism or hyperthyroidism. Nonfatal ischemic heart disease [SIR 1.23, 95% confidence interval (CI) 1.10-1.36] and dysrhythmias (SIR 1.32, 95% CI 1.11-1.57) were increased in treated hypothyroidism when adjusted for age, sex, diabetic status, and previous vascular disease. In treated stabilized hyperthyroidism, only the risk of dysrhythmias was increased (SIR 2.71, 95% CI 1.63-4.24). Risk of heart failure or cerebrovascular disease was not increased in either patient group. CONCLUSIONS: We found no increase in all-cause mortality in subjects with treated thyroid disease. However, there was increased risk of cardiovascular morbidity in patients with treated primary hypothyroidism and dysrhythmias in treated hyperthyroidism.     

Frequency of Thyroid Dysfunction in Diabetic Patients: Value of Annual Screening

A randomly selected group of 1310 adult diabetic patients attending a diabetic outpatient clinic received annual screening for thyroid disease, by estimating serum free thyroxine and TSH concentrations. The overall prevalence of thyroid disease was found to be 13.4%, and was highest (31.4%) in Type 1 diabetic females, and lowest in Type 2 diabetic males (6.9%). As a direct result of screening, new thyroid disease was diagnosed in 6.8% (89 patients) of the population screened; the commonest diagnosis was subclinical hypothyroidism (4.8%), followed by hypothyroidism (0.9%), hyperthyroidism 0.5%), and subclinical hyperthyroidism (0.5%). Female patients with Type 1 diabetes had the highest annual risk of developing thyroid disease (12.3%), but all patient groups had a higher incidence of thyroid dysfunction, compared to that reported in the general population. This study suggests that thyroid function should be screened annually in diabetic patients to detect asymptomatic thyroid dysfunction which is increased in frequency in a diabetic population.     

Subclinical hyperthyroidism in patients with type 2 diabetes

Both subclinical hyperthyroidism and type 2 diabetes (T2D) have been associated with an increase in cardiovascular disease risk and mortality. We aimed to assess the prevalence of newly diagnosed subclinical hyperthyroidism in a cohort of patients with T2D, and also to analyse the relationships between diabetes-related characteristics and the presence of subclinical hyperthyroidism. 933 diabetic patients without previous history of thyroid disease (45.4% females, mean age 66.3 years, median duration of diabetes 10 years) were evaluated. A sample of 911 non-diabetic subjects without known thyroid dysfunction was studied as control group. Serum concentrations of thyrotropin were measured in all subjects. Subclinical hyperthyroidism was present in 4.3% of female and 3.5% of male diabetic patients. Relative risk was significant only for the female gender (OR 3.69, 95% CI 1.56-8.71). In comparison with diabetic patients without thyroid hyperfunction, patients with subclinical hyperthyroidism were older, had longer duration of diabetes, showed lower fasting glucose levels, had greater proportion of goitre and diet therapy, and had lower proportion of treatment with oral agents. Logistic regression analysis showed that age and the presence of goitre were significantly related to subclinical hyperthyroidism in patients with T2D. The risk for subclinical hyperthyroidism is increased in women with T2D. Advanced age and the presence of goitre are significantly and independently related with the presence of subclinical hyperthyroidism in diabetic population.     

MTHFR gene polymorphism is susceptible to diabetic retinopathy but not to diabetic nephropathy in Japanese type 2 diabetic patients

AIMS: Previously, we have proposed that methylenetetrahydrofolate reductase (MTHFR) gene polymorphism (C677T) could be a risk factor for diabetic retinopathy. To support our suggestion, we examined in detail the association of MTHFR polymorphism with diabetic retinopathy and nephropathy in Japanese type 2 diabetic patients. METHODS: Subjects (n=190) were free of cardiovascular diseases and were not on hemodialysis. Retinopathy was assessed according to fundamental differentiation; nephropathy was determined according to urinary albumin level; and MTHFR genotype was determined by polymerase chain reaction-restriction fragment length polymorphism. We also analyzed how hyperglycemia affected these three conditions in 131 patients with glycosylated hemoglobin > or =6.5% and fasting blood sugar > or =110 mg/dl. RESULTS: The frequency of 677T/677T homozygous subjects with retinopathy was higher than the frequencies of the other two genotypes, and a significant difference was observed in the distribution of the genotypes (677C/677C, 41.9%; 677C/677T, 31.1%; 677T/677T, 61.5%; P<.05). The susceptibility of 677T/677T homozygote to retinopathy approached significance [odds ratio (OR)=2.17; 95% confidence interval (95% CI)=0.87-5.42]. However, in the population with hyperglycemia, the 677T/677T homozygote modified the risk for retinopathy (OR=4.30; 95% CI=1.42-13.1), especially the risk for nonproliferative retinopathy. In contrast, the 677T/677T homozygote did not affect the risk for nephropathy (OR=1.17; 95% CI=0.45-3.05), even in subjects with hyperglycemia (OR=1.50; 95% CI=0.50-4.48). CONCLUSIONS: Our results are highly suggestive of an important role for MTHFR genotype in susceptibility to retinopathy under hyperglycemia, but not to nephropathy. Preventive therapies based on MTHFR polymorphism could delay the onset of retinopathy in type 2 diabetic patients.     

Risk for ischemic heart disease and all-cause mortality in subclinical hypothyroidism

We investigated possible associations between subclinical hypothyroidism and atherosclerotic diseases (ischemic heart disease and cerebrovascular disease) and mortality. Of 2856 participants (mean age 58.5 yr) in a thyroid disease screening between 1984 and 1987, 257 subjects with subclinical hypothyroidism (TSH > 5.0 mU/liter) and 2293 control subjects (TSH range 0.6-5.0 mU/liter) were analyzed. In the baseline cross-sectional analysis, subclinical hypothyroidism was associated with ischemic heart disease independent of age, systolic blood pressure, body mass index, cholesterol, smoking, erythrocyte sedimentation rate, or presence of diabetes mellitus [odds ratio (OR), 2.5; 95% confidence interval (95% CI), 1.1-5.4 in total subjects and OR, 4.0; 95% CI, 1.4-11.5 in men] but not in women. However, there was no association with cerebrovascular disease (OR, 0.9; 95% CI, 0.4-2.4). We were unable to detect an influence of thyroid antibody presence on the association between subclinical hypothyroidism and ischemic heart disease. In a 10-yr follow-up study until 1998, increased mortalities from all causes in yr 3-6 after baseline measurement were apparent in men with subclinical hypothyroidism (hazard ratio, 1.9-2.1) but not in women, although specific causes of death were not determined. Our results indicate that subclinical hypothyroidism is associated with ischemic heart disease and might affect all-cause mortality in men.     

Homocysteine and vitamin B(12) concentrations and mortality rates in type 2 diabetes

OBJECTIVE: To assess the role of homocysteine as a risk factor for mortality in diabetic subjects. METHODS: Homocysteine, vitamin B(12), and folate concentrations were measured in stored sera of 396 diabetic Pima Indians aged > or = 40 years when examined between 1982 and 1985. Vital status was assessed through 2001. RESULTS AND CONCLUSIONS: Over a median follow-up of 15.7 years, there were 221 deaths-76 were due to cardiovascular disease (CVD), 36 to diabetes/nephropathy and 34 to infections. Homocysteine was positively associated with mortality from all causes (hazard rate ratio (HRR) for highest versus lowest tertile of homocysteine = 1.70, 95% confidence interval (CI) 1.18-2.46), from diabetes/nephropathy (HRR = 2.39, 95% CI 0.94-6.11) and from infectious diseases (HRR = 3.39, 95% CI 1.19-9.70), but not from CVD (HRR = 1.16, 95% CI 0.62-2.17) after adjustment for age, sex and diabetes duration. Homocysteine correlated with serum creatinine (r = 0.50), and the relationships with mortality rates were not significant after adjustment for creatinine. Vitamin B(12) was positively associated with all-cause mortality (HRR for 100 pg/mL difference adjusted for age, sex and diabetes duration = 1.15, 95% CI 1.08-1.22) and death from diabetes/nephropathy (HRR = 1.27, 95% CI 1.10-1.46). The association between homocysteine and mortality in type 2 diabetes is not causal, but is confounded by renal disease in Pima Indians.     

Absolute level and rate of change of albuminuria over 1 year independently predict mortality and cardiovascular events in patients with diabetic nephropathy.

AIMS: To determine the nature of the association between baseline albuminuria and risk of all-cause mortality and cardiovascular disease, and to determine if the rate of change of albuminuria from baseline over 1 year predicts these endpoints in patients with diabetic nephropathy. METHODS: Cohort study of 427 patients (161 Type 1 and 266 Type 2) with diabetic nephropathy defined as urinary albumin excretion (UAE) > or = 30 mg/24 h at baseline (mean age 53.4 years). Patients were recruited at the time of referral to a diabetic nephropathy clinic and followed up annually for an average of 5 years. UAE rate was re-measured at 1 year and the rate of change from baseline calculated. RESULTS: All-cause mortality and cardiovascular disease increased significantly and continuously across quintiles of baseline UAE (P for linear trend < 0.001 in both outcomes). The rate of change of albuminuria over 1 year (log10) independently predicted all-cause mortality (hazard ratio (95% confidence interval) 1.76 (1.39, 3.11)) and cardiovascular mortality (1.57 (1.13, 5.22)). Taken as a categorical variable, a rate of change of albuminuria > or = 30% independently predicted mortality and cardiovascular events (2.07 (1.5, 4.30) and 1.89 (1.33, 4.06), respectively). CONCLUSIONS: The rate of change of albuminuria over 1 year independently predicts mortality and cardiovascular disease in diabetic nephropathy and may have clinical utility as a risk marker in identifying a subgroup of patients at particular risk. The risk of these outcomes is continuous across the range of baseline albuminuria in patients with diabetic nephropathy.     

The prevalence of subclinical hypothyroidism at different total plasma cholesterol levels in middle aged men and women: a need for case-finding?

OBJECTIVE: In order to determine whether screening of thyroid function is justified in patients with hypercholesterolaemia, we determined the prevalence of subclinical hypothyroidism at different levels of total plasma cholesterol in middle-aged men and women. DESIGN AND METHODS: 1200 participants were selected from a population based cross sectional study on risk factors for cardiovascular diseases. The participants were divided into three groups: total plasma cholesterol < 5 mmol/l, total plasma cholesterol 5-8 mmol/l, total plasma cholesterol > 8 mmol/l. Each group was comparable in size and sex distribution. Subclinical hypothyroidism was defined as plasma TSH levels higher than 4 mU/l, in the presence of normal free thyroxine (FT4(4)) concentration. RESULTS: Plasma samples of a total of 1191 participants were analyzed. The overall prevalence of subclinical hypothyroidism was 1.9% in men and 7.6% in women of middle age. In women the prevalence of subclinical hypothyroidism increased from 4.0 percent in the lowest, to 10.3 percent in the highest cholesterol stratum (P = 0.02). In men, the mean prevalence was 1.8 percent and roughly similar in the various strata. After age correction, an increase of 1 mU/l TSH in women was associated with an increase of 0.09 mmol/l total plasma cholesterol (95% confidence interval (CI) 0.02-0.16 mmol/l). A similar trend was found in men (0.16 mmol/l, 95% CI -0.02-0.34 mmol/l). CONCLUSIONS: In the population, the prevalence of subclinical hypothyroidism is up to 10 percent in middle aged women with high levels of total plasma cholesterol and may justify case-finding. In these women approximately 0.5 mmol/l of total plasma cholesterol can be attributed to the subclinical thyroid dysfunction. In men a similar correlation between thyroid dysfunction and total plasma cholesterol is seen, but the prevalence of thyroid dysfunction is considerably lower.     

Diabetic retinopathy is associated with subclinical atherosclerosis in newly diagnosed type 2 diabetes mellitus

Aims

We aimed to evaluate the association between diabetic microangiopathy and subclinical atherosclerosis as a marker of cardiovascular disease (CVD) risk in patients with newly diagnosed type 2 diabetes.

Methods

A total of 142 newly diagnosed type 2 diabetics who were free from CVD underwent evaluation of diabetic microangiopathy. Subclinical atherosclerosis was assessed by measuring carotid intima-media thickness (IMT), and the 10-year absolute risk of CVD was estimated using the UK Prospective Diabetes Study (UKPDS) Risk Engine.

Results

Subclinical atherosclerosis was found in 27 subjects (19.0%). The rates of hypertension and diabetic retinopathy were significantly higher among patients with subclinical atherosclerosis. The UKPDS 10-year risk for CVD was significantly increased in subjects with subclinical atherosclerosis. Old age, hypertension and the presence of diabetic retinopathy showed a significant association to subclinical atherosclerosis after further adjustments for gender, body mass index, smoking status, HbA1c, HDL cholesterol, LDL cholesterol and the presence of diabetic nephropathy.

Conclusions

This study shows that diabetic retinopathy is an independent risk marker for subclinical atherosclerosis in patients with newly diagnosed type 2 diabetes. We suggest that a diagnosis of diabetic retinopathy may warrant a more careful cardiovascular assessment even in the early stages of diabetes.     

Subclinical hypothyroidism is associated with a low-grade inflammation, increased triglyceride levels and predicts cardiovascular disease in males below 50 years

OBJECTIVE: Mild thyroid failure is associated with an increased risk for development of atherosclerosis, but whether subclinical hypothyroidism is related to risk for cardiovascular disease is controversial. The purpose of the present study was to examine a possible association between subclinical hypothyroidism and cardiovascular disease. DESIGN: Cross-sectional study of a general population. PATIENTS: Twelve hundred and twelve subjects, men and women, between 20 and 69 years old without thyroid disease not treated with drugs interfering with thyroid function or analysis of TSH were included. MEASUREMENTS: Clinical signs of cardiovascular disease based on a questionnaire and medical records and laboratory analysis of lipids, atherothrombotic risk markers, C-reactive protein and TSH. RESULTS: The main findings were a high incidence of subclinical hypothyroidism (19.7%) in a general population. Subclinical hypothyroidism was associated with higher concentrations of triglycerides and C-reactive protein. Below 50 years of age cardiovascular disease was more frequent in males with subclinical hypothyroidism compared to euthyroid males. Subclinical hypothyroidism was a predictor of cardiovascular disease in males below 50 years with an odds ratio of 3.4 (95% confidence interval 1.6-6.8) for developing cardiovascular disease compared to euthyroid age-matched males. CONCLUSION: Our study demonstrates that patients with subclinical hypothyroidism have increased levels of triglycerides and signs of low-grade inflammation (raised C-reactive protein levels) and that subclinical hypothyroidism might be a risk factor for development of cardiovascular disease in younger males.     

Diabetic heart dysfunction: is cell transplantation a potential therapy?

The presence of long-standing diabetes mellitus leads to the development of a number of typical end organ complications. These complications include coronary heart disease, stroke, peripheral arterial disease, diabetic retinopathy, diabetic nephropathy, diabetic neuropathy and diabetic cardiomyopathy. From an epidemiological and clinical standpoint, cardiovascular disease remains the most important complication of diabetes. Cardiovascular complications are the most common causes of morbidity and mortality in diabetics, accounting for up to 85% of the mortality in diabetic patients [1]. The increasing prevalence of obesity and sedentary lifestyle in Western society are leading to an increase in the prevalence in diabetes. As such diabetes is an increasing cause of cardiovascular disease [2].     

Interactive effect of retinopathy and macroalbuminuria on all-cause mortality, cardiovascular and renal end points in Chinese patients with Type 2 diabetes mellitus.

AIMS: To examine the effect of albuminuria and retinopathy on the risk of cardiovascular and renal events, and all-cause mortality in patients with Type 2 diabetes. METHODS: A post-hoc analysis of 4416 Chinese patients without macrovascular complications at baseline (age 57.6 +/- 13.3 years). Glomerular filtration rate (eGFR) was estimated by the abbreviated Modification of Diet in Renal Disease Study Group Formula, further adjusted for Chinese ethnicity. Clinical end points were all-cause mortality, cardiovascular events (heart failure or angina, myocardial infarction, lower limb amputation, re-vascularization procedures and stroke) and renal end points (reduction in eGFR by more than 50% or eGFR < 15 ml/min/1.73 m2 or death as a result of renal causes or need for dialysis). RESULTS: Compared with individuals without complications, subjects with retinopathy and macroalbuminuria had higher rates of cardiovascular events (14.1 vs. 2.4%), renal events (40.0 vs. 0.8%) and death (9.3 vs. 1.7%, P < 0.001). For composite event of death, cardiovascular and renal events, the presence of retinopathy, microalbuminuria alone, macroalbuminuria alone, retinopathy with microalbuminuria or retinopathy with macroalbuminuria increased the risk [hazard ratio (95% CI)] by 1.61 (1.05 to 2.47; P = 0.04), 1.93 (1.38 to 2.69; P < 0.001), 4.34 (3.02 to 6.22; P < 0.001), 2.59 [1.76 to 3.81; P < 0.001) and 6.83 (4.89 to 9.55; P < 0.001) fold, respectively. The relative excess risk as a result of interaction between retinopathy and macroalbuminuria was 15.31, implying biological interaction in the development of renal events. CONCLUSIONS: In Chinese patients with Type 2 diabetes, retinopathy interacts with macroalbuminuria to increase the risk of composite cardio-renal events.     

Subclinical hypothyroidism and the risk of heart failure, other cardiovascular events, and death

BACKGROUND: Subclinical hypothyroidism has been associated with systolic and diastolic cardiac dysfunction and an elevated cholesterol level, but data on cardiovascular outcomes and death are limited. METHODS: We studied 2730 men and women, aged 70 to 79 years, with baseline thyrotropin (TSH) measurements and 4-year follow-up data to determine whether subclinical hypothyroidism was associated with congestive heart failure (CHF), coronary heart disease, stroke, peripheral arterial disease, and cardiovascular-related and total mortality. After the exclusion of participants with abnormal thyroxine levels, subclinical hypothyroidism was defined as a TSH level of 4.5 mIU/L or greater, and was further classified according to TSH levels (4.5-6.9, 7.0-9.9, and > or = 10.0 mIU/L). RESULTS: Subclinical hypothyroidism was present in 338 (12.4%) of the participants. Compared with euthyroid participants, CHF events occurred more frequently among those with a TSH level of 7.0 mIU/L or greater (35.0 vs 16.5 per 1000 person-years; P = .006), but not among those with TSH levels between 4.5 and 6.9 mIU/L. In multivariate analyses, the risk of CHF was higher among those with high TSH levels (TSH of 7.0-9.9 mIU/L: hazard ratio, 2.58 [95% confidence interval, 1.19-5.60]; and TSH of > or = 10.0 mIU/L: hazard ratio, 3.26 [95% confidence interval, 1.37-7.77]). Among the 2555 participants without CHF at baseline, the hazard ratio for incident CHF events was 2.33 (95% confidence interval, 1.10-4.96; P = .03) in those with a TSH of 7.0 mIU/L or greater. Subclinical hypothyroidism was not associated with increased risk for coronary heart disease, stroke, peripheral arterial disease, or cardiovascular-related or total mortality. CONCLUSIONS: Subclinical hypothyroidism is associated with an increased risk of CHF among older adults with a TSH level of 7.0 mIU/L or greater, but not with other cardiovascular events and mortality. Further investigation is warranted to assess whether subclinical hypothyroidism causes or worsens preexisting heart failure.     

Pregnancy-associated plasma protein A in a large cohort of Type 1 diabetic patients with and without diabetic nephropathy-a prospective follow--up study.

AIM: Pregnancy-associated plasma protein A (PAPP-A) has been implicated in the aetiology of acute coronary syndromes and carotid and peripheral artherosclerosis. Diabetic nephropathy is characterized by increased cardiovascular risk. We investigated the prognostic value of PAPP-A in a large cohort of Type 1 diabetic patients. METHODS: In a prospective observational follow-up study, 197 Type 1 diabetic patients with diabetic nephropathy and a matched group of 178 patients with normoalbuminuria were followed for 10.1 (0-10.3) years. PAPP-A was determined at baseline. RESULTS: In patients with diabetic nephropathy, plasma PAPP-A was elevated 3.6 (0.4-51.1) mIU/l [median (range)] vs. 2.1 (0.4-46.6) mIU/l in normoalbuminuric patients, P < 0.0001. For acute coronary syndromes, a PAPP-A threshold of 10 mIU/l has been suggested. Thirty-seven patients were above the threshold and of these 13 patients (35%) died, compared with 60 of 338 patients (18%) below the threshold; log rank test P = 0.007. PAPP-A significantly predicted mortality after adjustment for presence of nephropathy; hazard ratio for dying when PAPP-A was above the threshold 2.1 (95% CI 1.13-3.9); P = 0.019. After adjusting for traditional risk factors, the results were attenuated. When only patients with nephropathy were analysed, PAPP-A was significantly predictive of all-cause mortality [P = 0.008; 2.43 (1.26-4.67)] in unadjusted analysis. After adjustment, the predictive value of PAPP-A for all-cause mortality was attenuated (P = 0.064). CONCLUSION: We find PAPP-A to be associated with increased mortality in Type 1 diabetic patients with nephropathy in unadjusted analysis. After adjustment for traditional risk factors, the prognostic value of PAPP-A was no longer significant.