Sample selection may bias the outcome of an adolescent mental health survey: results from a five-year follow-up of 4171 adolescents.

OBJECTIVES: The representativeness of the data is one of the main issues in evaluating the significance of research findings. Dropping out is common in adolescent mental health research, and may distort the results. Nevertheless, very little is known about the types of systematic bias that may affect studies in a) the informed consent phase and b) later in follow-up phases. STUDY DESIGN: The authors addressed this gap in knowledge in a five-year follow-up study on a sample of adolescents aged 13-18 years. METHODS: The data were collected using self-report questionnaires. The baseline sample consisted of 4171 adolescents, 1827 (43.8%) of whom gave consent to be contacted for a follow-up survey, but only 797 (19.1%) participated in the follow-up. Binary logistic regression models were used to explain the participation. RESULTS: Young age, female gender, a high number of hobbies, good performance at school in the native language and general subjects, family disintegration such as divorce, high parental employment, and symptoms of depression and anxiety were associated with both consent and participation. However, the effect of mental health aspects was smaller than the effect of age and gender. CONCLUSIONS: This study confirmed the possibility of systematic selection bias by adolescents' sociodemographic characteristics. The representativeness of the study sample might have been improved by more intense recruitment strategies.

Fear of childbirth in nulliparous and multiparous women: a population-based analysis of all singleton births in Finland in 1997-2010.

OBJECTIVE: To identify risk factors for fear of childbirth (FOC) according to parity and socioeconomic status, and to evaluate associations between FOC and adverse perinatal outcomes. DESIGN: A cohort study. SETTING: The Finnish Medical Birth Register. POPULATION: All 788 317 singleton births during 1997-2010 in Finland. METHODS: Fear of childbirth was defined according to the International Classification of Diseases code O99.80, and its associations with several risk factors and perinatal outcomes were analysed by multivariable logistic regression. MAIN OUTCOME MEASURES: Prevalence of, risk factors for and outcomes of FOC. RESULTS: Fear of childbirth was experienced by 2.5% of nulliparous women and 4.5% of multiparous women. The strongest risk factors for FOC in nulliparous women were depression [adjusted odds ratio (aOR), 6.35; 95% confidence interval (CI), 5.25-7.68], advanced maternal age (aOR, 3.78; 95% CI, 3.23-4.42) and high or unspecified socioeconomic status. In multiparous women, the strongest risk factors for FOC were depression (aOR, 5.47; 95% CI, 4.67-6.41), previous caesarean section (CS) (aOR, 3.02; 95% CI, 2.93-3.11) and high or unspecified socioeconomic status. Among both nulliparous and multiparous women, FOC was associated with higher rates of CS (3.3-fold and 4.5-fold higher, respectively) and a lower incidence of low birthweight (<2500 g), small for gestational age babies, preterm birth and low Apgar scores at 1 minute. CONCLUSIONS: High and unspecified socioeconomic status, advanced maternal age and depression are predisposing factors for FOC regardless of parity. Among multiparous women, a previous CS increases vulnerability to FOC. FOC is associated with increased rates of CS, but does not adversely affect other pregnancy outcomes.

Proteinuria modifies the effect of systolic blood pressure on total and cardiovascular disease mortality in patients with type 2 diabetes.

OBJECTIVES: Hypertension and proteinuria are major risk factors for cardiovascular disease (CVD) mortality in patients with type 2 diabetes. Blood pressure (BP) targets have been progressively lowered in these patients to prevent or delay the progression of nephropathy. However, no long-term population-based studies have been reported on the interaction between BP and proteinuria with respect to total and CVD mortality in patients with type 2 diabetes. DESIGN: We prospectively followed 881 middle-aged type 2 diabetic patients, free of CVD events at baseline, for up to 18 years. Participants were categorized into four groups according to baseline systolic BP (<130, 130-139, 140-159 and ≥160 mmHg) and further stratified by proteinuria (≤150 or >150 mg L(-1)). Cox proportional hazards model was used to estimate the joint association between systolic BP and proteinuria and the risk of mortality. RESULTS: During follow-up, 607 patients died including 395 because of CVD. After adjustment for confounding factors, total and CVD mortality were significantly higher in patients with proteinuria and systolic BP <130 mmHg compared with those with systolic BP between 130 and 160 mmHg. The prognosis was similar in patients with systolic BP <130 mmHg or ≥160 mmHg. Among patients without proteinuria, systolic BP <130 mmHg was associated with a nonsignificant reduction in mortality. CONCLUSIONS: Type 2 diabetic patients with proteinuria and with systolic BP <130 mmHg may have an increased risk of CVD mortality. The presence of proteinuria should be taken into account when defining the target systolic BP level for the prevention of fatal CVD events in patients with type 2 diabetes.

How does lifestyle intervention affect depressive symptoms? Results from the Finnish Diabetes Prevention Study.

AIMS: To assess the effect of lifestyle intervention on depressive symptoms during a 36-month randomized clinical trial designed to prevent Type 2 diabetes. METHODS: A total of 522 middle-aged participants, who were overweight or obese and had impaired glucose tolerance, were randomized to the lifestyle intervention or control group in the Finnish Diabetes Prevention Study. The intervention group received individualized counselling aimed at reducing weight and increasing physical activity. Depressive symptoms were measured using the Beck Depression Inventory among a subgroup of 140 participants. RESULTS: On study entry, the mean Beck Depression Inventory scores ± sd were 6.8 ± 5.6 in the intervention group and 6.7 ± 5.5 in the control group. Beck Depression Inventory scores reduced during the intervention study: the mean ± sd (95% CI) reduction was 0.90 ± 4.54 (-1.99 to -0.19) scores in the intervention group and 0.75 ± 4.47 (-1.80 to 0.31) in the control group, with no difference between the groups. In a stepwise linear multivariate regression analysis, the variables with the strongest associations with the change in Beck Depression Inventory scores were baseline Beck Depression Inventory scores, marital status, weight change and change of total energy intake (R(2) = 0.209, P < 0.001). CONCLUSIONS: Participation in the study lowered depression scores, with no specific group effect. Among the lifestyle changes, particularly successful reduction of body weight was associated with the greater reduction of depressive symptoms. Thus, regardless of the intensity of the treatment, the success in executing alterations in one's lifestyle and behaviour is associated with beneficial changes in mood.

Proteinuria modifies the effects of physical activity on total and cardiovascular disease mortality rates in patients with type 2 diabetes.

AIMS/HYPOTHESIS: Physical activity reduces cardiovascular disease (CVD) and total mortality rates in patients with type 2 diabetes. However, it is not known whether or not the effects of physical activity on mortality rates depend on the presence of proteinuria in type 2 diabetic patients. METHODS: We prospectively followed up 577 patients with type 2 diabetes who were aged 45 to 64 years and were free of CVD at baseline. Participants were stratified according to the presence of proteinuria (300 mg/l) and the degree of physical activity (0-4 metabolic equivalent tasks [MET] or >4 MET). The Cox proportional hazards model was used to estimate the association of physical activity and proteinuria with risk of mortality. RESULTS: During the 18-year follow-up, 356 patients died, of whom 217 died from CVD. Physically more active patients had significantly reduced total, CVD and CHD mortality rates if they did not have proteinuria. In contrast, physically active proteinuric patients had significantly increased total and CVD mortality rates (HR 1.83, 95% CI 1.00-3.36, p=0.049) in univariate analyses, with HR 2.43 (95% CI 1.09-5.40, p=0.030) in multivariate analyses. CONCLUSIONS/INTERPRETATION: Physical activity reduces total and CVD mortality rates in type 2 diabetic patients without proteinuria. However, in proteinuric patients, no protective effect was observed. Larger studies are needed to confirm the latter finding and to define which exercise intensity leads to possible harmful effects.

Serum adiponectin and resistin levels in major depressive disorder.

OBJECTIVE: To examine the role of the adipose-tissue-derived low-grade inflammation markers adiponectin and resistin in major depressive disorder (MDD) in a population-based sample. METHOD: Serum levels of adiponectin and resistin were measured from 70 DSM-IV MDD subjects and 70 healthy controls. Depression severity was assessed with the 29-item Hamilton Depression Rating Scale. RESULTS: The MDD group had lowered serum adiponectin levels. Regression modelling with adjustments for age, gender, overweight, several socioeconomic and lifestyle factors, coronary heart disease and metabolic syndrome showed that each 5.0 microg/ml decrease in serum adiponectin increased the likelihood of MDD by approximately 20% (P = 0.01). The resistin levels correlated with atypical (P = 0.02), but not with typical depressive symptoms (P = 0.12). CONCLUSION: Our findings suggest that the lowered adiponectin levels in MDD are depression-specific and not explained by conventional low adiponectin-related factors such as such as coronary heart disease and metabolic disorders.

Link between plasma ceramides, inflammation and insulin resistance: association with serum IL-6 concentration in patients with coronary heart disease.

AIMS/HYPOTHESIS: Ceramides and IL-6 have a role in immune-inflammatory responses and cardiovascular diseases, and are suggested to be involved in insulin and glucose metabolism. We sought to assess the associations of circulating levels of IL-6, TNF-alpha and high-sensitivity C reactive protein (hsCRP), which are inflammatory markers related to insulin resistance (IR), with the plasma lipid metabolites ceramides and diacylglycerols (DAG) in patients with CHD. METHODS: Cross-sectional analyses were carried out on data from 33 patients with CHD. Serum levels of the inflammatory markers and plasma lipid metabolites (lipidomics approach performed by ultra-performance liquid chromatography coupled to electrospray ionisation MS) were measured at the same time point as insulin resistance (IR) (HOMA-IR index). RESULTS: Serum circulating levels of IL-6 were strongly correlated with plasma ceramide concentrations (r = 0.59, p < 0.001). Adjustments for serum TNF-alpha or hsCRP levels, smoking, BMI, age, sex or HOMA-IR did not change the results (p < 0.001). After adjustments for the effect of serum inflammatory markers (TNF-alpha or hsCRP), HOMA-IR and BMI the correlation between plasma DAG and serum IL-6 (r = 0.33) was also significant (p < 0.03). In a linear regression model, circulating levels of both ceramides and TNF-alpha had a significant independent influence on circulating levels of IL-6, altogether accounting for 41% of its variation (p < 0.001). CONCLUSIONS/INTERPRETATION: Our results strongly suggest that the link between ceramides, IR and inflammation is related to the inflammatory marker IL-6. Ceramides may contribute to the induction of inflammation involved in IR states that frequently coexist with CHD.

Association of depressive symptoms and metabolic syndrome in men.

OBJECTIVE: To explore the relationship between several indicators of depression and metabolic syndrome (MetS). METHOD: A population-based sample with high (HMS group) or low (LMS group) levels of mental symptoms, including those of depression, in three follow-ups participated in a clinical examination in 2005 (n = 223). MetS was determined according to the NCEP criteria. RESULTS: The prevalence of MetS was 49% in men and 21% in women. Men with MetS had higher rates of major depressive disorder than other men. They also displayed higher Hamilton Rating Scale for Depression (HDRS) scores and more often signs of suicidality. In logistic regression analyses, higher HDRS scores (OR 1.31, 95% CI 1.04-1.64) and belonging to the HMS group (OR 10.1, 95% CI 1.98-51.3) were independent associates for MetS but only in men. CONCLUSION: The results highlight that there is an association between long-term depressive symptoms and the emergence of MetS, especially in men.

TRPV1 antagonists that cause hypothermia, instead of hyperthermia, in rodents: Compounds' pharmacological profiles, in vivo targets, thermoeffectors recruited and implications for drug development.

AIM: Thermoregulatory side effects hinder the development of transient receptor potential vanilloid-1 (TRPV1) antagonists as new painkillers. While many antagonists cause hyperthermia, a well-studied effect, some cause hypothermia. The mechanisms of this hypothermia are unknown and were studied herein. METHODS: Two hypothermia-inducing TRPV1 antagonists, the newly synthesized A-1165901 and the known AMG7905, were used in physiological experiments in rats and mice. Their pharmacological profiles against rat TRPV1 were studied in vitro. RESULTS: Administered peripherally, A-1165901 caused hypothermia in rats by either triggering tail-skin vasodilation (at thermoneutrality) or inhibiting thermogenesis (in the cold). A-1165901-induced hypothermia did not occur in rats with desensitized (by an intraperitoneal dose of the TRPV1 agonist resiniferatoxin) sensory abdominal nerves. The hypothermic responses to A-1165901 and AMG7905 (administered intragastrically or intraperitoneally) were absent in Trpv1-/- mice, even though both compounds evoked pronounced hypothermia in Trpv1+/+ mice. In vitro, both A-1165901 and AMG7905 potently potentiated TRPV1 activation by protons, while potently blocking channel activation by capsaicin. CONCLUSION: TRPV1 antagonists cause hypothermia by an on-target action: on TRPV1 channels on abdominal sensory nerves. These channels are tonically activated by protons and drive the reflectory inhibition of thermogenesis and tail-skin vasoconstriction. Those TRPV1 antagonists that cause hypothermia further inhibit these cold defences, thus decreasing body temperature. SIGNIFICANCE: TRPV1 antagonists (of capsaicin activation) are highly unusual in that they can cause both hyper- and hypothermia by modulating the same mechanism. For drug development, this means that both side effects can be dealt with simultaneously, by minimizing these compounds' interference with TRPV1 activation by protons.

Blockade of mGluR1 receptor results in analgesia and disruption of motor and cognitive performances: effects of A-841720, a novel non-competitive mGluR1 receptor antagonist.

BACKGROUND AND PURPOSE: To further assess the clinical potential of the blockade of metabotropic glutamate receptors (mGluR1) for the treatment of pain. EXPERIMENTAL APPROACH: We characterized the effects of A-841720, a novel, potent and non-competitive mGluR1 antagonist in models of pain and of motor and cognitive function. KEY RESULTS: At recombinant human and native rat mGluR1 receptors, A-841720 inhibited agonist-induced calcium mobilization, with IC50 values of 10.7+/-3.9 and 1.0 +/- 0.2 nM, respectively, while showing selectivity over other mGluR receptors, in addition to other neurotransmitter receptors, ion channels, and transporters. Intraperitoneal injection of A-841720 potently reduced complete Freund's adjuvant-induced inflammatory pain (ED50 = 23 micromol kg(-1)) and monoiodoacetate-induced joint pain (ED50 = 43 micromol kg(-1)). A-841720 also decreased mechanical allodynia observed in both the sciatic nerve chronic constriction injury and L5-L6 spinal nerve ligation (SNL) models of neuropathic pain (ED50 = 28 and 27 micromol kg(-1), respectively). Electrophysiological studies demonstrated that systemic administration of A-841720 in SNL animals significantly reduced evoked firing in spinal wide dynamic range neurons. Significant motor side effects were observed at analgesic doses and A-841720 also impaired cognitive function in the Y-maze and the Water Maze tests. CONCLUSIONS AND IMPLICATIONS: The analgesic effects of a selective mGluR1 receptor antagonist are associated with motor and cognitive side effects. The lack of separation between efficacy and side effects in pre-clinical models indicates that mGluR1 antagonism may not provide an adequate therapeutic window for the development of such antagonists as novel analgesic agents in humans.

Multi-technique characterization of a nuclear bomb particle from the Palomares accident.

A January 1966 accident dispersed Pu and other nuclear bomb materials in the vicinity of Palomares, a village in southeastern Spain. Radioactive particles were identified in a soil sample collected in 1998 and analytical results obtained from one of the isolated particles are presented here. Isolation of the particle was performed using gamma-ray spectrometry and imaging plates. Scanning electron microscopy with X-ray microanalysis revealed the presence of U and Pu as well as Pb and Fe in the particle of approximately 10microm diameter. Radioisotopes of U, Pu, and Am were quantified using radiometric methods, inductively coupled plasma mass spectrometry and secondary ion mass spectrometry. The elevated (235)U/(238)U atom ratio indicates enriched U, and the Pu atom ratios are consistent with weapons-grade material. This work demonstrates that the analysis of individual particles provides information not available through bulk sample analysis.

Relationship of socioeconomic status to the incidence and prehospital, 28-day, and 1-year mortality rates of acute coronary events in the FINMONICA myocardial infarction register study.

BACKGROUND: Low socioeconomic status (SES) is associated with increased coronary heart disease mortality rates. There are, however, very little data on the relation of SES to the incidence, recurrence, and prognosis of myocardial infarction (MI) events. METHODS AND RESULTS: The FINMONICA MI Register recorded detailed information on all MI events among men and women aged 35 to 64 years in 3 areas of Finland during the period of 1983 to 1992. We carried out a record linkage of the MI register data with files of Statistics Finland to obtain information on indicators of SES, such as taxable income and education, for each individual who is registered. In the analyses, income was grouped into 3 categories (low, middle, and high), and education was grouped into 2 categories (basic and secondary or higher). Among men with their first MI event (n=6485), the adjusted incidence rate ratios were 1.67 (95% CI 1.57 to 1.78) and 1.84 (95% CI 1.73 to 1.95) in the low- and middle-income categories compared with the high-income category. For 28-day mortality rates, the corresponding rate ratios were 3.18 (95% CI 2.82 to 3.58) and 2.33 (95% CI 2.03 to 2.68). Significant differentials were observed for prehospital mortality rates, and they remained similar up to 1 year after the MI. Findings among the women were consistent with those among the men. CONCLUSIONS: The excess coronary heart disease mortality and morbidity rates among persons with low SES are considerable in Finland. To bring the mortality rates of low- and middle-SES groups down to the level of that of the high-SES group constitutes a major public health challenge.

Decline in out-of-hospital coronary heart disease deaths has contributed the main part to the overall decline in coronary heart disease mortality rates among persons 35 to 64 years of age in Finland: the FINAMI study.

BACKGROUND: Out-of-hospital deaths constitute the majority of all coronary heart disease (CHD) deaths and are therefore of considerable public health significance. METHODS AND RESULTS: We used population-based myocardial infarction register data to examine trends in out-of-hospital CHD deaths in Finland during 1983 to 1997. We included in out-of-hospital deaths also deaths in the emergency room and all deaths within 1 hour after the onset of symptoms. Altogether, 3494 such events were included in the analyses. The proportion of out-of-hospital deaths of all CHD deaths depended on age and gender. In the age group 35 to 64 years, it was 73% among men and 60% among women. These proportions did not change during the study. The annual average decline in the age-standardized out-of-hospital CHD death rate was 6.1% (95% CI, -7.3, -5.0%) among men and 7.0% (-10.0, -4.0%) among women. These declines contributed among men 70% and among women 58% to the overall decline in CHD mortality rate. In all, 58% of the male and 52% of the female victims of out-of-hospital CHD death had a history of symptomatic CHD. Among men with a prior history of myocardial infarction, the annual average decline in out-of-hospital CHD deaths was 5.3% (-7.2, -3.2%), and among men without such history the decline was 2.9% (-4.4, -1.5%). Among women, the corresponding changes were -7.8% (-14.2, -1.5%) and -4.5% (-8.0, -1.0%). CONCLUSIONS: The decline in out-of-hospital CHD deaths has contributed the main part to the overall decline in CHD mortality rates among persons 35 to 64 years of age in Finland.

Dyslipidemia and hyperglycemia predict coronary heart disease events in middle-aged patients with NIDDM.

Patients with NIDDM are at increased risk for coronary heart disease (CHD). However, information on the predictive value of cardiovascular risk factors and the degree of hyperglycemia with respect to the risk for CHD in diabetic patients is still limited. Therefore, we carried out a prospective study on risk factors for CHD, including a large number of NIDDM patients. At baseline, risk factor levels of CHD were determined in 1,059 NIDDM patients (581 men and 478 women), aged from 45 to 64 years. These patients were followed up to 7 years with respect to CHD events. Altogether, 158 NIDDM patients (97 men [16.7%] and 61 women [12.8%]) died of CHD and 256 NIDDM patients (156 men [26.8%] and 100 women [20.9%]) had a serious CHD event (death from CHD or nonfatal myocardial infarction). A previous history of myocardial infarction, low HDL cholesterol level (<1.0 mmol/l), high non-HDL cholesterol (> or =5.2 mmol/l), high total triglyceride level (>2.3 mmol/l), and high fasting plasma glucose (>13.4 mmol/l) were associated with a twofold increase in the risk of CHD mortality or morbidity, independently of other cardiovascular risk factors. High calculated LDL cholesterol level (> or =4.1 mmol/l) was significantly associated with all CHD events. The simultaneous presence of high fasting glucose (>13.4 mmol/l) with low HDL cholesterol, low HDL-to-total cholesterol ratio, or high total triglycerides further increased the risk for CHD events up to threefold. Our 7-year follow-up study provides evidence that dyslipidemia and poor glycemic control predict CHD mortality and morbidity in patients with NIDDM.

Cardiovascular risk factors associated with insulin resistance cluster in families with early-onset coronary heart disease.

Coronary heart disease (CHD) is a multifactorial disease caused by environmental and genetic factors. CHD clusters in families, but it is not known whether susceptibility to early-onset CHD is associated with the clustering of cardiovascular risk factors. Therefore, we determined the levels of cardiovascular risk factors among siblings with and without severe early-onset CHD drawn from 101 Finnish families. Probands with CHD, compared with their siblings without CHD, had, respectively, higher 2-hour insulin levels (475.7 versus 331.8 pmol/L, P=0.011) and 2-hour insulin areas (796.2 versus 640.4 pmol/L per hour, P=0.031) in an oral glucose tolerance test, lower high density lipoprotein cholesterol levels (1.22 versus 1.42 mmol/L, P=0.001), higher total triglyceride levels (1.91 versus 1.68 mmol/L, P=0.018), higher very low density lipoprotein triglyceride levels (1.25 versus 1.06 mmol/L, P=0.011), and higher fibrinogen levels (3.8 versus 3.4 g/L, P= 0.008). No significant differences were found in cardiovascular risk factors between affected siblings and probands with CHD. Environmental or lifestyle factors did not differ between siblings with or without early-onset CHD. We conclude that cardiovascular risk factors associated with the insulin resistance syndrome (hyperinsulinemia, low high density lipoprotein cholesterol, high total and very low density lipoprotein triglycerides, and high fibrinogen) are likely to contribute indirectly to early-onset CHD.

Intron 4 polymorphism of the endothelial nitric oxide synthase gene is associated with elevated blood pressure in type 2 diabetic patients with coronary heart disease.

The endothelial nitric oxide synthase (eNOS) gene is responsible for constitutive nitric oxide synthesis and arterial vasodilatation. Recently two polymorphisms, the 27-bp repeat sequence in intron 4 and the Glu298Asp substitution in exon 7 of the eNOS gene have been reported to be related to coronary heart disease (CHD). We screened these polymorphisms of the eNOS gene in 308 unrelated nondiabetic subjects with CHD, in 251 unrelated patients with type 2 diabetes with CHD, and in 110 randomly selected healthy subjects without CHD. The 4a and Asp298 allele frequencies of the eNOS gene were 0.19 and 0.36 in nondiabetic patients with CHD, 0.21 and 0.27 in type 2 diabetic patients with CHD, and 0.16 and 0.31 in nondiabetic subjects without CHD (n.s. between the groups). The Asp298 allele in exon 7 of the eNOS gene was not associated with elevated blood pressure in any of the study groups. Among type 2 diabetic patients with CHD the 4a allele in intron 4 of the eNOS gene was associated with elevated levels of systolic (P=0.035) and mean arterial blood pressure (P=0.040). In nondiabetic subjects these associations were not statistically significant. When all study groups were pooled in statistical analysis the 4a allele of the eNOS gene was associated with elevated diastolic (P=0.032) and mean (P=0.030) arterial blood pressure even after adjustment for confounding factors. We conclude that the 4a allele of the eNOS gene is not associated with CHD or type 2 diabetes, but that it is related to elevated blood pressure levels particularly among type 2 diabetic patients with CHD.

Apolipoprotein E gene promoter (-219G/T) polymorphism is associated with premature coronary heart disease.

The relationship of two apolipoprotein (apo) E gene polymorphisms and coronary heart disease (CHD) was investigated in 118 Finnish families with premature CHD and in 110 healthy control subjects. Affected siblings and probands with premature CHD had higher frequencies of the T allele of the -219G/T promoter polymorphism and the epsilon 4 allele (genotypes epsilon 4/3 or epsilon 4/4) of the apo epsilon 2/epsilon 3/ epsilon 4 polymorphism than those of healthy control subjects. Additionally, when the two apo E gene polymorphisms were combined, affected siblings and probands had a higher frequency of the -219T allele and the epsilon 4 allele combinations than did healthy controls. The -219T and the epsilon 4 alleles both separately and together were associated with higher levels of 2-h glucose in an oral glucose tolerance test. These results indicate that the two polymorphisms of the apo E gene have similar effects on the risk of coronary atherosclerosis in families with premature CHD. This risk was not explained by the effect of apo E gene polymorphisms on cholesterol metabolism, but their effect on cardiovascular risk factor clustering with insulin resistance may be of importance. We conclude that in addition to the epsilon 4 allele, also the -219G/T promoter polymorphism of the apo E gene is associated with early onset CHD.

Risk factors predicting lower extremity amputations in patients with NIDDM.

OBJECTIVE: To examine the predictors of lower extremity amputation in patients with NIDDM. RESEARCH DESIGN AND METHODS: At baseline, risk factors for amputation were determined in 1,044 NIDDM patients (571 men, 473 women) aged 45 to 64 years. These patients were followed up to 7 years with respect to amputation. RESULTS: The incidence of amputation was 5.6% in men and 5.3% in women. High fasting plasma glucose at baseline examination and the duration of diabetes were associated with a twofold risk for amputation. Similarly, glycemic control measured at baseline by HbA1 was an important predictor of amputation. There was a dose-response relationship between plasma glucose or HbA1 and the risk for amputation. The effect of hyperglycemia on the risk of amputation was seen clearly even after the adjustment for other cardiovascular risk factors. Signs of peripheral neuropathy and bilateral absence of Achilles tendon reflexes and vibration sense were important predictors for amputation. Furthermore, absent peripheral artery pulses and femoral artery bruit on auscultation predicted amputation. CONCLUSIONS: Our 7-year follow-up study gives strong evidence that poor glycemic control is an important predictor of amputation in patients with NIDDM in addition to clinically detectable peripheral arterial disease and peripheral neuropathy.