Reduced platelet serotonin content and release in familial hypercholesterolaemia

Plasma and platelet serotonin (5-HT) concentrations, and resting and collagen-induced 5-HT release in platelet-rich plasma were studied in normal and familial hypercholesterolaemic (FH) subjects. Platelet 5-HT concentrations were significantly reduced (−37%, P<0.01) in FH patients whilst mean plasma concentrations, although increased, were not significantly different from those in normal subjects. Platelet 5-HT correlated negatively with plasma cholesterol when the data for normal subjects and FH patients were combined (r=−0.48, P=0.005). It also correlated negatively with low-density lipoprotein (LDL) (FH data, r=−0.59, P=0.03; normal and FH data, r=−0.49, P=0.004) but positively with high-density lipoprotein (HDL) (FH, r=0.79, P=0.001; normal and FH, r=0.37, P=0.03). Collagen (5–160 μg/ml) stimulated platelet 5-HT release occurred in a concentration-dependent manner. In FH patients stimulated 5-HT release was reduced (10 μg/ml collagen, −40%, P<0.05) and accompanied by increased collagen EC₅₀ values (P<0.02). Resting 5-HT release was increased substantially in FH patients but not significantly. Our data provide evidence for a relationship between circulating cholesterol and platelet serotonergic mechanisms. It is proposed that abnormalities relating to platelet-plasma 5-HT dynamics, perhaps due to enhanced platelet activity or decreased platelet uptake, may contribute to the cardiovascular complications in FH.     

Discriminative value of serum amyloid A and other acute-phase proteins for coronary heart disease

We studied the value of serum amyloid A (SAA), a first-class acute-phase protein, as a marker for coronary heart disease (CHD) in a middle-aged male population. In a working population of 16 307 men (age, 35–59 years), 446 cases had a history of CHD or prominent Q:QS waves on electrocardiogram. For each case, two matched controls were investigated. SAA, measured by immunonephelometry, was correlated with other acute-phase proteins, cardiovascular risk factors, and infectious serology markers. SAA concentrations were significantly higher in the cases than in controls (P<0.05) and correlated with serum C-reactive protein (CRP) (r=0.61), plasma fibrinogen (r=0.39), serum haptoglobin (r=0.26), and body mass index (r=0.13) (P<0.001). Serum CRP is a better marker for CHD than SAA, which showed discriminative power only in a univariate model comparing highest versus lowest tertile (odds ratio, 1.39; 95% confidence interval, 1.03–1.87). Neither SAA nor other acute-phase proteins correlated with Chlamydia pneumoniae immunoglobulin (Ig)G, Helicobacter pylori IgG and IgA, and cytomegalovirus IgG. In conclusion, although SAA has a discriminative value for CHD, serum CRP is to be preferred as a first-class acute-phase reactant for detection of the disease.     

Microsomal triglyceride transfer protein: does insulin resistance play a role in the regulation of chylomicron assembly?

We have previously demonstrated that diabetes is associated with an increase in intestinal microsomal triglyceride transfer protein (MTP) mRNA in both the rat and rabbit models. The present study was designed to investigate the relationship between MTP expression and chylomicron assembly in an insulin resistant non-diabetic animal model. Ten insulin resistant Zucker obese fa/fa rats and ten lean fa/− rats were examined at 8–10 weeks of age. The lymph duct was cannulated and lymph collected for 4 h. Lymph chylomicrons were isolated by ultracentrifugation and their composition determined. RNA was extracted from intestinal mucosa and from the liver. MTP mRNA was measured using the RNase protection assay. Blood sugar in the fatty rats was significantly higher (6.3±1.2 vs. 5.4±0.4 P<0.05) and plasma insulin was almost six times that of the lean rats (P<0.001). Plasma cholesterol and phospholipid but not triglyceride were significantly increased in the obese animals (P<0.01). Obese animals secreted significantly more lymph chylomicron apo B48 (0.05±0.02 vs. 0.02±0.01mg/h P<0.005), triglyceride (9.7±5.3 vs. 3.8±1.9 mg/h P<0.005) and phospholipid (1.5±0.7 vs. 0.4±0.3 mg/h P<0.001). The only difference in the chylomicron particle composition between the two groups was a significant increase in phospholipid (P<0.01). Intestinal MTP mRNA expression was significantly higher in the fatty compared to the lean rats (22.1±9.5 vs. 7.8±5.6 amol MTP mRNA/μg total RNA P<0.001) as was hepatic MTP mRNA expression (6.9±3.5 vs. 3.4±1.5 amol MTP mRNA/μg total RNA, P<0.01). Thus in this animal model of insulin resistance, increased MTP, which was associated with increased chylomicron particle number, may play a crucial role in the development of atherosclerosis.     

Relation of family history of premature coronary heart disease and metabolic risk factors to risk of coronary arterial calcium in asymptomatic subjects

We studied 6,141 consecutive, asymptomatic, nondiabetic patients who underwent electron beam tomography and explored the interaction between metabolic risk factors (RFs) and premature family history (FH) of coronary heart disease (CHD) in predicting the presence and severity of coronary arterial calcium (CAC). In the presence of >2 metabolic RFs, patients with a positive FH of premature CHD had a significantly higher prevalence of any CAC, CAC >/=100, and CAC >/=75th age-gender percentile than those without a FH of CHD. Our study demonstrated that a familial propensity to subclinical atherosclerosis interacts with the presence of >/=2 metabolic RFs, magnifying the risks for those exposed to both.     

Cardiovascular risk factors and non-invasive assessment of subclinical atherosclerosis in youth

Our understanding of the natural history of atherosclerosis in childhood and its response to cardiovascular (CV) risk factor reduction have been hampered by the lack of a reliable, non-invasive measure of atherosclerosis. Carotid intima media thickness (IMT), a surrogate marker of atherosclerosis in adults, is increased in youth heterozygous for familial hypercholesterolemia (FH) and declines with lipid lowering pharmacotherapy. The age at which vascular changes can be reliably identified using IMT and the influence of CV risk factors beyond FH on IMT remains unclear.ObjectiveTo examine the influence of demographic, family history, anthropometric characteristics and traditional CV risk factors on IMT in children 5–16 years of age (mean age 11 year).MethodsIn a cross-sectional study, we assessed IMT in 148 children (51 with elevated low density lipoprotein (LDL)-cholesterol, 44 with overweight and 53 controls). Measures included: family history of premature coronary heart disease (CHD), physical activity, pubertal stage, smoking history, fasting glucose, insulin, lipid profile, apolipoproteins A1 and B, anthropometry, blood pressure and IMT.ResultsThe groups were similar for age and family history of premature CHD. Compared to controls, average maximum IMT (0.403 ± 0.04 vs 0.387 ± 0.029) and average mean IMT were elevated in the hyperlipidemia group (p < 0.05), but not in the overweight group (max IMT 0.393 ± 0.034; p vs control = 0.17). Using multiple regression modelling, age, family history of premature CHD and apoliprotein A1 and B predicted 17% of the variability in IMT. No measure of adiposity predicted IMT.ConclusionAge is an important predictor of IMT in youth. Among traditional CV risk factors, dyslipidemia and family history of premature CHD are independent predictors of IMT.     

The Validity of Screening for Hypercholesterolaemia at Different Ages from 2 to 17 Years*

Summary: This study was designed to test the proposition that an optimal age for screening for hypercholesterolaemia (HC) might be defined. The samples of children studied included 200 two-year-olds, 385 four-year-olds, and 230 primary and secondary children aged from eight to 17 years. The 95th percentile value for total serum cholesterol (TC) was used to define HC in children and to select children for family studies. Four of the 15HC two-year-olds had an HC parent with three having a history of early coronary heart disease (CHD). Twenty-three of the 310 parents sampled had HC, 15 having a family history of early CHD, but only four having an HC child. Family studies were done on 20 HC four-year-olds of whom half had a positive family history of premature coronary heart disease (CHD). Half of each group of parents were HC, but probable familial hypercholesterolaemia (FH) was detected only in three parents, environmental causes accounting for the HC of the others. Four primary and five secondary school students were HC, and selected for family studies. A positive family history of CHD was present in two of the primary and all of the secondary students, with five of the seven families having one or more HC parent, one having probable FH. It is proposed that programmes for detecting HC in childhood become valid only from four years of age, and that the presence of a positive family history of early CHD would reduce the proportion of children to be tested to a practical level without significantly impairing the accuracy of the case finding procedure. School entry might provide a suitable time to identify children with HC.     

Hypercoagulability and high lipoprotein(a) levels in patients with type II diabetes mellitus

Diabetes mellitus is associated with disturbances in hemostasis that could contribute to the development of diabetic vascular disease. We investigated the changes in parameters of blood coagulation and the fibrinolytic system and in plasma levels of lipoprotein(a) (Lp(a)) in 124 patients with type II diabetes mellitus and 44 healthy control subjects matched for age and body mass index (BMI) to determine whether hemostatic disturbances may lead to increased cardiovascular mortality. Median levels of fibrinogen (P < 0.0001), thrombin-antithrombin III complex (TAT) (P < 0.005), and plasminogen activator inhibitor-1 (PAI-1) activity (P < 0.05) in plasma were significantly elevated in diabetic patients compared with controls. The median concentration of Lp(a) was significantly higher in diabetic patients than in normal controls (18.2 vs. 12.6 mg/dl, P < 0.0005). Lp(a) levels tended to be elevated in patients with a prolonged history of diabetes. There was no evidence that Lp(a) levels were affected by metabolic control or by type of treatment. Twenty-two diabetics with coronary heart disease (CHD) had significantly higher levels of fibrinogen (P < 0.05), TAT (P < 0.05), and Lp(a) (24.7 vs. 13.7 mg/dl, P < 0.01) than the 51 patients without diabetic angiopathy. Our data indicate that impaired hemostatic balance in diabetes may cause hypercoagulability and may thus contribute to the increased cardiovascular mortality in diabetes.     

Reduced sympathetic inhibition in salt-sensitive Japanese young adults

The purpose of our study was to investigate the sympathetic response to excess salt loading of 54 normotensive young adults with and without a family history of hypertension. We examined muscle sympathetic nerve activity, plasma concentration and urinary excretion of catecholamines, and ambulatory blood pressures during low (4 g NaCl) and high (16 g NaCl) salt diet intake. Ambulatory blood pressure and urinary excretion of catecholamines are known to be reduced during sleep. These parameters were therefore calculated during waking and sleeping periods. The subject was defined as salt-sensitive when mean ambulatory systolic pressure during the waking period was ≥3mm Hg higher during high salt intake than during low salt intake (n = 26: 21.4 ± 0.3 years old). When mean systolic pressure was either lower or equal during high salt intake than during low salt intake, the subject was defined as salt-resistant (n = 24: 21.3 ± 0.3 years old). Muscle sympathetic nerve activity, plasma concentration and urinary excretion of norepinephrine in salt-resistant subjects were significantly reduced (P < .05) by salt intake, wheras plasma concentration of epinephrine was unchanged and urinary excretion of epinephrine was reduced. In contrast, urinary excretion of epinephrine in salt-sensitive subjects was significantly elevated (P < .05) during high salt intake, whereas muscle sympathetic nerve activity and urinary excretion of norepinephrine remained unchanged despite a significant increase (P < .01) of ambulatory blood pressure. Of the salt-sensitive subjects, 73% (19 of 26) had a positive family history of hypertension, whereas only 5 of 24 salt-resistant subjects had a positive family history. These data indicate that the inhibition of sympathetic activity during a high salt intake did not occur in salt-sensitive young adults, and this may be linked with a hereditary predisposition to hypertension.     

Impact of poverty on the prevalence of diabetes and its complications in urban southern India.

AIM: The impact of poverty on the profile of diabetes and its complications was studied. METHODS: A comparative study of low income group (LIG) (family income Rs. < 30,000/annum (approx. 432 pounds sterling) and high income group (HIG) (family income Rs. greater-than-or-equal 60,000/annum (approx. pounds sterling) subjects of > or = 40 years was done in Madras, India. By screening 1748 LIG subjects (M/W 844/904) 301 diabetic subjects were identified and 218 underwent tests for diabetic complications. Population data available in 635 (M/W 309/326) HIG subjects from the survey were used for comparison of glucose tolerance profile. Complications were studied in 221 diabetic HIG subjects. RESULTS: Age-standardized prevalences of diabetes (12.6% vs. 25.5%; chi(2) = 56.9, P < 0.0001) and impaired glucose tolerance (IGT) (8.9% vs. 19.0%) were significantly lower (chi(2) = 57.7; P < 0.0001) in the LIG. Hypertension was more common in LIG (53.7% vs. 40.0% in HIG; chi(2) = 34.9; P < 0.0001). LIG subjects were more physically active; 73.8% did not go to school. Parameters significantly associated with diabetes were body mass index (BMI), age, higher income, waist--hip ratio and physical inactivity. Higher income, BMI and age were associated with IGT. Diabetic LIG subjects had a higher prevalence of cardiac disease, neuropathy and cataract and a lower prevalence of retinopathy than HIG subjects. The risk variables such as hyperglycaemia, dyslipidaemia, hypertension, smoking and alcohol consumption were more in the LIG group. CONCLUSIONS: The urban poor in the developing world has a lower prevalence of diabetes than the urban poor in developed societies. However, they have higher rates of complications of diabetes.     

Familial predisposition to cardiovascular risk and disease contributes to cardiovascular risk and disease interacting with other cardiovascular risk factors in diabetes: implication for common soil (JDDM 14)

In diabetic population cardiovascular morbidity is high and the effects of genetic predisposition remain elucidated. In a large-scale multicenter-based diabetic population, clinical parameters including conventional cardiovascular risk factors and first-degree family history (FH) of diabetes, hypertension, coronary heart disease (CHD) and stroke were investigated in association with presence of CHD and stroke. Among 3611 diabetic patients, 181 (5.0%) had CHD and 118 (3.3%) had stroke. After adjustment for conventional risk factors, FH of CHD (OR 2.32, p<0.0001) and of diabetes (OR 1.44, p<0.05) were associated with CHD, and FH of stroke (OR 1.86, p<0.01) was associated with stroke. FH of hypertension was significantly associated with presence of hypertension and obesity. Synergistic effect of FH of CHD in combination with hypertension or aging on increasing CHD, and that of FH of stroke in combination with microalbuminuria on increasing stroke were found. FH of diabetes, of hypertension, of CHD and of stroke were significantly associated with FH of each disease, indicating clustering of FH. In diabetic population, FH of CHD and FH of stroke doubled the risk of CHD and stroke, respectively, and had synergistic effect in combination with other risk factors. Clustering of FH may indicate interrelation of genetic predisposition.     

Normal angiogram after myocardial infarction in young patients:: A prospective clinical-angiographic and long-term follow-up study

This is an observational study in which we compared the clinical characteristics and the long-term course of young patients having acute myocardial infarction and angiographically normal coronary arteries and young patients showing significant coronary artery disease. In 87 patients aged ≤40 years who suffered an acute myocardial infarction, enrolled in a prospective study over a period of 6.5 years, coronary anatomy was determined by angiography within a month of admission. The risk factors, clinical data, ventricular function and the long-term outcome were compared between patients with normal angiograms (Group 1, n=12) and patients with coronary artery disease (Group 2, n=75). Patients in Group 1 had a lower number of risk factors associated with them (17% vs. 64% with >1 risk factor, P<0.005), were younger (32±5 vs. 36±4, P<0.01), lighter smokers (25% vs. 55% for ≥2 packs per day, P<0.05), had less frequent hypertension (0 vs. 25%, P<0.05), hypercholesterolemia (17% vs. 52%, P=0.02) and had a lower mean total cholesterol level (201±42 vs. 245±60 mg/100 ml, P<0.05) than patients in Group 2. They also had a more common onset of their infarction during heavy physical exertion (67% vs. 17%, P<0.001). A history of previous myocardial infarction, infarct location, global left ventricular function and regional wall motion were similar in both groups. After a mean follow-up period of 41±23 months, no patient died or had a second myocardial infarction in Group 1, and 4 patients had died in Group 2. The appearance of angina, less frequent in Group 1 than Group 2, tended to correlate with the extension of the coronary artery disease. We concluded that young patients with myocardial infarction have good prognosis irrespective of the coronary anatomy, although patients with normal coronary angiograms had less risk factors and less frequent new ischaemic events.     

Platelet trans fatty acids in relation to angiographically assessed coronary artery disease

Epidemiological and metabolic studies indicate that a higher intake of trans fatty acids (TFA) may be associated with increased risk of coronary heart disease (CHD). In a cross-sectional study of patients who underwent coronary angiography, the relationships between TFAs, measured in platelets, and the degree of coronary artery disease (CAD) were examined in 191 non-diabetic patients (134 men and 57 women). The degree of CAD was quantified by using an angiographic scoring system developed to provide an estimate of the extent of coronary atherosclerosis: an ‘extent score’. The TFA composition of platelets, including palmitelaidic (16:1ω7t), elaidic (18:1ω9t), trans-10-octadecaenoic acid (18:1 ω8t), trans vaccenic (18:1ω7t), trans-12-octadecaenoic acid (18:1ω6t) and linoelaidic (18:2ω6tt) acids, was measured by using gas chromatography and quantified as a percentage of total fatty acids. After adjustment for established CHD risk indicators, including age, gender, cigarette smoking, hypertension and serum total cholesterol concentration, elaidic acid (P = 0.0300) and trans-10-octadecaenoic acid (P = 0.0434) were positively associated with the extent score of CAD. The adjusted associations between other individual TFAs, including palmitelaidic acid (P = 0.1189), vaccenic acid (P = 0.7651), trans-12-octadecaenoic acid (P = 0.0582) and linoelaidic acid (P = 0.8793), and the extent score were not significant. The results of this study, therefore, provide evidence for an association between particular platelet TFAs and the degree of CAD in the patient population studied.     

Association Between Family History and Hypertension Among Chinese Elderly

This study aimed to evaluate the association between family history and prevalence of hypertension among Chinese community elderly, and also explore the gender difference.A population-based cross-sectional study was conducted in Miyun district of Beijing, in 2014. The family history information was obtained from each subject and was divided into 3 categories, no family history (FH0), 1 generation of first-degree relatives with hypertension (FH1), and 2 generations of first-degree relatives with hypertension (FH2).The prevalence of hypertension was 53.0%. Participants with positive family history had a significantly higher prevalence of hypertension (67.5%, 95% CI: 63.3–71.7) than those without (47.9%, 95% CI: 45.2–50.6), and even among participants without hypertension, the blood pressure levels were higher with positive FH. Multiple logistic regression analysis showed that a significantly linear-trend increase in hypertension according to family history of first degree relative numbers was observed in both genders (P for trend < 0.001).This study suggests that family history had not only a significant but also graded association with hypertension and with blood pressure levels, and this association exists even among those without hypertension.     

No correlation and low agreement of imaging and inflammatory atherosclerosis' markers in familial hypercholesterolemia

Our purpose was to study the determinants of coronary and carotid subclinical atherosclerosis, aortic stiffness and their relation with inflammatory biomarkers in familial hypercholesterolemia (FH) subjects. Furthermore, we evaluated the agreement degree of imaging and inflammatory markers’ severity used for coronary heart disease (CHD) prediction. Coronary calcium scores (CCS), carotid intima media thickness (IMT), carotid-femoral pulse wave velocity (PWV), C reactive protein (CRP) and white blood cells count (WBC) were determined in 89 FH patients (39 ± 14 years, mean LDL-C = 279 mg/dl) and in 31 normal subjects (NL). The following values were considered as imaging and biomarkers’ severity: CCS > 75th% for age and sex, IMT > 900 μm, PWV > 12 m/s, and CRP > 3 mg/l.Coronary artery calcification (CAC) prevalence and severity, IMT, PWV and WBC values were higher in FH than in NL (all parameters, p < 0.05). After multivariate analysis, the following variables were considered independent determinants of (1) IMT: systolic blood pressure, 10-year CHD risk by Framingham risk scores (FRS) and apolipoprotein B (r² = 0.33); (2) PWV: age (r² = 0.35); (3) CAC as a continuous variable: male gender and LDL-cholesterol year score (LYS) (r² = 0.32); (4) presence of CAC as dichotomous variable: FRS (p = 0.0027) and LYS (p = 0.0228). With the exception of a moderate agreement degree between IMT and PWV severity (kappa = 0.5) all other markers had only a slight agreement level (kappa < 0.1). In conclusion, clinical parameters poorly explained IMT, CAC and PWV variability in FH subjects. Furthermore, imaging markers and inflammatory biomarkers presented a poor agreement degree of their severity for CHD prediction.     

Dynamic change in collateral flow associated with myocardial ischemia in humans

Background: This study sought to investigate how collateral flow changes during myocardial ischemia in patients. Methods: Myocardial contrast echocardiography (MCE) and rapid atrial pacing were performed in 20 patients with angiographically evidenced coronary collaterals from the right coronary artery (RCA) to the occluded left anterior descending coronary artery. Sonicated contrast medium was injected into the RCA before and immediately after atrial pacing to determine the peak background-subtracted contrast intensity (PI) in the collateral territory (PIA) and its ratio to PI in the control territory (PI ratio) as parameters of collateral blood flow. Lactate production in the coronary circulation during pacing was determined to assess myocardial ischemia in the collateral territory. Results: PIA showed a significant correlation with regional wall motion either before (r(squared)=−0.64, P<0.01) or after pacing (r(squared)=−0.65, P<0.01). Similarly, PI ratio was significantly correlated with regional wall motion either before (r(squared)=−0.54, P<0.05) or after pacing (r(squared)=−0.64, P<0.01). Rapid atrial pacing decreased both PIA and PI ratio significantly greater in patients with lactate production than in those without (PIA: −67±53 vs. −15±34%, P<0.05; PI ratio: −68±49 vs. −8.2±32%, P<0.05, respectively), while neither PIA nor PI ratio differ between the two groups of patients before pacing (PIA: 13.8±19. vs. 16.2±13.3U, P=0.75; PI ratio: 0.70±0.71 vs. 0.87±0.65, P=0.58, respectively). Conclusions: We concluded that (1) collateral flow determined by MCE was closely associated with regional cardiac function, and (2) not the amount of collateral flow at rest, but pacing-induced change of collateral flow seemed to be a determinant of regional ischemia in patients with coronary collaterals.     

The development of the adrenal gland zona glomerulosa in the rat. A morphological, immunohistochemical and biochemical study

We have studied the development of the adrenal gland in the rat comprising the ages ranging from 0 to 90 days after birth. The weight of the animals and that of the adrenal glands demonstrated a linear growth with time until 75 days, both in males and females. The area of the zona glomerulosa (ZG) increased in size from birth until ≈40 days of age. After that, growth had a much smaller slope (females, r=0.84, P<0.001; males, r=0.81, P<0.001). Aldosterone secretion had a marked increase until 20 days of age and thereafter demonstrated a tendency for a decrease (females, r=−0.19, P<0.02; males r=−0.26, P<0.001). Plasma renin activity followed a trend parallel to that of aldosterone. The steroid precursor 18-OH-deoxycorticosterone (18-OH-DOC) demonstrated a different course as it increased progressively with age especially in the females (females, r=0.57, P<0.001; males, r=0.40, P<0.001). The expression of the enzyme 3-β-hydroxysteroid dehydrogenase (3-β-HSD) was also studied by immunohistochemistry and it was shown to be very low at birth and starting to increase by 10 days of age. After 30/40 days of age the amount of this enzyme existing in the ZG was comparable with that of the outer zona fasciculata (ZF). We conclude that the development of the ZG in the rat has particularities that make it different from that of the rest of the cortex.     

A single nucleotide polymorphism in the promoter region of the osteoprotegerin gene is related to intima-media thickness of the carotid artery in hypertensive patients. The Swedish Irbesartan Left Ventricular Hypertrophy Investigation vs Atenolol (SILVHIA)

Osteoprotegerin (OPG) is a secreted member of the tumor necrosis factor receptor family, and in previous studies has been shown to regulate osteoclast activity and differentiation. Ablation of the OPG gene in mice results in calcification of the aorta and renal arteries. We have previously reported an association between a single nucleotide polymorphism in the promoter region of OPG and vascular morphology and function in healthy humans. The objective with this study was to confirm our previous results in a larger population, and in addition, to study subjects with hypertension. The OPG genotype was determined by restriction fragment length and the intima-media thickness (IMT) of the common carotid artery was measured by ultrasound in 100 patients with hypertension and left ventricular hypertrophy, and 75 healthy normotensive control subjects. In the hypertensive group subjects with the CC genotype (n = 24) showed a significantly increased IMT compared to those with the TC (n = 52, p = 0.007) and TT (n = 24, p = 0.009) genotype, in the hypertensive group only (mean ± SD for TT = 0.88 ± 0.21 mm, TC = 0.90 ± 0.16 mm, CC = 1.05 ± 0.31 mm). The allele distribution did not differ between hypertensive and control individuals. The present study confirms our previous finding and shows that polymorphism in the promoter region of OPG is associated with vascular morphology in hypertensive subjects.     

Clinical and biochemical outcomes of Type 2 diabetes mellitus in Canterbury, New Zealand: a 6-year cohort study

There is a paucity of data regarding outcomes of Type 2 diabetes mellitus. A cohort of 447 Type 2 diabetic subjects (208 male, 239 female; age range 30–82 years, median 62 years; and of predominantly European origin) was characterised in a clinic survey in 1989. Individual status (dead or alive) at 1 June 1995 was ascertained. At 6 years, 289 subjects were confirmed as alive and 133 as dead—only 25 were untraceable. Of those subjects identified as alive, follow-up clinical and biochemical data were obtained for 253 (87.5%) individuals. In those subjects, glycated haemoglobin deteriorated from 63.1±18.7 mmol/mol haem in 1989 to 71.7±24.4 in 1995, P<0.0001. An increased prevalence of retinopathy was evident at 6-year follow-up, 59.7% cases in 1995 compared with 39.5% in 1989, P<0.001. Similarly there was an increased prevalence of coronary artery disease (CAD) (33.6 vs 18.2% of cases), albuminuria (26.5 vs 19% of cases; P<0.001), and hypertension (71.5 vs 54.9% of cases; P<0.001) in 1995 vs 1989, respectively. Multiple logistic regression analysis showed that glycated haemoglobin (odds ratio (OR) for 18 mmol/mol haem change, 1.78; 95% CI, 1.15–2.85), hypertension (OR, 3.33; 95% CI, 1.40–8.41) and known duration of diabetes (OR for 7 year change, 2.12; 95% CI, 1.24–3.80) were predictors for development of retinopathy. There is therefore a deterioration in glycaemic control in Type 2 diabetes over 6 years and an increased prevalence of complications that present strategies in a multidisciplinary specialist diabetes clinic are unable to prevent on a sustainable basis.     

Effects of iodine intake on thyroid secondary lysosomes after subtotal thyroidectomy

This study tested the effects of different iodine intakes on thyroid ultrastructure and function in thyroid remnants after subtotal thyroidectomy (sub-tx). Removal of most of the thyroid gland causes an elevation of endogenous TSH, which chronically stimulates the residual tissue. Male Sprague-Dawley rats were divided into three groups; Low Iodine Group (LIG), Moderate Iodine Group (MIG), and High Iodine Group (HIG). There was no significant difference among total thyroid weights removed by sub-tx, but thyroid remnant weights and TSH levels were higher at death (6 weeks after sub-tx) in LIG than in MIG and HIG. Total specific activities of cathepsin D and of arylsulfatase A in the sedimentable and nonsedimentable subcellular fractions were at least 38% lower in LIG than in MIG and HIG. The ratio between relative follicular volume and colloid volume determined by morphometry was higher in LIG than in MIG and lower in HIG than in MIG. Ultrastructurally, the relative volume occupied by secondary lysosomes was higher in HIG than in MIG, whereas the number of secondary lysosomes was not higher in LIG than in controls. Autoradiographic studies with 125I revealed that a large part of the radioactivity was in thyroid cell secondary lysosomes in MIG and HIG when radioiodine was injected 3 weeks before death. It is concluded that after sub-tx, iodine 1) regulates the weight of thyroid remnants, perhaps only indirectly through TSH, 2) modulates the number of secondary lysosomes in thyroid cells, and 3) slows down the turnover of secondary lysosomes. An iodine-deficient regimen impedes the secondary lysosomes to increase. Because of these findings, we postulate that chronic TSH stimulation along with a possible toxic role of iodine after sub-tx could induce an accumulation of lysosomal bodies.     

Correlations between measures of atherosclerosis change using carotid ultrasonography and coronary angiography

Few studies have examined the correlation between change in carotid artery intima-media thickness (IMT) and change in coronary artery disease. In the Cholesterol Lowering Atherosclerosis Study, current nonsmoking men with coronary artery disease were randomized to colestipol-niacin or placebo. Among 133 subjects with baseline and on-trial coronary angiography and carotid ultrasonography, colestipol-niacin treatment significantly reduced progression of atherosclerosis by both end point measures (2-year average change in percent diameter stenosis by coronary angiography and rate of change in carotid IMT). Significant correlations between change in common carotid artery IMT and quantitative coronary angiographic measures of change were evident over all coronary artery lesions, and in mild/moderate (<50% diameter stenosis), but not severe (≥50% diameter stenosis) coronary artery lesions. In mild/moderate lesions, correlations with change in common carotid IMT were: percent diameter stenosis (r=0.28, P=0.002), minimum lumen diameter (r=−0.28, P=0.002), and vessel edge roughness (r=0.25, P=0.003). While measures obtained by carotid ultrasonography and coronary angiography are correlated, they each assess different aspects of atherosclerosis change.