Examining the role of mother-child interactions and DNA methylation of the oxytocin receptor gene in understanding child controlling attachment behaviors.

This study examined mother-child interactions and DNA methylation of the oxytocin receptor (OXTR) gene in the child, in relation with controlling-attachment behaviors at early preschool age. Maternal interactive behaviors were coded using the Emotional Availability Scales, and child attachment behaviors were assessed with the Separation-Reunion procedure and coded with the Preschool Attachment Rating Scales. DNA methylation data were captured from exon 3 of the OXTR. Results indicated that lower maternal sensitivity was associated with more controlling-caregiving behaviors, and that less maternal structuring was associated with more controlling-punitive behaviors. Hypomethylation of the OXTR gene was associated with greater maternal structuring behaviors, and with more child controlling-caregiving behaviors. The moderating role of the OXTR gene was examined in the association between interactive behaviors and child controlling behaviors, but no interaction effect was found. These results suggest that maternal interactive behaviors and OXTR methylation are independently associated with child controlling attachment.

Fourier transform Infrared spectroscopic characterization of mineralizing type I collagen enzymatic trivalent cross-links.

The most abundant protein of bone's organic matrix is collagen. One of its most important properties is its cross-linking pattern, which is responsible for the fibrillar matrices' mechanical properties such as tensile strength and viscoelasticity. We have previously described a spectroscopic method based on the resolution of the Amide I and II Fourier transform Infrared (FTIR) bands to their underlying constituent peaks, which allows the determination of divalent and pyridinoline (PYD) collagen cross-links in mineralized thin bone tissue sections with a spatial resolution of ~6.3 µm. In the present study, we used FTIR analysis of a series of biochemically characterized collagen peptides, as well as skin, dentin, and predentin, to examine the potential reasons underlying discrepancies between two different analytical methodologies specifically related to spectral processing. The results identified a novel distinct FTIR underlying peak at ~1,680 cm(-1), correlated with deoxypyridinoline (DPD) content. Furthermore, the two different methods of spectral resolution result in widely different results, while only the method employing well-established spectroscopic routines for spectral resolution provided biologically relevant results, confirming our earlier studies relating the area of the underlying 1,660 cm(-1) with PYD content. The results of the present study describe a new peak that may be used to determine DPD content, confirm our earlier report relating spectroscopic parameters to PYD content, and highlight the importance of the selected spectral resolution methodology.

Economic analysis of healthcare-associated infection prevention and control interventions in medical and surgical units: systematic review using a discounting approach.

Nosocomial or healthcare-associated infections (HCAIs) are associated with a financial burden that affects both patients and healthcare institutions worldwide. The clinical best care practices (CBPs) of hand hygiene, hygiene and sanitation, screening, and basic and additional precautions aim to reduce this burden. The COVID-19 pandemic has confirmed these four CBPs are critically important prevention practices that limit the spread of HCAIs. This paper conducted a systematic review of economic evaluations related to these four CBPs using a discounting approach. We searched for articles published between 2000 and 2019. We included economic evaluations of infection prevention and control of Clostridioides difficile-associated diarrhoea, meticillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, and carbapenem-resistant Gram-negative bacilli. Results were analysed with cost-minimization, cost-effectiveness, cost-utility, cost-benefit and cost-consequence analyses. Articles were assessed for quality. A total of 11,898 articles were screened and seven were included. Most studies (4/7) were of overall moderate quality. All studies demonstrated cost effectiveness of CBPs. The average yearly net cost savings from the CBPs ranged from $252,847 (2019 Canadian dollars) to $1,691,823, depending on the rate of discount (3% and 8%). The average incremental benefit cost ratio of CBPs varied from 2.48 to 7.66. In order to make efficient use of resources and maximize health benefits, ongoing research in the economic evaluation of infection control should be carried out to support evidence-based healthcare policy decisions.

Sleep quality is associated with vasopressin methylation in pregnant and postpartum women with a history of psychosocial stress.

BACKGROUND: The relationship between disturbed sleep and stress is well-documented. Sleep disorders and stress are highly prevalent during the perinatal period, and both are known to contribute to a number of adverse maternal and foetal outcomes. Arginine vasopressin (AVP) is a hormone and a neuropeptide that is involved in stress response, social bonding and circadian regulation of the sleep-wake cycle. Whether the AVP system is involved in regulation of stress response and sleep quality in the context of the perinatal mental health is currently unknown. The objective of the present study was to assess the relationship between levels of cumulative and ongoing psychosocial risk, levels of disordered sleep and AVP methylation in a community sample of pregnant and postpartum women. METHODS: A sample of 316 participants completed a battery of questionnaires during the second trimester of pregnancy (PN2, 12-14 weeks gestation), third trimester (PN3, 32-34 weeks gestation), and at 7-9 weeks postpartum (PP). Disordered sleep was measured using the Sleep Symptom Checklist at PN2, PN3 and PP; cumulative psychosocial risk was assessed with the Antenatal Risk Questionnaire (ANRQ) at PN2; salivary DNA was collected at the follow-up (FU, 2.9 years postpartum); and % methylation were calculated for AVP and for two of the three AVP receptor genes (AVPR1a and AVPR1b). Women were separated into high (HighPR) and low (LowPR) psychosocial risk groups, based on their scores on the ANRQ. RESULTS: Women in the HighPR group had significantly worse sleep disturbances during PN2 (p < .001) and PN3 (p < .001), but not at PP (p = .146) than women in the LowPR group. In HighPR participants only, methylation of AVP at intron 1 negatively correlated with sleep disturbances at PN2 (rs=-.390, p = .001), PN3 (rs=-.384, p = .002) and at PP (rs= -.269, p = .032). There was no association between sleep disturbances and AVPR1a or AVPR1b methylation, or between sleep disturbances and any of the AVP methylation for the LowPR group. Lastly, cumulative psychosocial stress was a moderator for the relationship between AVP intron 1 methylation and disordered sleep at PN2 (p < .001, adjusted R2 = .105), PN2 (p < .001, adjusted R2 = .088) and PP (p = .003, adjusted R2 = .064). CONCLUSIONS: Our results suggest that cumulative psychosocial stress exacerbates sleep disorders in pregnant women, and that salivary DNA methylation patterns of the AVP gene may be seen as a marker of biological predisposition to stress and sleep reactivity during the perinatal period. Further research is needed to establish causal links between AVP methylation, sleep and stress.

High density lipoproteins, but not other lipoproteins, provide a vehicle for sterol transport to bile.

Unesterified cholesterol (UC) that is taken up by the liver from lipoproteins is rapidly mixed by exchange with liver UC. Thus, it is not possible to quantitate the transport of UC from different lipoproteins into bile using radiolabeled UC. However, plant sterols do not exchange with UC and are secreted in bile with the same kinetics as UC. To compare the contribution to bile of sterols from different lipoproteins, we perfused isolated rat livers with VLDL, LDL, and HDL that were obtained from patients with hereditary phytosterolemia and were rich in plant sterols. After 30-min recirculating perfusions, hepatic concentrations of plant sterols were not different after different lipoproteins were perfused. However, biliary plant sterol secretion was markedly different: with the perfusion of either VLDL or LDL there was no increase in plant sterols in bile, but with perfusion of HDL, the secretion of plant sterols was increased two- to threefold (P = 0.0005). The increase in biliary plant sterols was detected 5-10 min after HDL was added to perfusates and was similarly large for each of three individual plant sterols that was tracked. Results show that when sterol transport from lipoproteins into bile can be determined, only HDL provides a vehicle for UC elimination in bile that is consistent with its putative function in reverse cholesterol transport.

Utilization of individual lecithins in intestinal lipoprotein formation in the rat.

To determine the molecular species composition of lecithins of different nascent lipoproteins, high density lipoproteins (HDL), very low density lipoproteins (VLDL), and chylomicrons (CM) were isolated from the mesenteric lymph of rats. Lymph was collected at 0 degrees C with 5,5'-dithiobis-2-dinitrobenzoic acid added to inhibit lecithin-cholesterol acyl transferase. CM were separated by ultracentrifugation and HDL from VLDL by dextran SO4-MG+2 precipitation. Molecular species of lecithin were directly isolated by reverse phase high performance liquid chromatography. In fasted animals, the lecithin compositions of lymph HDL and VLDL were virtually the same and closely resembled the lecithin composition of intestinal mucosa. When bile lecithin was eliminated (by bile diversion), there was a marked change in lecithin composition of all lipoprotein and mucosal samples, which was most notable for a reduction in 16:0-species (which are predominant in bile) and a relative increase in the corresponding 18:0-species. Feeding unsaturated triglycerides (triolein, trilinolein, or a combination of triolein and trilinolein) also resulted in a change in HDL and VLDL lecithin composition. The effect was similar whether bile lecithin was present or eliminated and was notable for a reduction in 16:0-species, an increase in 18:0-species, and the emergence of large amounts of diunsaturated lecithins that corresponded to the fatty acid composition of the triglycerides fed (i.e., 18:1-18:1, 18:2-18:2, and 18:1-18:2 lecithins). When bile-diverted rats were infused via the duodenum with a mix of [14C]choline-labeled lecithins (isolated from the bile of other rats), the incorporation of infused lecithins into different lymph lipoproteins was distinctly different. Individual lecithins were incorporated to a variable extent into each lipoprotein. In fasted rats the specific activities of all major molecular species of lecithin were relatively greater in VLDL than HDL, indicating that HDL derived proportionately more of its lecithins from an endogenous pool than did VLDL. Feeding triolein changed the specific activities of more of the lecithin species of VLDL than of HDL. The specific activities of lecithins in CM were more similar to VLDL than to HDL after triolein feeding. Results thus indicate that, although the lecithins of different mesenteric lymph lipoproteins are similar and may be derived from membrane sites with the same lecithin composition, lecithins incorporated into different lipoproteins originate from different metabolic pools and/or by different mechanisms.

A COL1A1 Sp1 binding site polymorphism predisposes to osteoporotic fracture by affecting bone density and quality.

Osteoporosis is a common disease with a strong genetic component. We previously described a polymorphic Sp1 binding site in the COL1A1 gene that has been associated with osteoporosis in several populations. Here we explore the molecular mechanisms underlying this association. A meta-analysis showed significant associations between COL1A1 "s" alleles and bone mineral density (BMD), body mass index (BMI), and osteoporotic fractures. The association with fracture was stronger than expected on the basis of the observed differences in BMD and BMI, suggesting an additional effect on bone strength. Gel shift assays showed increased binding affinity of the "s" allele for Sp1 protein, and primary RNA transcripts derived from the "s" allele were approximately three times more abundant than "S" allele--derived transcripts in "Ss" heterozygotes. Collagen produced from osteoblasts cultured from "Ss" heterozygotes had an increased ratio of alpha 1(I) protein relative to alpha 2(I), and this was accompanied by an increased ratio of COL1A1 mRNA relative to COL1A2. Finally, the yield strength of bone derived from "Ss" individuals was reduced when compared with bone derived from "SS" subjects. We conclude that the COL1A1 Sp1 polymorphism is a functional genetic variant that predisposes to osteoporosis by complex mechanisms involving changes in bone mass and bone quality.

Immunolocalization of extracellular matrix proteins during brain tumor invasion in BD IX rats.

The distribution of several native extracellular matrix proteins (type I, III, and IV collagens and fibronectin) using immunofluorescent localization is described for in two different malignant gliomas (BT4A and BT4An). In addition, antibodies against denatured forms of type I and III collagens were used to localize areas of active degradation within the tumors. We have shown that both tumors express the native connective tissue components studied, although the distribution of these components within and between the tumors was different. In addition, native type I and III collagens and fibronectin were overexpressed in the tumors compared to the normal brain. Morphometry on immunostained type IV collagen sections showed an increase in vascular elements in both tumors compared to normal brain tissue. The BT4A tumor, which by light microscopy showed a degradative mode of invasion, expressed denatured type I and III collagens at the tumor-brain border zone, suggesting that this tumor has collagenolytic activity. The present article suggests that the distribution and changes in extracellular matrix protein synthesis and degradation may play an important role in the progressive growth of brain tumors in vivo.

Regulation of body cholesterol pools. Influence of cholesterol input and excretion in an animal model.

Biliary cholesterol excretion closely parallels lecithin excretion in the rat and may be increased by feeding an excess of choline and decreased by choline deficiency. To determine the relative influence of cholesterol input and excretion on whole body cholesterol metabolism, we have measured by compartmental analysis rates of cholesterol transport and pool sizes when both input and choline-mediated biliary excretion were increased and diminished. In choline-deficient animals with impaired excretion, plasma cholesterol was reduced. However, in deficient animals more cholesterol was transported into the slowly exchanging pool to increase pool size, and, when input was increased (by addition of cholesterol to diet), the slowly exchanging pool was even more markedly enlarged. In contrast, when excess choline was fed, plasma cholesterol was increased but excretion so exceeded transport into the slowly exchanging pool that pool size was actually reduced. Furthermore, in choline-fed animals with unimpaired excretion, addition of cholesterol to the diet to increase input did not result in pool expansion. Thus, in this model, cholesterol excretion and tissue deposition were reciprocally related, and, regardless of plasma cholesterol concentration and cholesterol input, stores were found to increase only when biliary excretion was impaired.

Pyridinium crosslinks of bone collagen and their location in peptides isolated from rat femur.

The relative proportions of pyridinoline and deoxypyridinoline in bone showed large species variations, although the total number of pyridinium crosslinks in rat, rabbit and bovine bone collagen was only 25-30% of that found in articular cartilage. Three pyridinium-containing peptides were isolated from cyanogen bromide digests of rat femoral bone and were characterized by their Mr values and amino-acid compositions. The results showed that pyridinoline and its deoxy analogue were equally distributed at two locations stabilizing the 4D stagger through interactions involving both the N- and C-terminal telopeptide regions. Less than stoichiometric amounts of pyridinium crosslinks were present in the peptides, suggesting that the isolated peptides contained additional (unidentified) maturation products of the bifunctional, reducible crosslinks.

Some observations on the ageing in vitro of reprecipitated collagen fibres.

The changes in solubility and amounts of reducible cross-links have been studied during "ageing" in vitro of reprecipitated rat skin collagen fibres by incubation at 37 degrees C. Fibres from pre-reduced collagen devoid of aldehyde precursors became insoluble at the same rate as that of normal fibres during "ageing". Insolubilization occurred at a much faster rate in the presence of oxygen than in air and was almost completely inhibited when oxygen was excluded. The rate of decline of the reducible cross-links was, however, unaffected by oxygen tension. The results indicate that, during "ageing" in vitro, conversion of the lysine-derived cross-links to a non-reducible form is not associated with solubility changes. The relationship of these in vitro changes to those ocurring in vivo is unknown.

Distribution and quantification of pyridinium cross-links of collagen within the different maturational zones of the chick growth plate.

In order to assess alterations in the collagen network during endochondral ossification the pyridinium cross-links of collagen were quantified in sequential transverse sections through the chick growth plate. This was accomplished using both morphological (alkaline phosphatase (ALP) histochemistry and collagen type X immunostaining) and analytical (HPLC) analyses. In articular cartilage, pyridinoline concentrations were maximal in the deep mature zones. In contrast, the proliferating chondrocyte zone of the growth plate had approximately a 10-fold greater pyridinoline cross-link concentration than the mature hypertrophic zone. Deoxypyridinoline was first found in the prehypertrophic zone of the growth plate cartilage that reacted positively for ALP activity but before collagen type X was detected. However, deoxypyridinoline concentrations were highest in the most differentiated regions of the growth plate where it was the principal pyridinium cross-link. In tibial dyschondroplasia, where chondrocyte differentiation is arrested in the prehypertrophic zone, higher concentrations of both cross-links were found with increasing distance down the lesion. We conclude that the decrease in pyridinoline cross-link concentration down the growth plate may be an essential adaptation (via increased collagenase activity and collagen turnover) of the matrix for vascular invasion and osteoclastic resorption to occur.

Lipids of pigment gallstones.

The lipids of pigment gallstones were analyzed. In contrast to previous reports, pigment stones were found to contain a wide variety of free fatty acids. In addition, pigment stones contained unhydrolyzed phospholipids. Both free fatty acids and phospholipids were present in much higher concentrations in a brown stone obtained from a patient with a biliary tract infection than in a black stone obtained from a patient with sterile bile and a long-standing hemolytic anemia. However, the phospholipids in both kinds of stone consisted primarily of phosphatidylcholine. Separation of stone and bile phosphatidylcholines into their individual molecular species by high performance liquid chromatography indicated that the phosphatidylcholines in stones closely resemble those in bile. The data suggest that both the free fatty acids and the phosphatidylcholine of pigment stones derive from bile phosphatidylcholine, but that the extent of bile phosphatidylcholine participation in pigment stone formation may be variable.

The transport of lipoprotein cholesterol into bile: a reassessment of kinetic studies in the experimental animal.

Studies were undertaken to assess the contribution of lipoprotein cholesterol to bile and to determine whether already-existent hepatic free cholesterol and the free cholesterol which is newly generated from the hydrolysis of hepatic cholesteryl esters are equally available for secretion into bile or constitute metabolically separate pools. Rats with a bile fistula were injected with an intravenous bolus of high-density lipoprotein recombinants containing free [14C]cholesterol and [3H]cholesteryl esters. Results showed (1) that bile free [14C]cholesterol secretion was a constant and linear proportion of the whole liver free [14C]cholesterol pool, (2) that secretion into bile of free [3H]cholesterol was in direct proportion to the rate of hydrolysis of hepatic [3H]cholesteryl esters, and (3) that rates of biliary cholesterol secretion were very similar when secretion was calculated using the specific activity of free [14C]cholesterol and free [3H]cholesterol in the entire liver to 'label' the precursor free cholesterol pool. Furthermore, rates of secretion that were calculated using either isotope closely approximated the mass of free cholesterol that was directly measured in bile. Results thus indicate that because of equilibration and extensive dilution by the large pool of already-existent free cholesterol, the transport of isotopic cholesterol from lipoproteins cannot be used to directly assess the contribution of lipoprotein cholesterol to the cholesterol that is secreted in bile. These studies further suggest that the totality of preformed free cholesterol in the liver is in metabolic equilibrium in one single kinetic pool and that all hepatic free cholesterol is potentially available for secretion into bile.

Preparation and analysis of the products of non-enzymatic protein glycosylation and their relationship to cross-linking of proteins.

The presence of glycosylated protein-bound lysine residues has led to much speculation regarding changes in structure and function of the modified protein. The synthesis of hexose-lysine adducts and their separation using an amino acid analyser is described. These compounds are also produced during borohydride reduction and subsequent hydrolysis of modified proteins, and misidentification of these may occur depending upon precise chromatographic procedures. The possibility that glucose might participate in a cross-linking reaction between two protein-bound lysine residues was tested but no evidence for such a mechanism was found. The presence of 14C-labelled urinary hexosyllysine indicated that body protein breakdown in addition to ingested dietary hexosyllysine contributes to the excretion of this component.

Reducible components in the proteins of human erythrocyte membrane.

In contrast to a previous report, no collagen or elastin-type cross-linked derived from lysine-aldehydes were detected in human erythrocyte membranes. The major reducible components of erythrocyte membranes were shown to be hexosyllysines. From their structure it is clear that these components cannot act as cross-links between the protein subunits of the membrane. The components were also shown to be present in varying proportions in human serum albumin and haemoglobin. Whether the hexose attachments have any physiological significance or are artefacts of the analytical procedure has not yet been demonstrated. One other major reducible component was present but, although unidentified, this compound was shown to be unrelated to any of the known lysine-aldehyde-derived cross-links of collagen and elastin. A minor acidic component was identified as glucosylvaline derived from the N-terminus of the beta chain of haemoglobin A1c and not a lysine-aldehyde precursor of the collagen cross-links.

Turnover rates of different collagen types measured by isotope ratio mass spectrometry.

The rates of collagen turnover in different tissues have been estimated in growing rats previously exposed to gaseous 18O2. The abundance of the stable isotope was measured using isotope ratio mass spectrometry following combustion of isolated collagen-derived hydroxyproline. Using this method, problems of label reutilization associated with radiolabelling methods are avoided. In general the results confirm the slow turnover rates with half-lives of total collagen in skin, muscle and gut of 74, 45 and 244 d, respectively. The use of cyanogen bromide digests of whole tissues followed by isolation of collagen type-specific peptides has allowed the comparison of turnover rates of collagen types I and III, indicating that collagen type III is turned over more rapidly than type I.

Reduction in stroke with gemfibrozil in men with coronary heart disease and low HDL cholesterol: The Veterans Affairs HDL Intervention Trial (VA-HIT).

BACKGROUND: A low level of HDL cholesterol has been identified as a risk factor for stroke in observational studies. METHODS AND RESULTS: Our objective was to determine whether treatment aimed at raising HDL cholesterol and lowering triglycerides reduces stroke in men with coronary heart disease and low levels of both HDL and LDL cholesterol. The study was a placebo-controlled, randomized trial conducted in 20 Veterans Affairs medical centers. A total of 2531 men with coronary heart disease, with mean HDL cholesterol 0.82 mmol/L (31.5 mg/dL) and mean LDL cholesterol 2.9 mmol/L (111 mg/dL), were randomized to gemfibrozil 1200 mg/d or placebo and were followed up for 5 years. Strokes were confirmed by a blinded adjudication committee. Relative risks were derived from Cox proportional hazards models. There were 134 confirmed strokes, 90% of which were ischemic. Seventy-six occurred in the placebo group (9 fatal) and 58 in the gemfibrozil group (3 fatal), for a relative risk reduction, adjusted for baseline variables, of 31% (95% CI, 2% to 52%, P=0.036). The reduction in risk was evident after 6 to 12 months. Patients with baseline HDL cholesterol below the median may have been more likely to benefit from treatment than those with higher HDL cholesterol. CONCLUSIONS: In men with coronary heart disease, low HDL cholesterol, and low LDL cholesterol, gemfibrozil reduces stroke incidence.

Urinary pyridinium crosslinks of collagen: specific markers of bone resorption in metabolic bone disease.

The hydroxypyridinium compounds pyridinoline and deoxypyridinoline are specific constituents of mature skeletal collagens. They are released into the circulation and excreted in the urine. Their measurement in urine is a sensitive index of the extent of ongoing bone resorption. Currently, quantification of collagen crosslinks in urine is achieved by chromatographic techniques, but more convenient immunoassays will make these measurements more widely available in the near future. Clinical applications of hydroxypyridinium markers include numerous metabolic bone disorders such as osteoporosis, primary hyperparathyroidism, Paget's disease of bone, and metastatic bone disease. Urinary pyridinium crosslinks of collagen also show great promise as markers of therapeutic efficacy in bone disorders associated with accelerated bone resorption.

Correlates and consequences of diffuse atherosclerosis in men with coronary heart disease. Veterans Affairs High-Density Lipoprotein Intervention Trial Study Group.

BACKGROUND: Peripheral atherosclerosis is a strong and independent predictor of mortality even in patients with known coronary heart disease. However, the prevalence, correlates, and potential adverse effects on quality of life associated with combined coronary heart disease and clinically evident cerebrovascular or lower-extremity atherosclerosis are not known. Identification of patients with "diffuse atherosclerosis" may enhance treatment of modifiable risk factors and alter therapeutic strategies. METHODS: We conducted a cross-sectional analysis of 2531 men younger than 73 years with coronary heart disease, low-density lipoprotein cholesterol levels of 3.62 mmol/L (140 mg/dL) or less, and high-density lipoprotein cholesterol level of 1.03 mmol/L (40 mg/dL) or less who were participating in Department of Veterans Affairs Cooperative Study 363 (the Veterans Affairs High-Density Lipo-protein Intervention Trial. Baseline demographic, medication, comorbidity, and atherosclerotic risk factor data were assessed by means of a standardized questionnaire. All plasma lipid levels were determined after a 12-hour fast by a central standardized lipid laboratory. Health status was determined by baseline reported symptoms, medical comorbidities, and the Psychological General Well-being Index. Clinically evident diffuse atherosclerosis was defined as a documented history of lower-extremity atherosclerosis or cerebrovascular disease. RESULTS: The mean age of all participants was 63.5 years. The mean plasma lipid values were as follows: total cholesterol, 4,52 mmol/L (174.6 mg/dL); high-density lipo-protein cholesterol, 0.81 mmol/L (31.5 mg/dL); low-density lipoprotein cholesterol, 2.88 mmol/L (111.2 mg/dL); and triglycerides, 1.81 mmol/L (160.6 mg/dL). Diffuse atherosclerosis was present in 525 (21%). Lower-extremity atherosclerosis was reported in 10%, while cerebrovascular disease was present in 13%. After controlling for other variables, the following factors were associated with the presence of diffuse atherosclerosis: increased age, being unmarried, being retired, having less than a high school education, increased alcohol use, hypertension, cigarette smoking, and diabetes. There was no association between lipid levels and the presence of diffuse atherosclerosis. After adjustment for age, race, and comorbidities, men with diffuse disease still had a reduced quality of life compared with men without diffuse atherosclerosis, as defined by having a greater number of clinical symptoms, lower psychological well-being scores, and more advanced or complicated coronary heart disease. CONCLUSIONS: Clinically evident diffuse atherosclerosis is common in men with coronary heart disease and low levels of high-density lipoprotein cholesterol. Because diffuse atherosclerosis is associated with a reduced quality of life and several modifiable risk factors, early detection and aggressive risk factor intervention appear justified.