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High-density lipoprotein (HDL) contributes to reverse cholesterol transport, which is 1 of the main explanations for the described inverse association between HDL-cholesterol (HDL-C) and atherosclerotic cardiovascular disease (ASCVD) risk. However, efforts to therapeutically raise HDL-C levels with niacin, fibrates, or cholesteryl ester transfer protein inhibitors have not demonstrated a reduction in ASCVD events when compared with placebo among individuals treated with statins. Furthermore, mendelian randomization studies suggest that HDL-C is unlikely to be a direct biologic variable impacting ASCVD risk. More recently, observations from well-conducted epidemiologic studies have indicated a nonlinear U-shaped relationship between HDL-C and subclinical atherosclerosis, and that very high HDL-C (≥80 mg/dL in men, ≥100 mg/dL in women) is paradoxically associated with higher all-cause and ASCVD-related mortality. These observations suggest that HDL-C is not a universal protective factor for atherosclerosis. Thus, there are several opportunities for reframing the contribution of HDL-C to ASCVD risk and related clinical calculators. Here, we examine our growing understanding of HDL-C and its role in ASCVD risk assessment, treatment, and prevention. We discuss the biological functions of HDL-C and its normative values in relation to demographics and lifestyle markers. We then summarize original studies that observed a protective association between HDL-C and ASCVD risk and more recent evidence indicating an elevated ASCVD risk at very high HDL-C levels. Through this process, we advance the discussion regarding the future role of HDL-C in ASCVD risk assessment and identify knowledge gaps pertaining to the precise role of HDL-C in atherosclerosis and clinical ASCVD., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Few studies have comprehensively evaluated the association of depression with sleep disturbance using a controlled twin study design., Purpose: To cross-sectionally evaluate the association of depression with both objective and subjective sleep disturbance., Methods: We studied 246 members of the Vietnam Era Twin Registry. We measured depressive symptoms using the Beck Depression Inventory-II (BDI) and assessed major depression using structured clinical interviews. Twins underwent one-night polysomnography and 7-day actigraphy to derive measures of objective sleep and completed the Pittsburgh Sleep Quality Index for subjective sleep. Multivariable mixed-effects models were used to examine the association., Results: Twins were all male, mostly white (97%), with a mean (SD) age of 68 (2). The mean (SD) BDI was 5.9 (6.3), and 49 (20%) met the criteria for major depression. For polysomnography, each 5-unit higher BDI, within-pair, was significantly associated with 19.7 min longer rapid eye movement (REM) sleep latency, and 1.1% shorter REM sleep after multivariable adjustment. BDI was not associated with sleep architecture or sleep-disordered breathing. For actigraphy, a higher BDI, within-pair, was significantly associated with lower sleep efficiency, more fragmentation and higher variability in sleep duration. BDI was associated with almost all dimensions of self-reported sleep disturbance. Results did not differ by zygosity, and remained consistent using major depression instead of BDI and were independent of the presence of comorbid posttraumatic stress disorder and antidepressant use., Conclusions: Depression is associated with REM sleep disruption in lab and sleep fragmentation and sleep variability at home, but not with sleep architecture or sleep-disordered breathing., (© Society of Behavioral Medicine 2021. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Studies documenting self-reported experiences of discrimination over the life course have been limited. Such information could be important for informing longitudinal epidemiologic studies of discrimination and health. We characterized trends in self-reports of racial, socioeconomic status, and gender discrimination over time measured using the Experiences of Discrimination Scale, with a focus on whether individuals' reports of lifetime discrimination were consistent over time. Overall experiences of discrimination and the number of settings in which discrimination was reported in 1992, 2000, and 2010 were examined among 2,774 African-American and White adults in the Coronary Artery Risk Development in Young Adults (CARDIA) Study. Reports of "ever" experiencing discrimination decreased for all forms of discrimination across the 3 study visits. Approximately one-third (30%-41%) of the sample inconsistently reported ever experiencing any discrimination over time, which contributed to the observed decreases. Depending on the form of discrimination, inconsistent reporting patterns over time were more common among African-American, younger, less educated, and lower-income individuals and women-groups who are often most exposed to and severely impacted by the health effects of discrimination. Our findings highlight the possible underestimation of the lifetime burden of discrimination when utilizing the Experiences of Discrimination Scale to capture self-reports of discrimination over time., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Self-reported experiences of discrimination have been linked to indices of cardiovascular disease. However, most studies have focused on healthy populations. Thus, we examined the association between experiences of everyday discrimination and arterial stiffness among patients with a history of myocardial infarction (MI)., Purpose: We hypothesized that higher reports of discrimination would be associated with greater arterial stiffness and that associations would be more pronounced among Black women, in particular, relative to other race-gender groups, using an "intersectionality" perspective., Methods: Data were from 313 participants (49.2% female, mean age: 50.8 years) who were 6 months post-MI in the Myocardial Infarction and Mental Stress 2 study. Data were collected via self-reported questionnaires, medical chart review, and a clinic visit during which arterial stiffness was measured noninvasively using pulse wave velocity., Results: Reports of discrimination were highest in Black men and women and arterial stiffness was greatest in Black and White women. After adjustment for demographics and relevant clinical variables, discrimination was not associated with arterial stiffness in the overall study sample. However, discrimination was associated with increased arterial stiffness among Black women but not White women, White men, or Black men., Conclusions: Despite no apparent association between discrimination and arterial stiffness in the overall study sample, further stratification revealed an association among Black women but not other race-gender groups. These data not only support the utility of an intersectionality lens but also suggest the importance of implementing psychosocial interventions and coping strategies focused on discrimination into the care of clinically ill Black women., (© Society of Behavioral Medicine 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Study Objectives: The usage of wrist-worn wearables to detect sleep-wake states remains a formidable challenge, particularly among individuals with disordered sleep. We developed a novel and unbiased data-driven method for the detection of sleep-wake and compared its performance with the well-established Oakley algorithm (OA) relative to polysomnography (PSG) in elderly men with disordered sleep., Methods: Overnight in-lab PSG from 102 participants was compared with accelerometry and photoplethysmography simultaneously collected with a wearable device (Empatica E4). A binary segmentation algorithm was used to detect change points in these signals. A model that estimates sleep or wake states given the changes in these signals was established (change point decoder, CPD). The CPD's performance was compared with the performance of the OA in relation to PSG., Results: On the testing set, OA provided sleep accuracy of 0.85, wake accuracy of 0.54, AUC of 0.67, and Kappa of 0.39. Comparable values for CPD were 0.70, 0.74, 0.78, and 0.40. The CPD method had sleep onset latency error of -22.9 min, sleep efficiency error of 2.09%, and underestimated the number of sleep-wake transitions with an error of 64.4. The OA method's performance was 28.6 min, -0.03%, and -17.2, respectively., Conclusions: The CPD aggregates information from both cardiac and motion signals for state determination as well as the cross-dimensional influences from these domains. Therefore, CPD classification achieved balanced performance and higher AUC, despite underestimating sleep-wake transitions. The CPD could be used as an alternate framework to investigate sleep-wake dynamics within the conventional time frame of 30-s epochs., (© Sleep Research Society 2020. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.)

Ischaemic heart disease (IHD) remains the leading cause of morbidity and mortality among women and men yet women are more often underdiagnosed, have a delay in diagnosis, and/or receive suboptimal treatment. An implicit gender-bias with regard to lack of recognition of sex-related differences in presentation of IHD may, in part, explain these differences in women compared with men. Indeed, existing knowledge demonstrates that angina does not commonly relate to obstructive coronary artery disease (CAD). Emerging knowledge supports an inclusive approach to chest pain symptoms in women, as well as a more thoughtful consideration of percutaneous coronary intervention for angina in stable obstructive CAD, to avoid chasing our tails. Emerging knowledge regarding the cardiac autonomic nervous system and visceral pain pathways in patients with and without obstructive CAD offers explanatory mechanisms for angina. Interdisciplinary investigation approaches that involve cardiologists, biobehavioural specialists, and anaesthesia/pain specialists to improve angina treatment should be pursued., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Context: The diagnosis of metabolic syndrome (MetS) identifies individuals at risk for developing diabetes and cardiovascular disease. African Americans (AAs) have high rates of cardiovascular disease and subclinical vascular disease including arterial stiffness and microvascular dysfunction but have relatively low rates of MetS., Objective: The objective of the study was to evaluate the relationship between MetS and vascular function in a biracial cohort with the hypothesis that the diagnosis of MetS underestimates subclinical vascular disease in AAs., Design: We measured components of MetS in a community-based cohort of 951 AAs and white subjects (aged 48.8 ± 11 y, 47% AA, 55% female)., Main Outcome Measures: Using digital pulse amplitude tonometry, we estimated the reactive hyperemia index (RHI), a measure of microvascular endothelial function. Using applanation tonometry (Sphygmocor), central augmentation index (CAIx) and pulse wave velocity (PWV) were measured as indices of wave reflections and arterial stiffness, respectively., Results: MetS was present in 24.0% of subjects and was associated with increased PWV (P < .001) and CAIx (P < .001) and a trend to lower RHI (P = .068) in both races. However, in subjects without MetS, AAs had lower RHI (P < .001) and higher PWV (P = .003) and CAIx (P = .002) compared with white subjects. Addition of an extra MetS criterion point for AAs with hypertension eliminated the racial differences in PWV and CAIx but not RHI., Conclusion: Although MetS is associated with microvascular dysfunction and increased arterial stiffness in both racial groups, AAs without MetS have greater vascular dysfunction compared with whites. Additional weighting for hypertension in AAs attenuated the racial differences in subclinical disease associated with MetS.

Posttraumatic stress disorder (PTSD) is associated with an increased risk of ischemic heart disease, though the pathophysiologic mechanisms remain unclear. Carotid artery intima-media thickness (CIMT) is a measure of subclinical atherosclerosis. We examined whether PTSD and combat exposure were associated with CIMT in Vietnam War-era twins after controlling for shared genetic and childhood factors. Between 2002 and 2010, we studied 465 middle-aged twins from the Vietnam Era Twin Registry who were free from cardiovascular disease. PTSD was diagnosed using the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, and CIMT was measured by ultrasound. Mixed-effects regression models were used to examine individual, between-pair, and within-pair associations. Approximately 13% of participants met the criteria for PTSD, and 45% served in the Vietnam Theater. PTSD was associated with 32.7 μm higher CIMT (95% confidence interval (CI): 0.9, 64.5) after adjustment for confounders. The average CIMT for the pair increased by 59.7 μm for each additional twin with PTSD (95% CI: 15.9, 104.2). We found no significant within-pair differences in CIMT when comparing PTSD-discordant co-twins. Results for combat exposure were similar, but its association with CIMT weakened after adjustment for PTSD (95% CI: 7.0, 45.3). Among Vietnam War-era veterans, combat exposure and PTSD are associated with CIMT, though the associations are largely mediated by shared childhood factors., (© The Author 2014. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Context: Vitamin D insufficiency is associated with increased cardiovascular events in the general population. Additionally, low serum 25-hydroxyvitamin D [25(OH)D] is associated with endothelial dysfunction and arterial stiffness. However, little is known about the association between serum 25(OH)D level and myocardial blood flow., Objective: Our objective was to examine the association between serum 25(OH)D levels and coronary flow reserve (CFR) measured by (13)N-positron emission tomography in asymptomatic middle-aged male twins., Design: The Emory Twin Study is a cross-sectional study of soldiers from the Vietnam Era Registry., Setting: The study was conducted at the General Clinical Research Center, Emory University, Atlanta, GA., Participants: A total of 368 middle-aged male twins were enrolled for the study. Serum 25(OH)D levels were measured in all subjects and classified as vitamin D insufficiency [25(OH)D <30 ng/ml] or sufficiency [25(OH)D ≥30 ng/ml]. Positron emission tomography with [(13)N]ammonia was used to evaluate myocardial blood flow at rest and after adenosine stress. CFR was measured as the ratio of maximum to rest myocardial blood flow., Main Outcome Measure: Primary outcome was CFR measurement., Results: Mean overall serum 25(OH)D concentration was 37.0 ± 21.4 ng/ml; 167 twins (45%) were vitamin D insufficient. CFR was significantly lower in subjects with vitamin D insufficiency compared with subjects with vitamin D sufficiency (2.41 vs. 2.64; P = 0.007), even after adjustment for traditional cardiovascular risk factors, serum PTH, calcium, and phosphorus levels, and season. An abnormal CFR (CFR <2) was more prevalent in subjects with vitamin D insufficiency than with vitamin D sufficiency (31 vs. 20%; P = 0.03). In addition, in vitamin D status-discordant twin pairs, CFR was significantly lower in the vitamin D-insufficient twin than in the vitamin D-sufficient co-twin (2.35 vs. 2.58; P = 0.037)., Conclusion: Vitamin D insufficiency is associated with lower CFR in men. This association may help explain some of the increased cardiovascular risk reported in individuals with vitamin D insufficiency.

Background: Genome-wide association studies (GWAS) have identified novel variants associated with myocardial infarction (MI) in Caucasians. We hypothesized that those variants whose mechanism of risk is currently unknown, confer risk via pathways mediating arterial wave reflections which is an increasingly recognized risk factor for cardiovascular disease., Methods: Single-nucleotide polymorphisms (SNPs) at eight MI risk loci were genotyped and correlated with noninvasively determined pulse wave analysis (PWA)-derived central hemodynamic indexes (augmentation index (AIx); augmented pressure (AP); time to reflected wave (TrW) and central systolic blood pressure (SBP) and diastolic BP (DBP)) in two independent Caucasian populations including (i) those free of measured cardiovascular risk factors (n = 133) and (ii) a community-based population (n = 270)., Results: Of the eight SNPs examined in the healthy group, the variants at loci 6p24 (AIx and AP both P < 0.001, TrW P = 0.02) and 21q22 (AIx P = 0.002, TrW P = 0.037) were significantly associated with PWA indexes. In the replication group, only the 6p24 variant correlated with these phenotypes (AIx P = 0.005, AP P = 0.049, TrW P = 0.013). In the pooled population (n = 403), no new associations were identified but the association with 6p24 and AIx remained significant even after Bonferroni correction and adjustment for covariates including age, mean arterial pressure, height, gender, glucose, cholesterol, body mass index (BMI), and smoking (AIx (P = 0.03)). Each copy of the risk allele C increased the AIx by 3.5%., Conclusions: The GWAS discovered MI risk variant at 6p24 in the protein phosphatase 1 regulator gene (PHACTR1) is associated with adverse arterial wave reflection indexes and may mediate MI risk through this pathway.

Aims: we tested the hypothesis that the 9p21 risk locus promotes atherosclerosis by examining the association between rs10757278 and coronary artery disease (CAD) severity and progression determined by semi-quantitative angiographic scores., Methods and Results: the rs10757278 single nucleotide polymorphism (SNP) was genotyped as the marker for the 9p21 locus in 2334 Caucasian patients undergoing cardiac catheterization (mean age 63, male 67%). Angiographic CAD was assessed using two semi-quantitative scoring systems with one estimating severity (Gensini) and the other extent (Sullivan). A subset of 308 patients who underwent two or more coronary angiograms at least 6 months apart were examined for net change in Gensini and Sullivan scores over time to determine the rate of CAD progression by genotype and were further classified as 'progressors' or 'non-progressors' based on absolute change per year in angiographic severity score. We replicated the association between the rs10757278 SNP and myocardial infarction and binary (presence/absence) angiographic classifications of CAD. Furthermore, we observed a significant additive association with this SNP, and both severity and extent of CAD using angiographic scores, after adjustment for age, gender, body mass index, traditional cardiovascular risk factors, myocardial infarction, and statin use (Gensini P = 0.016, Sullivan P = 0.005). In addition, there was a significant linear association with CAD progression before and after adjustment for covariates (Gensini P = 0.023, Sullivan P = 0.003) with homozygotes for the risk variant having three-fold greater odds of CAD progression compared with the referent group., Conclusion: the 9p21 risk locus is associated with angiographically defined severity, extent, and progression of CAD, suggesting a role for this locus in influencing atherosclerosis and its progression.

Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) are compounds that do not occur in nature but have been widely used since World War II and persist indefinitely in the environment. They are present in the serum of Americans with median levels of 4 ng/mL and 21 ng/mL, respectively. PFOA has been positively associated with cholesterol in several studies of workers. A cross-sectional study of lipids and PFOA and PFOS was conducted among 46,294 community residents aged 18 years or above, who drank water contaminated with PFOA from a chemical plant in West Virginia. The mean levels of serum PFOA and PFOS in 2005-2006 were 80 ng/mL (median, 27 ng/mL) and 22 ng/mL (median, 20 ng/mL), respectively. All lipid outcomes except high density lipoprotein cholesterol showed significant increasing trends by increasing decile of either compound; high density lipoprotein cholesterol showed no association. The predicted increase in cholesterol from lowest to highest decile for either compound was 11-12 mg/dL. The odds ratios for high cholesterol (>/=240 mg/dL), by increasing quartile of PFOA, were 1.00, 1.21 (95% confidence interval (CI): 1.12, 1.31), 1.33 (95% CI: 1.23, 1.43), and 1.40 (95% CI: 1.29, 1.51) and were similar for PFOS quartiles. Because these data are cross-sectional, causal inference is limited. Nonetheless, the associations between these compounds and lipids raise concerns, given their common presence in the general population.

Serum phosphorus levels in the general population have been reported to be associated with cardiovascular morbidity and mortality and increased carotid intima-media thickness. The authors examined gender heterogeneity in the association of phosphorus with all-cause mortality and incident coronary artery disease using data from the Atherosclerosis Risk in Communities Study (1987-2001). Baseline phosphorus levels were higher in women and were associated differently among men and women with traditional atherosclerosis risk factors such as age, low density lipoprotein cholesterol, diabetes mellitus, and hypertension. In a multivariable-adjusted model, men in the highest quintile of serum phosphorus level (>3.8 mg/dL) had an increased mortality rate (hazard ratio = 1.45, 95% confidence interval: 1.12, 1.88), while women did not (hazard ratio = 1.18, 95% confidence interval: 0.89, 1.57). The multivariable likelihood ratio test of effect modification by gender was significant at alpha = 0.1 (P = 0.085) for all-cause mortality. Although the associations of phosphorus with coronary artery disease also appeared to differ substantially by gender, the multivariable test for effect modification suggested that the difference was consistent with random variation (P = 0.195). These results suggest the need for further investigation into gender differences in the contribution of mineral metabolism to cardiovascular disease in the general population.

Background: Women with polycystic ovary syndrome (PCOS) have a greater clustering of cardiac risk factors. However, the link between PCOS and cardiovascular (CV) disease is incompletely described., Objective: The aim of this analysis was to evaluate the risk of CV events in 390 postmenopausal women enrolled in the National Institutes of Health-National Heart, Lung, and Blood Institute (NIH-NHLBI) sponsored Women's Ischemia Syndrome Evaluation (WISE) study according to clinical features of PCOS., Methods: A total of 104 women had clinical features of PCOS defined by a premenopausal history of irregular menses and current biochemical evidence of hyperandrogenemia. Hyperandrogenemia was defined as the top quartile of androstenedione (> or = 701 pg/ml), testosterone (> or = 30.9 ng/dl), or free testosterone (> or = 4.5 pg/ml). Cox proportional hazard model was fit to estimate CV death or myocardial infarction (n = 55)., Results: Women with clinical features of PCOS were more often diabetic (P < 0.0001), obese (P = 0.005), had the metabolic syndrome (P < 0.0001), and had more angiographic coronary artery disease (CAD) (P = 0.04) compared to women without clinical features of PCOS. Cumulative 5-yr CV event-free survival was 78.9% for women with clinical features of PCOS (n = 104) vs. 88.7% for women without clinical features of PCOS (n = 286) (P = 0.006). PCOS remained a significant predictor (P < 0.01) in prognostic models including diabetes, waist circumference, hypertension, and angiographic CAD as covariates., Conclusion: Among postmenopausal women evaluated for suspected ischemia, clinical features of PCOS are associated with more angiographic CAD and worsening CV event-free survival. Identification of postmenopausal women with clinical features of PCOS may provide an opportunity for risk factor intervention for the prevention of CAD and CV events.

The objective of this study was to determine the relation between bone mass and the incidence of coronary heart disease in women and men. Participants included 2,059 cohort members of the Framingham Study (1,236 women and 823 men aged 47-80 years) who underwent posteroanterior hand radiography and were free from cardiovascular disease at baseline (1967-1970) and who were then followed for 30 years through the end of 1997 for the incidence of coronary heart disease. The incidence of coronary heart disease decreased from 15.65/1,000 person-years among women in the lowest metacarpal cortical area quartile to 11.76/1,000 person-years among women in the highest quartile (p(trend) = 0.03), and the inverse relation persisted after adjustment for confounders (highest vs. lowest quartile of metacarpal cortical area: hazard ratio = 0.73, 95% confidence interval: 0.53, 1.00; p(trend) = 0.03). In contrast, no association was present in men (highest vs. lowest quartile of metacarpal cortical area: hazard ratio = 1.14, 95% confidence interval: 0.84, 1.56; p(trend) = 0.55).

The purpose of this study was to determine to what extent a single measure, self-rated health (SRH), independently predicts long-term hospitalizations due to all causes and to cardiovascular diseases by using both the standard Cox proportional hazards model and a more robust events model. The study cohort consisted of 2,812 elderly subjects residing in New Haven, Connecticut, who were followed from 1982 to 1996 as part of the Established Populations for Epidemiologic Study of the Elderly. After adjustment for baseline risk factors, using the Cox model, a favorable SRH was associated with a significantly lowered risk for a first hospitalization for all causes (risk ratio (RR) = 0.850, 95% confidence interval (CI): 0.774, 0.934) and congestive heart failure (RR = 0.599, 95% CI: 0.426, 0.841) but not for myocardial infarction (RR = 0.882, 95% CI: 0.565, 1.379). With the adjusted robust events model, a positive SRH was associated with a decreased risk in both a first (RR = 0.813, 95% CI: 0.744, 0.889) and a second (RR = 0.870, 95% CI: 0.782, 0.968) hospitalization for any cause. These results indicate that a single measurement of SRH predicts long-term patterns of hospitalization, especially for heart failure, among older adults.

Because of women's survival advantage, the impact of myocardial infarction (MI) on long-term mortality in women compared with men may be underestimated. The authors examined this issue in a community sample of 2,462 persons aged > or = 65 years living in New Haven, Connecticut, who were free of MI at baseline and were followed for 10 years (1982-1992). By using proportional hazards models with MI hospitalizations and the sex-MI interaction as time-dependent covariables, survival for the MI cases from the date of MI was compared with survival of persons who, at the same follow-up time, were still alive and free of MI. Women survived longer than men mainly in the absence of MI. The multivariable-adjusted hazard ratios of death were 0.53 in the absence and 0.87 in the presence of MI, and MI was associated with a greater risk of death in women (adjusted hazard ratio = 5.9) than in men (adjusted hazard ratio = 3.6) (p = 0.01 for the sex-MI interaction). When out-of-hospital fatal infarctions were considered, the impact of MI on survival in women compared with men increased. In conclusion, in this elderly cohort, when viewed from a population perspective, MI had a greater impact on mortality in women and significantly narrowed women's typical survival advantage over men.

A cross-sectional study of 2650 male and 751 female employees of the IBM company in the Milan area was conducted in 1987 to compare risk profiles for coronary heart disease between men and women and to analyse the awareness of risk status of people at risk. After age adjustment, the rate of cigarette smoking was higher in women (35%) than in men (25%). Other coronary heart disease risk factors were more common in men than in women. After controlling for age, 38% of the men and 19% of the women met the study criteria for hypertension, and 22% of the men and 17% of the women had high blood cholesterol. However, an analysis by age groups showed that, although in the younger age groups women had lower levels of cardiovascular risk factors, except smoking, compared to men, in the age brackets 50 or older women had similar or more adverse risk factor profiles than men. Of the people with hypertension, only 22% of the men and 19% of the women were aware of their hypertension, and only 2% of the men and 4% of the women had successful control by drugs. Even when subjects with mild hypertension were excluded, high proportions of undiagnosed and uncontrolled hypertension were found in both sexes. Of the individuals with serum cholesterol > or = 240 mg.dl-1, less than half of the men and less than 20% of the women were aware of their high blood cholesterol levels. Multiple risk factors were frequently present in the same individuals, especially among males and older women.(ABSTRACT TRUNCATED AT 250 WORDS)

Familial hypercholesterolaemia (FH) is a monogenic disorder, with a strong family history, characterized by a deficiency in functional receptors for low density lipoproteins (LDL). The case of a patient with all the clinical traits of FH, including elevated cholesterol, xanthomas and early coronary and peripheral arterial lesions, but with a normal LDL receptor function, is described. In the patient the molecular weight and immunological properties of apolipoprotein (apo) B were normal; furthermore, autoantibodies to either LDL or to their receptor were also absent. The increased apo B/cholesterol ratio in LDL was compatible with the diagnosis of hyperapobetalipoproteinaemia. With the help of a turnover study using 131I homologous and 125I autologous LDL, it could be established that the patient had an almost three-fold increase in LDL-apo B biosynthesis, with, however, a fractional catabolic rate within normal limits. These findings pointed to the possibility of a genomic alteration in the region responsible for the control of apo B biosynthesis. However, extensive studies both at the cDNA level and in the 5' region of the apo B gene, failed to detect any significant alteration vs published nucleotide sequences. Although the exact mechanism for this unusual clinical presentation of an FH-like syndrome could not be uncovered, this case provides an extreme example of hypercholesterolaemia, with early and severe arterial disease, solely explained by an increased LDL biosynthesis.