The household economic burden of non-communicable diseases in 18 countries

BACKGROUND: Non-communicable diseases (NCDs) are the leading cause of death globally. In 2014, the United Nations committed to reducing premature mortality from NCDs, including by reducing the burden of healthcare costs. Since 2014, the Prospective Urban and Rural Epidemiology (PURE) Study has been collecting health expenditure data from households with NCDs in 18 countries. METHODS: Using data from the PURE Study, we estimated risk of catastrophic health spending and impoverishment among households with at least one person with NCDs (cardiovascular disease, diabetes, kidney disease, cancer and respiratory diseases; n=17 435), with hypertension only (a leading risk factor for NCDs; n=11 831) or with neither (n=22 654) by country income group: high-income countries (Canada and Sweden), upper middle income countries (UMICs: Brazil, Chile, Malaysia, Poland, South Africa and Turkey), lower middle income countries (LMICs: the Philippines, Colombia, India, Iran and the Occupied Palestinian Territory) and low-income countries (LICs: Bangladesh, Pakistan, Zimbabwe and Tanzania) and China. RESULTS: The prevalence of catastrophic spending and impoverishment is highest among households with NCDs in LMICs and China. After adjusting for covariates that might drive health expenditure, the absolute risk of catastrophic spending is higher in households with NCDs compared with no NCDs in LMICs (risk difference=1.71%; 95% CI 0.75 to 2.67), UMICs (0.82%; 95% CI 0.37 to 1.27) and China (7.52%; 95% CI 5.88 to 9.16). A similar pattern is observed in UMICs and China for impoverishment. A high proportion of those with NCDs in LICs, especially women (38.7% compared with 12.6% in men), reported not taking medication due to costs. CONCLUSIONS: Our findings show that financial protection from healthcare costs for people with NCDs is inadequate, particularly in LMICs and China. While the burden of NCD care may appear greatest in LMICs and China, the burden in LICs may be masked by care foregone due to costs. The high proportion of women reporting foregone care due to cost may in part explain gender inequality in treatment of NCDs. (AU)

Stroke survivors' experiences of team support along their recovery continuum.

BACKGROUND: A coordinated stroke rehabilitation care team is considered optimal for supporting stroke survivors from diagnosis to recovery. Despite this recognition, many stroke survivors cannot access essential rehabilitation services. Furthermore, there is a lack of understanding of stroke patients' and their caregivers' rehabilitation needs and wishes. We sought to gain insight into healthcare and social structures from the perspective of patients and caregivers that can better support long-term stroke recovery. METHODS: We conducted individual interviews with 24 participants comprised of stroke survivors, spousal caregivers, stroke support group coordinators, and speech pathologist. Participants were recruited through three stroke survivor support groups. An empowerment lens was integrated into data analysis and data interpretation. RESULTS: Two dominant themes captured participants' experiences through stroke survivors' trajectory of care. 1) Experiences of managing stroke. This theme identified stroke survivors and spousal caregivers' experiences with stroke recovery, rehabilitation, and fulfilling unmet needs. 2) Resources of support. This theme described the social and financial support structures drawn upon to assist with stroke rehabilitation. CONCLUSIONS: The study highlighted a lack of teamwork between stroke survivors, spousal caregivers, and health professionals. This fragmented care was compounded by inequities in rehabilitation programs and health services resulting in what appeared to be a disempowering rehabilitation process. Although stroke recovery groups were a significant source of support for stroke survivors and spousal caregivers, participants perceived they were overlooked, by stroke recovery healthcare providers, as a site for stroke recovery healthcare services. An empowerment approach to stroke rehabilitation involves collaboration between stroke survivors, caregivers, healthcare providers, health services, and existing community stroke support structures. Framing stroke based care through an empowerment lens may serve to address stroke rehabilitation inadequacies and inequities.

Correlates of elevated blood pressure in healthy children: a systematic review.

The prevalence of hypertension in children is increasing globally. Addressing this will require a robust understanding of associated risk factors. To this end, we conducted a systematic review to identify correlates of elevated blood pressure (BP) in children. Literature searches were conducted using pre-defined search terms from three academic databases. The abstract and full text of identified studies were screened for eligibility by two independent reviewers. A total of 100 studies were included in this systematic review. An assessment tool was first used to assess study quality; a narrative synthesis was then performed. We found a broad range of physiological, social and behavioural factors associated with elevated BP in children. The most common correlate observed was adiposity, suggesting that childhood obesity may be implicated in the increased prevalence of hypertension observed in children. However, the broad range of other factors identified underscores the multi-factorial aetiology of hypertension. Data from a broad range of studies showed that the correlates of hypertension in children are multi-factorial. Therefore, approaches aimed at preventing hypertension must in turn be multi-factorial to ensure that the burden of hypertension in childhood is addressed.

Examining risk factors for cardiovascular disease among food bank members in Vancouver.

Food banks provide supplemental food to low-income households, yet little is known about the cardiovascular health of food banks members. This study therefore described cardiovascular disease (CVD) risk factors among food bank members and explored associations between food insecurity and CVD risk. Adults ≥18 years (n = 77) from three food bank sites in metro Vancouver, British Columbia completed surveys and physical assessments examining a range of socio-demographic variables and CVD risk factors. A composite measure of myocardial infarction (MI) risk called the INTERHEART score was assessed and household food insecurity was measured using the Household Food Security Survey Module. Regression models were used to explore associations between food insecurity and CVD risk measures, including the INTERHEART score. Ninety-seven percent of food bank members reported experiencing food insecurity, 65% were current smokers, 53% reported either chronic or several periods of stress in the past year, 55% reported low physical activity levels and 80% reported consuming fewer than five servings of fruit and vegetables daily. Prevalence of self-reported diabetes and hypertension were 13% and 29% respectively. Fifty-two percent of the sample were at high risk of non-fatal MI. No statistically significant associations were found between increased severity of food insecurity and CVD risk factors among this sample where both severe food insecurity and high CVD risks were prevalent. Food bank members were at elevated risk for CVD compared with the general population. Strategies are needed to reduce prevalence of food insecurity and CVD risk factors, both of which disproportionately affected food bank members.

Total chemical synthesis of lassomycin and lassomycin-amide.

Herein we report a practical synthetic route to the lasso peptide lassomycin () and C-terminal variant lassomycin-amide (). The biological evaluation of peptides and against Mycobacterium tuberculosis revealed that neither had any activity against this bacterium. This lack of biological activity has led us to propose that naturally occurring lassomycin may actually exhibit a standard lasso peptide threaded conformation rather than the previously reported unthreaded structure.

Psychosocial factors and obesity in 17 high-, middle- and low-income countries: the Prospective Urban Rural Epidemiologic study.

BACKGROUND/OBJECTIVES: Psychosocial stress has been proposed to contribute to obesity, particularly abdominal, or central obesity, through chronic activation of the neuroendocrine systems. However, these putative relationships are complex and dependent on country and cultural context. We investigated the association between psychosocial factors and general and abdominal obesity in the Prospective Urban Rural Epidemiologic study. SUBJECTS/METHODS: This observational, cross-sectional study enrolled 151 966 individuals aged 35-70 years from 628 urban and rural communities in 17 high-, middle- and low-income countries. Data were collected for 125 290 individuals regarding education, anthropometrics, hypertension/diabetes, tobacco/alcohol use, diet and psychosocial factors (self-perceived stress and depression). RESULTS: After standardization for age, sex, country income and urban/rural location, the proportion with obesity (body mass index ≥30 kg m(-)(2)) increased from 15.7% in 40 831 individuals with no stress to 20.5% in 7720 individuals with permanent stress, with corresponding proportions for ethnicity- and sex-specific central obesity of 48.6% and 53.5%, respectively (P<0.0001 for both). Associations between stress and hypertension/diabetes tended to be inverse. Estimating the total effect of permanent stress with age, sex, physical activity, education and region as confounders, no relationship between stress and obesity persisted (adjusted prevalence ratio (PR) for obesity 1.04 (95% confidence interval: 0.99-1.10)). There was no relationship between ethnicity- and sex-specific central obesity (adjusted PR 1.00 (0.97-1.02)). Stratification by region yielded inconsistent associations. Depression was weakly but independently linked to obesity (PR 1.08 (1.04-1.12)), and very marginally to abdominal obesity (PR 1.01 (1.00-1.03)). CONCLUSIONS: Although individuals with permanent stress tended to be slightly more obese, there was no overall independent effect and no evidence that abdominal obesity or its consequences (hypertension, diabetes) increased with higher levels of stress or depression. This study does not support a causal link between psychosocial factors and abdominal obesity.

The association between cardiorespiratory fitness and abdominal adiposity in postmenopausal, physically inactive South Asian women.

In South Asians, a unique obesity phenotype of high abdominal fat is associated with increased cardiovascular risk. Low cardiorespiratory fitness (CRF) is associated with abdominal fat and an increased risk of cardiovascular disease. The purpose of this paper is to determine whether CRF as assessed by VO2 peak, in post-menopausal South Asian women, was associated with body fat distribution and abdominal fat. Physically inactive post-menopausal South Asian women (n = 55) from the Greater Vancouver area were recruited and assessed from January to August 2014. At baseline, VO2 peak was measured with the Bruce Protocol, abdominal fat with CT imaging, and body composition with dual energy X-ray absorptiometry. ANOVA was used to assess differences in subcutaneous abdominal adipose tissue (SAAT), visceral adipose tissue (VAT) and total abdominal adipose tissue (TAAT) between tertiles of CRF. Bivariate correlation and multiple linear regression analyses explored the association between VO2 peak with SAAT, VAT, TAAT and body composition. Models were further adjusted for body fat and body mass index (BMI). Compared to women in the lowest tertile of VO2 peak (13.8-21.8 mL/kg/min), women in the highest tertile (25.0-27.7 mL/kg/min) had significantly lower waist circumference, BMI, total body fat, body fat percentage, lean mass, SAAT, VAT and TAAT (p < 0.05). We found VO2 peak to be negatively associated with SAAT, VAT and TAAT, independent of age and body fatness but not independent of BMI. Further research is necessary to assess whether exercise and therefore improvements in CRF would alter SAAT, VAT and TAAT in post-menopausal South Asian women.

Alcohol consumption and cardiovascular disease, cancer, injury, admission to hospital, and mortality: a prospective cohort study

BACKGROUND:Alcohol consumption is proposed to be the third most important modifiable risk factor for death and disability. However, alcohol consumption has been associated with both benefits and harms, and previous studies were mostly done in high-income countries. We investigated associations between alcohol consumption and outcomes in a prospective cohort of countries at different economic levels in five continents.METHODS:We included information from 12 countries participating in the Prospective Urban Rural Epidemiological (PURE) study, a prospective cohort study of individuals aged 35-70 years. We used Cox proportional hazards regression to study associations with mortality (n=2723), cardiovascular disease (n=2742), myocardial infarction (n=979), stroke (n=817), alcohol-related cancer (n=764), injury (n=824), admission to hospital (n=8786), and for a composite of these outcomes (n=11,963).FINDINGS:We included 114,970 adults, of whom 12,904 (11%) were from high-income countries (HICs), 24,408 (21%) were from upper-middle-income countries (UMICs), 48,845 (43%) were from lower-middle-income countries (LMICs), and 28,813 (25%) were from low-income countries (LICs). Median follow-up was 4.3 years (IQR 3.0-6.0). Current drinking was reported by 36,030 (31%) individuals, and was associated with reduced myocardial infarction (hazard ratio [HR] 0.76 [95% CI 0.63-0.93]), but increased alcohol-related cancers (HR 1.51 [1.22-1.89]) and injury (HR 1.29 [1.04-1.61]). High intake was associated with increased mortality (HR 1.31 [1.04-1.66]). Compared with never drinkers, we identified significantly reduced hazards for the composite outcome for current drinkers in HICs and UMICs (HR 0.84 [0.77-0.92]), but not in LMICs and LICs, for which we identified no reductions in this outcome (HR 1.07 [0.95-1.21]; pinteraction<0.0001)...

The association between physical activity and liver fat after five years of follow-up in a primary prevention multi-ethnic cohort.

OBJECTIVE: Excess liver fat (LF) is associated with dyslipidemia, insulin resistance and cardiovascular disease. Evidence suggests that there is an independent relationship between physical activity (PA) and LF although little is known of the role of PA intensity in reducing LF. The purpose was to evaluate whether meeting PA guidelines, the amount of PA and the intensity of PA at baseline were associated with LF after five-years. METHODS: Men and women (n=478) living in Vancouver, Canada of Aboriginal, Chinese, European or South Asian background completed baseline measurements in 2004-2005. Liver fat was assessed using CT scans at 5-year follow-up, and PA using a PA questionnaire at baseline as well as demographics and anthropometry. RESULTS: In separate unadjusted models, meeting moderate-vigorous PA (MVPA) guidelines (p=0.009), vigorous PA (p=0.002) and MVPA (p=0.017) but not moderate PA (p=0.068) was predictive of LF at five years (p=0.009). In multiple linear regression models, when adjusted for covariates, meeting MVPA guidelines and MVPA with LF at five years was no longer significant (p>0.05) while vigorous PA remained significant (p=0.021). CONCLUSION: Meeting PA guidelines through MVPA may not be adequate to prevent the accumulation of LF and PA guidelines may require revision. Vigorous PA should be encouraged to prevent LF accumulation.

Respiratory infection and primary immune deficiency - what does the general physician need to know?

This review, based on a talk given at the RCPE Respiratory Medicine Symposium 2014, outlines the clinical spectrum of immune deficiency - antibody (B cell) deficiency, T cell defects and innate/phagocytic disorders - and discusses the relevant clinical presentations, investigations and treatments, focusing particularly on the management of adults with recurrent respiratory infections. It describes when to suspect a primary immunodeficiency, the first-line investigations to perform and the triggers that should prompt referral for further specialist opinion. The paper concludes with a look at a novel primary immunodeficiency, Activated PI3 Kinase Delta Syndrome (APDS).

Cardiovascular risk and events in 17 low-,middle-, and high-income countries

BACKGROUNDMore than 80% of deaths from cardiovascular disease are estimated to occur inlow-income and middle-income countries, but the reasons are unknown.METHODSWe enrolled 156,424 persons from 628 urban and rural communities in 17 countries(3 high-income, 10 middle-income, and 4 low-income countries) and assessedtheir cardiovascular risk using the INTERHEART Risk Score, a validated score forquantifying risk-factor burden without the use of laboratory testing (with higherscores indicating greater risk-factor burden). Participants were followed for incidentcardiovascular disease and death for a mean of 4.1 years.RESULTSThe mean INTERHEART Risk Score was highest in high-income countries, intermediatein middle-income countries, and lowest in low-income countries (P<0.001).However, the rates of major cardiovascular events (death from cardiovascularcauses, myocardial infarction, stroke, or heart failure) were lower in high-incomecountries than in middle- and low-income countries (3.99 events per 1000 personyearsvs. 5.38 and 6.43 events per 1000 person-years, respectively; P<0.001). Casefatality rates were also lowest in high-income countries (6.5%, 15.9%, and 17.3%in high-, middle-, and low-income countries, respectively; P = 0.01). Urban communitieshad a higher risk-factor burden than rural communities but lower ratesof cardiovascular events (4.83 vs. 6.25 events per 1000 person-years, P<0.001) andcase fatality rates (13.52% vs. 17.25%, P<0.001). The use of preventive medicationsand revascularization procedures was significantly more common in high-incomecountries than in middle- or low-income countries (P<0.001).CONCLUSIONSAlthough the risk-factor burden was lowest in low-income countries, the rates ofmajor cardiovascular disease and death were substantially higher in low-incomecountries than in high-income countries. The high burden of risk factors in highincome...

Pharmacology of AMG 181, a human anti-α4 ß7 antibody that specifically alters trafficking of gut-homing T cells.

BACKGROUND AND PURPOSE: AMG 181 is a human anti-α4 ß7 antibody currently in phase 1 and 2 trials in subjects with inflammatory bowel diseases. AMG 181 specifically targets the α4 ß7 integrin heterodimer, blocking its interaction with mucosal addressin cell adhesion molecule-1 (MAdCAM-1), the principal ligand that mediates α4 ß7 T cell gut-homing. EXPERIMENTAL APPROACH: We studied the in vitro pharmacology of AMG 181, and the pharmacokinetics and pharmacodynamics of AMG 181 after single or weekly i.v. or s.c. administration in cynomolgus monkeys for up to 13 weeks. KEY RESULTS: AMG 181 bound to α4 ß7 , but not α4 ß1 or αE ß7 , and potently inhibited α4 ß7 binding to MAdCAM-1 (but not vascular cell adhesion molecule-1) and thus inhibited T cell adhesion. Following single i.v. administration, AMG 181 Cmax was dose proportional from 0.01 to 80 mg·kg(-1) , while AUC increased more than dose proportionally. Following s.c. administration, dose-proportional exposure was observed with single dose ranging from 5 to 80 mg·kg(-1) and after 13 weekly doses at levels between 20 and 80 mg·kg(-1) . AMG 181 accumulated two- to threefold after 13 weekly 80 mg·kg(-1) i.v. or s.c. doses. AMG 181 had an s.c. bioavailability of 80%. The linear elimination half-life was 12 days, with a volume of distribution close to the intravascular plasma space. The mean trend for the magnitude and duration of AMG 181 exposure, immunogenicity, α4 ß7 receptor occupancy and elevation in gut-homing CD4+ central memory T cell count displayed apparent correlations. CONCLUSIONS AND IMPLICATIONS: AMG 181 has in vitro pharmacology, and pharmacokinetic/pharmacodynamic and safety characteristics in cynomolgus monkeys that are suitable for further investigation in humans.

Physical activity for obese individuals: a systematic review of effects on chronic disease risk factors.

The purpose of this review was to determine the effectiveness of physical activity in improving chronic disease risk factors in obese individuals. A systematic review was conducted to identify randomized physical activity intervention studies reporting changes in risk factors among obese individuals published prior to March 2010. Studies included in the review were randomized trials of at least 10 weeks in duration, with a sample mean body mass index ≥ 30 kg/m(2) at baseline, and reporting a relevant risk factor (blood pressure, blood lipids, glucose/insulin or C-reactive protein). Forty-four studies met the inclusion criteria for this review. Overall, physical activity had no more than a modest effect on chronic disease risk factors in obese individuals. There was great heterogeneity in responses of risk factors across studies. In many studies it was difficult to determine the effect of physical activity, independent of changes in body mass consequent to the intervention. Obese individuals should be encouraged to undertake physical activity following general recommendations for weight loss and health. The degree to which physical activity is effective at lowering risk factor levels among high-risk obese individuals is not known.

Appropriateness of waist circumference and waist-to-hip ratio cutoffs for different ethnic groups.

Current waist circumference (WC) and waist-to-hip ratio (WHR) cutoffs have been identified from studies of predominantly European-derived populations. However, these cutoffs may not be appropriate for other ethnic groups. This paper reviews the literature regarding ethnic differences in body composition and the appropriateness of ethnic-specific WC and WHR cutoffs in various ethnic groups. Studies investigating ethnic-specific cutoffs were identified among Aboriginal, Asian, African (Sub-Saharan), African-American, Hispanic, Middle Eastern, Pacific Islander and South American populations. Abstracts that recommended WC and/or WHR cutoffs (or rejected the use of cutoffs) were included with their supporting literature. The evidence for ethnic-specific WC and/or WHR cutoffs was then rated as either convincing, probable, possible or insufficient. The majority of studies recommending ethnic-specific cutoffs was for Asian populations. Few studies recommended cutoffs in Aboriginal, African (Sub-Saharan), Pacific Islanders and South American populations. All studies were cross-sectional, and the overwhelming majority of studies used receiver operating characteristic curves. The studies used a number of methods for assessing WC and WHR, and a variety of outcome measures, making cross-study comparison difficult. There is possible evidence that Asians should have a lower WC cutoff than Europeans. The evidence is insufficient for specific cutoffs for African-American, Hispanic and Middle Eastern populations but some studies indicate current cutoffs for Europeans may be appropriate, whereas there is insufficient evidence for the other ethnic groups. Future studies are needed to address the methodological limitations of the current literature.

The discrimination of dyslipidaemia using anthropometric measures in ethnically diverse populations of the Asia-Pacific Region: the Obesity in Asia Collaboration.

Dyslipidaemia is a major risk factor for cardiovascular disease and is only detectable through blood testing, which may not be feasible in resource-poor settings. As dyslipidaemia is commonly associated with excess weight, it may be possible to identify individuals with adverse lipid profiles using simple anthropometric measures. A total of 222 975 individuals from 18 studies were included as part of the Obesity in Asia Collaboration. Linear and logistic regression models were used to assess the association between measures of body size and dyslipidaemia. Body mass index, waist circumference, waist : hip ratio (WHR) and waist : height ratio were continuously associated with the lipid variables studied, but the relationships were consistently stronger for triglycerides and high-density lipoprotein cholesterol. The associations were similar between Asians and non-Asians, and no single anthropometric measure was superior at discriminating those individuals at increased risk of dyslipidaemia. WHR cut-points of 0.8 in women and 0.9 in men were applicable across both Asians and non-Asians for the discrimination of individuals with any form of dyslipidaemia. Measurement of central obesity may help to identify those individuals at increased risk of dyslipidaemia. WHR cut-points of 0.8 for women and 0.9 for men are optimal for discriminating those individuals likely to have adverse lipid profiles and in need of further clinical assessment.

Ethnic comparisons of the cross-sectional relationships between measures of body size with diabetes and hypertension.

Recent estimates indicate that two billion people are overweight or obese and hence are at increased risk of cardiovascular disease and its comorbidities. However, this may be an underestimate of the true extent of the problem, as the current method used to define overweight may lack sensitivity, particularly in some ethnic groups where there may be an underestimate of risk. Measures of central obesity may be more strongly associated with cardiovascular risk, but there has been no systematic attempt to compare the strength and nature of the associations between different measures of overweight with cardiovascular risk across ethnic groups. Data from the Obesity in Asia Collaboration, comprising 21 cross-sectional studies in the Asia-Pacific region with information on more than 263,000 individuals, indicate that measures of central obesity, in particular, waist circumference (WC), are better discriminators of prevalent diabetes and hypertension in Asians and Caucasians, and are more strongly associated with prevalent diabetes (but not hypertension), compared with body mass index (BMI). For any given level of BMI, WC or waist:hip ratio, the absolute risk of diabetes or hypertension tended to be higher among Asians compared with Caucasians, supporting the use of lower anthropometric cut-points to indicate overweight among Asians.

Anti-tumour necrosis factor-alpha therapy for severe enteropathy in patients with common variable immunodeficiency (CVID).

We present three common variable immunodeficiency (CVID) patients with severe inflammatory bowel disease of unknown aetiology, resistant to steroid treatment, treated with infliximab. After exclusion of any infection, infliximab was given at a dose of 5 mg/kg every 4 weeks for a 3 month induction followed by every 4-8 weeks depending on clinical response. Two of these patients had predominantly small bowel disease; they both showed clinical response to infliximab with weight gain and improvement of quality of life scores. The third patient had large bowel involvement with profuse watery diarrhea; this patient improved dramatically within 48 hours of having infliximab treatment. All three patients have been maintained on infliximab treatment for between 5 and 53 months (mean 37 months) with no evidence of increased susceptibility to infections in the patients with small bowel disease, although the third patient developed two urinary tract infections and a herpes zoster infection following therapy. This is the first small case series to show that infliximab is a useful addition to current therapy in this rare group of patients with potentially life threatening enteritis.

Meningococcal meningitis in two patients with primary antibody deficiency treated with replacement intravenous immunoglobulin.

The current treatment of primary antibody deficiency (PAD) is the early recognition of the condition and replacement immunoglobulin combined with prompt treatment of infections and complications. The route of administration (intravenous or subcutaneous), dose and frequency of administration of immunoglobulin still vary between centres and countries. Most infections in patients with PAD are reduced but not entirely prevented by replacement immunoglobulin, with sinopulmonary infections accounting for the bulk of the remainder. Although there have been reports of meningitis in patients with PAD before replacement treatment, we describe the first two cases of bacterial meningitis (group B Neisseria meningitidis) on adequate immunoglobulin replacement and discuss the involvement of potential cofactors.

The role of risk factors in the development of atherosclerosis.

Our understanding of risk factors for atherogenesis has changed significantly over the last decade. In addition to better grasp of the mechanism of action of the "classic" (causal) risk factors, a number of potentially important new factors has emerged. In this review we briefly summarize the evidence of the relation between atherosclerosis and the currently recognized causal risk factors, namely, age, smoking, LDL cholesterol, HDL cholesterol, hypertension, and diabetes. More emphasis has been put on description of the emerging entities such as atherogenic profile of plasma lipoproteins with discussion of LDL and HDL subclasses, Lp(a), homocysteine, and, last but not least, on the role of infection and inflammation in atherogenesis. Whenever possible, we tried to summarize the relevant lines of evidence such as epidemiological, pathological, genetic, and clinical trial data linking the specific factor with atherosclerosis.