Browsing by Subject "cardiovascular disease"

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    Open Access
    Acetaldehyde Adducts in Alcoholic Liver Disease
    (2010) Setshedi, Mashiko; Wands, Jack R; de la Monte, Suzanne M
    Chronic alcohol abuse causes liver disease that progresses from simple steatosis through stages of steatohepatitis, fibrosis, cirrhosis, and eventually hepatic failure. In addition, chronic alcoholic liver disease (ALD), with or without cirrhosis, increases risk for hepatocellular carcinoma (HCC). Acetaldehyde, a major toxic metabolite, is one of the principal culprits mediating fibrogenic and mutagenic effects of alcohol in the liver. Mechanistically, acetaldehyde promotes adduct formation, leading to functional impairments of key proteins, including enzymes, as well as DNA damage, which promotes mutagenesis. Why certain individuals who heavily abuse alcohol, develop HCC (7.2–15%) versus cirrhosis (15–20%) is not known, but genetics and co-existing viral infection are considered pathogenic factors. Moreover, adverse effects of acetaldehyde on the cardiovascular and hematologic systems leading to ischemia, heart failure, and coagulation disorders, can exacerbate hepatic injury and increase risk for liver failure. Herein, we review the role of acetaldehyde adducts in the pathogenesis of chronic ALD and HCC.
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    Open Access
    An investigation into the risk factors of musculoskeletal diseases and the association between chronic diseases of lifestyle in an under-resourced area of the Cape Town Metropole
    (2019) Britz, Carmen; Hendricks, Candice; Jelsma, Jennifer
    Background: A recent shift in the global burden of disease from communicable to noncommunicable has shown that a third of the global burden of disease is attributable to noncommunicable disease, with the heaviest burden affecting poor communities in urban areas. Musculoskeletal disease (MSD) is the most common cause of severe chronic or persistent pain, functional limitations, and physical disability, affecting 20-50% of adults. Globally, disability due to musculoskeletal disease is estimated to have increased by 45% from 1990 to 2010 accounting for 6.8% of total years lived with disability. Research has highlighted a possible co-existence of musculoskeletal disease and chronic noncommunicable diseases of lifestyle, however, there is inadequate South African evidence regarding these inter-relationships and possible risk factors. This highlights a gap in research as management may not be appropriately targeted toward risk factors and thus may not reduce the high prevalence rates of musculoskeletal disease. Aim: The main aims of this study were firstly to determine the prevalence and patterns of acute and chronic musculoskeletal disease. The secondary aim was to explore the relationship between these factors by examining the patterns of onset of musculoskeletal disease, chronic diseases of lifestyle, and risk factors across gender and six age categories (from 18 years to 70 years and older) in patients seeking medical services at a community health centre in Cape Town, South Africa. It was hypothesised that if some conditions were found to have an earlier onset, these conditions might lay the foundation for the development of other chronic diseases of lifestyle and musculoskeletal disease. Methodology: A descriptive, cross-sectional, analytical study design was used at primary health care level at a community health centre in Cape Town, South Africa. All males and females aged 18 years and older, except those who were pregnant or unable to answer the English, Afrikaans, or isiXhosa versions of the selected questionnaires, were eligible to participate. The outcome measures were the Community Orientated Program for Control of Rheumatic Diseases (COPCORD) screening tool for musculoskeletal disease, the Brief Pain Inventory (BPI), the European Quality of Life-5 Dimensions (EQ-5D) health-related quality of life measure, the International Physical Activity Questionnaire (IPAQ), and anthropometric measures of weight, height, and waist and hip circumference. Data were collected via interview and anthropometric measurement. Responses were captured by online questionnaires on mobile devices using the mobile data collection application Magpi by DataDyne Group, LLC. Data were exported to Microsoft Office Excel spreadsheets for descriptive and inferential statistical analysis. Ethical permission was obtained from the University of Cape Town. Results: This study recruited 1115 participants, with a mean age of 48.7 ± 16.8 years. A prevalence rate of 33.6% (95% Confidence Intervals; CI: 30.1-36.5%) for acute MSD and 43.3% (CI: 40.4-46.3%) for chronic MSD was found. The number of participants reporting an overall prevalence of any MSD was 505 (45.7%; CI: 42.8-48.7%). The highest prevalence of MSD was found in females aged 40-59 years. The most common anatomical sites of chronic MSD were the knees (35.6%; CI: 31.5-39.9%), low back/pelvis (33.8%; CI: 29.8- 38.0%), shoulders (26.8%; CI: 23.1-30.9%), and hands/fingers (21.9%; CI: 18.5-25.7%). Of those with MSD, exercise was reported as the best management strategy for musculoskeletal pain (35.6% of 191 respondents; CI: 29.1-42.6%). Hypertension was found to be the most prevalent chronic disease of lifestyle (47.8%; CI: 44.8-50.7%), followed by type 2 diabetes mellitus (21.4%; CI: 19.1-23.9%), and hypercholesterolaemia (20.2%; CI: 17.9-22.6%). All chronic diseases, except chronic obstructive airway disease (COAD), increased with age, while COAD and both acute and chronic MSD peaked around the 50-59 age category and then decreased with age. Most females reported to be highly physically active (46.0%) while males reported mostly low physical activity levels (47.8%). Around the 50-59 year old age group the proportion of participants with a ‘high’ physical activity level decreased while that of participants with a ‘low’ physical activity level increased at the same age group. A higher proportion of those without MSD reported ‘high’ levels of physical activity (41% compared to 32%). In the 30-39 and 40-49 age groups, low levels of physical activity were associated with chronic MSD (70.6% compared to 37.5% of those. with high levels; Chi-Square=13.833; df=2; p=0.001). Body mass index (BMI) category was found to be associated with MSD (p< 0.001) with 73% of those with MSD being overweight or obese and 27% being extremely obese. There were significant differences in BMI between those with and without hypertension (p< 0.001), hypercholesterolaemia (p <0.001), and type 2 diabetes mellitus (p< 0.001). A trend of increasing obesity, high waisthip ratio and low levels of physical activity with age was observed. In smokers, being 30 years of age or older was associated with an increased risk of MSD (42% compared to 21.1%). Gender emerged as a risk factor in the 40-49 and 50-59 age categories with 76.2% of females in these categories reporting chronic MSD compared to 45.1% of the males. However, no risk factor seemed to track the plot of MSD. Age emerged as having the highest association with chronic MSD (Chi-Square=136.6; p< 0.001). Conclusions: Bivariate associations of musculoskeletal disease and chronic diseases of lifestyle were detected because they all become more prevalent with age. The comorbidity of musculoskeletal disease and chronic disease of lifestyle appeared to almost entirely be due to the aging process, rather than the mutual influence that musculoskeletal disease and chronic diseases of lifestyle may have. Low levels of physical activity were only associated with musculoskeletal disease among those in the 30-49 age categories. As previous evidence has shown that increased levels of physical activity can reduce pain in chronic or persistent musculoskeletal disease, a window of opportunity is suggested where increasing physical activity levels in the 30-49 age group may result in a decrease in the prevalence of musculoskeletal disease in the older age group. The only factor that emerged as being predictive in the group with the highest prevalence of musculoskeletal disease, the 40-59 age categories, was gender. Although gender is clearly not modifiable, this finding should inform the development of culturally appropriate intervention strategies. Implications: Although it was not possible to detect any evidence supporting causation, the co-existence of chronic musculoskeletal disease, chronic diseases of lifestyle, and risk factors highlights the need for holistic care to address the multiple problems experienced by adults, specifically as age progresses. The impact of chronic musculoskeletal disease is large, both in terms of prevalence and impact on health-related quality of life. The management of chronic musculoskeletal disease should thus focus on the most effective and affordable intervention strategies and healthcare systems and coherent policies for dealing with this condition should be developed. This management should not only be based on a pharmacological model but on biopsychosocial integration emphasising self management.
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    Crystal structure of the N domain of human somatic angiotensin I-converting enzyme provides a structural basis for domain-specific inhibitor design
    (Elsevier, 2006) Corradi, Hazel R; Schwager, Sylva L U; Nchinda, Aloysius T; Sturrock, Edward D; Acharya, K Ravi
    Human somatic angiotensin I-converting enzyme (sACE) is a key regulator of blood pressure and an important drug target for combating cardiovascular and renal disease. sACE comprises two homologous metallopeptidase domains, N and C, joined by an inter-domain linker. Both domains are capable of cleaving the two hemoregulatory peptides angiotensin I and bradykinin, but differ in their affinities for a range of other substrates and inhibitors. Previously we determined the structure of testis ACE (C domain); here we present the crystal structure of the N domain of sACE (both in the presence and absence of the antihypertensive drug lisinopril) in order to aid the understanding of how these two domains differ in specificity and function. In addition, the structure of most of the inter-domain linker allows us to propose relative domain positions for sACE that may contribute to the domain cooperativity. The structure now provides a platform for the design of “domain-specific” second-generation ACE inhibitors.
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    Open Access
    Towards an understanding of the relationship between sleep and cardiovascular disease risk in adults of African descent living in a low socioeconomic status community
    (2025) Forshaw, Philippa; Rae, Dale; Roden, Laura; Lambert, Estelle
    Background: Individuals of African descent, specifically African Americans and those from Sub-Saharan Africa, experience a higher burden of cardiovascular disease (CVD) and its associated risk factors (such as obesity, diabetes and hypertension) as well as shorter, poorer sleep quality, compared to Caucasian American individuals. Blood pressure (BP) non-dipping (i.e. the failure of BP to decrease at night during sleep) and nocturnal hypertension are important markers of CVD risk and are substantially more prevalent in African American, compared to Caucasian American, individuals. Two additional layers that need consideration are socioeconomic status (SES) and sex. In contrast to much of the research in the Global North predominantly demonstrating shorter objective and subjective sleep durations (around 6- 7h per night) among African descended individuals living in low SES environments, South Africans of African descent living in low SES communities report much longer sleep durations, around 8-10h per night. Thus, while on one hand, lower SES has been associated with higher risk for CVD possibly through shorter sleep, the nature of the relationship between long sleep duration and CVD risk in the South African context is not well understood. Given the significant sex-specific differences in both CVD risk and sleep, there is a need for research focused on understanding sex-specific associations between CVD and sleep health. Thus, the purpose of this thesis was to investigate sex-specific relationships between CVD risk, nocturnal BP and sleep health in adults of African descent living in a low SES community in South Africa. This purpose was achieved through the following aims: i) to investigate sex-specific relationships between self-reported sleep characteristics and CVD risk among individuals of African descent living in a low SES community, ii) to investigate sex-specific relationships between actigraphy-derived sleep characteristics and CVD risk in these same individuals, iii) to systematically review the literature on sleep and BP dipping in apparently healthy individuals, iv) to explore sex-specific associations between actigraphy-derived sleep characteristics, nocturnal BP and CVD risk among adults of African descent living in a low SES community and v) to conduct qualitative interviews with these same individuals to explore how external (e.g. environmental barriers to and promoters of good sleep) and internal (e.g. individual knowledge, attitudes, beliefs and perceptions around sleep) factors might impact sleep health. This thesis explored the hypothesis that adverse environmental conditions associated with living in low SES communities are not conducive to healthy sleep, driving BP non-dipping, nocturnal hypertension and higher CVD risk. Methods: For Chapters 2 and 3, individuals of African descent (56% women, 29-51y, 40% employed) living in Khayelitsha (an informal settlement in South Africa characterised by high rates of crime, violence and poverty) were recruited and studied. Sleep characteristics were measured subjectively using self-reported questionnaires (Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), Insomnia Severity Index (ISI); n=412) and objectively with seven days of wrist-worn actigraphy (n=194). CVD risk was assessed using the body mass index (BMI)-modified Framingham 10-year CVD risk score and clinical measures (BMI, waist circumference, resting BP, fasting glucose). We then conducted a systematic review (Chapter 4) exploring associations between BP dipping and sleep in healthy individuals. In Chapter 5 we measured twenty-four hour ambulatory BP in a sub-set of individuals from the original cohort (n=59) to explore associations between BP dipping, nocturnal hypertension, sleep characteristics and CVD risk scores. Finally, we conducted one-on-one qualitative interviews (Chapter 6) in a further sub-set of participants (n=15) to explore possible external (e.g. environmental barriers to and promoters of good sleep) and internal (e.g. individual knowledge, attitudes, beliefs and perceptions around sleep) factors related to sleep health in this population.Results: When we examined associations between subjectively measured sleep and CVD risk (Chapter 2), found that men (n=178) reporting poor sleep quality (PSQI>5, OR: 1.95, 95%CI: 1.07, 3.51, p=0.025) and earlier bedtimes (OR: 0.54, 95%CI: 0.39, 0.74, p<0.001)were more likely to have higher CVD risk scores. Women (n=234) reporting earlier bedtimes (OR: 0.72, 95%CI: 0.55, 0.95, p=0.020) and wake-up times (OR: 0.30, 95%CI: 0.13, 0.73, p=0.007), longer sleep onset latencies (OR: 1.47, 95%CI: 1.43, 1.88, p=0.003), shorter total sleep times (OR: 0.84, 95%CI: 0.72, 0.98, p=0.029), higher PSQI global scores (OR: 1.93, 95%CI: 1.29, 2.90, p=0.001) and more moderate to severe insomnia symptoms (ISI≥15, OR: 3.24, 95%CI: 1.04, 10.04, p=0.042) were more likely to have higher CVD risk scores. We confirm actigraphy derived long (men: 9.4 ± 1.4h, women: 8.9 ± 1.2h) but disturbed sleep (low sleep efficiencies [men: 81.8 (76.8, 85.7)%), women: 79.9 (72.5, 84.6)%], high sleep fragmentation indices [men: 58.3 (52.5, 65.2)%, women: 63.4 (56.3, 68.2)%] and high wake after sleep onset (WASO) times [men: 103.1 (76.1, 127.0)min, women: 84.9 (68.8, 110.4)min]) in this population, for whom obesity (specifically among women: 60.3%) and hypertension (men: 48%, women: 44%) are prevalent. Associations between actigraphy-derived sleep measures and CVD risk (Chapter 3) found that among men (n=94), earlier midsleep time was associated with higher CVD risk scores (b =–0.17, 95%CI:–0.33, –0.02, p=0.030) while shorter sleep duration was associated with obesity (OR: 0.48, 95%CI: 0.25, 0.90, p=0.023). Among women (n=100), earlier wake-up times (b: –0.24, 95%CI: –0.41, –0.07, p=0.007) and midsleep times (b: – 0.18, 95%CI: –0.39, 0.00, p=0.046) were associated with higher CVD risk scores. Women with earlier bedtimes (OR: 0.53, 95%CI: 0.33, 0.85, p=0.009) and midsleep times (OR: 0.47, 95%CI: 0.26, 0.83, p=0.010) were more likely to have elevated BP, and those with earlier wake-up times (OR: 0.54, 95%CI: 0.35, 0.81, p=0.003) and midsleep times (OR: 0.46, 95%CI: 0.27, 0.77, p=0.003) were also more likely to be obese. Interaction effects revealed that among women, CVD risk scores were higher in those who had shorter sleep combined with later bedtimes or in those who had longer sleep combined with earlier bedtimes (β:–2.38, 95%CI: –0.35, –0.12, p<0.001). A weaker interaction effect was found for WASO such that CVD risk score was higher in women with longer sleep and more WASO or shorter sleep with less WASO (β: 0.004, 95%CI: 0.00, 0.00, p=0.014). The systematic review (Chapter 4) showed that BP non dipping in apparently healthy individuals was associated with short sleep duration, more sleep fragmentation, less sleep depth and increased variability in sleep timing. Measuring 24h ambulatory BP (Chapter 5) found a high proportion of SBP non-dipping (men: 50%, women: 61%), with 48% of men and 72% of women also presenting with nocturnal hypertension. Among the women (n=36), shorter total sleep times (rho: 0.42, p=0.020) and worse sleep efficiencies (rho: 0.51, p=0.003) were correlated with smaller SBP dipping percentages. Similarly, shorter sleep durations (rho: 0.39, p=0.029), shorter total sleep times (rho: 0.44, p=0.014) and worse sleep efficiencies (rho: 0.37, p=0.037) were correlated with smaller DBP dipping percentages. Women with worse sleep efficiencies (rho: –0.39, p=0.016) has higher nocturnal SBP. Among the men (n=23), worse sleep efficiencies (SBP rho: –0.47, p=0.024; DBP rho: – 0.50, p=0.015), greater WASO (SBP rho: 0.59, p=0.003; DBP rho: 0.50, p=0.014) and greater sleep fragmentation indices (SBP rho: 0.59, p=0.003; DBP rho: 0.59, p=0.003) were correlated with higher nocturnal SBP and DBP. Worse sleep duration regularity scores were correlated with lower SBP (rho: – 0.48, p=0.025) and DBP (rho: –0.52, p=0.013) dipping percentages. Men with nocturnal hypertension had higher WASO (116.8 (88.8, 163.3)min vs. 88.1 (65.1, 98.3)min, p=0.031) and sleep fragmentation indices (36.4(33.4, 40.8)% vs. 29.6(25.8, 34.7)%, p=0.019) compared to those without nocturnal hypertension. Insights from the qualitative interviews (Chapter 6) revealed that external factors such as high-density living, noise, crime, violence and excessive alcohol use within the community primarily contributed to disturbing the sleep of participants. Conclusions: This thesis provides new insights, from a Global South lens, to relationships between sleep and cardiovascular health as they relate to adults of African descent living in a low SES environment. 4 Two main features of sleep emerge as important risk factors for CVD in these study participants: mistimed sleep and disturbed sleep, despite adequate sleep opportunities. By considering the lived experiences of individuals in this low SES community, we gained an understanding of the major role that the adverse conditions of the neighbourhood has on impairing sleep health in this population. We speculate that this earlier timed sleep observed predominantly in women, but to some extent in men, might be a direct consequence of environment-related fear, prompting residents to seek refuge in bed at a time which may be too early, potentially contributing to circadian misalignment, which in turn may increase CVD risk. We further hypothesise that when faced with these adverse neighbourhood conditions, some residents may be in a state of hypervigilance at night, resulting in insufficient sympathetic nervous system (SNS) withdrawal, which in turn leads to disturbed sleep. Disturbed sleep may contribute to BP non-dipping or nocturnal hypertension, which may subsequently increase CVD risk, potentially through insufficient cardiovascular system recovery at night. Interestingly, we note that some participants appear to demonstrate resilience through attaining healthy sleep despite living in a challenging neighbourhood environment. Perhaps these are the individuals in whom appropriate SNS withdrawal takes place at night, improving their sleep health and reducing their CVD risk. Considering all the evidence generated though these studies, this thesis proposes the term Sleep Health Insecurity - a lack of regular access to healthy sleep (that which is of sufficient duration, regular, appropriately timed, consolidated, satisfying and refreshing), which is essential for optimal mental and physical health, emotional well-being and cognition. Although we propose that residents of Khayelitsha are experiencing Sleep Health Insecurity, which may increase their CVD risk, these residents likely represent not only a large sector of the South African population but also other similar low SES populations around the world, making this concept a fundamental global health issue.
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    Working on wellness (WOW): A worksite health promotion intervention programme
    (BioMed Central Ltd, 2012) Kolbe-Alexander, Tracy; Proper, Karin; Lambert, Estelle; van Wier, Marieke; Pillay, Julian; Nossel, Craig; Adonis, Leegale; Van Mechelen, Willem
    BACKGROUND: Insufficient PA has been shown to cluster with other CVD risk factors including insufficient fruit and vegetable intake, overweight, increased serum cholesterol concentrations and elevated blood pressure. This paper describes the development of Working on Wellness (WOW), a worksite intervention program incorporating motivational interviewing by wellness specialists, targeting employees at risk. In addition, we describe the evaluation the effectiveness of the intervention among employees at increased risk for cardiovascular disease. METHODS: The intervention mapping (IM) protocol was used in the planning and design of WOW. Focus group discussions and interviews with employees and managers identified the importance of addressing risk factors for CVD at the worksite. Based on the employees' preference for individual counselling, and previous evidence of the effectiveness of this approach in the worksite setting, we decided to use motivational interviewing as part of the intervention strategy. Thus, as a cluster-randomised, controlled control trial, employees at increased risk for CVD (N=928) will be assigned to a control or an intervention group, based on company random allocation. The sessions will include motivational interviewing techniques, comprised of two face-to-face and four telephonic sessions, with the primary aim to increase habitual levels of PA. Measures will take place at baseline, 6 and 12months. Secondary outcomes include changes in nutritional habits, serum cholesterol and glucose concentrations, blood pressure and BMI. In addition, healthcare expenditure and absenteeism will be measured for the economic evaluation. Analysis of variance will be performed to determine whether there were significant changes in physical activity habits in the intervention and control groups at 6 and 12months.DISCUSSION:The formative work on which this intervention is based suggests that the strategy of targeting employees at increased risk for CVD is preferred. Importantly, this study extends the work of a previous, similar study, Health Under Construction, in a different setting. Finally, this study will allow an economic evaluation of the intervention that will be an important outcome for health care funders, who ultimately will be responsible for implementation of such an intervention.TRIAL REGISTRATION:United States Clinical Trails Register NCT 01494207