Browsing by Subject "CVD"

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  • Tucker, Philip; Harma, Mikko; Ojajärvi, Anneli; Kivimäki, Mika; Leineweber, Constanze; Oksanen, Tuula; Salo, Paula; Vahtera, Jussi (2019)
    Objective This study examined the associations between shift work and use of antihypertensive, lipid-lowering, and antidiabetic medications. Methods Survey data from two cohorts of Finnish men (N=11998) and women (N=49 944) working in multiple occupations where shift work was used were linked to national Drug Prescription Register data, with up to 11 years of follow-up. In each cohort, age-stratified Cox proportional hazard regression models were computed to examine any incident use of prescription medication for each of the three medical conditions, separately comparing each of two groups of rotating shift workers (those whose schedules included night shifts. and those whose schedules did not include night shifts) with day workers who worked in a similar range of occupations. Results In the larger cohort, among participants aged 40-49 at baseline, shift work without night shifts was associated with increased use of type-2 diabetes medication after adjustments for sex, occupational status, marital status, alcohol consumption, smoking, and physical activity [hazard ratio (HR) 1.28, 95% confidence interval (CI) 1.01-1.62], while shift work with night shifts was associated with increased use of dyslipidemia medication after adjustments (HR 1.33, 95% CI 1.12-1.57). There were no such associations among younger and older shift workers. Also in the larger cohort, among those aged Conclusions There was mixed evidence regarding the use of medications for cardiovascular risk factors by shift workers. Selection effects may have affected the associations.
  • Taskinen, Marja-Riitta; Packard, Chris J.; Boren, Jan (2019)
    Purpose of ReviewApolipoprotein C-III (apoC-III) is known to inhibit lipoprotein lipase (LPL) and function as an important regulator of triglyceride metabolism. In addition, apoC-III has also more recently been identified as an important risk factor for cardiovascular disease. This review summarizes the mechanisms by which apoC-III induces hypertriglyceridemia and promotes atherogenesis, as well as the findings from recent clinical trials using novel strategies for lowering apoC-III.Recent FindingsGenetic studies have identified subjects with heterozygote loss-of-function (LOF) mutations in APOC3, the gene coding for apoC-III. Clinical characterization of these individuals shows that the LOF variants associate with a low-risk lipoprotein profile, in particular reduced plasma triglycerides. Recent results also show that complete deficiency of apoC-III is not a lethal mutation and is associated with very rapid lipolysis of plasma triglyceride-rich lipoproteins (TRL). Ongoing trials based on emerging gene-silencing technologies show that intervention markedly lowers apoC-III levels and, consequently, plasma triglyceride. Unexpectedly, the evidence points to apoC-III not only inhibiting LPL activity but also suppressing removal of TRLs by LPL-independent pathways.SummaryAvailable data clearly show that apoC-III is an important cardiovascular risk factor and that lifelong deficiency of apoC-III is cardioprotective. Novel therapies have been developed, and results from recent clinical trials indicate that effective reduction of plasma triglycerides by inhibition of apoC-III might be a promising strategy in management of severe hypertriglyceridemia and, more generally, a novel approach to CHD prevention in those with elevated plasma triglyceride.
  • Bhalke, Monika (Helsingin yliopisto, 2020)
    Lipoproteins are biochemical carriers of the insoluble lipids. They are complexes combining lipids and proteins for the transport of lipids. Amongst the type of lipoproteins are low-density lipoproteins (LDL) which are prevalent in various diseases such as obesity, diabetes, atherosclerosis, and other cardiovascular diseases (CVD). Omega-3 fatty acids are polyunsaturated fatty acids (PUFA) that are essential components of lipid metabolism and play a significant role in the human diet. Omega-3 PUFAs such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are derived from fish and are necessary for proper cardiovascular functioning. Because the human body is unable to produce enough quantities of some omega-3, diet is an important source for its availability. When a diet is rich in saturated fats, the above-mentioned diseases transpire. This study investigated how consumption of two fish diets, Lean fish and Fatty fish, influence the lipid species of human LDL particles. The lipid species analysed in this study are phospholipids such as phosphatidylcholine (PC), sphingomyelin (SM), and lysophosphatidylcholine (LPC), and cholesteryl esters (CE), and triacylglycerols (TAG). A total of 42 volunteers with a history of impaired fasting glucose had randomly been divided into two groups: fatty fish (4 fish meals/week) and lean fish (4 fish meals/week) for 12 weeks. Blood samples had been collected from the volunteers before and after consumption of the fish meals and LDL particles had been isolated from the blood samples by ultracentrifugation. In this study, the lipids were extracted by Folch method, and the extracted lipids were analysed using Triple quadrupole mass spectrometry. The lipid class profile did not change due to the two fish type diets. However, the consumption of fatty fish diet increased the levels of lipid species of PC, LPC, and CE containing EPA and DHA acyl chains, while decreasing levels of several TAG species. Lean fish induced minor changes in the lipid composition of LDL particles. Based on these results, fatty fish diet alters the plasma LDL lipidome profile with changes induced to both the surface and the core composition of the LDL particles in a positive way regarding cardiovascular health.
  • Olkkonen, Vesa M.; Sinisalo, Juha; Jauhiainen, Matti (2018)
    Remarkably good results have been achieved in the treatment of atherosclerotic cardiovascular diseases (CVD) by using statin, ezetimibe, antihypertensive, antithrombotic, and PCSK9 inhibitor therapies and their proper combinations. However, despite this success, the remaining CVD risk is still high. To target this residual risk and to treat patients who are statin-intolerant or have an exceptionally high CVD risk for instance due to familial hypercholesterolemia (FH), new therapies are intensively sought. One pathway of drug development is targeting the circulating triglyceride-rich lipoproteins (TRL) and their lipolytic remnants, which, according to the current view, confer a major CVD risk. Angiopoietin-like protein 3 (ANGPTL3) and apolipoprotein C-III (apoC-III) are at present the central molecular targets for therapies designed to reduce TRL, and there are new drugs emerging that suppress their expression or inhibit the function of these two key proteins. The medications targeting these components are biological, either human monoclonal antibodies or antisense oligonucleotides. In this article, we briefly review the mechanisms of action of ANGPTL3 and apoC-III, the reasons why they have been considered promising targets of novel therapies for CVD, as well as the current status and the most important results of their clinical trials. (C) 2018 Elsevier B.V. All rights reserved.
  • Torssander, Jenny; Moustgaard, Heta; Peltonen, Riina; Kilpi, Fanny; Martikainen, Pekka (2018)
    Because people tend to marry social equals – and possibly also because partners affect each other’s health – the social position of one partner is associated with the other partner’s health and mortality. Although this link is fairly well established, the underlying mechanisms are not fully identified. Analyzing disease incidence and survival separately may help us to assess when in the course of the disease a partner’s resources are of most significance. This article addresses the importance of partner’s education, income, employment status, and health for incidence and survival in two major causes of death: cancer and cardiovascular diseases (CVD). Based on a sample of Finnish middle-aged and older couples (around 200,000 individuals) we show that a partner’s education is more often connected to incidence than to survival, in particular for CVD. Once ill, any direct effect of partner’s education seems to decline: The survival chances after being hospitalized for cancer or CVD are rather associated with partner’s employment status and/or income level when other individual and partner factors are adjusted for. In addition, a partner’s history of poor health predicted higher CVD incidence and, for women, lower cancer survival. The findings suggest that various partner’s characteristics may have different implications for disease and survival, respectively. A wider focus on social determinants of health at the household level, including partner’s social resources, is needed.
  • Hotakainen, Ronja (Helsingin yliopisto, 2019)
    Diabetes is a group of chronic metabolic disorders caused by the inability of the body to produce or utilize insulin efficiently. Globally, diabetes affects over 422 million people (WHO 2014) and one third of the patients suffer from diabetes-related complications, which cause a considerable economic burden on the healthcare. Diabetic kidney disease (DKD) is one of the most severe complications, since one in five patients develop end-stage renal disease, which requires dialysis or kidney transplantation for survival. In addition, diabetes is a risk factor for cardiovascular disease (CVD), the most common cause of mortality among individuals with diabetes. Conventional clinical risk factors for both DKD and CVD have been established and include an altered lipoprotein profile, an abnormal glucose balance and hypertension. While the clinical risk factors are fairly well recognized, the genetic background of both DKD and CVD is rather unknown. The aim of this thesis was to study the effects of rare genetic variants altering lipids and other cardiometabolic risk factors and to determine their impact on diabetic complications. This study focused on loss of function and missense variants from whole exome- (N=500) and whole genome sequencing data (N=600) in type 1 diabetics from the Finnish Diabetic Nephropathy Study cohort. Single variant and gene-based association analysis were used to detect lipid-associated genetic variants and suggestive genes involved in lipid metabolism. Meta-analysis of whole exome- and whole genome single variants was performed to increase the sample size and detect additional lipid-associated variants. Three lipid-associated variants were genotyped in a cohort of 3000 patients to confirm the detected associations. Single variant association analysis detected a novel, previously unpublished, 21bp deletion located in the RBM47 gene, which was associated with lower apoC-III serum concentrations. To fully understand the impact of the 21bp deletion in RBM47 on apoC-III, further studies investigating the role of RBM47 in lipid metabolism are requested. Furthermore, single variant meta-analysis detected several lipid-associated variants. We showed that the rs451195 in PPIC was significantly associated with DKD. This study sheds light on the genetic background of diabetic dyslipidemia.
  • Taskinen, Marja-Riitta; Boren, Jan (2016)
    ApoC-III was discovered almost 50 years ago, but for many years, it did not attract much attention. However, as epidemiological and Mendelian randomization studies have associated apoC-III with low levels of triglycerides and decreased incidence of cardiovascular disease (CVD), it has emerged as a novel and potentially powerful therapeutic approach to managing dyslipidemia and CVD risk. The atherogenicity of apoC-III has been attributed to both direct lipoprotein lipase-mediated mechanisms and indirect mechanisms, such as promoting secretion of triglyceride-rich lipoproteins (TRLs), provoking proinflammatory responses in vascular cells and impairing LPL-independent hepatic clearance of TRL remnants. Encouraging results from clinical trials using antisense oligonucleotide, which selectively inhibits apoC-III, indicate that modulating apoC-III may be a potent therapeutic approach to managing dyslipidemia and cardiovascular disease risk.