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MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial
Abstract
Throughout the usual LDL cholesterol range in Western populations, lower blood concentrations are associated with lower cardiovascular disease risk. In such populations, therefore, reducing LDL cholesterol may reduce the development of vascular disease, largely irrespective of initial cholesterol concentrations. METHODS: 20,536 UK adults (aged 40-80 years) with coronary disease, other occlusive arterial disease, or diabetes were randomly allocated to receive 40 mg simvastatin daily (average compliance: 85%) or matching placebo (average non-study statin use: 17%). Analyses are of the first occurrence of particular events, and compare all simvastatin-allocated versus all placebo-allocated participants. These "intention-to-treat" comparisons assess the effects of about two-thirds (85% minus 17%) taking a statin during the scheduled 5-year treatment period, which yielded an average difference in LDL cholesterol of 1.0 mmol/L (about two-thirds of the effect of actual use of 40 mg simvastatin daily). Primary outcomes were mortality (for overall analyses) and fatal or non-fatal vascular events (for subcategory analyses), with subsidiary assessments of cancer and of other major morbidity. FINDINGS: All-cause mortality was significantly reduced (1328 [12.9%] deaths among 10,269 allocated simvastatin versus 1507 [14.7%] among 10,267 allocated placebo; p=0.0003), due to a highly significant 18% (SE 5) proportional reduction in the coronary death rate (587 [5.7%] vs 707 [6.9%]; p=0.0005), a marginally significant reduction in other vascular deaths (194 [1.9%] vs 230 [2.2%]; p=0.07), and a non-significant reduction in non-vascular deaths (547 [5.3%] vs 570 [5.6%]; p=0.4). There were highly significant reductions of about one-quarter in the first event rate for non-fatal myocardial infarction or coronary death (898 [8.7%] vs 1212 [11.8%]; p<0.0001), for non-fatal or fatal stroke (444 [4.3%] vs 585 [5.7%]; p<0.0001), and for coronary or non-coronary revascularisation (939 [9.1%] vs 1205 [11.7%]; p<0.0001). For the first occurrence of any of these major vascular events, there was a definite 24% (SE 3; 95% CI 19-28) reduction in the event rate (2033 [19.8%] vs 2585 [25.2%] affected individuals; p<0.0001). During the first year the reduction in major vascular events was not significant, but subsequently it was highly significant during each separate year. The proportional reduction in the event rate was similar (and significant) in each subcategory of participant studied, including: those without diagnosed coronary disease who had cerebrovascular disease, or had peripheral artery disease, or had diabetes; men and, separately, women; those aged either under or over 70 years at entry; and--most notably--even those who presented with LDL cholesterol below 3.0 mmol/L (116 mg/dL), or total cholesterol below 5.0 mmol/L (193 mg/dL). The benefits of simvastatin were additional to those of other cardioprotective treatments. The annual excess risk of myopathy with this regimen was about 0.01%. There were no significant adverse effects on cancer incidence or on hospitalisation for any other non-vascular cause. INTERPRETATION: Adding simvastatin to existing treatments safely produces substantial additional benefits for a wide range of high-risk patients, irrespective of their initial cholesterol concentrations. Allocation to 40 mg simvastatin daily reduced the rates of myocardial infarction, of stroke, and of revascularisation by about one-quarter. After making allowance for non-compliance, actual use of this regimen would probably reduce these rates by about one-third. Hence, among the many types of high-risk individual studied, 5 years of simvastatin would prevent about 70-100 people per 1000 from suffering at least one of these major vascular events (and longer treatment should produce further benefit). The size of the 5-year benefit depends chiefly on such individuals' overall risk of major vascular events, rather than on their blood lipid concentrations alone.
... In clinical trials, a tenfold increase in serum creatine kinase (CK) is also included as a side effect. 5,7,8 Occasionally myopathy can develop into rhabdomyolysis (muscle breakdown), resulting in myoglobinuria (excretion of myoglobin in the urine), and acute renal failure. In very rare cases, a fatal outcome may occur. ...
... The patients in these trials were carefully monitored, and certain interacting drugs were excluded. 7,8 Other listed side effects of simvastatin were gastrointestinal (constipation, abdominal pain, diarrhea, nausea, and vomiting), neurological (headache, paresthesia, and dizziness), and dermatological (pruritus, rash, and hair loss). All side effects have been classified as rare ($1/10,000, ,1/1000). ...
... In the larger clinical trials on statins, no specific differences in the frequency of side effects between study samples and control groups have been reported. 7,8 The frequency of myopathy in combination with a tenfold rise in CK levels has been reported to be 0.02%-0.08%. 9 In the present study, measurement of CK was not included, thus it is not possible to fully relate to these numbers. ...
... A number of large, international, multi-centre trials have clearly demonstrated the beneficial impact of statin therapy in CHD. For example, the 4S, 41 the WOSCOPS, 42 the CARE trial 43 and the HPS 44 have clearly and unequivocally shown that statin therapy is highly beneficial in reducing the risk of vascular disease. On average, the risk for vascular end-points is reduced by around 25-40% by statins. ...
... Downstream metabolites, including GGPP and FPP regulate prenylation within several critical signalling pathways 60 and one indirect effect of GGPP modulation by statins is activation of PPARα. 61 This latter effect may explain both the HDL-cholesterol raising property of statins [41][42][43][44] and their anti-inflammatory effects since PPARα activation leads to inhibition of inflammatory pathways. Indeed, statin-induced changes in serum CRP concentrations have been inversely associated with changes in HDL-cholesterol but not, as noted before, to LDL-cholesterol. ...
Rheumatoid arthritis is characterised by uncontrolled chronic inflammation of the joints, which leads to their destruction and functional disability. It is also associated with increased and early cardiovascular mortality. This is thought to be linked to chronic systemic inflammation, which can lead to accelerated atherosclerosis, and thus earlier and more severe CHD. The beneficial effects of statins in the primary and secondary prevention of CHD are wellestablished. These are not only due to their lipid-lowering properties. Statins have several anti-inflammatory and immunomodulatory effects through which they may modify the inflammatory mechanisms involved in the generation and rupture of atherosclerotic plaques. These effects may also be useful for controlling rheumatoid inflammation. Thus statins may be an important adjunctive therapy in RA, aiming to both reduce joint inflammation and improve cardiovascular outcome. This needs to be tested in randomised controlled trials designed specifically for the purpose.
... However, studies on the association between statin therapy and dementia risk are currently controversial. Randomized clinical trials have not drawn evident conclusions [16,17] and some studies have found no beneficial effects of statin therapy on dementia [11,18] due to the lack of a suitable sample size and insufficient follow-up durations. Furthermore, these studies have not focused on the population of patients with IHD. ...
... Interestingly, however, the results of atorvastatin and simvastatin in Taiwan patients were not consistent with our findings in Korean IHD patients, for which a significantly protective effect of atorvastatin was shown in both males and females, and that of simvastatin was shown in only females. In addition, several studies have further indicated a statin type-varying association between statin use and dementia incidence; however, they did not mainly focus on sex differences [11,18,28,29]. The inconsistency in the association between statin types and dementia incidence may be due to the lack of generalization of the study population. ...
This study aimed to determine the association between statins and the prevention of dementia according to sex differences in elderly patients with ischemic heart disease (IHD). We performed a nationwide retrospective cohort study using the Korean Health Insurance Review and Assessment Service database (2007–2015). Among the 264,036 eligible patients aged ≥65 years with IHD, statin users were compared with non–users by propensity score matching at a 1:1 ratio (71,587 in each group). The primary outcome was dementia risk by estimating hazard ratios (HRs) and 95% confidence intervals (CIs). Differential risks of dementia were assessed by sex in the subgroups of statin types, exposure duration, and patient age, implying that sex is an influential factor for the link between statin use and dementia incidence. Among seven commonly prescribed statins, rosuvastatin was associated with the greatest preventive effect on dementia incidence, with an adjusted HR of 0.82 (95% CI = 0.78–0.87). In a subgroup analysis organized by sex, the differential risk of dementia incidence was assessed in each statin group, implying that sex is an influential factor for the link between statin and dementia. This study suggests that appropriate statin use considering sex differences may have beneficial effects on the development of dementia.
... There is established evidence on the improvement that statin therapy has on cardiovascular disease (CVD), particularly atherosclerotic CVD [69,70], which is among the main causes of morbidity and mortality worldwide [135]. Statins have decreased CVD morbidity and mortality more than 50% in the general population [69][70][71]. ...
... There is established evidence on the improvement that statin therapy has on cardiovascular disease (CVD), particularly atherosclerotic CVD [69,70], which is among the main causes of morbidity and mortality worldwide [135]. Statins have decreased CVD morbidity and mortality more than 50% in the general population [69][70][71]. Results from several clinical trials have demonstrated that statins decrease blood cholesterol levels and reduce the risk of CV events with an excellent safety profile [72,73]. In atherosclerosis, statins may have additional advantages by decreasing the anti-inflammatory responses that lead to plaque stabilization, prevention of plaque rupture and eventually reduce the risk of CVD development [68]. ...
The toll-like receptors (TLRs) are a class of transmembrane-spanning receptors that are sentinels of both innate and adaptive immunity. Statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) are the most commonly prescribed therapeutic agents for treating hypercholesterolemia globally. However, statin therapy appears to have pleiotropic effects including attenuation of chronic low-grade inflammation and modulation of TLR activity. Statins through abolition of TLR4 expression and regulation of the TLR4/Myd88/NF-κB signaling pathway may slow the progression of atherosclerosis and other inflammatory diseases. In this review, we have focused on the impact and mechanism of action of statins on cardiovascular and non-cardiovascular diseases.
... In a metaanalysis limited to patients without stroke, BP lowering was associated with less cognitive decline but not dementia.[16] In respect of lipid lowering, there is no positive evidence that statins (currently the main lipid intervention) prevent cognitive decline or dementia, as reported in secondary analyses from the PROSPER (pravastatin) and HPS (simvastatin) trials.[17][18][19]Overall, systematic reviews of trials using statins to prevent or treat dementia have reported no benefit.[4, ...
... OD- CAST results are compatible with this hypothesis with the nadir lying in the systolic BP range of 130–140 mmHg although the exact level presumably varies by patient and stroke type. Evidence that lowering cholesterol levels reduces cognitive impairment and dementia is missing since both large and small trials have not identified any benefit.[4, 19, 20] PODCAST confirms that intensive lipid lowering did not alter the primary measure of cognition. Nevertheless , a number of secondary outcomes were positive in favour of intensive lipid lowering (following adjustment for baseline scores). Vascular cognitive impairment more commonly affects executive function and sub-cortical processes ...
Background
Stroke is associated with the development of cognitive impairment and dementia. We assessed the effect of intensive blood pressure (BP) and/or lipid lowering on cognitive outcomes in patients with recent stroke in a pilot trial.
Methods
In a multicentre, partial-factorial trial, patients with recent stroke, absence of dementia, and systolic BP (SBP) 125–170 mmHg were assigned randomly to at least 6 months of intensive (target SBP <125 mmHg) or guideline (target SBP <140 mmHg) BP lowering. The subset of patients with ischaemic stroke and total cholesterol 3.0–8.0 mmol/l were also assigned randomly to intensive (target LDL-cholesterol <1.3 mmol/l) or guideline (target LDL-c <3.0 mmol/l) lipid lowering. The primary outcome was the Addenbrooke’s Cognitive Examination-Revised (ACE-R).
Results
We enrolled 83 patients, mean age 74.0 (6.8) years, and median 4.5 months after stroke. The median follow-up was 24 months (range 1–48). Mean BP was significantly reduced with intensive compared to guideline treatment (difference –10·6/–5·5 mmHg; p<0·01), as was total/LDL-cholesterol with intensive lipid lowering compared to guideline (difference –0·54/–0·44 mmol/l; p<0·01). The ACE-R score during treatment did not differ for either treatment comparison; mean difference for BP lowering -3.6 (95% CI -9.7 to 2.4), and lipid lowering 4.4 (95% CI -2.1 to 10.9). However, intensive lipid lowering therapy was significantly associated with improved scores for ACE-R at 6 months, trail making A, modified Rankin Scale and Euro-Qol Visual Analogue Scale. There was no difference in rates of dementia or serious adverse events for either comparison.
Conclusion
In patients with recent stroke and normal cognition, intensive BP and lipid lowering were feasible and safe, but did not alter cognition over two years. The association between intensive lipid lowering and improved scores for some secondary outcomes suggests further trials are warranted.
Trial Registration
ISRCTN ISRCTN85562386
... As melhores e mais contundentes evidências no que se refere à prevenção de mortalidade com o tratamento da dislipidemia são disponíveis para sinvastatina (22,39) e pravastatina (23,24). A lovastatina apresenta evidência de benefício no que diz respeito a prevenção de infarto do miocárdio, revascularização, angina e desfecho combinado de infarto, angina e mortalidade cardiovascular (26). ...
Dislipidemia para a Prevenção de Eventos Cardiovasculares e Pancreatite
Portaria Conjunta SAS/MS nº 8 - 30/07/2019
... The cholesterol concentration directly affects the cholesterol metabolism in the central nervous system and the incidence of coronary heart disease. The downregulation of cholesterol synthesis in the central nervous system can reduce the incidence of dementia (Dietschy and Turley, 2004;Group., 2002;Pedersen et al., 2004;Raffai and Weisgraber, 2003;Simons et al., 2001). Biologically related prenol lipids, including fatsoluble vitamins and antioxidant molecules, can modulate and improve brain aging-related diseases (Lukiw et al., 2005;Scorletti and Byrne, 2013). ...
... Actually, there is no consensus on the frequency of SAMS. In randomized trials, the frequency of muscle symptoms in patients treated with statins was often not different from or close to placebo [24][25][26][27][28]. In comparison, in patient registries or trials focusing on muscular symptoms, the frequency of statin associated muscle symptoms is higher. ...
Statins lower the serum low-density lipoprotein cholesterol and prevent cardiovascular events by inhibiting 3-hydroxy-3-methyl-glutaryl-CoA reductase. Although the safety of statins is documented, many patients ingesting statins may suffer from skeletal muscle-associated symptoms (SAMS). Importantly, SAMS are a common reason for stopping the treatment with statins. Statin-associated muscular symptoms include fatigue, weakness and pain, possibly accompanied by elevated serum creatine kinase activity. The most severe muscular adverse reaction is the potentially fatal rhabdomyolysis. The frequency of SAMS is variable but in up to 30% of the patients ingesting statins, depending on the population treated and the statin used. The mechanisms leading to SAMS are currently not completely clarified. Over the last 15 years, several research articles focused on statin-induced mitochondrial dysfunction as a reason for SAMS. Statins can impair the function of the mitochondrial respiratory chain, thereby reducing ATP and increasing ROS production. This can induce mitochondrial membrane permeability transition, release of cytochrome c into the cytosol and induce apoptosis. In parallel, statins inhibit activation of Akt, mainly due to reduced function of mTORC2, which may be related to mitochondrial dysfunction. Mitochondrial dysfunction by statins is also responsible for activation of AMPK, which is associated with impaired activation of mTORC1. Reduced activation of mTORC1 leads to increased skeletal muscle protein degradation, impaired protein synthesis and stimulation of apoptosis. In this paper, we discuss some of the different hypotheses how statins affect skeletal muscle in more detail, focusing particularly on those related to mitochondrial dysfunction and the impairment of the Akt/mTOR pathway.
... These signaling proteins play an important role in the control of various biological processes including cell signaling, cell differentiation and proliferation, myelination, cytoskeleton dynamics and endocytotic/ exocytotic transport [25]. Statins are not only known to reduce the levels of LDL-C, but also it prevents isoprenylation of Rho-and Rhoassociated kinases (ROCK) [26]. Rho/ROCK has several functions, such as regulation of contraction, migration and adhesion of vascular smooth muscle cells and by inhibiting Rho/ROCK activation, statins cause an increase in the bioavailability of NO (REFs). ...
Heat shock proteins (HSP or stress proteins) are intracellular molecules that participate in physiological cell metabolism and growth, although they are known to be involved in many stress conditions. Statins inhibit the action of the enzyme 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA), which is important in the synthesis of cholesterol and essential isoprenoid intermediates, thereby lowering circulating low-density lipoprotein cholesterol (LDL), a major risk factor for cardiovascular disease (CVD). This review provides new insights into the mechanisms of action of statins in the regulation of HSPs. A better understanding of this involvement can help in development of new and more effective treatment strategies for CVD.
... A statin should be used as first-line cholesterol-lowering drug therapy, unless contraindicated; current evidence supports a moderate-to high-intensity statin (192-195). Numerous randomized clinical trials and meta-analyses conducted in primary and secondary prevention populations have demonstrated that statins significantly reduce the risk of cardiovascular events and death in patients with T2D ( 192,[194][195][196][197][198]). However, considerable residual risk persists even after aggressive statin monotherapy in primary prevention patients with multiple cardiovascular risk factors and in secondary prevention patients with stable clinical ASCVD or acute coronary syndrome (ACS) ( 195,199,200). ...
Abbreviations:
A1C = hemoglobin A1C; AACE = American Association of Clinical Endocrinologists; ACCORD = Action to Control Cardiovascular Risk in Diabetes; ACCORD BP = Action to Control Cardiovascular Risk in Diabetes Blood Pressure; ACEI = angiotensin-converting enzyme inhibitor; ADVANCE = Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation; AGI = alpha-glucosidase inhibitor; apo B = apolipoprotein B; ASCVD = atherosclerotic cardiovascular disease; BAS = bile acid sequestrant; BCR-QR = bromocriptine quick release; BMI = body mass index; BP = blood pressure; CCB = calcium channel blocker; CHD = coronary heart disease; CKD = chronic kidney disease; CVD = cardiovascular disease; DASH = Dietary Approaches to Stop Hypertension; DPP4 = dipeptidyl peptidase 4; eGFR = estimated glomerular filtration rate; ER = extended release; FDA = Food and Drug Administration; GLP1 = glucagon-like peptide 1; HDL-C = high-density lipoprotein cholesterol; IMPROVE-IT = Improved Reduction of Outcomes: Vytorin Efficacy International Trial; LDL-C = low-density lipoprotein cholesterol; LDL-P = low-density lipoprotein particle; Look AHEAD = Look Action for Health in Diabetes; NPH = neutral protamine Hagedorn; OSA = obstructive sleep apnea; RCT = randomized controlled trial; SU = sulfonylurea; SGLT2 = sodium glucose cotransporter-2; SMBG = self-monitoring of blood glucose; T2D = type 2 diabetes; TZD = thiazolidinedione; VADT = Veterans Affairs Diabetes Trial.
... Statins are a class of drugs that inhibit an enzyme in cholesterol synthesis pathway called HMGCoA reductase (20). Thus, statins reduce serum cholesterol and have proved efficacious in management of CAD (21). ...
Coronary artery disease (CAD) is a major cause of cardiovascular death worldwide. Prevalence of CAD is highly variable among different races. Asian Indians have been noted to have the highest CAD rates and the conventional risk factors fail to explain this difference completely. Asian Indians constitute a fifth of the global population, and the higher rates of CAD in this population constitute a major health challenge. There have been studies in the early 2000s that investigate the risk factors in this population; however, very few studies have been done since then that explore the higher CAD rates in Asian Indians. This is a comprehensive and current review of the known risk factors for CAD in Asian Indians and strategies physicians should consider relieving this burden.
... Statin treatment has been shown to be very effective in reducing LDL levels, but it is estimated that some 70% of cardiovascular events cannot be prevented by such treatment. [51][52][53][54][55][56] Not only are patients with overt coronary artery disease commonly seen to have persistently low levels of HDL even after statin therapy, but there have also been a number of clinical studies that convincingly demonstrate the benefits of interventions that target HDL. These trials are reviewed elsewhere 57,58 but include the Veterans Affairs HDL Intervention Trial (VA-HIT), the Helsinki Heart Study (HHS), the Bezafibrate Infarction Prevention Study (BIP) and the HDL Atherosclerosis Treatment Study (HATS). ...
... Past trials, however, have either excluded patients with dyslipidemia or were not focused on patients with dementia or AD. For example, two largescale, randomized, placebo-controlled trials of simvastatin[71]and pravastatin[72,73]in subjects with or at risk for cardiovascular disease showed no effect on cognitive function. In both of these trials, however, cognition was only a tertiary endpoint and subjects with dementia at baseline were excluded. ...
Background
Despite substantial research and development investment in Alzheimer’s disease (AD), effective therapeutics remain elusive. Significant emerging evidence has linked cholesterol, β-amyloid and AD, and several studies have shown a reduced risk for AD and dementia in populations treated with statins. However, while some clinical trials evaluating statins in general AD populations have been conducted, these resulted in no significant therapeutic benefit. By focusing on subgroups of the AD population, it may be possible to detect endotypes responsive to statin therapy. Methods
Here we investigate the possible protective and therapeutic effect of statins in AD through the analysis of datasets of integrated clinical trials, and prospective observational studies. ResultsRe-analysis of AD patient-level data from failed clinical trials suggested by trend that use of simvastatin may slow the progression of cognitive decline, and to a greater extent in ApoE4 homozygotes. Evaluation of continual long-term use of various statins, in participants from multiple studies at baseline, revealed better cognitive performance in statin users. These findings were supported in an additional, observational cohort where the incidence of AD was significantly lower in statin users, and ApoE4/ApoE4-genotyped AD patients treated with statins showed better cognitive function over the course of 10-year follow-up. Conclusions
These results indicate that the use of statins may benefit all AD patients with potentially greater therapeutic efficacy in those homozygous for ApoE4.
... A statin should be used as first-line cholesterol-lowering drug therapy, unless contraindicated; current evidence supports a moderate-to high-intensity statin (192)(193)(194)(195). Numerous randomized clinical trials and meta-analyses conducted in primary and secondary prevention populations have demonstrated that statins significantly reduce the risk of cardiovascular events and death in patients with T2D (192,(194)(195)(196)(197)(198). However, considerable residual risk persists even after aggressive statin monotherapy in primary prevention patients with multiple cardiovascular risk factors and in secondary prevention patients with stable clinical ASCVD or acute coronary syndrome (ACS) (195,199,200). ...
Abbreviations:
A1C = hemoglobin A1C AACE = American Association of Clinical Endocrinologists ACCORD = Action to Control Cardiovascular Risk in Diabetes ACCORD BP = Action to Control Cardiovascular Risk in Diabetes Blood Pressure ACEI = angiotensin-converting enzyme inhibitor ADVANCE = Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation AGI = alpha-glucosidase inhibitor apo B = apolipoprotein B ASCVD = atherosclerotic cardiovascular disease BAS = bile acid sequestrant BMI = body mass index BP = blood pressure CHD = coronary heart disease CKD = chronic kidney disease CVD = cardiovascular disease DASH = Dietary Approaches to Stop Hypertension DPP-4 = dipeptidyl peptidase 4 eGFR = estimated glomerular filtration rate FDA = Food and Drug Administration GLP-1 = glucagon-like peptide 1 HDL-C = high-density lipoprotein cholesterol IMPROVE-IT = Improved Reduction of Outcomes: Vytorin Efficacy International Trial LDL-C = low-density lipoprotein cholesterol LDL-P = low-density lipoprotein particle Look AHEAD = Look Action for Health in Diabetes NPH = neutral protamine Hagedorn OSA = obstructive sleep apnea SFU = sulfonylurea SGLT-2 = sodium glucose cotransporter-2 SMBG = self-monitoring of blood glucose T2D = type 2 diabetes TZD = thiazolidinedione VADT = Veterans Affairs Diabetes Trial.
... El estudio GREACE (Greek Atorvastatin and Coronaryheart-disease Evaluation) encontró que la atorvastatina reduce las LDL en un 46% y el CHO en un 36%, con lo que disminuye el riesgo relativo de ictus en un 0,53% [29]. Otro estudio, el MRC/BHF Heart Protection Study, demostró que la administración diaria de 40 mg de simvastatina reduce los índices de infarto de miocardio, de ictus y de revascularizaciones en, al menos, un cuarto de los pacientes en tratamiento [30]. Por último, un análisis reciente del estudio LIPID, sobre el efecto de la administración de pravastatina en la aparición de eventos cardiovasculares, aporta que el grupo sujeto al tratamiento farmacológico presentó un 5% de ictus, respecto a un 6% en el grupo placebo (p= 0,015) [27]. ...
Introduction. In order to determine the role lipids play in cerebral infarction (CI), the different aetiological subgroups of this disease should first be separated. Aims and methods. We conducted case-control studies to identify whether there is a relation between blood lipid levels and the occurrence of cerebral infarction caused by atheromatosis (CIA). Our study involved a total of 98 patients with cerebral infarction of an atherothrombotic or lacunar aetiopathogenesis that were included in the CIA category. Two control groups were set up: one consisted of 23 patients with non-atheromatous cerebral infarction (NACI), which included other aetiologies (cardioembolic, unusual and unspecified), and the other was made up of 101 healthy subjects who had not had a stroke. Results. The group of patients with CIA presented higher average cholesterol rates than the group of subjects with NACI (p= 0.005). Nevertheless, compared to the control group they had higher average levels of cholesterol (p= 0.003), triglycerides (p= 0.011), VLDL (p= 0.028) and LDL (p= 0.000), as well as a higher average atherogenic index (p= 0.028). Furthermore, the average levels of LDL (p= 0.030) and the atherogenic index (p= 0.008) were seen to be statistically higher in the group of subjects with NACI than in the control group. Lastly, it must be pointed out that no differences in the average HDL levels were found between the three groups studied (p= 0.500). The presence of high blood pressure and a history of ischemic heart disease in patients with CI did not modify the variations that were observed in the lipids. Conclusions. Patients with CIA have a more atherogenic lipid profile than healthy individuals, while subjects with NACI are situated midway between the two groups. [REV NEUROL 2003; 36: 625-8] Key words. Atherosclerosis. Case-control studies. Cerebral infarction. Lipids. Risk factors. Stroke.
... aterogénnu metabolickú triádu, ktorá veľmi dobre koreluje s obvodom pása a hladinou TAG nalačno [11,13]. V Heart Protection Study v priebehu 5-ročného sledovania pacientov s PAO DK v ramene so simvastatínom 40 mg denne bola preukázaná 24% redukcia relatívneho a 6,3% absolútneho rizika KV-príhod oproti placebovej skupine [14]. K redukcii KV-rizika došlo pri poklese LDL-C pod 2,59 mmol/l, benefit bol dosiahnutý aj u starších pacientov a diabetikov. ...
AtheroRev 2016; 1(3): 000–000 Čelovská D. Periférne artériové ochorenie dolných končatín a dyslipidémia 27 Úvod Periférne artériové ochorenie dolných končatín (PAO DK) predstavuje predominantne manifestáciu aterotrombo-tického procesu. Klaudikácie nie sú lokálny problém, ale často upozorňujú na postihnutie viacerých cievnych rie-čísk. Starnutím populácie je multivaskulárne postihnu-tie chorých stále aktuálnejšie. V iniciácii i progresii PAO DK zohrávajú významnú úlohu početné rizikové faktory (RF), z ktorých najvýznamnejšie sú fajčenie, diabetes mel-litus, dyslipidémia a artériová hypertenzia (AH). Veľkou výzvou pre medicínu je, že sú to modifikovateľné RF. Na-priek pokrokom v diagnostike, prevencii i liečbe prevalen-cia artériovej hypertenzie, diabetu, metabolického syn-drómu s aterogénnou dyslipidémiou, a tým aj vaskulárnych ochorení alarmujúco stúpa. Asymptomatická alebo aty-pická forma PAO DK sú v populácii frekventne zastúpené, čo vedie k poddiagnostikovaniu ochorenia, ale aj nedosta-točnej liečbe pacientov. Členkovo-brachiálny tlakový index (ankle brachial index – ABI) je markerom subklinickej atero-sklerózy i najbežnejší funkčný marker PAO DK, ktorý záro-veň slúži na stratifikáciu kardio-vaskulárneho (KV) rizika u všetkých rizikových pacientov. V liečbe šitej na mieru u pacienta s PAO DK má nenahraditeľné miesto interven-cia modifikovateľných rizikových faktorov aterotrombózy. Abstrakt Periférne artériové ochorenie dolných končatín (PAO DK) predstavuje predominantne manifestáciu aterotrombotic-kého procesu. Efektívne ovplyvnenie kardio-vaskulárneho rizika u pacientov s PAO DK je často v klinickej praxi podceňo-vané napriek významnému zvýšeniu kardio-cerebrovaskulárnej morbidity a mortality aj u asymptomatických chorých. Aterogénna dyslipidémia prestavuje významný rizikový faktor pre spresnenie vaskulárneho rizika u pacientov s PAO DK. Pacienti s PAO DK majú veľmi vysoké KV-riziko, preto je u nich žiaduce dosiahnuť cieľovú hladinu LDL-cholesterolu < 1,8 mmol/l a podľa najnovších poznatkov aj menej. Liekom prvej voľby u pacientov s PAO DK je statín. Pri nedosaho-vaní cieľových hodnôt LDL-cholesterolu výhodne jeho užitie v kombinácii s ezetimibom. Novú perspektívu u vysokori-zikových pacientov a chorých, ktorí netolerujú statín, predstavujú monoklonálne protilátky PCSK9 inhibítory. Nemožno však zabúdať na modifikáciu životného štýlu hlavne pri redukcii remnantných lipoproteínov, ktoré majú význam práve v periférnej cirkulácii. Kľúčové slová: dyslipidémia – kardio-vaskulárne riziko – periférne artériové ochorenie dolných končatín Peripheral arterial disease (PAD) of lower extremity and dyslipidemia Abstract Peripheral arterial disease (PAD) of lower extremity is predominantly a manifestation of atherothrombotic process. Effective cardiovascular (CV) risk treatment is underestimated in clinical practice despite significantly increased car-dio-cerbrovascular mortality and morbidity in symptomatic and even in asymptomatic PAD patients. Atherogenic dys-lipidemia is a significant risk factor for vascular risk stratification in PAD patients. PAD patients have very high CV risk and the goal level of LDL cholesterol is less than 1.8 mmol/l or even lower according to new studies. First line therapy in PAD patients is statin treatment. However, in not reaching the LDL-cholesterol goal level conveniently, ezitimibe is added. PCSK9 inhibitors are a new perspective in high risk patients and in statin intolerance. What cannot be forgotten is modification of lifestyle especially in reduction of remnant lipoproteins, which play an important role in peripheral circulation.
Cardiovascular disease, and in particular coronary heart disease, is the predominant cause of death and disability worldwide in populations older than 65 yr of age; about half of elderly individuals in industrialized countries have clinical evidence of coronary heart disease. The World Health Organization (WHO) Study Group report on the epidemiology and prevention of cardiovascular diseases in elderly people (1) identified coronary heart disease as the major cause of mortality in industrialized nations, where 50% of such deaths occur in the population older than 65 yr of age and 60% at older than age 75. Coronary heart disease is responsible for half of all deaths in the population older than 80 yr of age (2). Forty-five percent of octogenarians have clinical evidence of cardiovascular disease, with coronary heart disease being the most common problem. However, the variation in rates of cardiovascular mortality in elderly populations indicates a substantial potential for effective coronary prevention because many risk factors for coronary heart disease are modifiable. The highest risk for development of clinical evidence of coronary heart disease is in the population 65 yr of age and older, double that in the under age 65 population, with the difference more pronounced among women.
It has long been known that administering insulin or insulin secretagogues to treat diabetes has the unfavorable side effect of hypoglycemia. Because hypoglycemia can disrupt normal brain function, it can have a profound impact on people's lives. Studies have shown a connection between hypoglycemia and a higher risk of death and cardiovascular disease. Through experimental studies, numerous potential reasons for the start of cardiovascular events have been discovered. In addition, studies on people have demonstrated that hypoglycemia can result in ventricular arrhythmias. According to recent studies, a number of factors may affect the relationship between hypoglycemia, cardiovascular events, and mortality. Confounding factors may explain the apparent correlation, at least in part. People with comorbidities may experience more hypoglycemia, increasing their risk of mortality. Those who have type 1 or type 2 diabetes, however, seem to be more susceptible to the negative effects of hypoglycemia on the cardiovascular system. When choosing appropriate glucose-lowering treatments and setting glycemic objectives with patients, clinicians should be aware of this risk.
Purpose:
Coronary artery disease (CAD) is one of the major cardiovascular diseases and the leading cause of death globally. Blood lipid profile is associated with CAD early risk. Therefore, we aim to establish machine learning models utilizing blood lipid profile to predict CAD risk.
Methods:
In this study, 193 non-CAD controls and 2001 newly-diagnosed CAD patients (1647 CAD patients who received lipid-lowering therapy and 354 who did not) were recruited. Clinical data and the result of routine blood lipids tests were collected. Moreover, low-density lipoprotein cholesterol (LDL-C) subfractions (LDLC-1 to LDLC-7) were classified and quantified using the Lipoprint system. Six predictive models (k-nearest neighbor classifier (KNN), logistic regression (LR), support vector machine (SVM), decision tree (DT), multilayer perceptron (MLP), and extreme gradient boosting (XGBoost)) were established and evaluated by the confusion matrix, area under the receiver operating characteristic (ROC) curve (AUC), recall (sensitivity), accuracy, precision, and F1 score. The selected features were analyzed and ranked.
Results:
While predicting the CAD development risk of the CAD patients without lipid-lowering therapy in the test set, all models obtained AUC values above 0.94, and the accuracy, precision, recall, and F1 score were above 0.84, 0.85, 0.92, and 0.88, respectively. While predicting the CAD development risk of all CAD patients in the test set, all models obtained AUC values above 0.91, and the accuracy, precision, recall, and F1 score were above 0.87, 0.94, 0.87, and 0.92, respectively. Importantly, small dense LDL-C (sdLDL-C) and LDLC-4 play pivotal roles in predicting CAD risk.
Conclusions:
In the present study, machine learning tools combining both clinical data and blood lipid profile showed excellent overall predictive power. It suggests that machine learning tools are suitable for predicting the risk of CAD development in the near future.
Objectives: Serum lipid profile viz the level of total cholesterol (TC), Triglyceride (TG), HDL-cholesterol and LDL-cholesterol of type2 diabetic patients have been studied and compares them with levels of control subjects. Results: The mean value of the TG level for male diabetics was higher than that for the female diabetics and the mean values of TC, HDL-C and LDL-C were not found significantly different between male and female diabetics. Hyperlipidemia has a documented causative relation with CAD, but the major risk associated with diabetes may be due to the associated hyperlipidemia. The study revealed that dyslipi-demia is very common in type2 diabetics and the most common abnormality observed was increased serum triglyceride levels (58%). The next common abnormality was decreased serum high-density lipoprotein cholesterol (HDL-C) levels and increased serum low-density lipoprotein cholesterol (LDL-C) levels. A high total serum cholesterol levels was found in 41% patients. 39% of the patients examined were overweight, and 7% were overtly obese. Conclusion: Thus, the study clearly shows the relationship between type2 diabetes and hyperlipidemia, which may influence the mechanism by which type2 diabetes is associated with increased CAD risk.
Aim
To provide information on the balance between the cardiovascular (CV) benefit and the diabetogenic harm of statin therapy in the current clinical practice.
Methods
All the 115,939 residents (older than 50 years) in the Italian Lombardy Region newly treated with statins between 2003 and 2005, were followed from the first statin prescription until 2012 to identify those experiencing a macrovascular complication and those with at least one sign suggestive of new onset diabetes. The proportion of days of follow-up covered by statin prescriptions measured adherence with statins. Hazard ratio, and relative 95% confidence interval (CI), for the two considered outcomes associated with statin adherence, were separately estimated (proportional hazard models). Number needed to treat (NNT) and number needed to harm (NNH), i.e., number of individuals who must be treated with statins in order to prevent a macrovascular complication, or to generate a new onset diabetes, respectively, were calculated to evaluate the balance between CV benefit and diabetogenic harm of statin therapy.
Results
Compared to those at very low adherence with statins, patients at high adherence showed a significant reduction of macrovascular risk (28%, 95% CI: 23%-33%) and a greater risk of developing diabetic condition (67%, 50%-86%). In the whole cohort, the NNT was 26, whereas the NNH 65. NNT was lower than NNH also in all considered strata of age, gender, clinical profile.
Conclusions
This large cohort investigation provides real-world evidence that the balance between CV benefit and diabetogenic harm of statin therapy is largely favourable to treatment benefits.
Background: Non-high density lipoprotein cholesterol (non-HDL-c) has emerged as an important tool in primary prevention of atherosclerotic cardiovascular disease (ASCVD), especially among those at high risk. The main objective of this study was to evaluate the predictive value of non-HDL-c for the coexistence aggregation of multiple ASCVD risk factors and compare this with LDL-c in general subjects with normal or near normal triglycerides from Maracaibo city in Venezuela.
Methods: This is a descriptive, cross-sectional study with a randomized multistage sampling. 2026 subjects were selected for this study, all were adults ≥18 years old of both genders and inhabitants of Maracaibo city, Venezuela. A complete history and physical medical assessment was performed. A multivariate logistic regression model was used to determine the odds ratio (CI95%) for the coexistence of multiple risk factors for ASCVD.
Results: The median (p25-p75) of non-HDL-c was 143 mg/dL (114-174 mg/dL). 52.1% (n=1056) of the sample were women, with a median of 144 mg/dL (115-174 mg/dL) among women and 143 mg/dL (114-17 4mg/dL) among men; p=0.740. Individuals ≥50 years old, smokers, those with hypertension, obesity, diabetes, high waist circumference and elevated hs-C Reactive Protein, all had higher levels of non-HDL-c. A lower median was observed among those <30 years of age with elevated physical activity levels in their leisure time. Non-HDL-c between 130-159 mg/dL (OR=2.44; CI 95%=1.48-4.02; p<0.001) and ≥160 mg/dL (OR=3.28; CI 95%=1.72-6.23; p<0.001) was associated with greater risk of coexistent multiple risk factors for ASCVD, albeit LDL-c was not significant in the multivariate model.
Conclusions: Elevated non-HDL-c was associated with conglomeration of multiple risk factors for ASCVD. This suggests evaluation of non-HDL-c may be of better utility in primary care for early identification of subjects for high risk of ASCVD. Future research might focus on the influence of non-HDL-c in cardiovascular mortality.
Background
In HIV treatment, TAF is associated with greater increases in all fasting cholesterol subgroups compared to TDF. Because lipid abnormalities may contribute to cardiovascular morbidity and mortality, cardiovascular risk assessment is integral to routine HIV care. This post-hoc study evaluates the impact of lipid changes on predicted atherosclerotic cardiovascular disease (ASCVD) risk and statin eligibility in treatment-naïve adults living with HIV treated with TAF or TDF.
Methods
Participants (N=1,744) were randomized (1:1) to initiate TAF or TDF, each co-formulated with elvitegravir/cobicistat/emtricitabine (studies GS-US-292-0104 and GS-US-292-0111). Eligibility for statin therapy and estimated 10-year ASCVD risk among adults aged 40-79 years treated with TAF or TDF for 96 weeks (W96) were analyzed based on AHA/ACC Pooled Cohort Equations. Categorical shifts in 10-year ASCVD risk from <7.5% to ≥7.5% by W96 on TAF vs. TDF were calculated.
Results
Participants initiating TAF versus TDF in the overall study population showed small but significant increases in median fasting lipid parameters at Week 96, including total cholesterol (191 mg/dL vs 177 mg/dL; p<0.001), LDL (119 mg/dL vs 112 mg/dL; p<0.001), and HDL (51 mg/dL vs 48 mg/dL; p<0.001), respectively. At baseline, 18% and 23% on TAF vs. TDF had a 10-year ASCVD risk score ≥7.5%, with mean risk scores low overall for TAF vs. TDF at baseline (4.9% vs 5.4%;p=0.35) and W96 (6.1% vs 6.2%;p=0.04). Increases in ASCVD risk from baseline to W96 were driven by both increasing age and changes in total (TC) and HDL cholesterol. At W96, TC:HDL ratios (median) were 3.7 for both groups (p=0.69). There was no difference between shifts in categorical risk for TAF vs. TDF (9% vs. 5%;p=0.19). Eligibility for high intensity statin therapy were similar for TAF vs. TDF groups (19% vs 21%;p=0.47).
Conclusions
Lipid changes with TAF as part of coformulated regimens do not substantively affect CVD risk profiles compared to TDF.
Background:
Distance education or reminder by texting short message may improve HbA1c level and medication adherence to type-2 diabetes.
Methods:
Electronic databases (PubMed, EBSCO, Elsevier, Springer, Wiley, and Cochrane) were searched systematically for published studies up to Mar 2019. SMD and 95% confidence interval (CI) were used to evaluate the intervention effect on HbA1c level and medication adherence. The heterogeneity of the study was estimated with the I2 statistic. The publication bias was described by Beggs' test, Egger's test and plot.
Results:
Ten studies with 380 interventions and 275 controls were included in this meta-analysis. The Hba1c overall SMD was -0.49%, 95% CI -0.75 to 0.22%, and the overall SMD was 0.96%, 95% CI 0.45-1.47 for medication adherence. The I2 and P were 64.90%, 0.002 and 56.40%, 0.10 respectively for Hba1c level and medication adherence.
Conclusion:
SMS intervention was effective for HbA1c level and medication adherence according to this study for T2DM over first 6 months.
The prevalence of diabetes mellitus is increasing all over the world and it is apparent that treatment of diabetic complications has the same importance as primary diabetes treatment and glycemic control. Diabetic complications occur as a result of prolonged hyperglycemia and its consequences, such as advanced glycation end products and reactive oxygen species. Impairment of lipid profile is also contributed to worsening diabetic complications. Therefore, it seems that the application of lipid‐lowering agents may have positive effects on reversing diabetic complications besides glycemic control. Statins, a group of lipid‐lowering compounds, have been shown to exert antioxidant, immunomodulatory, anti‐inflammatory, and antiproliferative properties beyond their lipid‐lowering effects. Furthermore, they have been reported to improve diabetic complications with different pathways. In this review, we will discuss the clinical importance, molecular biology of the most important microvascular/macrovascular diabetic complications, possible application of statins and their mechanism of action in retarding these complications. Diabetic complications decrease the quality of life in diabetic patients ‐ Management of dyslipidemia further to glycemic control has been shown to be helpful in diabetic patients. ‐ The pleiotropic effects of statins are helpful in reversing microvascular and macrovascular diabetic complications.
High-density lipoprotein (HDL) has received increasing interest due to observations of an inverse relationship between its systemic levels and cardiovascular risk and targeted interventions in animal models that have had favourable effects on atherosclerotic plaque. In addition to its pivotal role in reverse cholesterol transport, HDL has been reported to possess a range of functional properties, which may exert a protective influence on inflammation, oxidation, angiogenesis and glucose homeostasis. This has led to the development of a range of HDL targeted therapeutics, which have undergone evaluation in clinical trials. The current state of HDL in cardiovascular prevention will be reviewed.
Risk factors for first-ever stroke have been studied extensively, while those for recurrent stroke are not accurately understood. To provide the adequate secondary prevention for the patients, it is necessary to reveal the risk factors that dominate recurrent stroke. Multiple databases were adopted to search for the relevant studies and full-text articles involving in the risk factors for stroke recurrence were reviewed. Meta-analyses were performed with Review Manager 5.0 to estimate the impact of risk factors included, and forest plots, quality analysis and bias analysis for the articles included were also conducted. Finally 11 studies which eventually satisfied the eligibility criteria were included in this study, and patients with initial stroke and recurrent stroke were 14,455 and 1545, respectively. The meta-analyses showed that hypertension (OR = 1.67, 95%CI [1.45, 1.92], P < 0.00001), diabetes mellitus (OR = 1.50, 95%CI [1.30, 1.72], P < 0.00001), atrial fibrillation (OR = 1.88, 95%CI [1.56, 2.25], P < 0.00001) and coronary heart disease (OR = 1.77, 95%CI [1.31, 2.39], P = 0.0002) played a certain role in the process of stroke recurrence, while the influences of dyslipidemia (OR = 0.92, 95%CI [0.67, 1.27], P = 0.62) and smoking (OR = 0.96, 95%CI [0.80, 1.15], P = 0.62) were not significant. Hypertension, diabetes mellitus, atrial fibrillation and coronary heart disease of patients with stroke have statistical associations with recurrent stroke, and secondary prevention and treatment should be provided to curb the recurrence.
Background and aims:
Statins improve clinical outcomes in patients with ischemic stroke but there is no evidence of the effect of continuing long-term statin therapy in patients with intracerebral hemorrhage (ICH). The aim of this study was to evaluate the impact of continuing statin after ICH.
Methods:
Data on patients with ICH was retrieved from the National Health Insurance Research Database of Taiwan. The final population was separated into two groups according to those who continued and those who discontinued statin treatment. All-cause mortality and cardiovascular outcomes were analyzed after a 3 year follow-up after propensity score matching (PSM).
Results:
Of the 114,101 patients with ICH, who were initially enrolled, 2468 patients with dyslipidemia and ICH were included. After PSM, the benefit of statin therapy on mortality appeared from 1 year to the end of the 3-year follow-up period after discharge (statin group versus non-statin group: 4.9% vs.12.3% at 1 year (hazard ratio [HR], 0.38; 95% confidence interval [CI], 0.26-0.57) and 12.9% vs. 25.3% at the end of the 3 year follow-up period (HR, 0.45; 95% CI, 0.35-0.58). Compared with the patients using lipophilic statins, those using hydrophilic statins had a significantly lower incidence of all-cause mortality (HR = 0.65, 95% CI = 0.43-0.99). There were no differences between those prescribed moderate-intensity statins and those prescribed high-intensity statins in terms of stroke and all-cause mortality (HR = 0.76; 95% CI = 0.40-1.46).
Conclusions:
There was a lower risk of all-cause mortality following ICH in patients who continued statin treatment compared with those without statin treatment, especially in those treated with hydrophilic statins.
Background:
Patients with stroke have an increased risk of dementia. Some studies have found that statin use might lower the risk of incident dementia; however, there is still a lack of data from patients with stroke. Therefore, the aim of our study was to investigate the impact of statin use on the risk of dementia in patients with stroke.
Methods:
We used the National Health Insurance Research Database in Taiwan to identify 14,807 patients diagnosed with stroke from 1997 to 2005. These patients were classified as statin users and nonusers. Propensity score matching was performed to balance selected confounders between the statin users and nonusers. Cox proportional hazard regression models were used to evaluate the association between statin use and the risk of dementia.
Results:
During the follow-up period (median, 7.5 years), 1895 patients were diagnosed with incident dementia. Statin use was associated with a significantly lower incidence of dementia (adjusted hazard ratio, .81; 95% confidence interval, .73-.89) than nonuse was. In particular, lipophilic and high-potency statins were associated with lower risk of dementia. Statin exposure duration was inversely related to the risk of dementia (P < .001 for the trend). No significant effect modification for the relationship between statin use and the risk of dementia was found for either age or sex.
Conclusion:
In this nationwide cohort study, statin use was associated with decreased risk of dementia among patients with stroke. The use of high-potency statins, lipophilic statins, and prolonged exposure to statins may be associated with greater benefits.
Background
Epidemiological evidence has associated Alzheimer’s disease (AD) with vascular risk factors (VRFs), but whether treatment of VRFs reduces the incidence of dementia and AD is uncertain.
Objective
To conduct a systematic review and meta-analysis to summarize available data on the impact of treatment of VRFs on dementia and AD incidence.
Methods
Pertinent studies published until 1 January 2018 were identified from PubMed. Both randomized controlled trials (RCT) and prospective studies that investigated the impact of treatment of VRFs on dementia or AD incidence were included.
Results
Eight RCTs and 52 prospective studies were identified. Antihypertensive treatment was associated with a non-significant reduced risk of dementia in RCTs (n = 5; relative risk [RR], 0.84; 95% confidence interval [CI], 0.69–1.02) and prospective studies (n = 3; RR, 0.77; 95% CI, 0.58–1.01) and with reduced AD risk in prospective studies (n = 5; RR = 0.78; 95% CI, 0.66–0.91). In prospective studies, treatment of hyperlipidemia with statins, but not nonstatin lipid-lowering agents, was associated with reduced risk of dementia (n = 17; RR, 0.77; 95% CI, 0.63–0.95) and AD (n = 13; RR, 0.86; 95% CI, 0.80–0.92). The single RCT on statins and dementia incidence showed no association. Data from one RCT and six prospective studies did not support a beneficial impact of antidiabetic drugs or insulin therapy on dementia risk.
Conclusion
Current evidence indicates that antihypertensives and statins might reduce the incidence of dementia and AD. Further trials to determine the effect of VRF on AD are needed.
Background: Non-high density lipoprotein cholesterol (non-HDL-c) has emerged as an important tool in primary prevention of atherosclerotic cardiovascular disease (ASCVD), especially among those at high risk. The main objective of this study was to evaluate the predictive value of non-HDL-c for the coexistence aggregation of multiple ASCVD risk factors and compare this with LDL-c in general subjects with normal or near normal triglycerides from Maracaibo city in Venezuela.
Methods: This is a descriptive, cross-sectional study with a randomized multistage sampling. 2026 subjects were selected for this study, all were adults ≥18 years old of both genders and inhabitants of Maracaibo city, Venezuela. A complete history and physical medical assessment was performed. A multivariate logistic regression model was used to determine the odds ratio (CI95%) for the coexistence of multiple risk factors for ASCVD.
Results: The median (p25-p75) of non-HDL-c was 143 mg/dL (114-174 mg/dL). 52.1% (n=1056) of the sample were women, with a median of 144 mg/dL (115-174 mg/dL) among women and 143 mg/dL (114-17 4mg/dL) among men; p=0.740. Individuals ≥50 years old, smokers, those with hypertension, obesity, diabetes, high waist circumference and elevated hs-C Reactive Protein, all had higher levels of non-HDL-c. A lower median was observed among those <30 years of age with elevated physical activity levels in their leisure time. Non-HDL-c between 130-159 mg/dL (OR=2.44; CI 95%=1.48-4.02; p<0.001) and ≥160 mg/dL (OR=3.28; CI 95%=1.72-6.23; p<0.001) was associated with greater risk of coexistent multiple risk factors for ASCVD, albeit LDL-c was not significant in the multivariate model.
Conclusions: Elevated non-HDL-c was associated with conglomeration of multiple risk factors for ASCVD. This suggests evaluation of non-HDL-c may be of better utility in primary care for early identification of subjects for high risk of ASCVD. Future research might focus on the influence of non-HDL-c in cardiovascular mortality.
En France, la maladie cardio-vasculaire est la première cause de mortalité, a fortiori chez le patient âgé. La relation entre dyslipidémie et risque cardio-vasculaire se discute chez les sujets âgés de plus de 80 ans (spécificité gériatrique ?). Pour le patient âgé, polypathologique, la lutte contre les facteurs de risque cardio-vasculaire garde-t-elle son intérêt ? Cette thèse a permis la description détaillée de 80 patients de plus de 80 ans traités par hypolipémiants (majorité de statines) chez une patientèle de 9 médecins généralistes d'un secteur semi-rural limité. Nous essayons de clarifier l'intérêt de traiter des patients en prévention secondaire. Nous constatons la réalité du traitement en prévention primaire lors de l'existence d'un haut risque cardio-vasculaire. L'étude montre l'intérêt de mieux définir l'espérance de vie du patient. Le lien visite à domicile et polymédication est un bon critère d exclusion au traitement. Un entretien avec chaque généraliste a permis de montrer les difficultés et les motivations de prescription du médecin traitant.
Because cardiovascular diseases are the leading cause of death in the world, providing clinicians with reliable and straightforward imaging techniques to identify "vulnerable" patients from the general population appears like the Holy Grail of the cardiovascular field. Atherosclerosis, identified as the underlying condition for most acute cardiovascular events, is characterized by the constitution of a lipidrich atheroma plaque, driven both by excess cholesterol and inflammation, which eventual rupture triggers clotting into the blood flow. It involves a wealth of cellular and molecular actors, which are so many potential markers for molecular imaging, aiming at deciphering how to warn clinicians about the possible occurrence of myocardial infarction or stroke. Here, human antibodies (HuAbs) selected by phage-display for their recognition of over-expressed biomarkers of the pathology are proposed as targeting ligands. They were further engineered for site-specific grafting, either by introducing Cysteine or Sortase recognition tags, and used to target contrast agents for MRI, fluorescence, or PET imaging. In vitro and ex vivo validation studies were carried out on atheroma sections of animal models. In vivo studies in the ApoE-/- mouse model were realized with the anti-platelet TEG4 HuAb using MRI, which provided insights on the biological relevance and feasibility to detect platelets-rich, high-risk atheroma plaques. The development of contrast agents useful in multi-modality imaging, and multi-functionalized with HuAbs is underway. It should serve as an accurate molecular imaging method for atherosclerosis, further more easily translated into the clinical arena.
The modes of action and clinical implications of several of the newest classes of antidiabetic drugs used as monotherapy and as add-on therapy have been extensively reviewed in recent publications.1 2 Sodium-glucose cotransporter 2 (SGLT-2) inhibitors (eg, empagliflozin) belong to one such novel class and act via interference with proximal renal tubular reabsorption of glucose; about 90% of such reabsorption depends on this cotransporter. They therefore reduce blood glucose concentrations, promote weight reduction and lower blood pressure through glycosuria and osmotic diuresis. Moreover, since their activity is independent of insulin, they are efficacious even in the presence of pancreatic beta cell failure, which is in marked contrast to many other antidiabetic drugs. Furthermore, polyuria and polydipsia are uncommon. Gliptins (eg, saxagliptin) form another new class of oral antidiabetic agents that reduce glucagon secretion but promote insulin release by interfering with the degradation of incretins (intestinal hormones produced in response to ingested meals), and are generally well tolerated. Glucagon-like-peptide 1 (GLP1) receptor agonists (eg, exenatide) are incretin mimetics that constitute yet another class of new antidiabetics and, together with SGLT2 inhibitors, are the only antidiabetic drugs that have a favourable weight loss effect. Subcutaneous administration and gastrointestinal side effects are distinct disadvantages. In contrast to many other antidiabetic agents, treatments with drugs in these three classes and metformin confer a lower risk of hypoglycaemia.
Type 2 diabetes mellitus (T2DM) is more than just a disorder of glucose metabolism. Patients with T2DM die prematurely because of cardiovascular disease and renal failure. The goal of drug treatment of diabetes should therefore be more than just controlling the blood glucose. In the aftermath of the rosiglitazone controversy,3 …
General approach to preventing recurrent stroke and other serious vascular eventsPrognosis and prediction of future vascular eventsPharmacological blood pressure reductionPharmacological cholesterol reductionAntiplatelet drugsAnticoagulantsLifestyle modificationDietary supplements: B vitamins and antioxidantsManagement of diabetes mellitus and glucose intoleranceTreatment of specific underlying causesEndarterectomy for symptomatic carotid stenosisEndarterectomy for asymptomatic carotid stenosisCarotid angioplasty and stentingCarotid endarterectomy before, during or after coronary artery surgery?Extra-to-intracranial bypass surgerySurgery and angioplasty for vertebrobasilar ischaemiaOther surgical proceduresPutting secondary prevention into practice
Background/aims:
Cardiovascular disease (CVD) is the leading cause of death in dialysis patients. Little is known about the relationship between very low-density lipoprotein cholesterol (VLDL-C) and cardiovascular mortality in these patients.
Methods:
A total of 1324 incident patients who began continuous ambulatory peritoneal dialysis (CAPD) therapy at our hospital between January 1, 2005, and September 30, 2014, with baseline serum VLDL-C values were investigated. The associations of the VLDL-C levels with all-cause and cardiovascular mortality were assessed.
Results:
The mean age of the cohort was 50.2 ± 14.8 years, and the mean VLDL-C level was 33.6 ± 18.0 mg/dl. One hundred sixty-five (12.5%) patients died during the study period. Multivariable models revealed that the high VLDL-C group was associated with significantly higher all-cause (HR, 2.08, 95% CI, 1.13 to 3.29, P = 0.002) and cardiovascular mortality (HR, 1.92, 95% CI, 1.18 to 4.29, P = 0.013) compared with the low VLDL-C group even after adjusting for various covariates. Using the VLDL-C level as a continuous variable, the hazard ratios (HRs) of all-cause and cardiovascular mortality associated with a 10-mg/dl increase in VLDL-C level were 1.12 (95% CI, 1.02 to 1.26, P = 0.025) and 1.11 (95% CI, 1.02 to 1.22, P = 0.029), respectively. VLDL-C was associated more strongly to all-cause (e.g., Akaike information criteria of 1990.205 vs. 1994.451) and cardiovascular (e.g., Akaike information criteria of 984.146 vs. 985.634) mortality than triglyceride (TG) levels.
Conclusions:
An elevated VLDL-C level is an independent risk factor for all-cause and cardiovascular mortality in peritoneal dialysis (PD) patients.
Background
Older patients are prone to multimorbidity and polypharmacy, with an inherent risk of adverse events and drug interactions. To the best of our knowledge, available information on the appropriateness of lipid-lowering treatment is extremely limited. AimThe aim of the present study was to quantify and characterize lipid-lowering drug use in a population of complex in-hospital older patients. Methods
We analyzed data from 87 units of internal medicine or geriatric medicine in the REPOSI (Registro Politerapie della Società Italiana di Medicina Interna) study, with reference to the 2010 and 2012 patient cohorts. Lipid-lowering drug use was closely correlated with the clinical profiles, including multimorbidity markers and polypharmacy. Results2171 patients aged >65 years were enrolled (1057 males, 1114 females, mean age 78.6 years). The patients treated with lipid-lowering drugs amounted to 508 subjects (23.4%), with no gender difference. Atorvastatin (39.3%) and simvastatin (34.0%) were the most widely used statin drugs. Likelihood of treatment was associated with polypharmacy (≥5 drugs) and with higher Cumulative Illness Rating Scale (CIRS) score. At logistic regression analysis, the presence of coronary heart disease, peripheral vascular disease, and hypertension were significantly correlated with lipid-lowering drug use, whereas age showed an inverse correlation. Diabetes was not associated with drug treatment. Conclusions
In this in-hospital cohort, the use of lipid-lowering agents was mainly driven by patients’ clinical history, most notably the presence of clinically overt manifestations of atherosclerosis. Increasing age seems to be associated with lower prescription rates. This might be indicative of cautious behavior towards a potentially toxic treatment regimen.
Atrial fibrillation is the commonest cause of cardioembolic stroke, which
accounts for approximately 20% of ischaemic stroke. Cardioembolic
stroke has a higher risk of morbidity and mortality, resulting in greater
disability, longer hospital stays, costlier rehabilitation, and complications
that greatly affect the quality of life. Appropriate treatment with anticoagulants,
in conjunction with the management of hypertension, diabetes
and cholesterol, will reduce the risk of stroke. Complications of stroke
include dysphagia, post-stroke seizures, dry mouth, depression and
post-stroke pain. The treatment strategies involve medication, however
this leads to polypharmacy which has can increases the risk of adverse
drug reactions. Also, some patients are averse to taking multiple medications.
Die Behandlung von Patienten mit peripherer arterieller Verschlusskrankheit (PAVK) der unteren Extremitäten ist eine komplexe Aufgabe, die nur durch interdisziplinäre Bemühungen zu bewerkstelligen ist. Neben der endovaskulären und chirurgischen arteriellen Revaskularisation kommt der medikamentösen Behandlung eine hohe Bedeutung zu. Die Ziele der medikamentösen Behandlung liegen einerseits in der Behandlung der Symptome der PAVK und andererseits in der Verhinderung der Progression der systemischen Atherothrombose. Der vorliegende Beitrag fasst den aktuellen Stand hinsichtlich der sekundärpräventiven medikamentösen Behandlung von PAVK-Patienten zusammen und gibt einen Einblick in die Möglichkeiten des Gehtrainings zur Behandlung von Patienten mit Claudicatio intermittens.
The BJC is owned by Cancer Research UK, a charity dedicated to understanding the causes, prevention and treatment of cancer and to making sure that the best new treatments reach patients in the clinic as quickly as possible. The journal reflects these aims. It was founded more than fifty years ago and, from the start, its far-sighted mission was to encourage communication of the very best cancer research from laboratories and clinics in all countries. The breadth of its coverage, its editorial independence and it consistent high standards, have made BJC one of the world's premier general cancer journals. Its increasing popularity is reflected by a steadily rising impact factor.
This chapter reviews the synergistic effects of aging and diabetes on the vasculature, and the prevention and management of major risk factors for Coronary Heart Disease (CHD) in older people with diabetes. Prevention of CHD is most important as individuals with diabetes continue to have worse prognosis following cardiac events. Prevention and management of cardiovascular risk factors should include both lifestyle modification and pharmacological interventions. Aspirin therapy should be considered selectively in older patients with diabetes and high cardiovascular risk but after assessment of their bleeding risk. Dyslipidemia is associated with obesity and other features that define metabolic syndrome and it is possible that much of the CVD that is associated with metabolic syndrome may be explained by the presence of insulin resistance. In summary, the risk reduction with hypertension control in patients with diabetes is substantially greater than that in people without diabetes who have similar blood pressure levels.
Lipids disorder is the principal cause of atherosclerosis and may present with several forms, according to blood lipoprotein prevalence. One of the most common forms is combined dyslipidemia, characterized by high levels of triglycerides and low level of high-density lipoprotein. Single lipid-lowering drugs may have very selective effect on lipoproteins; hence, the need to use multiple therapy against dyslipidemia. However, the risk of toxicity is a concerning issue. In this review, the effect and safety of an approved combination therapy with simvastatin plus fenofibrate are described, with an analysis of pros and cons resulting from randomized multicenter trials, meta-analyses, animal models, and case reports as well.
Cerebrovascular disease typically manifests with stroke, cognitive impairment, or both. Vascular cognitive impairment refers to all forms of cognitive disorder associated with cerebrovascular disease, regardless of the specific mechanisms involved. It encompasses the full range of cognitive deficits from mild cognitive impairment to dementia. In principle, any of the multiple causes of clinical stroke can cause vascular cognitive impairment. Recent work further highlights a role of microinfarcts, microhemorrhages, strategic white matter tracts, loss of microstructural tissue integrity, and secondary neurodegeneration. Vascular brain injury results in loss of structural and functional connectivity and, hence, compromise of functional networks within the brain. Vascular cognitive impairment is common both after stroke and in stroke-free individuals presenting to dementia clinics, and vascular pathology frequently coexists with neurodegenerative pathology, resulting in mixed forms of mild cognitive impairment or dementia. Vascular dementia is now recognized as the second most common form of dementia after Alzheimer's disease, and there is increasing awareness that targeting vascular risk may help to prevent dementia, even of the Alzheimer type. Recent advances in neuroimaging, neuropathology, epidemiology, and genetics have led to a deeper understanding of how vascular disease affects cognition. These new findings provide an opportunity for the present reappraisal of vascular cognitive impairment. We further briefly address current therapeutic concepts.
Background
One of the risk factors for the development of coronary heart disease is high low-density lipoprotein (LDL) cholesterol levels. National Cholesterol Education Program ATP III guidelines suggest drug therapy to be considered at LDL-cholesterol levels >130 mg/dl. This makes accurate reporting of LDL cholesterol crucial in the management of Coronary heart disease. Estimation of LDL cholesterol by direct LDL method is accurate, but it is expensive. Hence, We compared Friedewald's calculated LDL values with direct LDL values.
Aim
To evaluate the correlation of Friedewalds calculated LDL with direct LDL method.
Materials and Methods
We compared LDL cholesterol measured by Friedewald's formula with direct LDL method in 248 samples between the age group of 20–70 years. Paired t-test was used to test the difference in LDL concentration obtained by a direct method and Friedewald's formula. The level of significance was taken as P < 0.05. Pearsons correlation formula was used to test the correlation between direct LDL values with Friedewald's formula.
Results
There was no significant difference between the direct LDL values when compared to calculated LDL by Friedewalds formula (P = 0.140). Pearson correlation showed there exists good correlation between direct LDL versus Friedewalds formula (correlation coefficient = 0.98). The correlation between direct LDL versus Friedewalds calculated LDL was best at triglycerides values between 101 and 200 mg/dl.
Conclusion
This study indicates calculated LDL by Friedewalds equation can be used instead of direct LDL in patients who cannot afford direct LDL method.
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