Grace Lindsay

Regulation of plasma HDL cholesterol and subfraction distribution by genetic and environmental factors. Associations between the TaqI B RFLP in the CETP gene and smoking and obesity.

This study investigated in a healthy population (n = 220) the association of the TaqI B restriction fragment length polymorphism (RFLP) in the cholesteryl ester transfer protein (CETP) gene with plasma high-density lipoprotein (HDL) cholesterol concentration and subfraction distribution. A raised HDL cholesterol level was found in B2B2 homozygotes (B2 cutting site absent) and was associated specifically with a 45% increase in HDL2 compared with B1B1 homozygotes (B1B1, 77 +/- 39 mg/100 mL, mean +/- SD; B2B2, 112 +/- 59 mg/100 mL; P < 0.01). Total plasma, very-low-density lipoprotein, and HDL triglyceride levels did not differ among the genotype groups, nor did plasma apolipoprotein AI levels (B1B1, 1.45 +/- 0.35 mg/mL, mean +/- SD; B2B2, 1.56 +/- 0.33 mg/mL). Thus, the genetic variation appeared to be independent of metabolic factors that are known to regulate HDL levels. Plasma CETP exchange activity was unlikely to be the cause of the association, since it did not differ between genotype groups and was not correlated with HDL2 concentration. Multivariate analysis demonstrated that the TaqI B polymorphism had an effect on HDL cholesterol and HDL2 that was independent of age, sex, body mass index, oral contraceptive use, exercise, alcohol consumption, and plasma triglycerides. In smokers, the presence of the B2B2 genotype did not result in increased HDL cholesterol or HDL2, whereas in obese subjects, the difference between B1B1 and B2B2 individuals was diminished. We conclude that the TaqI B RFLP is associated with a quantitatively significant effect on plasma HDL2 levels that is independent of plasma triglycerides and interacts with lifestyle factors.

Effects of simvastatin on apoB metabolism and LDL subfraction distribution.

Seven moderately hypercholesterolemic subjects were studied before and after 10 weeks of simvastatin therapy (20 mg/day). Therapy reduced low density lipoprotein (LDL) cholesterol by 39% (p < 0.001), whereas high density lipoprotein and very low density lipoprotein (VLDL) cholesterol were unchanged. Apolipoprotein (apo) B-containing lipoproteins were divided into VLDL1 (Sf 60-400), VLDL2 (Sf 20-60), intermediate density lipoprotein (IDL) (Sf 12-20), and LDL (Sf 0-12), and metabolic changes were sought in dual-tracer VLDL1 and VLDL2 turnover studies. VLDL1 apoB pool size was unaltered by therapy, as were its rates of synthesis, catabolism, and delipidation to VLDL2. Similarly, the VLDL2 apoB pool size was unchanged, but its metabolic fate was altered. The IDL pool size fell significantly (27%, p < 0.01) due entirely to an increased fractional catabolism of the lipoprotein. In our subjects, the circulating mass of LDL apoB decreased (49%, p < 0.01) primarily due to a reduction in its synthesis. Before therapy, 30% of the apoB entering the delipidation cascade in these hyperlipidemic subjects was converted to LDL. On therapy the input remained the same, but direct catabolism from VLDL2 and IDL was increased (p < 0.05), and as a result only 16% eventually appeared in LDL. These kinetic changes were associated with a fall in particle cholesteryl ester content throughout the delipidation cascade. We also observed a link between LDL kinetics and its subfraction distribution. Simvastatin influences the metabolism of LDL, IDL, and VLDL2 but not VLDL1.

Assessment of changes in general health status using the short-form 36 questionnaire 1 year following coronary artery bypass grafting

OBJECTIVE The problem addressed in the study was to gain a greater understanding of the health benefits of coronary artery bypass grafting (CABG). The purpose of the study was to assess general health status, using the short-form (SF)-36 questionnaire, approximately 12 months following CABG, and to document any associations between pre-operative health status, level of social support, coronary artery disease (CAD) risk factors, CAD symptom severity and post-operative health status. METHODS The study was prospective and observational in design and included assessments at two time points, namely pre-operatively in a hospital outpatient department (1995-1996) and post-operatively at home (1996-1997). Two hundred and fourteen patients awaiting elective CABG were recruited a month before the expected date of operation. Pre-operative assessment included: (1), severity of symptoms; (2), CAD risk factors; (3), SF-36 questionnaire; and (4), social activities questionnaire. Post-operative assessment measured health status using the SF-36 instrument (mean, 16.4 months). Correlation and multiple linear regression analyses were used to identify factors associated with improved health status following CABG. RESULTS Two hundred and fourteen patients were assessed pre-operatively and underwent CABG. There was a 4.8% 30-day mortality rate, and 183 patients were followed for a mean of 16.4 months after CABG. SF-36 scores following CABG were improved across all of the eight domains (P<0.001). A higher social network score and higher pre-operative health status were associated with improved health status. Patients with lower health levels (SF-36 scores) prior to CABG were less likely to gain improvement in health (SF-36 scores) following CABG. Lower SF-36 scores following operation were influenced by the presence of diabetes mellitus, cigarette smoking, younger age, a high socio-economic deprivation category and higher alcohol intake. Many patients had uncorrected CAD risk factors at pre-operative assessment. CONCLUSIONS The SF-36 instrument was shown to be a useful and sensitive tool to assess differences and changes in the general health status of patients before and following CABG. High levels of social support were associated with improved health status post-operatively. Lower pre-operative general health status, the presence of diabetes mellitus and cigarette smoking were associated with poorer post-operative general health status.

Effects of ciprofibrate on LDL metabolism in man

This study examined the effects of ciprofibrate therapy (100 mg/day) on plasma lipids, lipoproteins and low density lipoprotein (LDL) kinetic heterogeneity in moderately hypercholesterolaemic subjects. The drug lowered plasma triglyceride and cholesterol by 41% and 17%, respectively. Very low density lipoprotein (VLDL) cholesterol fell by 38%, LDL cholesterol fell by 22%, while the content of the lipid in high density lipoprotein (HDL) increased by 11%. LDL structural and metabolic heterogeneity were assessed before and during therapy in eight subjects. Density gradient centrifugation was used to fractionate LDL into three species. LDL-I, the least dense, was not affected by therapy whereas LDL-II and LDL-III were decreased by 28% (P < 0.01) and 31% (N.S.). Baseline turnover studies revealed that LDL catabolism was subnormal and this was the cause of the raised cholesterol in these subjects. Ciprofibrate therapy increased the apoLDL fractional catabolic rate (FCR) by 19%, principally by inducing a 38% enhancement (P < 0.03) in apoLDL removal by the receptor pathway. ApoLDL kinetics exhibited metabolic heterogeneity both before and during drug therapy. Analysis of plasma decay curves for the LDL tracer and urinary excretion data indicated that the lipoprotein comprised two metabolically distinct species, one with an FCR of about 0.50 pools/day (Pool A), the other with an FCR of about 0.18 pools/day (Pool B). Drug therapy decreased synthesis of and hence reduced the plasma mass of apoLDL in the slow metabolised pool B. This perturbation in synthesis was linked to the change in plasma triglyceride concentration. The resultant reduced proportion of pool B vs. pool A material accounted for the observed promotion of LDL receptor-mediated clearance. Ciprofibrate, therefore, produced beneficial changes in the plasma levels of VLDL, LDL and HDL and in the metabolism of LDL.

Experience of cardiac rehabilitation after coronary artery surgery: effects on health and risk factors

OBJECTIVE Cardiac rehabilitation (CR) programs are provided to support the recovery process following acute myocardial infarction and coronary artery bypass grafting (CABG). Attendance varies. We related attendance following CABG to severity of cardiac symptoms, general health status (Short Form-36) and prevalence of modifiable coronary artery disease (CAD) risk factors. METHODS 209 patients due to undergo CABG were recruited and assessed preoperatively as well as at a mean of 16.4 months postoperatively. General health status was measured using the Short Form-36 questionnaire. Severity of cardiac symptoms was assessed on a visual analogue scale. Modifiable coronary artery disease risk factors (smoking, body mass index, hypertension and elevated cholesterol) and social deprivation index were noted. RESULTS There were ten early and three late deaths. Thirteen patients withdrew consent for investigation, therefore 183 were fully studied. Of these 65.0% completed a CR programme and 24.6% did not attend any programme; 10.4% partially completed (less than 50% of time) and were excluded from analysis. Nonattenders were more likely to be smokers (P=0.002), diabetic (P=0.028) and were more from socially deprived geographical areas (P=0.013), but the proportion of patients with BMI>25, BP>140/90 or cholesterol >5.0 mmol l(-1) were the same. There were no differences in age, preoperative NYHA score, number of grafts, angina recurrence (46 vs. 38%, P=0.35) or breathlessness (62 vs. 69%, P=0.40) between attenders and nonattenders. The severity scores of angina (2.7 vs. 3.2, P=0.286) and breathlessness (3.5 vs. 3.6; P=0.79) were no different. However, four of the eight health domains measured showed significantly better values for attenders than nonattenders; namely: general health (60 vs. 46%, P=0.001), physical function (64 vs. 51% P=0.01), role limitation physical (48 vs. 29%; P=0.02) and social function 74 vs. 62%, P=0.04). CONCLUSIONS This is the first report using SF 36 to evaluate benefits from attending CR. Higher general health scores (SF-36) were associated with attendance at CR although CAD risk factors and cardiac symptoms were not improved but this may be due to the long interval between assessments.

Patients' perspectives on statin therapy for treatment of hypercholesterolaemia: a qualitative study.

Background : Health Care Practitioners’ attempts to implement secondary prevention targets for coronary heart disease (CHD) may be restricted by low rates of persistence with statin therapy. There is a need to understand why some patients, despite having established CHD and elevated cholesterol, do not comply with their prescribed statin regimen. Aim : To explore patients’ perspectives on compliance with statin therapy. Setting: Primary care, West of Scotland. Methods: The research approach was qualitative. Thirty-three patients prescribed statin therapy and identified as having different patterns of compliance (poor moderate and good) were interviewed. The in-depth interviews were conducted on a one to one basis. Patients prescribed statin therapy for less than three months were excluded. Data were analysed thematically with the assistance of QSR Nudist. Findings: From analysis of the narrative data, two broad categories, i.e. ‘Patient–health care provider communication’ and ‘Health beliefs’ were identified. These categories encompassed six main themes: ‘Initiation of therapy’; ‘Subsequent feedback’; ‘Sources of misconceptions’; ‘Unconditional acceptance’; ‘Conditional acceptance’; ‘Deferment and Rejection’. Acceptance of and compliance with statin therapy appeared to be associated with the provision, interpretation and feedback of information during patient-practitioner consultations, and patients’ beliefs about personal health status, cholesterol, and recommended cholesterol-lowering strategies. Conclusions: Patients’ beliefs and understanding about cholesterol, and the role of cholesterol modifying strategies should be determined prior to the initiation of therapy and at appropriate intervals thereafter.

Are older patients’ cardiac rehabilitation needs being met?

Aims. The primary aim of this study was to examine the needs of older people in relation to cardiac rehabilitation and to determine if these were currently being met. A secondary aim was to compare illness representations, quality of life and anxiety and depression in groups with different levels of attendance at a cardiac rehabilitation programme. Background. Coronary heart disease accounted for over seven million cardiovascular deaths globally in 2001. Associated deaths increase with age and are highest in those older than 65. Effective cardiac rehabilitation can assist independent function and maintain health but programme uptake rates are low. We have, therefore, focussed specifically on the older patient to determine reasons for the low uptake. Design. Mixed methods. Methods. A purposive sample of 31 older men and women (≥65 years) completed three questionnaires to determine illness representations, quality of life and anxiety and depression. They then underwent a brief clinical assessment and participated in a face-to-face audio-taped interview. Results. Quantitative: Older adults, who did not attend a cardiac rehabilitation programme, had significantly poorer personal control and depression scores (p < 0·01) and lower quality of life scores than those who had attended. Few achieved recommended risk factor reduction targets. Qualitative: The three main themes identified as reflecting the views and experiences of and attendance at the cardiac rehabilitation programme were: ‘The sensible thing to do’, ‘Assessing the impact’ and ‘Nothing to gain’. Conclusions. Irrespective of level of attendance, cardiac rehabilitation programmes are not meeting the needs of many older people either in terms of risk factor reduction or programme uptake. More appropriate programmes are needed. Relevance to clinical practice. Cardiac rehabilitation nurses are ideally placed to identify the rehabilitation needs of older people. Identifying these from the older person’s perspective could help guide more appropriate intervention strategies.

Effects of Colestipol Alone and in Combination With Simvastatin on Apolipoprotein B Metabolism

The effects of colestipol therapy alone (20 g/d) or combined with simvastatin (20 mg/d) were examined in a group of eight male patients with primary moderate hypercholesterolemia (total cholesterol > or = 6.5 mmol/L [> or = 250 mg/dL]) who had undergone coronary artery bypass grafting more than 3 months previously. Colestipol therapy decreased total cholesterol by 14% (P < .001) and LDL cholesterol (LDL-C) by 23% (P < .001), while dual therapy decreased total cholesterol by 38% and LDL-C by 52% (both P < .001 versus baseline). No significant changes were observed in plasma triglyceride, VLDL cholesterol, or HDL cholesterol levels. VLDL subfraction turnovers were conducted at baseline and again on each regimen. ApoB kinetic parameters derived from a multicompartmental model suggested that colestipol therapy resulted in an expansion of the total VLDL apoB pool (36%, P < .05) that was largely due to a fall in the clearance rate of VLDL1 apoB (49%), while the LDL apoB pool decreased 23% as a result of diminished direct LDL input. The model used also revealed that addition of simvastatin to the resin therapy caused increases in the fractional transfer rates of VLDL2 to IDL and IDL to LDL together with a 37% increment in the LDL apoB fractional catabolic rate. Compared with baseline, combined therapy generated falls in both IDL (35%, P = .01) and LDL (37%, P < .04) apoB pools due to enhanced clearance of IDL (214%, P < .03) and reduced total input of LDL (39%, P < .003).

The Association Between Mild Cognitive Impairment and Self-care in Adults With Chronic Heart Failure: A Systematic Review and Narrative Synthesis.

Background:Emerging evidence suggests that heart failure (HF) patients who have mild cognitive impairment (MCI) may experience greater difficulty with self-care. Objective:This article reports a systematic review that addressed the objective “What is the evidence for an association between MCI and self-care, measured in 1 or more of the self-care domains related to HF, in adults who have a diagnosis of chronic HF?” Method:We adopted Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for the review and synthesis of quantitative research studies that formally measured both cognitive function and self-care in HF patients and sought to describe the relationship between these factors. Results:Ninety-one potentially relevant studies were located; 10 studies (2006–2014) were included. Because of heterogeneity in the retrieved studies, meta-analysis was not possible. Narrative synthesis found growing evidence regarding the association between MCI and adverse effects on self-care in HF. Nine studies reported significant positive associations between MCI and self-care in HF, either specifically in relation to medication adherence or more generic measures of self-care activity. One study reported a significant, negative correlation between cognitive function and self-care, suggesting that worse cognitive function was associated with better self-care; however, this is partially explained by a small sample size and mixed methodology. Conclusions:These findings have implications for clinical practice. It is known that HF patients have difficulty with self-care, and the influence of cognitive function needs to be considered when providing professional support. Further research to determine the feasibility and acceptability of cognitive assessment in routine clinical care is recommended.

Smoking after coronary artery bypass: high three-year mortality.

BACKGROUND Coronary artery bypass grafting (CABG) is carried out for prognosis and symptomatic relief. Smoking is associated with increased postoperative complications, although its precise influence on long-term survival is unclear. We examined the influence of smoking and other risk factors on survival and myocardial ischaemia seven years after CABG. METHODS 208 patients underwent elective CABG; 25 % were persistent smokers. 165 were alive at seven years. 128 (78 % of survivors) agreed to reexamination and 79 had thallium scans. RESULTS Angina and dyspnoea were reported by 52 % and 69 %, respectively, of survivors; these were associated with smoking ( P = 0.029 and 0.0 009) but with no other risk factors. Smokers had higher stress thallium scores ( P = 0.057) and ischaemia scores (10.6 +/- 6.5 vs. 6.8 +/- 6.0; P = 0.036); ejection fractions were equivalent. Obesity was prevalent and worsened in men. 33 patients (17 %) died during follow-up. Initially there was no survival difference between smokers and nonsmokers but as early as three years postoperation smoking was associated with an increased mortality ( P = 0.011; log-rank test). CONCLUSIONS Patients experienced almost universal improvement with the operation. However, persistent smoking completely removed the prognostic benefits of CABG by accelerating late mortality which was higher than previously reported. Higher indices of ischaemia in smokers were suggested by symptoms and confirmed by perfusion scans.