Philip C Hannaford

Hypertensive diseases of pregnancy and risk of hypertension and stroke in later life: results from cohort study

Abstract Objective: To examine the association between hypertensive diseases of pregnancy (gestational hypertension and pre-eclampsia) and the development of circulatory diseases in later life. Design: Cohort study of women who had pre-eclampsia during their first singleton pregnancy. Two comparison groups were matched for age and year of delivery, one with gestational hypertension and one with no history of raised blood pressure. Setting: Maternity services in the Grampian region of Scotland. Participants: Women selected from the Aberdeen maternity and neonatal databank who were resident in Aberdeen and who delivered a first, live singleton from 1951 to 1970. Main outcome measures: Current vital and cardiovascular health status ascertained through postal questionnaire survey, clinical examination, linkage to hospital discharge, and mortality data. Results: There were significant positive associations between pre-eclampsia/eclampsia or gestational hypertension and later hypertension in all measures. The adjusted relative risks varied from 1.13-3.72 for gestational hypertension and 1.40-3.98 for pre-eclampsia or eclampsia. The adjusted incident rate ratio for death from stroke for the pre-eclampsia/eclampsia group was 3.59 (95% confidence interval 1.04 to 12.4). Conclusions: Hypertensive diseases of pregnancy seem to be associated in later life with diseases related to hypertension. If greater awareness of this association leads to earlier diagnosis and improved management, there may be scope for reducing a proportion of the morbidity and mortality from such diseases. What is already known on this topic Much is known about the effect of cardiovascular risks factors that are shared by men and women, but less on those specific to women Retrospective studies, based on patient recall, suggest that hypertension in pregnancy may be associated with increased risk of cardiovascular diseases in later life What this study adds Prospective recording of blood pressure and proteinuria shows that women who experienced raised blood pressure in pregnancy have a long term risk of hypertension Women who experience raise blood pressure in pregnancy have an increased risk of stroke and, to a lesser extent, an increased risk of ischaemic heart disease Long term cardiovascular risks are greater for women who had pre-eclampsia than those who experienced gestational hypertension (hypertension without proteinuria)

Maternal obesity during pregnancy and premature mortality from cardiovascular event in adult offspring: follow-up of 1 323 275 person years

Objectives To determine whether maternal obesity during pregnancy is associated with increased mortality from cardiovascular events in adult offspring. Design Record linkage cohort analysis. Setting Birth records from the Aberdeen Maternity and Neonatal databank linked to the General Register of Deaths, Scotland, and the Scottish Morbidity Record systems. Population 37 709 people with birth records from 1950 to present day. Main outcome measures Death and hospital admissions for cardiovascular events up to 1 January 2012 in offspring aged 34-61. Maternal body mass index (BMI) was calculated from height and weight measured at the first antenatal visit. The effect of maternal obesity on outcomes in offspring was tested with time to event analysis with Cox proportional hazard regression to compare outcomes in offspring of mothers in underweight, overweight, or obese categories of BMI compared with offspring of women with normal BMI. Results All cause mortality was increased in offspring of obese mothers (BMI >30) compared with mothers with normal BMI after adjustment for maternal age at delivery, socioeconomic status, sex of offspring, current age, birth weight, gestation at delivery, and gestation at measurement of BMI (hazard ratio 1.35, 95% confidence interval 1.17 to 1.55). In adjusted models, offspring of obese mothers also had an increased risk of hospital admission for a cardiovascular event (1.29, 1.06 to 1.57) compared with offspring of mothers with normal BMI. The offspring of overweight mothers also had a higher risk of adverse outcomes. Conclusions Maternal obesity is associated with an increased risk of premature death in adult offspring. As one in five women in the United Kingdom is obese at antenatal booking, strategies to optimise weight before pregnancy are urgently required.

Mortality among contraceptive pill users: cohort evidence from Royal College of General Practitioners’ Oral Contraception Study

Objective To see if the mortality risk among women who have used oral contraceptives differs from that of never users. Design Prospective cohort study started in 1968 with mortality data supplied by participating general practitioners, National Health Service central registries, or both. Setting 1400 general practices throughout the United Kingdom. Participants 46 112 women observed for up to 39 years, resulting in 378 006 woman years of observation among never users of oral contraception and 819 175 among ever users. Main outcome measures Directly standardised adjusted relative risks between never and ever users for all cause and cause specific mortality. Results 1747 deaths occurred in never users of oral contraception and 2864 in ever users. Compared with never users, ever users of oral contraception had a significantly lower rate of death from any cause (adjusted relative risk 0.88, 95% confidence interval 0.82 to 0.93). They also had significantly lower rates of death from all cancers; large bowel/rectum, uterine body, and ovarian cancer; main gynaecological cancers combined; all circulatory disease; ischaemic heart disease; and all other diseases. They had higher rates of violent deaths. No association between overall mortality and duration of oral contraceptive use was observed, although some disease specific relations were apparent. An increased relative risk of death from any cause between ever users and never users was observed in women aged under 45 years who had stopped using oral contraceptives 5-9 years previously but not in those with more distant use. The estimated absolute reduction in all cause mortality among ever users of oral contraception was 52 per 100 000 woman years. Conclusion Oral contraception was not associated with an increased long term risk of death in this large UK cohort; indeed, a net benefit was apparent. The balance of risks and benefits, however, may vary globally, depending on patterns of oral contraception usage and background risk of disease.

The influence of oral contraceptives on the risk of multiple sclerosis

Objective To examine the risk of multiple sclerosis in users of combined oral contraceptives.

Size does matter

Journal of Family Planning and Reproductive Health Care 2003: 29(1) Introduction When designing an epidemiological study or clinical trial it is important to make it large enough to have a reasonable chance of detecting differences between groups that really exist. In other words, the study should have adequate statistical power. Unfortunately the scientific literature is cluttered with numerous small studies reporting negative results. Individually, each study can only make a modest contribution to clinical practice since it is impossible to know whether a negative result was due to a true lack of effect or limited ability to detect an effect. Absence of evidence is not the same as evidence of absence. In this paper we describe the concepts behind statistical power, including the pieces of information needed when determining the sample size of a study (i.e. how many individuals need to be selected from the study population).

Factors related to the onset and persistence of chronic back pain in the community: results from a general population follow-up study

Introduction. We compared the prevalence of chronic back pain (CBP) at two points 4 years apart and examined socio-demographic, health, and pain-related factors associated with its onset and persistence. Method. A random population sample of 2,184 adults was surveyed in 1996 and resurveyed in 2000. The questionnaire included chronic pain case definition questions (pain for 3 months or longer); the cause (1996) or site (2000) of any chronic pain; the Chronic Pain Grade questionnaire; the Level of Expressed Need (LEN) questionnaire; the SF-36 general health questionnaire; and demographic questions. Those with CBP in 1996 and 2000 had “persistent” CBP; those with CBP in 1996 but not 2000 had “recovered” CBP; those with CBP in 2000 but not 1996 had “new” CBP. Results. Corrected response rates were 82.3% (1996) and 83.0% (2000). The sample prevalence of CBP was 16% (1996) and 27% (2000). Factors in 1996 independently associated with “persistent” compared with “recovered” CBP were preexisting arthritis, high LEN, poor mental health, and not living alone. Factors independently predicting “new” CBP compared with no previous CBP were previous chronic pain elsewhere and poor physical health. “Persistent” CBP was associated with more severe pain, higher LEN, and poorer general health than “new” CBP. Discussion. CBP is a common and lasting problem, whose persistence and onset are predicted by clinical (especially pain) and help-seeking behavior factors, rather than socio-demographic. Prevention should focus on these factors.

Issues Related to Monitoring the Safety of Over-The-Counter (OTC) Medicines

Pharmaceutical advances over the past 50 years have benefited many people in terms of disease prevention and management. However, probably without exception, most pharmaceutical products can cause adverse consequences of varying severity and frequency.In the last 10 years, many medicines that were originally prescription only have now become available over the counter (OTC), either from pharmacies or other general retail outlets. The volume and value of OTC medicine sales have increased accordingly. These switches have been well regulated and based on clear criteria and evidence of safety. Benefits of the changes include increased convenience to patients, greater self-management of minor ailments and a reduction in government drug expenditure.However, there are important differences between medicines supplied OTC and on medical prescription. With OTC medicines there is generally less health-care professional input into the recommendation or ongoing monitoring of use. There is an absence of records per se, or linkage to other medication records elsewhere, and most countries allow direct-to-consumer advertising of the product. Taken together these differences can result in inappropriate expectations, demand and use of the OTC medicines, with limited opportunity for ongoing patient follow-up and monitoring of safety.Methodologies for pharmacy-based epidemiological studies of OTC medicines need to be developed. Studies should be large enough to detect associations that might exist, and to consider other explanations for associations such as chance, bias or confounding. There have already been some pilot studies with encouraging results with respect to follow-up rates. Outcome data however have usually been self-reported and the studies have lacked a suitable comparison group.Methodologies for pharmacy-based epidemiological studies of OTC medicines need to be developed. Studies should be large enough to detect associations that might exist, and to consider other explanations for associations such as chance, bias or confounding. There have already been some pilot studies with encouraging results with respect to follow-up rates. Outcome data however have usually been self-reported and the studies have lacked a suitable comparison group.While available OTC medicines are perceived to be generally safe, problems have occasionally arisen with some earlier switched products (e.g. terfenadine). There have also been concerns about some traditional herbal and homeopathic remedies such as St John’s wort. While such adverse events are rare, they emphasise the need for healthcare professionals and the public to understand and manage such risks. Many doctors are unaware of the range of OTC preparations available, and therefore do not consider them as a possible cause of presenting symptoms. Neither do they take them into account when making a new prescribing decision. The public need to be aware that OTC medicines should be treated with the same care as prescribed medicines, and that advice on recommended dose, contraindications and interactions should be adhered to.

Effect of multivitamin and multimineral supplements on morbidity from infections in older people (MAVIS trial): pragmatic, randomised, double blind, placebo controlled trial

Abstract Objective To examine whether supplementation with multivitamins and multiminerals influences self reported days of infection, use of health services, and quality of life in people aged 65 or over. Design Randomised, placebo controlled trial, with blinding of participants, outcome assessors, and investigators. Setting Communities associated with six general practices in Grampian, Scotland. Participants 910 men and women aged 65 or over who did not take vitamins or minerals. Interventions Daily multivitamin and multimineral supplementation or placebo for one year. Main outcome measures Primary outcomes were contacts with primary care for infections, self reported days of infection, and quality of life. Secondary outcomes included antibiotic prescriptions, hospital admissions, adverse events, and compliance. Results Supplementation did not significantly affect contacts with primary care and days of infection per person (incidence rate ratio 0.96, 95% confidence interval 0.78 to 1.19 and 1.07, 0.90 to 1.27). Quality of life was not affected by supplementation. No statistically significant findings were found for secondary outcomes or subgroups. Conclusion Routine multivitamin and multimineral supplementation of older people living at home does not affect self reported infection related morbidity. Trial registration ISRCTN: 66376460.

Effect of multivitamin and multimineral supplementation on cognitive function in men and women aged 65 years and over: A randomised controlled trial

BackgroundObservational studies have frequently reported an association between cognitive function and nutrition in later life but randomised trials of B vitamins and antioxidant supplements have mostly found no beneficial effect. We examined the effect of daily supplementation with 11 vitamins and 5 minerals on cognitive function in older adults to assess the possibility that this could help to prevent cognitive decline.MethodsThe study was carried out as part of a randomised double blind placebo controlled trial of micronutrient supplementation based in six primary care health centres in North East Scotland. 910 men and women aged 65 years and over living in the community were recruited and randomised: 456 to active treatment and 454 to placebo. The active treatment consisted of a single tablet containing eleven vitamins and five minerals in amounts ranging from 50–210 % of the UK Reference Nutrient Intake or matching placebo tablet taken daily for 12 months. Digit span forward and verbal fluency tests, which assess immediate memory and executive functioning respectively, were conducted at the start and end of the intervention period. Risk of micronutrient deficiency at baseline was assessed by a simple risk questionnaire.ResultsFor digit span forward there was no evidence of an effect of supplements in all participants or in sub-groups defined by age or risk of deficiency. For verbal fluency there was no evidence of a beneficial effect in the whole study population but there was weak evidence for a beneficial effect of supplementation in the two pre-specified subgroups: in those aged 75 years and over (n 290; mean difference between supplemented and placebo groups 2.8 (95% CI -0.6, 6.2) units) and in those at increased risk of micronutrient deficiency assessed by the risk questionnaire (n 260; mean difference between supplemented and placebo groups 2.5 (95% CI -1.0, 6.1) units).ConclusionThe results provide no evidence for a beneficial effect of daily multivitamin and multimineral supplements on these domains of cognitive function in community-living people over 65 years. However, the possibility of beneficial effects in older people and those at greater risk of nutritional deficiency deserves further attention.

Evidence for Age and Sex Differences in the Secondary Prevention of Stroke in Scottish Primary Care

Background and Purpose— Secondary preventive measures play an important role in the reduction of stroke, the third largest cause of death in Scotland. We investigated whether sex, age, or deprivation differences existed in the secondary prevention of stroke in primary care. Methods– A retrospective cross-sectional study using a computerized database with 61 practices (377 439 patients) to identify group differences in secondary preventive therapy between March 2003 and April 2004 for 10 076 patients with a diagnosis of any stroke. Results— Women with any stroke were more likely than men to be prescribed a thiazide (odds ratios [OR], 1.60; 95% confidence interval [CI], 1.46 to 1.75) but less likely to be prescribed an angiotensin-converting enzyme inhibitor (OR, 0.73; 95% CI, 0.67 to 0.81). Women with ischemic stroke were less likely to receive either an antiplatelet or warfarin (OR, 0.84; 95% CI, 0.75 to 0.94) or statin therapy (OR, 0.82; 95% CI, 0.74 to 0.90) than men. Women with atrial fibrillation received less warfarin (OR, 0.62; 95% CI, 0.48 to 0.81) but more antiplatelet therapy than men (OR, 1.30; 95% CI, 1.00 to 1.68). The oldest patients (older than 75 years) with ischemic stroke received more antiplatelet therapy than the youngest patients (younger than 65 years) (OR, 1.83; 95% CI, 1.64 to 2.06). No significant differences in secondary preventative treatment across deprivation groups were found. Conclusion— Important sex and age differences exist in the care of patients with stroke and suggest that women and the elderly need to be targeted for secondary prevention therapy.