Military personnel present a mixed picture for cardiovascular risk (Bergman et al. 2014b); they generally benefit from a higher level of physical activity during service (although this varies with trade or occupational group), but are known to have a higher prevalence of smoking than their civilian peers (Brown 2010) although the difference has changed over time (Lewthwaite and Graham 1992). Paradoxically, military personnel and veterans have been shown to be more likely to exhibit unfavourable health behaviours than those who have never served (Hoerster et al. 2012). Diet during service is likely to have been relatively high in energy, in accordance with the needs and choices of a predominantly young, physically active population (Andersen et al. 1995, Edholm et al. 1970), especially for earlier generations of veterans, but diet post-service may be influenced more by family and societal norms. In-service nutrition, and research on the prevalence of
obesity in serving personnel and veterans, are discussed in more detail in Appendix 3, and the use of tobacco in the Armed Forces is explored in Appendix 4. Achieving health behaviour change in young people presents challenges (Gibbons and Gerrard 1995), especially in military personnel who are known to exhibit higher levels of risk-taking behaviour (Verrall 2011). Nonetheless, physical exercise and obesity avoidance are in keeping with the military ethos (Crowdy 1987). Risk factors such as type 2 diabetes or severe hypertension are unlikely to affect serving personnel to any large extent, as they are likely to lead to medical discharge, but they will contribute to risk in the veteran population, as will cases developing after leaving service. No studies have been identified which examine their prevalence in UK veterans.
A review of cardiovascular risk factors in US military personnel examined known risk factors in relation to the serving population, and cited a number of studies reporting an association between war-related stressors and acute cardiac events, whilst noting significant gaps in the literature on cardiovascular risk assessment in military personnel (McGraw et al. 2007). As early as 1990, Blanchard predicted a “wave of cardiovascular and other diseases” as the Vietnam-era cohort ages (Blanchard 1990), predominantly in relation to the well-documented association between post-traumatic stress disorder and cardiovascular disease (Bedi and Arora 2007, Coughlin 2011). Long-term follow-up has indeed indicated higher cardiovascular mortality among Vietnam veterans with PTSD, HR 1.7, p=0.034 (Boscarino 2006), although perhaps at a lower level than was anticipated by
Scottish Veterans Health Study Chapter 4 – Cardiovascular Disease 89
Blanchard (Blanchard 1990). Traumatic lower limb amputation is a risk factor for IHD; in a major study of US veterans of World War 2 followed up for 31 years, there was a relative risk for cardiovascular mortality of 1.58, p<0.001 for unilateral above-knee amputation and 4.00, p<0.01, for bilateral above-knee amputation, compared with controls with disfigurement only (Hrubec and Ryder 1980). A review by Naschitz and Lenger found the increased risk to be consistent across a number of studies, and in addition an increased risk of abdominal aortic aneurysm has been demonstrated. Both haemodynamic changes and altered lifestyle have been postulated as explanatory factors (Naschitz and Lenger 2008).
Other than the studies that have been published on cardiovascular outcomes in military veterans who have taken part in specific conflicts or who have been exposed to
hazardous agents (Boscarino 2008, Kang and Bullman 2009) or undergone amputation (Hrubec and Ryder 1980), there is a paucity of studies examining long-term cardiovascular outcomes in a general population of veterans to assess the net effect of all aspects of military service. In one of the few such studies identified, Brown reported an age- adjusted prevalence of self-declared CHD of 6.5% in US male veterans compared with 5.5% in male non-veterans, with comparative rates for females of 4.5% and 3.5%
respectively, using data from the CDC Behavioral Risk Factors Surveillance Study (BRFSS) (Brown 2010). Hoerster reported a prevalence of 20.9% for all cardiovascular disease in male veterans, using the same dataset, compared with 6.4% for male non-veterans (Hoerster et al. 2012). A study of long-term mortality in Australian veterans of the 1951 Korean War found increased mortality from IHD in those who had served in the Army and Navy although not in former Air Force personnel (Harrex et al. 2003). This paucity of research is surprising as UK studies in the early 1980s highlighted increased
cardiovascular risk amongst serving military personnel (Lynch and Oelman 1981, Lynch 1985), and it might have been expected that follow-up studies would be performed to investigate whether they remained at risk in later life. The Scottish Veterans Health Study therefore provided an opportunity to examine long-term cardiovascular outcomes in veterans with a wide range of military experience.
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4.4.1
Smoking and Cardiovascular Disease
The earliest suggestion of an association between smoking and coronary artery disease appears to have been made in 1934 when an increased incidence of coronary disease was noted in Europe in the years following the First World War, coinciding with an increase in smoking rates (Lakier 1992). The first major epidemiological study was published in 1958 and examined death rates in a cohort of 187,783 men followed for 44 months; a mortality ratio of 1.68 was found for all-cause deaths in cigarette smokers compared with non- smokers. There was a strong dose-response relationship with a ratio of 1.34 for those smoking less than half a pack80
per day, rising to 2.23 in men smoking two or more packs per day, compared with non-smokers. A quarter of the excess deaths were due to cancer and half the excess to coronary artery disease (Hammond and Horn 1958).
Evidence for an association between smoking and CHD continued to accrue and, by 1983, a report by the US Surgeon General presented the results of five major cohort studies, including the Framingham study81
, which showed a risk ratio for incidence of CHD ranging from 2.2 to 3.3 for smokers using more than one pack per day compared with light smokers, pipe/cigar smokers and non-smokers. Epidemiological studies covering over 20 million person-years of exposure in a variety of national settings were reviewed and showed a high degree of consistency, with smokers overall experiencing a 70% higher risk of CHD mortality than non-smokers. The excess risk for CHD was independent of other risk factors (Shopland 1983).
In the UK, a review of 20-year mortality in the British male physicians’ study demonstrated a 37% higher IHD mortality in all smokers (including pipe and cigar
smokers, who may be at lower risk) than in non-smokers (Doll and Peto 1976). This high- quality study, using a large sample (34,000) with almost complete follow-up, and
diagnoses confirmed from death certificates, also demonstrated a highly significant gradient in IHD mortality (p<0.001) from non-smokers through light smokers to heavy
80
In the 1950s the standard pack size was 10 cigarettes, as opposed to the modern pack which normally contains 20 cigarettes, although the tar and nicotine content was higher. Ten cigarettes in the 1950s had approximately the same nicotine content as 25 modern cigarettes and the same tar content as 34 modern cigarettes [nicotine and tar data from International Smoking Statistics http://www.pnlee.co.uk/ISS.htm accessed 18 December 2012].
81
The US Framingham study was set up in 1948 under the direction of the then National Heart Institute to monitor the cardiovascular health of 5,209 adults who were in good health at baseline. It remains in progress and now encompasses the children and grandchildren of the original cohort.
Scottish Veterans Health Study Chapter 4 – Cardiovascular Disease 91
smokers, with an annual mortality rate of 413 per 100,000 in non-smokers, 608 per 100,000 in people smoking less that 15 cigarettes per day and 792 in those smoking 25 or more per day. The reduction in IHD mortality after stopping smoking was variable but the greatest benefit was seen in the youngest ex-smokers. After 15 or more years as an ex- smoker, the ratio of the number of observed deaths in ex-smokers to the number which would have been expected in non-smokers was 1.3 in men aged 30-64, falling from 3.5 at baseline in men aged 30-54 and 1.7 in men aged 55-64. The small number of study subjects who stopped smoking before the age of 30, after smoking for an average of 7 years, showed a similar all-cause mortality rate to non-smokers. The authors
categorised the level of evidence for attributability of the observed excess IHD mortality as “2A82
– Probably wholly or partly attributable to smoking”, the uncertainty arising largely in respect of the older age groups. A follow-up study at the 50-year point
demonstrated a gain in life expectancy of 10 years after stopping smoking at age 30 years, reducing with age at cessation although even at age 60 years there was a gain of 3 years of life (Doll et al. 2004). Although stopping smoking reduces cardiovascular risk, the benefit increasing with time (Ockene and Miller 1997), levels of CRP, a marker of inflammation known to be related to cardiovascular risk, remain strongly correlated to pack-years smoked even in old age, irrespective of time since smoking cessation (Tracy et al. 1997).
4.4.1.1 Environmental Tobacco Smoke
The first reports of the adverse health effects of environmental tobacco smoke (ETS) exposure were in relation to lung cancer, and the association between ETS and IHD was not recognised until much later. One of the earliest studies to identify an association followed a cohort of 91,909 individuals recorded in a private census in Maryland, USA for 12 years from 1963. The study demonstrated a relative risk for deaths from
arteriosclerotic heart disease in non-smoking men with household exposure to ETS of 1.31, 95% CI 1.1-1.6, and for women, RR = 1.24, 95% CI 1.1-1.4. Men aged 25-44 exposed to high levels of ETS were found to be at greatest risk (RR 5.70, 95% CI 1.5-21.4) (Helsing
82
Categorisation by levels of evidence is a fundamental tenet of evidence-based medicine. Many authors and organisations have developed systems to categorise levels of evidence; that used by Doll and Peto is described at Table XII of their paper. Burns, P. B., Rohrich, R. J. and Chung, K. C. (2011) 'The levels of evidence and their role in evidence-based medicine', Plastic and Reconstructive Surgery, 128(1), 305. Doll, R. and Peto, R. (1976) 'Mortality in relation to smoking: 20 years' observations on male British doctors',
Scottish Veterans Health Study Chapter 4 – Cardiovascular Disease 92
et al. 1988). A Scottish study followed up 16,171 healthy middle-aged adults to 1982 after establishing their smoking pattern at baseline in 1972 and noted that myocardial infarction was more common in both men and women exposed to ETS, although the study had a number of methodological limitations including self-reporting of ETS
exposure, small numbers of incident disease and deaths, and the absence of any tests of statistical significance from the data analysis (Gillis et al. 1984). The first UK cohort study to use salivary cotinine as an objective measure of ETS exposure was the British Regional Heart Study; this demonstrated an 86% fall in cotinine levels in non-smokers over 20 years, from 1978-1980 to 1998-2000. The percentage of men with a cotinine level
previously found to be associated with low cardiovascular risk rose from 27% to 83% over the same period (Jefferis et al. 2009). A study of Norwegian Army conscripts showed that although the prevalence of smoking was 51%, 91% were exposed to ETS in dormitories (Schei and Sogaard 1994), suggesting that even non-smoking military personnel may have experienced substantial exposure to tobacco from this source. There is evidence from the EPIC83
study that exposure to ETS is more harmful to former smokers than to never- smokers (Vineis et al. 2005), which may be especially relevant to military (and, by
extension, veteran) populations where a high percentage are former smokers (Figure 8-4) (Lodge 1991).
A meta-analysis of 19 studies examining the risk of IHD in never-smoking spouses of smokers demonstrated a relative risk of 1.30, 95% CI 1.22-1.38, p<0.001, and noted that earlier, smaller meta-analyses had found similar results (Law et al. 1997). The excess risk associated with inhaling ETS was approximately half the excess risk which would result from smoking 20 cigarettes per day although the exposure84
equates to only about 1% of that experienced by a smoker. In order to try and explain this disproportionate risk, the authors assessed possible confounders and sources of bias. They dismissed publication bias as requiring an implausibly large number of studies, and assessed the role of diet, body mass index, social class, blood pressure and serum cholesterol to be insufficient to explain the findings. They examined dose-response relationships in five major studies and concluded that although the risk of IHD increased with number of cigarettes smoked, the relationship was non-linear and extrapolation back to zero dose did not yield a RR of
83
European Prospective Investigation into Cancer and Nutrition. 84
Scottish Veterans Health Study Chapter 4 – Cardiovascular Disease 93
1.0; the weighted average risk of smoking one cigarette per day was 1.38, 95% CI 1.18- 1.64, p<0.001, increasing to a RR of 1.78 at 20 cigarettes per day. The authors
hypothesised that platelet aggregation would explain IHD not only in smokers but also in those inhaling ETS, on the basis of experimental studies on platelet aggregation
demonstrating an immediate increase in risk of IHD of 43% for smoking and 34% for ETS, close to the observed excess risk (Law et al. 1997). This was disputed by Smith and co- workers (Smith et al. 2000) who considered that it was inconsistent with the biochemistry and physiology of platelets. Ahijeviych and Wewers have summarised the evidence and concluded that the mechanism is multifactorial; increased platelet aggregation plays a part, as does reduced oxygen transport due to elevated carbon monoxide levels. Coronary artery endothelial dysfunction has also been shown to occur following ETS inhalation and is especially important as it is associated with an increased risk of atherosclerosis (Ahijevych and Wewers 2003). Furthermore, ETS is predominantly
composed of sidestream tobacco smoke, which carries a higher content of volatile agents than does the mainstream smoke inhaled by the smoker (Brunnemann et al. 1977). Studies of biomarkers have confirmed the disproportionately higher cardiovascular risk which arises from the inhalation of even low concentrations of ETS, compared with actively smoking (Lu et al. 2014).