Thursday, June 16, 2011

Global Strategies in the Prevention of Cardiovascular Disease: Asia Pacific Perspectives

Global Strategies in the Prevention of Cardiovascular Disease: Asia Pacific Perspectives
In May 2009, the Non-Communicable Disease (NCD) Alliance launched a successful campaign for a United Nations High-Level Summit on Non-Communicable Diseases (NCDs). This will take place on 19-20 September 2011 in New York.[i] The convening of this NCD Summit will highlight the growing pandemic of preventable yet escalating risk factors, which predisposes more and more citizens around the world to premature death and morbidity.
One of its major premises is to “prioritize measures to reduce the NCD burden in developed and developing countries by strengthening health systems and primary care infrastructures across the continuum of care – prevention, early diagnosis, treatment, adherence and ongoing disease management.”

An important NCD Alliance resolution recognizes “the lack of sufficient statistical data on non-communicable diseases, particularly in developing countries, and the need for the development and wide utilization of a set of standardized indicators for data collection and information on trends in respect of non-communicable diseases and their risk factors at the global, regional and national levels.”

Development, Ageing & Lifestyle changes in Asia Pacific populations
In Asia Pacific countries, population health profiles have been changing drastically, with greater percentages of their population ageing rapidly. Cardiovascular diseases have become the predominant causes of mortality and morbidity. In 2005, Asia Pacific countries account for more than half the world’s Disability Adjusted Life Years (DALYs) lost due to CVD for both men and women.[ii]

In the United States, cardiovascular disease accounts for >800 000 deaths, >7 million hospital discharges and chronically affects >80 million adults, per year.[iii] The projected US healthcare cost of CVD in 2010 is half a trillion dollars. Although CVD death rates among younger Americans (35-54 years)[iv] appear to have plateaued, the overall future CVD burden is projected to increase due to population ageing and increasing prevalence of obesity and diabetes.[v]

Similarly in the Asia Pacific region, rapid economic development has also led to the rising prevalence of overweight and obesity, with diabetes increasing even more quickly.[vi] A moderate increase in body mass index and central obesity makes South Asians more prone to insulin resistance. In Malaysia, our population rate for diabetes has reached 14.9% of adults (>30 years old), surveyed recently in 2006.[vii]  But there are ethnic differences in the association between diabetes mellitus, ischemic heart disease and stroke within Asian populations.[viii],[ix]

Women, Menopause and CV Risks
Globally there is increased awareness that women have been neglected somewhat in our approach to the management or under-identification of cardiovascular risks and disease. We are increasingly aware that women could become the next potential health risk explosion in CVD. As more and more women outlive men and join the ranks of the elderly, they would become the next under-estimated cohort of CVD patients.

Post-menopausal changes are recognized as influencing more adverse CV risk profiles for women. In Malaysia, the National Heart Association of Malaysia has formed our WH2O, (Women Heart Health Organisation) to re-emphasise our commitment to addressing this societal need.

The SWAN (Study of Women’s Health Across the Nation) studied the influence of aging and menopause on cardiovascular risk factors in a subset of 1,054 women.[x] Matthews et al., found that following menopause and beyond 50 years of age, lipid profiles change for the worse, i.e. total cholesterol, LDL-cholesterol, apo-B lipoprotein increase, while HDL-cholesterol and apo-A1 lipoprotein decrease. Whether the threshold levels for lipid-lowering therapy should change around the time of menopause or whether the absolute or relative degree of change in lipids (independent of premenopausal levels) predicts future CHD events merits further study.[xi] However, the menopause-associated changes in total cholesterol, LDL-C, and Apo B probably contribute to women’s increased risk of CHD in the post-menopausal years.

Major take-home points for the clinician are that risk factor levels do change around the menopausal transition, in part due to chronologic aging and some related to the climacteric itself. Women should be made aware that their cardiovascular risk is likely to increase during this period. They should be counseled to emphasize therapeutic lifestyle changes to combat such increases. During this time it may be prudent to increase the frequency of risk factor monitoring to identify higher risk women, who may benefit from pharmacologic management of their risk factors beyond simply lifestyle modification.11

Lifetime Risk of Developing Coronary Heart Disease (CHD)
Lifetime risk of developing CHD increases with age, primarily because of progressive atherosclerosis due to deteriorating risk profiles, which affects the ageing vascular system.
At any given age however, men are at greater risk (49% higher) for CHD than women (32% higher), after the age of 40 years. Coronary Heart Disease (CHD) rates in women after menopause are 2 to 3 times higher than in women of the same age before menopause.[xii]

In a 1999 analysis of the Framingham Study database, 7733 patients were followed up for a total of 109 948 person-years. Overall, 1157 participants developed coronary heart disease. 1312 died from non-coronary heart disease causes. Lifetime risk of coronary heart disease at age 40 years was 48.6% (95% CI 45.8—51.3) for men and 31.7% (29.2—34.2) for women. At age 70 years, lifetime risk was 34.9% (31.2—38.7) for men and 24.2% (21.4—27.0) for women. After excluding isolated angina pectoris as an initial event, the lifetime risk of coronary artery disease events at age 40 years was 42·4% for men and 24·9% for women. Lifetime risk at age 40 years is one in two for men and one in three for women. Even at age 70 years it is one in three for men and one in four for women.[xiii]

A 2006 re-analysis of the Framingham data yielded and confirmed that lifetime prediction of CV risks can be carried out consistently.[xiv] The test cohort studied included all Framingham Heart Study participants who were free of CVD (myocardial infarction, coronary insufficiency, angina, stroke, claudication) at 50 years of age. Lifetime risks to 95 years of age were estimated for men and women, with death free of CVD as a competing event. 3564 men and 4362 women were followed for 111,777 person-years.

1757 had CVD events and 1641 died free of CVD. At 50 years of age, lifetime risks were 51.7% (95% CI, 49.3 to 54.2) for men and 39.2% (95% CI, 37.0 to 41.4) for women, with median survivals of 30 and 36 years, respectively. With more adverse levels of single risk factors, lifetime risks increased and median survivals decreased. Compared with participants with 2 major risk factors, those with optimal levels had substantially lower lifetime risks (5.2% versus 68.9% in men, 8.2% versus 50.2% in women) and markedly longer median survivals (39 versus 28 years in men, 39 versus 31 years in women).

Data from the UK also show similar outcomes: those with optimal CV risks (optimal cholesterol level, non-smoking, BP levels) have clearly better survival curves.[xv] In brief, those who have lowest CV risks at age 50 years are expected to have longer life expectancies by up to as many as 10 years over those who are of the highest CV risks!

Current Status & Controversies of CVD Prevention
An impressive array of epidemiological data has suggested that primary prevention is now a must to meaningfully impact on health outcomes for most nations of the world. Together with evidence-based medical and procedural therapies, we can now decrease case-fatality and reduce recurrent CVD events very aggressively (secondary prevention).

But primary prevention, i.e. to reduce chances of first event, is difficult to implement. Often, resources for the public who are relatively ‘well’ or symptom-free are limited and sporadic. Convincing the relevant authorities is difficult and large-scale community level projects are expensive and compete with other more urgent and concrete pressing social needs and services. Getting the public themselves to abide by or buy into prevention programmes is at best voluntary and may not be sustainable. These are often seen as unnecessary, imposing and restrictive, especially on lifestyle choices!

Many CVD patients have common predisposing risk factors, i.e. smoking, adverse dietary patterns, overweight, and sedentary lifestyles — leading to adverse blood lipid, blood glucose, & blood pressure levels. However, the majority of first CVD events occur in individuals with average or only mildly elevated levels of risk factors (who would not typically qualify for intensive prevention efforts).[xvi] In this category of indeterminate risks, the problem arises as to how we can recommend any wide-scale public health measure.

We currently have studies, which show that treating pre-hypertension,[xvii] or pre-diabetes[xviii],[xix],[xx] may actually delay the full-fledged development of hypertensive or diabetic complications and sequelae. Just how we can persuade ‘well’ but just marginally-off (the bell-curve tails) patients to consider long-term medications, remains a challenge. We do not have longer outcome data to convince us that survival and/or quality of life are actually improved and that the adverse effects of prolonged medications are entirely benign.

Even though we do have extensive and convincing primary prevention data on lowering LDL cholesterol,[xxi],[xxii] many among the public remain unconvinced that using statins interminably and aggressively is the answer. There are lingering public fears that longer term adverse effects remain undisclosed or worse suppressed by the ‘drug’ vendors![xxiii],[xxiv],[xxv] The respected Cochrane database systematic review stated that while the benefits of statin use in primary prevention is proven with no major adverse effects, caution should still be taken in prescribing statins for primary prevention among people at ‘low’ cardiovascular risk.24

Controversy therefore remains whether there are any subsets (high CRP?) of patients with supposedly higher risks that really need treatment.[xxvi] Thus, population-based CVD prevention should still best be achieved through lifestyle and environmental modifications. Long-term and indiscriminate or blunderbuss medication prescription is still considered inappropriate by many,[xxvii] and other strategies are needed to shift the entire distribution of risk. Over-the-counter statin (simvastatin 10 mg) policy changes in the UK have not reached thresholds to make this a meaningful public health programme a success story, even as of now.

Primordial Prevention: Moving beyond primary and secondary prevention
Recently, there has been wider discussion on targeting the population for modification, even before some of these risk factors rear their heads—a term titled primordial prevention. Primordial prevention strategies have the potential to reduce the population burden of CVD substantially by preventing the development of adverse risk factors.3

This radical concept is gaining ground. Recent studies show that individuals, who maintain a profile of ideal cardiovascular risk factor levels from young adulthood into middle age, can essentially avoid (even escape) major CV events for their remaining lifetime. Indeed, achieving ideal cardiovascular profiles younger can reduce both CVD and non-CVD mortality rates, resulting in an average additional 10 years of longevity!13,14 These individuals also have markedly better health-related quality of life at older ages and also have lower annual Medicare costs. Conversely, any adverse level of a risk factor in middle age substantially increases lifetime risks for CVD. The American Heart Association recently endorsed primordial prevention as a powerful new mechanism for improving cardiovascular health in all Americans in the coming decade.5

Capewell et al,3 argued that if a majority of the population attains middle age with a prescribed ideal or optimal ‘phenotype’, more than 90% of the coronary heart disease deaths otherwise expected, might be prevented. However, barely 5% of the US population now maintains this ideal CV profile into middle age. It is likely that in Malaysia this is also the case, if not worse.

Thus, it begs an important question: Which effective public health policies could promote primordial prevention and maintain ideal cardiovascular health into middle age? This change would require a drastically different but conducive environment that supports health, rather than, as now, promoting obesity, hypertension, hyperlipidemia, diabetes, and inactivity.

Effective CV Prevention Strategies[xxviii]
Prevention efforts are classified into 2 complementary categories: “high-risk” and “population-based” strategies. High-risk strategies focus on identifying, detecting and treating individuals, who have high short-term risk for CVD. High-risk strategies are medically based and usually proven effective for persons with high CVD risk. These are immediately result-oriented and are usually very cost-effective even if rather costly, on a per individual basis.

Complementary “population-based” strategies aim to improve the entire population by favorably shifting the distribution of risk factors. They modify or force behavioural change for the masses. Population-based strategies while difficult to implement are surprisingly effective and have resulted in quite rapid measurable benefits.

Several meta-analyses and reviews on indoor smoking bans and secondhand smoke in the United States, Canada Italy and Scotland have shown "remarkable consistency" in the association between bans and reductions in heart attack rates, ranging from 6 % to 47 %.[xxix],[xxx],[xxxi]

Likewise, CVD rates in Poland decreased within 3 years after the repeal of subsidies for meat and animal fats in the early1990s.[xxxii]

The successful North Karelia Project, begun in Finland in the 1970s, is the classic example of a national public health policy at its best. Its comprehensive, community-based and national policy interventions, which focused on favorably influencing dietary habits (drastically discouraging fatty meat and dairy product consumption) and reducing smoking, resulted in huge decreases (80%) in CVD mortality rates over 25 years.[xxxiii]

CV Prevention: Regulatory & Dietary Options[xxxiv]
National and local governments and health organizations are now addressing CVD prevention with both such approaches.

First, physicians must be actively encouraged to identify and treat individuals at high cardiovascular risk. Second, policy and regulatory initiatives must be enacted, to incentivize population-wide behavioural change (e.g. promoting good dietary habits, smoke-free legislation, salt or sugar reduction, regular physical activity).

However, some government policies may sometimes be conflicted; e.g. continued subsidies for certain crops (tobacco, corn) that can promote disease rather than health. Agricultural subsidies can be used more positively; e.g. encouraging or incentivizing a farming shift from dairy to berry production; and making fruits cheap and favoured for schoolchildren.

Enlightened governments may also provide favorable subsidies or policies that promote and prefer polyunsaturated vegetable oils, skim milk, whole grains, or fresh fruits and vegetables. Regulation, legislation, and partnering with the food industry have great potential too. Concerted and consistent efforts of reducing salt in the food chain can also lead to substantial benefits. Likewise, potentially large benefits might occur from implementation of broader dietary strategies for reducing or avoiding intake of greasy high-calorie fast foods, re-used trans fats and/or saturated fats.

Economic concerns[xxxv]
Rising health care cost is a perennial problem for all governments, globally. Cardiovascular disease burden is rising worldwide. The Asia Pacific region is poised to taking the lead of being affected by disproportionately highest rates of disease-adjusted life years (DALYs) lost due to CVD!

This growing CVD economic burden is driven by 3 factors: new technology and tertiary specialist care such as revascularization procedures, hospital care, and prescriptions for costly medications, e.g. statins, antihypertensive, diabetes, and obesity drugs. Thus, reliable cost-effective strategies and estimates for preventive interventions are critically important.

Thus far, medication-based primary prevention appears relatively costly; the number needed to treat (NNT) statistic remains to be better refined and improved to the point of acceptable cost-efficacy pertinent to every socio-economic entity and nation. Initial outlays for these measures for poorer countries must be made affordable through the wider and more appropriate use of cheaper and yet equivalently effective generic medicines.

The cost of these on a nationwide scale must not compete with budgets for other more pressing social needs and priorities. Conversely, primordial prevention interventions might generate savings when targeting specific behaviors such as smoking cessation, dietary cholesterol reduction, or increasing physical activity; but such measures are difficult to inculcate as a population or cultural behaviour change.

Studies from United States, Australia, and United Kingdom consistently suggest & show that population-wide prevention programs substantially reduce health care expenditures. Thus, these must be taken as effective role models to emulate.

An economic model commissioned by the UK National Institute for Health and Clinical Excellence (NICE) was recently developed for the entire UK population of 60 million.[xxxvi] Conservative estimates suggest that any policy intervention, which results to a 1% population-wide reduction in CVD risk factor level, would be cost saving. Reducing mean population cholesterol levels or blood pressure levels by 5% or enacting legislation to eliminate trans fats or reduce dietary salt intake by 3 g per day, was each estimated to cost save in excess of $1 billion per year!

Greater Commitment to Prevention Strategies for the Population
Health officials, including doctors and patients, need a better understanding of the consequences of conflicting trends in CVD risk factors and the different options for reducing the future burden of CVD globally. Ideally, large population-based research should compare various mixes of intervention strategies, but many such studies are not readily feasible or forthcoming.

Large-scale prevention strategies need to be validated via policy models. The best models use extensive data-mining of population risk-factor profiles and disease prevalence, with subsequent computer-intense simulation of the effects of different interventions. But developing nations must allocate more resources and training personnel to collecting basic and more in-depth data of their own population’s health profiles, disease patterns and needs.

We need greater understanding of the potential benefits and optimal mix of current and future preventive strategies. Escalating current and future projected health care costs and the huge immediate costs of implementing long-term CVD prevention programs, may hamper and delay effective strategies for CVD prevention. The status quo is not acceptable politically, ethically, or economically.

Disclosure & Provenance statement
No conflict of interest or disclosure is relevant in the writing of this paper. Certain points in the above paper have been presented as a lecture “Managing Cardiovascular Disease in the Asia Pacific”, at the 4th Scientific Meeting of the Asia Pacific Menopause Federation (APMF) in Sydney, Australia on 26-29 September 2010.


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