A family history of premature CHD is a well-established, but unmodifiable risk factor for future CHD and can sometimes be the crucial and single most important risk factor in predisposing an individual to early CHD [1]. A large proportion of heart attacks or strokes occurring at a young age are felt to be attributable to inherited or familial pre- disposition. Hence, knowledge of an individual’s family history can help guide preventive efforts. In recent years, with the ability to sequence the entire human genome, key single-nucleotide polymorphisms (SNPs) have been identified and linked to the likelihood of CHD, although with a much higher threshold required to confirm a statistically significant relationship [2]. One region that has received significant attention is 9p21 because of its strong association with CHD [3]. However, the utility of such SNPs in improving the ability to predict CHD over traditional risk factors is only modest and current guidelines have not recommended genomic screening due to the thus far limited demonstrated clinical utility. 

Diabetes mellitus is a major risk factor for CVD and is associated with a greater risk for CHD, stroke, chronic kidney disease and peripheral vascular disease [4]. Clinical trial evidence to show whether intensive glycaemic control in people with diabetes lowers CVD event rates has shown mixed results. The United Kingdom Prospective Diabetes Study (UKPDS) originally showed a borderline, non-significant 16 per cent reduction in risk of myocardial infarction among those with newly diagnosed type 2 diabetes who were treated with intensive glucose lowering therapy, but the 10-year post-interventional follow-up of this study, which was recently published, showed that these benefits continued with a 15 per cent significant reduction in risk of myocardial infarction [5]. A similar, extended post-interventional follow-up of the Diabetes Control and Complications Trial of Type 1 diabetes, which did not initially show a significant reduction in CVD events at the end of the randomized trial, showed years later a continued effect of the original intensive glucose-lowering treatment, with a 42 per cent reduction in the risk of any cardiovascular event [6]. Such a continued post-trial effect of the randomized glycaemic therapy has been termed a ‘glycaemic legacy’ effect. More recently, however, three important randomized clinical trials (the Action to Control Cardiovascular Risk in Diabetes (ACCORD), ADVANCE and the Veterans Affairs Diabetes Trial (VADT)) failed to show that intensive glucose lowering to a HbA1c range of 6–6.5 per cent significantly reduced CVD event rates, as compared to more standard maintenance of the HBA1c in the 7–9 per cent range. In fact, those randomized to the intensive therapy group in ACCORD actually had a higher rate of CVD mortality [7], although this increased risk was restricted to those with prior macrovascular disease and where there was unsuccessful lowering of the glucose as a result of the intensive therapy. Those with less complicated diabetes (e.g. patients who were more recently diagnosed and without prior macrovascular disease) actually showed a benefit in the primary end point. Moreover, an important lipid sub study of ACCORD tested the efficacy of adding the fibric acid derivative fenofibrate or placebo to ongoing statin therapy and found no benefit in terms of reducing CVD event rates (although there was a benefit seen in the subgroup with high triglycerides and low high-density lipo- protein cholesterol (HDL-C)) [8]. In addition, in the blood pressure sub study of ACCORD, intensive blood pressure therapy to achieve a systolic blood pressure less than 120 mmHg, as compared with less than 140 mmHg, was also found to provide no significant benefit in terms of CVD risk reduction, although there was a significant benefit in stroke reduction [9].

Elevated blood pressure and particularly systolic blood pressure, is strongly and positively related to the risk of future CHD and stroke. Hypertension is currently defined as a systolic blood pressure of 140 mmHg or higher, diastolic blood pressure of 90 mmHg or higher (or on pharmacological treatment to lower blood pressure). Numerous clinical trials have shown that lowering blood pressure substantially decreases the risk of future cardiovascular events, stroke and end-stage renal disease. A large meta-analysis of active treatment (with initial low dose diuretic, beta blocker, angiotensin-converting enzyme (ACE) inhibitor or calcium antagonist) compared to placebo showed significant reductions in the risk for heart failure (36 per cent), stroke (33 per cent), CHD (16 per cent), CVD death (15 per cent), overall CVD (25 per cent) and total mortality (12 per cent) [10].

Increased levels of total and LDL-C have long been recognized as major risk factors for CHD. A direct curvilinear relation exists between total and LDL-C and the risk of CHD. For example, com- pared to those with total cholesterol levels of 200 mg/dL, those with levels of 240 mg/dL are at approximately twofold greater risk, while those with levels of 300 mg/dL have a fourfold increased risk. A population optimal LDL-C level has been designated as less than 100 mg/dL with levels of 130 mg/dL, 160 mg/dL or 190 mg/dL often considered the thresholds for beginning lipid-lowering therapy in those at high, intermediate or low CHD risk, respectively [11]. However, there is significant overlap in total or LDL-C levels between those who experience CHD events versus those who do not and approximately one-third of heart attacks occur in people with ‘normal’ levels of total cholesterol below 200 mg/dL. Importantly, a low level of HDL-C (typically defined as < 40 mg/dL in men and < 50 mg/dL in women), regardless of level of total cholesterol, is strongly associated with an increased risk of CHD [12].

Tobacco smoking is among the leading preventable causes of death globally. Cigarette smokers are 2 to 4 times more likely to develop CHD than non-smokers. Also, their risk of stroke is doubled and risk for peripheral vascular disease is more than ten times higher than that of non-smokers [13].

Obesity has been shown by numerous studies to be associated with an approximate 1.5- to twofold increase in risk of death from CHD, with the increase in risk beginning below the 25 kg/m2 cut-off point for overweight. Numerous studies also show approximately 20–40 per cent lower risks of mortality and cardiovascular events associated with increased levels of physical activity or measured fitness. Several cardiovascular risk factors are linked to obesity, including hypertension, dyslipidaemia (including low HDL-C levels), type 2 diabetes, obstructive sleep apnoea and hyperinsulinaemia. Increases in physical fitness have also been shown to be linked to increases in HDL-C levels and reductions in systolic and diastolic blood pressure, insulin resistance and glucose intolerance. Abdominal obesity, most commonly indicated by a waist circumference of greater than 40 inches (102 cm) in men or greater than 35 inches (89 cm) in women, is a major component of the metabolic syndrome. Studies demonstrate that weight loss can substantially improve many cardiometabolic risk factors [14].

Prevention

In recent years, the AHA [15] has promoted a goal to improve the cardiovascular health. These goals introduce the concept of promoting cardiovascular health which is more positive and motivating than the concept of preventing cardiovascular disease and have focused on examining the proportion of individuals (and the relation to CVD risk) who achieve one or more ‘ideal levels’ based on the following seven metrics (also known as AHA’s Life’s Simple Seven TM): 

• Cigarette smoking (non-smoking is ideal)

• Physical activity (150 minutes or more moderate intensity or equivalent exercise per week is ideal)

• Body mass index (< 25 kg/m2 is ideal)

• Healthy diet (achieving at least four of five key dietary components focusing on fruit/vegetable, fish, fibre and sodium intake and sweetened beverage intake)

• cholesterol (< 200 mg/dL ideal in adults, < 170 mg/dL in children)

• Blood Pressure (< 120/80 mmHg is ideal)

• Fasting plasma glucose (< 100 mg/dL is ideal)

CVD accounts for the greatest burden of morbidity and mortality worldwide, both in developed and in developing countries. Key cardiovascular risk factors, including hypertension, cigarette smoking, high blood glucose, physical inactivity, obesity and elevated cholesterol are (in that order) the top leading causes of death worldwide. It has been estimated that elimination of obesity, unhealthy diets and physical inactivity could reduce up to 80 per cent of heart disease, stroke and diabetes.

Concerted global efforts aimed at coordinating care for those with pre-existing CVD (secondary prevention), primary prevention, identifying people with cardiovascular risk factors and getting them the necessary treatments, as well as primordial prevention aimed at prevention of obesity and other major risk factors in the first place, are critical for reducing the morbidity and mortality associated with CVD.

1. Hopkins, P.N. et al. "Family history and genetic factors." In Preventive Cardiology: A Practical Approach, edited by N. D. Wong, H. R. Black and J. M. Gardin, McGraw Hill, 2000, pp. 94–128.

2. Schunkert, H. et al. "Large-Scale association analysis identifies 13 new susceptibility loci for coronary artery disease." Nature Genetics, vol. 43, no. 4, 2011, pp. 333–338.

3. Palomaki, G.E. et al. "Association between 9p21 genomic markers and heart disease: a meta-analysis." JAMA, vol. 303, no. 7, 2010, pp. 648–656.

4. Kaseta, J. and Sowers, J.R. "Diabetes and the metabolic syndrome." In Preventive Cardiology: A Practical Approach (2nd ed.), edited by N.D. Wong, H.R. Black and J.M. Gardin, McGraw Hill, 2005, pp. 212–232.

5. Holman, R.R. et al. "10-Year follow-up of intensive glucose control in type 2 diabetes." New England Journal of Medicine, vol. 359, no. 15, 2008, pp. 1577–1589.

6. Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Study Research Group. "Intensive Diabetes Treatment and Cardiovascular Disease in Patients with Type 1 Diabetes." New England Journal of Medicine, vol. 353, no. 25, 2005, pp. 2643–2653.

7. Action to Control Cardiovascular Risk in Diabetes Study Group. "Effects of Intensive Glucose Lowering in Type 2 Diabetes." New England Journal of Medicine, vol. 358, no. 24, 2008, pp. 2545–2559.

8. ACCORD Study Group. "Effects of combination lipid therapy in type 2 diabetes mellitus." New England Journal of Medicine, vol. 362, no. 17, 2010, pp. 1563–1574.

9. Cushman, W.C. et al. "Effects of intensive blood-pressure control in type 2 diabetes mellitus." New England Journal of Medicine, vol. 362, no. 17, 2010, pp. 1575–1585.

10. Elliott, W. "Cardiovascular events in clinical trials of antihypertensive drugs vs. placebo/no treatment: A meta-analysis." Journal of Hypertension, vol. 23, June 2005, pp. S273–S273.

11. Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). "Executive summary of the third report of the national cholesterol education program." JAMA, vol. 285, no. 19, 2001, pp. 2486–2497.

12. Castelli, W.P. et al. "Incidence of coronary heart disease and lipoprotein cholesterol levels: the framingham study." JAMA, vol. 256, no. 20, 1986, pp. 2835–2838.

13. Luepker, R.V. and Lando, H.A. "Tobacco use, passive smoking and smoking cessation interventions." In Preventive Cardiology: A Practical Approach (2nd ed.), edited by N.D. Wong, H.R. Black and J.M. Gardin, McGraw Hill, 2005, pp. 217–250.

14. McCowen, K.C. and Blackburn, G.L. "Obesity and weight control." In Preventive Cardiology: A Practical Approach (2nd ed.), edited by N. D. Wong, H. R. Black and J. M. Gardin, McGraw Hill, 2005, pp. 233–255.

15. Go, A.S. et al. "Heart disease and stroke statistics—2013 update: a report from the american heart association." Circulation, vol. 127, no. 1, 2013, pp. e6–e245.