Multiple observational cohort studies, either single or pooled, have been conducted to explore the association of combined hypertension-dyslipidemia and future CVD incidence and consistently found that individuals with both hypertension and dyslipidemia have a greater risk of CVD than those with either hypertension or dyslipidemia alone in a variety of populations [9–13]. One of the earliest studies involved 316,099 white men screened for the Multiple Risk Factor Intervention Trial (MRFIT). The study showed that high cholesterol levels (>180 mg/dL), elevated systolic BP (>110 mmHg), and diastolic BP (>70 mmHg) were strongly correlated with increased risk of CHD-related death [9]. Also, the impact of LDL-C seems weaker among older patients based on data from the Cardiovascular Health Study (CHS), which revealed that in those ≥ 65 years, elevated BP was associated with increased risk across all lipid levels while increased LDL-C added risk mainly when BP <140/90 mmHg [10]. On the contrary, a French study including subjects under 55 years of age showed a combination of high systolic blood pressure and high serum cholesterol dramatically increased cardiovascular disease and coronary heart disease risk, especially in men [11]. One recent large pooled cohort study from Japan additionally found the synergistic increase in risk for coronary heart disease death in the Asian population: the adjusted hazard ratios of systolic increase with increases in total cholesterol categories and similar increase hazard ratios of total cholesterol was seen with increases in systolic BP categories (Fig. 13.2) [12]. The Turkish study compared the risk of CVD between dyslipidemic hypertension and simple hypertension and found that the dyslipidemic hypertensions have 58 % higher risk [8]. Besides, those with dyslipidemic hypertension also have 47 % higher risk of CVD than those with MetS but no dyslipidemic hypertension, indicating that the coexistence of hypertension and dyslipidemia may aggregate the risk of future CVD.

Although clinical trials have proved the efficacy of combined therapy and guidelines are continuously updated, control of hypertension-dyslipidemia remains inadequate. It was estimated that among the 78 million Americans with hypertension, although 81 % of them were aware of the disease and 75 % received treatment, only 53 % were under control [14]. The control rate of both hypertension and dyslipidemia is even lower. Wong et al. found that among those with the two conditions, the control of both was as low as 9 % [4]. Control of HTN-DYS was worse in women, nonwhites, and those with DM or CVD [4, 15]. From 1988 to 2010 in the USA, control of concomitant high blood pressure and LDL-C increased from 5.0 to 30.7 % (and from 1.8 to 26.9 % if non-high-density lipoprotein cholesterol control was added) [16].

Individual antihypertensive therapy and lipid-lowering drugs reduce CVD events by approximately 25 % and 30 %, respectively [17]. But the combined therapy can more rapidly control blood pressure and lipids to target levels compared to single therapies alone due mainly to better adherence of a single fixed-dose combination agent [18]. Trials of combined therapy of amlodipine and atorvastatin showed comparable control rates (Table 13.1). Within the designed study period, which varies from 8 weeks to 20 weeks, the control rate of both risks ranged from 48.3 to 67.8 %. It is consistent across all the studies that LDL-C level is better controlled than blood pressure. In addition, there is no obvious trend that higher blood pressure/LDL-C level corresponds with poorer control rates, indicating the control of risk factors, either combined or single, might be influenced by other reasons. Combined valsartan/simvastatin in different titrations were also investigated and showed similar (50%) control rate of both risk factors. However, the results also showed that increasing the dose of simvastatin does not help improve the combined control rate [28].

Treating hyperlipidemia in hypertensive patients significantly reduces future CHD risk compared to single medication strategy or placebo [29, 30]. The Anglo-Scandinavian Cardiac Outcomes Trial–Lipid-Lowering Arm (ASCOT-LLA) demonstrated that adding atorvastatin will result in an additional 29 % risk reduction for CHD and 21 % for CVD events [30]. Observed CHD event rates reduced by 79 % in those assigned amlodipine-based treatment and atorvastatin, compared to the estimates of CHD risk by Framingham algorithm at baseline [31]. If patients present more risk factors, for example, in those with metabolic syndrome, controlling blood pressure, LDL-C, and HDL-C to normal levels will prevent 51.3 % of events for men and 42.6 % for women and prevent 80.5 and 82.1 % of events if controlling to optimal levels, respectively [32]. Emberson J et al. used estimates of the relative risk reductions from meta-analyses of randomized trials in combination with data from a prospective observational study of CVD (the British Regional Heart Study) to analyze the impact of different risk reduction strategies in primary prevention [33]. The study examined the effects of prevention strategies based on single risk factor assessment or total risk assessment. They concluded that assessment of overall risk leads to more effective intervention than assessment based on single risk factors. Furthermore, multiple interventions have considerably greater benefits than interventions based on targeting single risk factors. A 10 % reduction in long-term mean blood cholesterol and BP could have reduced major CVD by 45 %.

But the additional prognostic benefit beyond the blood-pressure-lowering and cholesterol-lowering effects in the combined treatment in secondary prevention seems still questionable. The Japanese Coronary Artery Disease (JCAD) study of 13,812 patients with angiographically demonstrable significant coronary narrowing showed no statistically significant difference in the cardiovascular event rate between those on the combined therapy of calcium channel blocker (CCB) plus statin and those with neither CCB nor statin [13]. Another meta-analysis also found that compared with placebo, single drug active component, or usual care, the effects of fixed-dose combination therapy on all-cause mortality or CVD events are still uncertain, although most of them reached prescribed control targets [34]. Statins and some hypertension medications are also believed to have pleiotropic actions beyond their lipid-lowering and antihypertensive effects.